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ON 
 
 DIABETES MELLITUS 
 
 AND 
 
 GLYCOSURIA 
 
 BY 
 
 EMIL KLEEN, Ph.D., M.D. 
 
 PHILADELPHIA 
 
 P. BLAKISTON'S SON & CO. 
 
 IOI2 Walnut Street 
 1900 
 
I3oo 
 
 COPYRIGHT, 1900, BY P. BLAKISTON'S SON & CO. 
 
 PRESS OF Wm. F. Fell & Oo^ 
 
 1220-24 SANSOM ST., 
 PHILADELPHIA. 
 
PREFACE. 
 
 Among the thousands annually visiting Carlsbad in search of 
 health the diabetics present the greatest clinical interest, and from 
 my first years as a practitioner in the Bohemian Spa I sought some 
 relief from the monotony and many other unsatisfactory aspects of 
 a practice of this kind in a careful study of the gly cos uric dystrophy 
 with its manifold complications. 
 
 Early in the nineties I conceived the project of publishing a 
 book upon this subject, hoping thereby to fill a want in the medical 
 literature of the day. Others, however, at about the same time 
 undertook the same assiduous task. A few months after my 
 reading, early in 1895, a paper on "Digestion, Metabolism, and 
 Nutritive Needs in Diabetes " before the Swedish Association of 
 Physicians,* v. Noorden's highly scientific work on diabetes was 
 published, and almost simultaneously with the appearance of my 
 own long-delayed book in the Swedish language, Naunyn's mag- 
 nificent monograph was welcomed by the profession. 
 
 Still, the more than kind reception that has been accorded this 
 book by the physicians of my native country has led me to enter- 
 tain the hope that the most important part of my clinical, experi- 
 mental, and literary work of recent years has not been entirely in 
 vain. I resolved to give my book publicity in some more widely 
 used language than the one most familiar to me, and myself, with 
 some few additions and changes, translated my book into English. 
 In doing this I derived considerable assistance from a dear Ameri- 
 can friend. Finally, Dr. Eshner, of Philadelphia, has revised the 
 manuscript and added his most valuable aid to change my own 
 
 * See the " Transactions of the Association " (" Hygiea ") for the same year, and 
 the chapter on Metabolism in this book. In the latter I have added some references to 
 the researches of the last few years. 
 
 V 
 
VI PREFACE. 
 
 somewhat deficient English into good English, for which work I 
 hereby render my public thanks. For the substance and scientific 
 matter of this book I am myself alone responsible. 
 
 I have treated the vast subject of diabetes and glycosuria with 
 as much brevity as is compatible with my purpose of giving as 
 full a viev/ of it as the present time allows, never having out of 
 sight that my chief aim is to facilitate for the general practitioner 
 the acquisition of the knowledge of the glycosuric dystrophy, to 
 which I have devoted considerable time and work. 
 
 At the end of the book I give a Hst of names of the chief 
 
 authors on the subject of diabetes but no list of their works, 
 
 as this alone would fill a small volume, and now that we have the 
 
 "Index Medicus " and the "Catalogue," seems to me entirely 
 
 superfluous. 
 
 Emil Kleen. 
 Carlsbad, September, 1899. 
 
CONTENTS. 
 
 Chapter Page 
 
 I. Definition and History 9 
 
 II. Geographic Distribution and Etiology 15 
 
 III. Glycosurias, 26 
 
 IV. Symptoms and Complications of Mild and Severe Diabetes, 70 
 V. Diabetes Infantilis, 157 
 
 VI. Diabetes Mellitus Following Extirpation of the Pancreas, 164 
 
 VII. Metabolism and Nutritive Needs 169 
 
 VIII. Investigation of a Case of Diabetes 236 
 
 IX. Treatment, 253 
 
 Table of the Commonest Kinds of Food in Percentages of Pro- 
 TEiD, Fat, and Carbohydrate, 295 
 
 Personal Register, 299 
 
 Index 307 
 
 vu 
 
DIABETES MELLITUS 
 
 GLYCOSURIA. 
 
 CHAPTER I.— DEFINITION AND HISTORY. 
 
 Under the name diabetes mellitus are included different pathologic 
 conditions which, however imperfectly understood, undoubtedly in 
 most cases affect the central nervous system, and which are charac- 
 terized by a faulty metabolism, as a result of which, under ordinary 
 diet, there takes place the excretion in the urine of an abnormally 
 large amount of sugar. 
 
 Thus, diabetes mellitus, so far as is at present known, is not a 
 clinical unit, but a syndrome, the chief and most constant symptom 
 of which is glycosuria, and which is represented by very varying 
 clinical types. 
 
 There are, however, numerous cases attended with the excretion 
 in the urine of minute yet distinctly pathologic amounts of sugar, 
 which cases differ widely in clinical aspect and in prognosis from 
 the diabetic type, and which generally are not included in the 
 designation diabetes mellitus. 
 
 When the power of consuming the ingested and digested carbo- 
 hydrates is but little or momentarily impaired, and when the patho- 
 logic excretion of sugar, under ordinary mixed diet, only slightly 
 exceeds the traces of sugar found in normal urine, or is but transi- 
 tory, the condition is not called diabetes mellitus, but simple 
 glycosuria. 
 
 When the excretion of sugar becomes considerable and more 
 persistent, but disappears when the carbohydrates are decreased or 
 2 9 
 
lO DIABETES MELLITUS AND GLYCOSURIA. 
 
 withdrawn from the food, the condition, which generally is accom- 
 panied by other more or less well-defined symptoms, constitutes 
 the mild stage of diabetes. 
 
 The severe stage of diabetes is characterized by the occurrence 
 of glycosuria even when the carbohydrates are withdrawn from 
 the food. 
 
 We shall find that the limits thus fixed are far more distinct on 
 paper than in the reality of cHnical experience, in which w^e see 
 represented all imaginable intermediate stages between the normal 
 capability of consuming the sugar of the blood and the greatest 
 possible deterioration of this capability. 
 
 Our knowledge of diabetes has essentially developed during the nineteenth 
 century, but for many ages previously something was known of it, as is shown 
 in notices occurring here and there in ancient works. 
 
 The term diabetes {dia^ij-Tig : 6ia, through ; ^alveiv, to go) is attributed to the 
 Roman, Celsus, who lived in the beginning of the Christian era. The term 
 then probably comprised both diabetes mellitus and diabetes insipidus. 
 
 In the Indian Yajur-Vedas we find definite statements upon this subject, 
 and it seems from these ancient documents, discovered about a hundred years 
 ago, that Susruta, whose existence was passed in the native land of the 
 cobra, the Brahman, and the tiger during the seventh century, was familiar 
 with both the clinical picture and the sweet urine of diabetes mellitus, which 
 probably then, as now, was more general among the Hindus than among any 
 other race. 
 
 Europe was far behind India in knowledge of diabetes mellitus during those 
 times. As is always the case, single instances occur of correct guesses long 
 before science had acquired the facts. Paracelsus suspected that a change in 
 the blood is the cause of the symptoms of diabetes. It was, however, not until 
 as late as 1674 that the sweet taste of the urine was first noticed by Thomas 
 Willis (1622-1675), and a whole century more elapsed before Dobson showed 
 that this sweetness is due to a variety of sugar. The idea of the presence of 
 sugar in the blood of diabetics then began to gain ground, and we find this 
 opinion general at the commencement of the nineteenth century. Rollo and 
 Cruikshank accepted the existence of blood-sugar in diabetes ; but Nicolas and 
 Gueudeville, Segalas and Vauquelin, as also Sobeiran, tried in vain definitely 
 to demonstrate its presence. Wollaston at first (181 1) denied, but afterward 
 acknowledged, its existence. Maitland and Ambrosiani (1835) believed they 
 had found it. McGregor observed fermentation of diabetic blood, and Simons 
 found in the blood of a diabetic patient after a hearty meal 0.25 per cent, of 
 sugar, although only traces had been present before the meal. 
 
 All of these observations, however, concerned diabetes exclusively ; but as 
 early as 1826 Tiedemann and Gmelin deemed sugar a normal ingredient of 
 the blood, and considered that they had proved its presence in dogs, whether 
 
DEFINITION AND HISTORY, I I 
 
 the animals were fed with carbohydrates or with meat. Early in the forties this 
 observation was confirmed by Magendie and by Frerichs, and in 1845 Thom- 
 son, by fermentation, made (far too low) a determination of the sugar in the 
 blood of fowls. 
 
 At the close of the forties Claude Bernard began his all-important investi- 
 gations, which proved successively the presence of sugar in the normal blood 
 under all dietetic conditions ; its production from glycogen in the liver ; its 
 dependence on nervous influences ; its increase above the normal ratio in cases 
 of diabetes, and many other facts, a knowledge of which is essential for a 
 comprehension of diabetes mellitus, and to which we shall have to return in 
 the chapter on Metabolism. 
 
 The enormous amount of work afterward performed in this field by others 
 has, on the whole, simply served to prove the correctness of Bernard's obser- 
 vations and conclusions, and it is only within quite recent times that experi- 
 mental pathology has provided us with any material additions to what that 
 most admirable physiologist taught us. 
 
 In 1848 Traube observed that sugar disappeared from the urine of a dia- 
 betic patient when carbohydrates were withdrawn from his food, and that the 
 same individual exhibited glycosuria at a later period, in spite of this with- 
 drawal. He thus discovered the difference between the mild and the severe 
 stage of diabetes, on which others, especially Seegen, afterward attempted to 
 found a division into two different forms of disease. 
 
 Toward the close of the fifties Briicke and Bence Jones, independently of 
 each other, found small traces of sugar in normal urinCf an event of import- 
 ance chiefly because it led to further investigations for small amounts of sugar 
 in urine and brought to light many instances of slight glycosuria, pathologic 
 though often unessential, that present themselves under different conditions. 
 Our knowledge of the simple glycosurias, however, has been chiefly developed 
 during the last two decades, and is still increasing year by year. 
 
 Gerhardt, in 1865, discovered that a solution of ferric chlorid causes a wine- 
 colored reaction with the urine of patients suffering from severe diabetes. This 
 observation has proved of immense importance, as it greatly facilitated the 
 diagnosis of severe diabetes and promoted the study and the comprehension 
 of certain pathologic metabolic products, and of those acid blood-toxins that 
 essentially invest the severe stage of diabetes with its clinical peculiarities. 
 
 Lavoisier had, in the latter part of the eighteenth century, laid down the 
 principles of metabolism, but it was not until the middle of the present century 
 that our knowledge of this most important subject began rapidly to develop 
 through the works of Liebig, G. Lehmann, Bidder and Schmidt, Bischoff, 
 Reignault and Reiset, and others. In 1867 Pettenkofer and Voit — though 
 they themselves at first misinterpreted their own results — taught us that the 
 consumption of oxygen, the excretion of carbonic acid, the production of heat, 
 and the nutritive needs in the diabetic are governed by the usual laws, and 
 that they are not attended with other deviations from the normal than those 
 that arise directly from the loss of sugar through its excretion with the urine. 
 When, later, Rubner (in the middle of the eighties) gave us his calorimetric 
 tables of the nutritive value of different articles of food, the conditions were 
 
12 DIABETES MELLITUS AND GLYCOSURIA. 
 
 fulfilled for arranging a rational diet for diabetics, as for others, and we have 
 been enabled more effectually to obviate the mistake of dieting diabetics, with 
 the one view in mind of eliminating hyperglycemia and glycosuria, and with 
 out due regard to dietetic possibilities and to nutritive needs. 
 
 In 1886 von Mering discovered phloridzin-glycosuria, which is curiously 
 characterized by the excretion of large amounts of glucose, with a diminished 
 quantity of sugar in the blood. Three years later von Mering and Minkowski, 
 thanks to the great accuracy of their mode of investigation, had the good 
 fortune to discover that severe diabetes can be produced by total extirpation 
 of the pancreas — the one " artificial " method at present known of bringing 
 about with certainty this variety of diabetes. By reason of these two discov- 
 eries, and in view of the far-reaching consequences of the latter, von Mering 
 must be considered as the investigator that, next to Claude Bernard, has con- 
 tributed most effectively to our knowledge of diabetes mellitus. 
 
 During the last few decades an extensive literature has accumulated, and 
 many valuable contributions have been made to the knowledge of this dystro- 
 phy. In addition to those already mentioned, a great number of authors have 
 distinguished themselves in this connection, among whom I may name Frerichs, 
 Bouchardat, Cantani, Seegen, Pavy, Bouchard, G. A. Hoffmann, Griesinger, 
 E. Kiitz, von Voit, Naunyn, Ebstein, Chauveau and Kaufmann, Lepine, 
 Weintraud and von Noorden — passing over no small number of others who 
 have written more or less important works on the subject. 
 
 Diabetes mellitus, being in its "mechanism" a peculiarly mys- 
 terious disease, with an undiscovered, or at least not fully explained, 
 pathologic anatomic basis, has been made the subject of many 
 theories, at present amounting to more than thirty. In no other 
 department has medicine made such extended excursions into the 
 domain of purely speculative science, and nowhere has this led to 
 greater liberties with the imagination. It is not my intention in 
 this work, which is designed for the practitioner, to enter upon a 
 consideration of all of these thirty theories ; but in order to show 
 how weak and uncertain our search for truth has been in this field, 
 and how many different theoretic possibilities present themselves, 
 I will cursorily mention the main currents of opinions that have 
 prevailed. 
 
 In former times the cause of diabetes was looked for in those organs whose 
 functions show the most manifest abnormity — /. <?., the kidneys. This idea, 
 in all its naivete, has been to a certain degree revived, though with numerous 
 modifications, additions, and limitations by our views on phloridzin-glycosuria, 
 and by the auxiliary influence on the excretion of glucose, attributed on strong 
 grounds by many authors to the kidneys. 
 
DEFINITION AND HISTORY. 1 3 
 
 Rollo, the greatest authority on diabetes at the beginning of the present 
 century, supposed the cause of the dystrophy to be a disturbance of the diges- 
 tive functions, which resulted in an excessive resorption of carbohydrate. 
 Similar opinions, however absurd they may seem at present, have been ex- 
 pressed quite recently by many authors, and, among others, by no less an 
 authority than Bouchardat in his earlier days. The importance in the causa- 
 tion of diabetes of changes in the pancreas was suspected long before Lance- 
 reaux wrote his paper on this subject, and before we knew the effect of total 
 extirpation of the pancreas, and could assign to this organ a rational position 
 in the pathogenesis of diabetes. An intuition of such a relation was at the 
 bottom of the views of Bouchardat and others, and later found expression in 
 Popper's idea of faulty digestion, in consequence of a defective secretion of 
 the pancreatic juice as a cause of diabetes mellitus. 
 
 Since Bernard's great discoveries and his theory of the formation of the 
 sugar of the blood in the liver from glycogen, and of its consumption in the 
 tissues for the production of vital force, two great schools have arisen, in each 
 of which several divisions are apparent. One of these schools considers the 
 cause of hyperglycemia and glycosuria — i. e., of diabetes — to be a ditninisked 
 consumption of sugar in the tissues. For the sake of brevity, we may be per- 
 mitted to say that the other school considers the cause to be an increased pro- 
 duction of sugar m the liver. According to some views, this excessive produc- 
 tion, however, is of an entirely passive kind, and is more correctly expressed 
 as a diminished capability of the organ of transforming into, and storing as, 
 glycogen the sugar conveyed to it through the portal vein, so that a larger 
 part of the sugar reaches the circulation by the hepatic veins than can be stored 
 in the muscles as glycogen, or be consumed by them. A large number of 
 authors consider this view corroborated by the frequency with which sugar 
 appears in the urine in cases of cirrhosis of the liver, A positive participation 
 on the part of the liver may also be conceived. Claude Bernard and his 
 numerous followers believe this to consist in increased activity of a normal 
 function pathologically excited by hyperemia. Pavy and Schiff thought the 
 production of glucose in the liver an entirely pathologic phenomenon. In 
 both views a diastatic ferment and a central nervous influence transmitted 
 through the vasomotor nerves are accepted. The latter influence must be given 
 a place in every general theory of diabetes. 
 
 Those that have conceived the idea of defective consumption of the sugar 
 of the blood have either accepted the disappearance from the organism of a 
 ferment that normally should cause decomposition of glucose into glycerin and 
 its aldehyd, and the cessation of which embarrasses further oxidation (Schult- 
 zen, Schermetjewski, Nencki and Sieber, Bence Jones), or have thought of 
 defective oxidation in the lungs (Araki), or have placed the fault with the 
 muscles (Zimmer). Since the theory of an " internal secretion " of the various 
 glands of the body was adopted, and the production of diabetes by total 
 extirpation of the pancreas was demonstrated, a large number of scientists 
 have come to consider the cause of diabetes to be the disappearance from, or 
 the diminution in, the blood of a "glycolytic ferment," present normally, and 
 sent into the blood by the pancreas for the combustion of glucose. 
 
14 DIABETES MELLITUS AND GLYCOSURIA. 
 
 There are, moreover, a considerable number of observers who have sup- 
 posed that there takes place a diminution in, or a retardation of, the entire 
 " internal respiration," which goes on in all of the tissues, — an opinion which at 
 first obtained some support from Pettenkofer and Voit's experiments on metab- 
 olism in diabetes by reason of their erroneous interpretation of their results 
 (Cantani, Jaccoud, Bouchard, Lecorche, Naunyn, Huppert). 
 
 Diametrically opposed to this opinion is another advocated by Robin, who 
 speaks of an increased metabolism, of a " suractiviie de la nutrition^ 
 
 In this cursory retrospect I wish to mention also Ebstein's carbonic-acid 
 theory, which, however ingenious, entirely lacks support in facts. Ebstein 
 placed reliance on the incorrect but once wide-spread supposition that a 
 diabetic ceteris paribus always consumes less oxygen and produces less car- 
 bonic acid than a healthy individual. The carbonic acid he supposed to act as 
 a check on the diastatic (glucose forming) ferment, and also to render certain 
 proteids — especially globulins — more tenacious. Thus, when the carbonic acid 
 — in consequence of a defect in the protoplasm, with resulting disturbances of 
 the " internal respiration " — is lessened in diabetes, in the first instance and in 
 the milder stage of the dystrophy, the carbohydrate — i. e., glycogen — is attacked 
 by the diastatic ferment more vigorously than under normal conditions. In 
 the severe stage the globulins are also decomposed more readily, and an exces- 
 sive formation of glucose begins at their expense. After Schierbeck's investi- 
 gations on the diastatic ferment in alkaline and acid solutions, Ebstein and 
 Schultze, in 1893, came to the conclusion that carbonic acid in alkaline solu- 
 tions aiigmeftts the diastatic activity, and retards it in neutral solutions, while 
 even a very slight degree of acidity inhibits it altogether. It is rather difficult 
 to understand how these facts, together with the qualities of the blood under 
 normal conditions and in the presence of severe diabetes, could be made to fit 
 in with Ebstein's theory, which, moreover, falls to pieces in the face of the fact, 
 now fully proved, that the diabetic produces as much carbonic acid as a 
 healthy individual. Ebstein's citation, in support of his theory, that Hoesslin 
 found a sojourn at a high altitude, which had been considered as increasing 
 the production of carbonic acid, to be favorable for the diabetic, is an unfortu- 
 nate one, as Hoesslin's experience in this respect, at the time his treatise was 
 written, was limited to a single case. On such a foundation not even a sup- 
 position should be hazarded on the subject of diabetes, and far more reliable 
 facts indicate that residence at great heights does not in any way counteract 
 diabetes. (See the following chapter.) The opinion that a sojourn at a high 
 altitude in rarefied air materially increases the production of carbonic acid 
 (Mermod, Marcet) does not seem to be borne out by facts. U. Mosso came to 
 the conclusion, a few years ago, from investigations conducted on Monte Rosa 
 and in rarefied air, that the quantity of carbonic acid produced in respiration 
 under these conditions at an altitude of 6400 meters differs but slightly from 
 that produced at an altitude of 286 meters (Turin). 
 
 Of late years there have been advanced in France — where, since Ber- 
 nard's time, diabetes mellitus has been the object of constant study — theories 
 concerning its pathogenesis, in which the nervous system, the pancreas, and 
 the liver are all involved. Even if these theories can not as yet be said to be 
 
GEOGRAPHIC DISTRIBUTION ETIOLOGY. I 5 
 
 more than hypotheses, they are nevertheless founded on definite observations 
 and are of actual interest. I shall, therefore, return to them in the chapter on 
 Metabolism, when we shall see that the theories of an increased production 
 and of a decreased consumption of sugar both have solid bases, and that they 
 ought not to be pitted against each other as utterly irreconcilable. To the 
 present comprehension of special pathogenetic factors in the dystrophic group, 
 the future will assuredly bring many additions and corrections, and the 
 present generation will, perhaps, in time be forced to confess that " all our 
 wisdom was but folly." 
 
 CHAPTER II.— GEOGRAPHIC DISTRIBUTION— ETIOLOGY. 
 
 Diabetes mellitus is a common phenomenon among civilized 
 humanity,* and is constantly increasing in {x^Q^oncy pari passu 
 with the intensity of cultivated life. 
 
 Some time ago I saw it stated — I believe it was by Worms — 
 that among men occupied in intellectual pursuits (statesmen, learned 
 men, professional men, merchants) of an age between forty and sixty 
 no less than ten per cent, are diabetics. Most physicians will be 
 inclined to protest against this figure as far too high, as it is, if by the 
 expression diabetic is meant a person that displays a cUnical type 
 of diabetes. It would be nearer the truth to place the number of 
 diabetics among the classes named at one per cent. On the other 
 hand, if we call every person a diabetic that, taking ordinary food, 
 excretes habitually and daily an inconsiderable though pathologic 
 quantity of sugar in the urine, Worms' figure would be rather too 
 low than too high. If samples of urine be taken an hour after 
 dinner from a hundred brain-workers between the ages of forty and 
 sixty, it will doubtless be found, on testing with Nylander's solu- 
 tion, or with Trommer's test, verified by the fermentation-test, that 
 about fifteen of the hundred samples contain an amount of sugar 
 
 * In animals diabetes mellitus — unless designedly caused for experimental purposes — 
 is very rare, but it has been observed in the ape (Leblanc, Beranger-Ferand), the horse 
 (Hiibner), and the dog (Thiermesse, Schindelka). Slight glycosuria has also been 
 noticed in animals. 
 
1 6 DIABETES MELLITUS AND GLYCOSURIA. 
 
 that attains to hundredths of a per cent. — i. e., are distinctly patho- 
 logic. It will, however, also be found that the greater part of the 
 "patients" in question consist of quasi-healthy, or, to use a better 
 expression, very slightly affected, persons, who neither for the 
 moment present, nor are likely in the future to present, decided 
 symptoms of the clinical type that we are accustomed to call 
 diabetes. 
 
 Among the European and the American, Aryan, highly civilized 
 races, the difference in the frequency of diabetes, on comparing large 
 areas, will not be found to be very great : not greater than it may 
 be in different parts of the same country. Different conditions of 
 life — altitude, climate, and state of culture, even within very narrow 
 limits — give rise to very considerable variations. Thus we find 
 that diabetes is more common in Malta and Gibraltar than else- 
 where on the shores of the Mediterranean, in Tuscany than in the 
 rest of Italy, in Normandy than in the other provinces of France, 
 in Vermont than in the other States of the Union. 
 
 The statistical figures that are available are assuredly far too low, as the 
 diabetic type is often not yerY pronounced, and in the milder form does not 
 cause death, except through complications which have no definite relation to 
 diabetes. Moreover, these figures have doubtless been obtained in very differ- 
 ent ways in various places, and allow of no absolute comparison. On learn- 
 ing from Saundby that the number of deaths annually from diabetes mellitus 
 per 100,000 inhabitants is in London 5.88, in Berlin 5.04, in Paris 9.6, in 
 Christiania 3.9, in Rome 1.67, in Malta 13.1 (the highest European figure), we 
 can scarcely conclude with certainty that the correct figure for Berlin is higher 
 than the correct figure for Rome, for which latter city the figure cited is 
 assuredly far too low. In Malta, however, diabetes is undoubtedly very 
 common. 
 
 In Norway, among 10,000 deaths, 21 are owing to diabetes mellitus (Kiaer). 
 
 There is scarcely any doubt that in large communities diabetes mellitus is 
 rapidly increasing. According to Bertillon's statistics (cited from Lepine), dia- 
 betes caused the following deaths per annum among 100,000 Parisians : 
 
 From 1865 to 1873, a total of 2.3 From 1885 to 1886, a total of 11 
 
 " 1873 " 1877, " 4 " 1887 " 1892, " 12.13 
 
 " 1878 " 1883, " 9 
 
 In Copenhagen the mortality from diabetes has also increased rapidly and 
 constantly during the past few decades. From i860 to 1864, according to 
 Caroe, there was but one death per 62,840 inhabitants, while from 1890 to 1894 
 there was one per 12,855. 
 
GEOGRAPHIC DISTRIBUTION ETIOLOGY. 1/ 
 
 Purdy's statistics for the United States are demonstrative and show : 
 
 In 1850, 72 per 10,000 deaths. In 1870, 170 per 10,000 deaths. 
 
 " i860, 98 " " " " 1890, 191 " " " 
 
 Purdy, undoubtedly with due cause, ascribes the enormous increase after 
 i860 to the rapid increase of prosperity, the luxurious mode of life, and the 
 more arduous struggle for existence after the Civil War. 
 
 Of all races, the Hindu is most susceptible to diabetes. In India 
 and Ceylon diabetes is a very common disease among the upper 
 classes, — so common that, according to the editor of the " Indian 
 Medical Gazette," almost every family in Calcutta belonging to 
 these classes of society has lost one or more members by death 
 from this dystrophy, while another author (Bose) estimates the 
 number of deaths from diabetes in Calcutta at lo per cent, of the 
 entire mortality (! ! !), — a circumstance that must be attributed to 
 the highly nervous constitution of the Hindus, their early marriage, 
 and excessive sexual life in general, the high intellectual cul- 
 ture at present prevalent in India among these classes, their 
 sedentary mode of life, and perhaps also their diet, so rich in 
 sugars and other carbohydrates. The preponderance of male over 
 female patients seems to be at least as great as in Europe. Among 
 the Mohammedan population in India diabetes, though not rare, is 
 not nearly so common as among the Hindus. 
 
 Next to the Hindus the Jews — who in many respects occupy 
 the same relative position to Europeans in general as do the Hindus 
 to the Jews — are highest in the scale of diabetic frequency. No 
 specialist in diabetes can avoid noticing the comparatively large 
 percentage of patients among Hebrews, who also are a nervous 
 race, and who for centuries have devoted themselves almost exclu- 
 sively to intellectual and sedentary pursuits. 
 
 It has been of interest to me to form some estimate of the 
 frequency of diabetes among the Chinese, who seemed to me, 
 during the few weeks I spent among a vast number of their race, 
 to be a nation with a highly developed intellectual, but compara- 
 tively slightly developed emotional, life, rather difficult of compre- 
 hension for any other than a Chinaman. Saundby's statements 
 seem to prove that diabetes is very rare among Chinese laborers. 
 Graham, who at Sumatra practised among 15,000 of them, discov- 
 
1 8 DIABETES MELLITUS AND GLYCOSURIA. 
 
 ered but a single case during his seven years' sojourn. In the 
 United States, I have myself, from various sources of information, 
 come to the conclusion that the disease is far more uncommon 
 among the lower classes of the Chinese than among the same 
 classes of Americans and Europeans. On the other hand, Dr. 
 Cantlie, who for many years has practised in Hong Kong, has kindly 
 informed me that among the ricJicr Chinese diabetes is not at all 
 uncommon, adding the interesting information that it more espe- 
 cially attacks those that change from the usual Chinese diet, with 
 its preponderance of rice, to a more mixed European diet. I 
 presume this observation to be perfectly correct ; — just as I have 
 repeatedly found that in cases of very slight glycosuria I can cause 
 a larger quantity of sugar to appear in the urine by mixed test- 
 meals than by those that consist exclusively of carbohydrates. 
 
 Among the contented Japanese, whose education has hitherto 
 been Spartan in many respects, diabetes is not common. If, as is 
 probable, they ere long provide reliable statistics, it will doubt- 
 less be seen that with the nation's wonderful and rapid adop- 
 tion of European culture, the frequency of diabetes will quickly 
 increase. 
 
 Among the Persians diabetes is said to be less general than 
 among Europeans, and the same is stated of the Turks (Tholozan). 
 Among the Arabs of the part of North Africa under French sway 
 the dystrophy is not rare (Calmette and others). 
 
 It is interesting to learn that among the laborers on the sugar- 
 plantations of the Mauritius and British Guiana, where, relatively 
 speaking, the lower classes consume an enormous amount of cane- 
 sugar, diabetes meUitus is rarely encountered (Blair, Saundby), 
 From Venezuela the same statement has been forwarded to me. 
 Almost all these laborers are " colored " and belong to those races 
 among which diabetes mellitus is uncommon as a general rule. 
 Circumstances, however, seem to indicate that a strongly saccharine 
 diet has per se but little etiologic influence. 
 
 Among all people beyond the pale of culture, diabetes is very 
 rare. This I believe to be the correct way of viewing the afore- 
 mentioned immunity among Africans, and the reason why so little 
 is heard of diabetes among the Indians of America, or among the 
 numerous and various aborigines of AustraUa, or in the English 
 
GEOGRAPHIC DISTRIBUTION ETIOLOGY. 1 9 
 
 colonies of mixed but predominant colored population. With 
 greater intellectual exertion, keener emotions, higher nervous 
 development, more earnest struggle for existence, more urgent 
 demands, a more intense culture, in fine, we are bound to find 
 more diabetes mellitus. 
 
 From what we have already learned we should a priori be 
 inclined to believe diabetes to be far more common among a given 
 number of residents in cities than among the same number of per- 
 sons in the country. There is, therefore, nothing remarkable in 
 the large number of statements that support such a supposition. 
 On the other hand, it is an interesting fact that statistics point, in 
 some degree, in the opposite direction. In Great Britain there are 
 several counties with a large urban population which are low in the 
 scale of diabetes, while others with a far greater rural population 
 are high in the scale. Purdy has compared the figures in the 
 United States, and has come to the conclusion that in the North 
 diabetes is more general among the rural population, and in the 
 South among the urban population ; and he ascribes this difference 
 to the better protection against cold afforded by the cities as com- 
 pared with the country, which holds good only for the North. In 
 the South other differences determine the result. These, in my 
 opinion, do not, as Purdy supposes, consist in the better oxidation 
 secured through the country air, but in the mode of hfe of the inhabi- 
 tants of the country, which, as a general rule, is far more free from 
 nervous influences. Except during the first decades of life, when 
 diabetes mellitus is very rare, and attacks fully as many, or perhaps 
 more, girls than boys, this dystrophy is far more common among 
 males than among females — naturally, in consequence of the severe 
 struggle for existence on the part of men, and their greater prone- 
 ness to excesses. The difference plainly appears in the second 
 decade, and is manifest in all following decades. Generally, there 
 are three times as many male patients as female. Exclusive of the 
 ages under twenty, Pavy had 928 males and 373 females ; Grube 
 had 137 male and 40 female cases, while my own experience shows 
 nearly three male to every female patient. 
 
 Diabetes is rare in childhood and youth, the greater number of 
 the patients being attacked during the most exacting period of their 
 life — from forty to sixty years of age. 
 
20 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Pavy's* table shows : 
 
 Age. 
 
 < 
 
 < 
 s 
 
 M 
 
 < 
 
 h 
 
 
 h 
 
 Male. 
 
 Female. 
 
 Total. 
 
 Under lo, . . 
 
 3 
 
 5 
 
 8 
 
 0.22 per cent. 
 
 0.36 per cent. 
 
 0.58 per cent. 
 
 From lo to 20, 
 
 35 
 
 22 
 
 57 
 
 2.57 " 
 
 0.61 " 
 
 4.19 
 
 " 20 to 30, 
 
 69 
 
 28 
 
 97 
 
 5.07 " 
 
 2.05 " 
 
 7.13 " 
 
 " 30 to 40, 
 
 154 
 
 70 
 
 224 
 
 11.32 " 
 
 5-14 " 
 
 16.47 " 
 
 " 40 to 50, 
 
 260 
 
 79 
 
 339 
 
 19. II " 
 
 5.80 
 
 24.92 " 
 
 " 50 to 60, 
 
 281 
 
 137 
 
 418 
 
 20. 66 ' ' 
 
 10.07 " 
 
 30.73 " 
 
 " 60 to 70, 
 
 i.3« 
 
 44 
 
 182 
 
 10.14 " 
 
 3-23 " 
 
 13-37 " 
 
 " 70 to So, 
 
 25 
 
 9 
 
 34 
 
 1.83 " 
 
 0.66 " 
 
 2.49 " 
 
 " 80 to 90, 
 
 I 
 
 
 I 
 
 0.07 " 
 
 
 0.07 " 
 
 A mild and warm diviate seems to give rise to less diabetes than 
 a severe and cold one. High altitude tends to increase the fre- 
 quency of diabetes. The mortality among diabetics is also greater 
 during the cold than during the warm season. 
 
 The diabetic patient of Northern Europe passes the winter on the Riviera 
 with decided advantage to his health, and his brother in misfortune in North 
 America derives benefit from a sojourn in Florida, or in Southern California, 
 during the severe cold season. Statistics from the United States speak strongly 
 for the unfavorable influence of rigorous climates. According to Purdy, Ver- 
 mont, with 6.3 deaths from diabetes per 1000 deaths, stands highest in the scale 
 among all the States. It is remarkable for its cold winters, and a large part of the 
 State is from 3000 to 5000 feet above the level of the sea. Next comes Maine, 
 with 4.41 deaths per 1000, and having also a severe climate, though less severe 
 than that of Vermont, and at a lower level. As a rule, the " northeastern hills 
 and plateaus " constitute those parts of the United States that are most favorable 
 to the development of diabetes. Purdy gives the mortality from diabetes in 
 thirty of the most populous States, the average for a// being 1.93 among 1000 
 deaths. Taking the figures from Arkansas, Alabama, Texas, Louisiana, 
 Georgia, and the Carolinas, I find an average of 0.84 among 1000 deaths, while 
 the corresponding figure for Connecticut, Massachusetts, Maine, Vermont, 
 Illinois, Wisconsin, Michigan, and Minnesota is 3.21. Although I entirely 
 agree with Dr. Purdy that cold and altitude are the chief climatic features that 
 
 *Schmitz, who (1892) had treated 2700 diabetic patients, and who has the largest 
 private statistics, furnishes similar figures. I am unable, at this moment, to produce his 
 latest table. He practised chiefly at a health resort, and his figures are, therefore, as 
 will be easily understood, of less weight than Pavy's, who obtained his from an estab- 
 lished urban practice. The English reports of the Registrar-General can not be used, 
 as they include both diabetes mellitus and insipidus. 
 
GEOGRAPHIC DISTRIBUTION ETIOLOGY. 21 
 
 determine high mortality from diabetes, I can not escape the thought that this 
 comparison of mine is only apparently so very demonstrative. The figures 
 would be conclusive but for the larger colored population and less intensity of 
 life and strife in the Southern States. 
 
 Hereditary influences are of great importance in the etiology of 
 diabetes. In a large number of cases it will be found on careful 
 investigation* that the diabetic patient is the descendant of a dia- 
 betic ; and still more frequently, the nervous predisposition, which 
 in the patient has found its expression in diabetes, has, in preceding 
 generations, shown itself in the form of other affections with well- 
 known changes in the central nervous system, in fully developed 
 psychoneuroses, or in psychopathic manifestations of various 
 kinds. It is often found that several members of the same 
 family — brothers and sisters — are diabetic, sometimes exhibiting 
 different forms of the dystrophy. Now and again I have found 
 slight glycosuria and mild and severe diabetes in members of the 
 same family. 
 
 All of the " learned " /r(?/£'i'j'/<?;/i' provide, comparatively speak- 
 ing, a vast clinical material for the specialist in diabetes. Physi- 
 cians especially — who are compelled to devote themselves to study 
 assiduously, to sustain great responsibilities, are disturbed at 
 night, and are harrassed by the suffering and unreasonable public 
 — are often victims of diabetes or exhibit simple glycosuria. 
 Statesmen and politicians are still more common subjects of the 
 dystrophy in a greater or less degree. The position of the specu- 
 lator and the business man is best illustrated by the adage from 
 Wall Street, New York : " When stocks fall, glycosuria rises." 
 Among the comparatively " unlearned " occupations it seems to 
 
 * Close investigation, which in this connection is far more necessary in order to ob- 
 tain reliable information than under ordinary conditions, is not only trouhlesome, but is 
 attended with numerous difficulties. Many a layman considers neither hypochondria nor 
 the slighter forms of melancholia as diseases of the mind, and, as a general rule, he is 
 not willing in his own case or in that of his relatives to acknowledge any disorder as 
 such that has not been treated in an asylum. Many laymen also entirely disregard 
 Graves' disease, if not very pronounced, slight attacks of epilepsy, etc. Others con- 
 sciously conceal a history of both psychoses and neurotic tendencies in their own family, 
 and feel ill at ease and irritated by being questioned too closely on those subjects. In 
 fully a quarter of all cases of diabetes there exists a direct diabetic hereditary predispo- 
 sition, while a neurotic heredity is present in the great majority. 
 
2 2 DIABETES MELLITUS AND GLYCOSURIA. 
 
 me that sailors furnish the largest contingent of cases of diabetes. 
 It is not among the crews, but among the officers, that the greater 
 number of diabetic patients will be discovered. I must have seen 
 a score of sea-captains, usually affected but slightly, middle-aged, 
 often corpulent, whose voices and figures often remind one of 
 " Captain Cuttle." The great responsibility, the disturbed sleep 
 at night, the good table, the drinks, and the limited exercise, possi- 
 bly also the low temperature prevailing on board, all contribute to 
 the development of diabetes. 
 
 The presence of pathologic quantities of sugar in the urine is 
 far more common among the higher classes, with their more nervous, 
 sedentary, and luxurious mode of life, than in the lower classes. 
 On the other hand, a far greater percentage of cases of diabetes 
 occurring among the last-mentioned classes is of the severe kind 
 than is the case among well-to-do people. In making this state- 
 ment I am perfectly aware that the less serious variety of diabetes 
 is more often overlooked or neglected by the poor than by the rich, 
 and that for this reason, also, far fewer mild cases are treated in 
 the public hospitals than in private practice. 
 
 At Carlsbad, with a visiting public consisting almost exclusively of persons 
 of some means, I not rarely discover a case of previously overlooked mild 
 diabetes, and far more often cases of slight glycosuria. For a number of 
 years, during the winter, in the capacity of physician in one of the dispensaries 
 for the poor in Stockholm, I had ample opportunities of proving how compara- 
 tively rare glycosuria is among such patients. 
 
 Among occasional causes painful, depressing, or irritating emotions 
 must doubtless be placed first. The patient often — and doubtless 
 correctly — states the cause of his disease to be constant vexation 
 in consequence of changes in external circumstances, grief at the 
 loss of wife, husband, child, etc. In far rarer cases a violent fit 
 of anger or fright — influences that invariably increase glycosuria in 
 a diabetic and at times engender an occasional attack in a healthy 
 individual — may give rise to a real, even severe, form of diabetes. 
 One of my Carlsbad patients, — long ago deceased, — a brave and 
 loyal officer of the Prussian Guards, dated both his Iron Cross and 
 his diabetes from that fearful time outside St. Privat, before the 
 longed-for order to storm was given. (See Glycosurias.) 
 
 Intellectual overexertion, and more especially the tiresome, unin- 
 
GEOGRAPHIC DISTRIBUTION ETIOLOGY. 23 
 
 teresting acquisition of sterile facts, also plays a certain role in the 
 etiology of diabetes. In Sweden, where an enormous amount of 
 time is spent at the universities in preparing for examinations, 
 more than one case of diabetes in early years has come under my 
 observation, in which the "corpus delicti" was probably the 
 "cramming." 
 
 Sexual excesses, both natural and unnatural, doubtless are most 
 deleterious. Here, as always, we find that what in one person 
 causes diabetes, in another causes glycosuria, and the presence of 
 small quantities of sugar in the urine in cases of sexual neuras- 
 thenia — especially in youths that have practised much masturba- 
 tion — is not uncommon. Such an occurrence is sometimes only 
 transient ; but at other times diabetes develops in persons of middle 
 age, in whose case no other point of importance can be discovered 
 in the history than neurasthenia acquired in youth in the manner 
 described. The sudden enormous increase in the frequency of 
 diabetes just about the fifteenth year of life and the first manifesta- 
 tion of its preponderance among males as compared with females 
 at this time, is doubtless owing partly to the strained intellectual 
 activity often entered upon even at that early period, but also in 
 part to masturbation, which is then so often practised. Both of 
 these causes are far more prevalent am.ong boys than among 
 girls. 
 
 Some of our habitual luxuries that powerfully affect the nervous 
 system certainly exercise a predisposing influence in the development 
 of diabetes. This is principally the case with spirits for the occa- 
 sional effects of which I must refer the reader to Alcoholic 
 Glycosuria. I suspect, however, that a similar influence is exerted 
 by other habitual poisons, and my attention has been called especially 
 to the frequency of glycosuria in patients suffering from what we 
 (incorrectly) term " nicotin poisoning," as a result of excessive 
 smoking. This statement is made with a full realization of the 
 difficulty, if not impossibility, of furnishing anything approaching 
 statistical proof of its accuracy. 
 
 A sedentary life seems to favor the development of diabetes mel- 
 litus, which is seldom found in laborers, and is deemed by many to 
 arise from decreased consumption of the blood-sugar in the 
 muscles. 
 
24 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Profuse consumption of carbohydrates, especially of sugar, is often 
 mentioned among the etiologic factors of diabetes. It stands to 
 reason that any article of food that always increases glycosuria in 
 diabetics will, if taken in large quantities, predispose to this dys- 
 trophy ; nor can it be denied that a large number of diabetics have 
 been fond of sweets. For my part, however, I am inclined to 
 think that, on the whole, it is too rich a diet, both as regards the 
 mixed nutriment, and more especially as regards alcohol, that plays 
 the predominating role in this connection, and that the importance 
 of large quantities of starch and sugar has been exaggerated. I 
 beg to remind the reader that no carbohydrate other than grape- 
 sugar causes glycosuria* in healthy individuals, and that laborers 
 on sugar plantations show no special disposition to glycosuria or 
 diabetes; and, finally, that just those classes in China and Japan 
 that live almost exclusively on rice enjoy almost complete immu- 
 nity from diabetes. 
 
 Starvation, especially if continued for any length of time, doubt- 
 less predisposes to diabetes. I refer the reader to the glycosuria 
 following starvation, discovered by Claude Bernard, and more 
 closely investigated by Hofmeister. (See the following chapter.) 
 This form of glycosuria, however, is generally of short duration, 
 although cases are sometimes encountered in practice in which 
 insufficiency of food seems to be the immediate cause of severe 
 diabetes. 
 
 Some time ago I attended a girl, eleven years of age, in whose case a care- 
 ful investigation failed to reveal any other etiologic factor than insufficiency of 
 food. For two months the child had been visiting some very poor relatives, 
 and during that time had been constantly underfed. On her return, when she 
 resumed her usual diet, severe diabetes set in. (See case, chapter v.) 
 
 Exposure to cold, if severe or often repeated, is universally con- 
 sidered one of the causes of diabetes. 
 
 Trauma now and then may undoubtedly cause diabetes, which 
 sometimes follows immediately, but sometimes not until months 
 have elapsed after the accident. The development of diabetes 
 under these circumstances is more likely to follow trauma of the 
 
 *The glycosurias of the Trappists who make their liqueur (Charcot); of the German 
 students who consume large quantities of ale (Kratschmer); or of Swedish students who 
 drink arrack and sugar or Swedish punch, are examples of alcoholic glycosurias. 
 
GEOGRAPHIC DISTRIBUTION ETIOLOGY. 2$ 
 
 head ; Griesinger was the first to call attention to the fact that 
 contusions of various parts of the body, however distant from the 
 nervous centers, may lead to a similar result. Nevertheless, only 
 an exceedingly small percentage of traumata give rise to diabetes, 
 and such accidents, though common, do not act as a cause in more 
 than about one per cent, of all cases of diabetes in adults. Among 
 nearly 200 of my own cases of diabetes in which the etiology has 
 been carefully investigated, I find only two cases in which I con- 
 sider trauma the cause with practical certainty. Among diabetic 
 children, however, the percentage is larger. 
 
 Finally, sunstroke is, in rare cases, mentioned as a plausible cause 
 of glycosuria or diabetes. 
 
 There are two dystrophies that have some, though as yet un- 
 explained, connection with diabetes mellitus, and which undoubtedly 
 constitute a predisposition to it — viz., obesity -dXid. gout. 
 
 All three of these dystrophies are not rarely present in the same 
 family, and sometimes even in the same individual. 
 
 For other pathogenetic points I must refer to the next chapter. 
 All the evidence seems to indicate that whatever may, as a tran- 
 sient or less profound influence, cause glycosuria, may, as a more 
 persistent or more profound influence, cause diabetes in a mild or 
 in a severe degree. 
 
 Diabetes, like all other dystrophies, is sometimes found in hus- 
 band and wife, and Schmitz conceived the original, but not well- 
 founded, idea that this may be the result of direct diabetic infection. 
 I have myself seen several such instances in practice, just as I have 
 seen married couples suffer from gout and adiposity, and I have 
 always favored other explanations, too evident to any one to detain 
 us further, which seem more rational than the theory of a diabetic 
 infection. Tessier, however, has written a thesis in which this asso- 
 ciation receives further consideration. 
 
26 DIABETES MELLITUS AND GLYCOSURIA. 
 
 CHAPTER III.— GLYCOSURIAS. 
 
 Since Briicke and Bence Jones found a reducing and fermenting 
 substance in normal urine, the presence of minute quantities of sugar 
 in the urine of healthy persons, and its possible amount within physi- 
 ologic limits, have been much discussed. As representatives of 
 the extreme views on this subject I may mention, on the one hand, 
 Seegen, who, particularly in the beginning of his career, attributed 
 vast pathologic significance to the slightest trace of sugar in the 
 urine ; and, on the other hand, we have Kiihne, who considered 
 O.I per cent., and Roos, who even mentioned 0.3 per cent., as 
 possible under normal conditions. Breul has recently estimated 
 the amount of sugar in normal urine as varying between 0.04 and 
 0.2 per cent. The larger amount is reached especially, he thinks, 
 with a small expenditure of heat, high surrounding temperature, 
 and bodily rest. 
 
 From the researches of Abeles, Wedenski, Schilders, Moritz, and 
 Baisch, and a large number of my own investigations, I have come 
 to the conclusion that there is a trace of glucose in normal urine, 
 and that the amount in twenty-four hours scarcely exceeds a 
 thousandth of i per cent. Some slight or occasional increase 
 beyond this may often occur without noteworthy significance, but 
 as soon as we reach hundredths or tenths of a per cent, we are within 
 pathologic limits. The finding by Worm-Miiller of sugar in 18 and 
 by Nylander in 14 samples of urine from 100 " healthy " individuals 
 by their tests, of which neither yields a reaction in the presence of 
 less than a hundredth of a per cent. ; and a similar experience on 
 the part of Breul with Fischer's test, are for me evidences of the 
 great commonness of slight but pathologic glycosuria, and I have 
 always observed tnat such individuals, though they can not be pro- 
 nounced diabetics, are not perfectly healthy, but will be found to 
 suffer from nervous or gouty or other disorders. 
 
 As experimental pathology has of late proved that various 
 operations, especially on the nervous system, cause excretion of 
 sugar, so also has clinical experience shown that glucose may 
 occur, over and above the normal traces, under several pathologic, 
 but otherwise entirely dissimilar, conditions, some of which are of 
 
GLYCOSURIAS. 2/ 
 
 a passing nature, though others may last for the greater part of 
 a long life. We should never disregard or pass over without 
 thorough investigation a measurable quantity of glucose in the 
 urine ; but we must avoid attaching too great an importance to the 
 excretion of minute amounts, even if repeated daily, and pro- 
 nouncing at once as diabetic every person whose urine yields a 
 positive reaction to tests for grape-sugar. It is now impossible to 
 change the clinical and prognostic idea that physicians and laymen 
 alike for centuries have attached to the expression diabetes melli- 
 tus. A person that, upon an abundant mixed food, excretes, e. g., 
 0.5 gram of glucose in the twenty -four hours is no diabetic in this 
 sense, even if this insignificant excretion is maintained for years. 
 Such manifestations occur more especially, and in large numbers, 
 among neurasthenic and among gouty patients. The division of 
 all the various forms and conditions attended with pathologic excre- 
 tion of glucose into simple glycosuria, mild and severe diabetes is 
 the one that best corresponds to the clinical reality, and the only 
 one that seems to me possible at the present day. 
 
 A rational classification of the different forms of simple glyco- 
 suria is at present entirely impossible, owing to our defective knowl- 
 edge of pathogenetic details ; we must, for the time being, content 
 ourselves with a table. At the head of the list we place alimentary 
 glycosuria, common alike to healthy and to diabetic persons after 
 the ingestion of large quantities of grape-sugar. Next come the 
 glycosurias that arise from disorders in those organs that, even 
 though the modus operandi is not as yet completely understood, 
 undoubtedly influence directly the metabolism of the carbohy- 
 drates : the nervous system, the pancreas, and the liver. The 
 7ievvous glycosurias may be subdivided into organic and functional, 
 with known or unknown lesions of the nervous system. (The 
 former include a number of experimental glycosurias.) Lesions in 
 the pancreas may give rise to simple glycosurias, or to mild or 
 severe diabetes ; but the pancreatic glycosurias are treated of at 
 length in a special chapter, and are therefore omitted from further 
 consideration here. There are also hepatic glycosurias, but these 
 are only known imperfectly from experimental and clinical obser- 
 vations. 
 
 Among toxic glycosurias, that due to alcohol possesses the 
 
28 DIABETES MELLITUS AND GLYCOSURIA. 
 
 greatest practical importance ; and those due to pliloriddn and to 
 carbon nionoxid, the greatest theoretic interest. Among glycos7irias 
 from infectioti, those that complicate malaria or influenza are the 
 most common. In this category we include also that excretion of 
 sugar in the urine that has been observed in association with puru- 
 lent processes. Among "concomitant" glycosurias, special stress 
 should be laid on those that occur in conjunction with obesity, gout, 
 and diabetes insipidus, all of which are allied to diabetes mellitus. 
 Glycosuria sometimes arises, further, from cold, from starvation, and 
 from fatigue. It may occur, also, in the fetus, and it may be of 
 puerperal origin. Finally, pathologic quantities of sugar are often 
 observed in the urine in senility and in cachectic states. Of late 
 years much has been written of renal glycosuria, and there seems 
 to be no doubt that the kidneys have some influence on the excre- 
 tion of sugar. The glycosuria from phloridzin may also be 
 included in the renal variety. With regard to the glycosuria that 
 is attributed to cardiac disease (Reynoso, Neumann), our knowledge 
 seems at present to be too scanty to permit of any conclusion. 
 
 Of all these forms of glycosuria the acute alcoholic and the 
 chronic functional neurotic, and the equally chronic gouty, are 
 the most common, occurring much oftener than all the others 
 together. 
 
 One attribute is common to all nondiabetic glycosurias with the 
 exception of the one caused by phloridzin : viz., the excretion of 
 sugar in varying, though never considerable, amount. The gly- 
 cosurias are, so far as measurable quantities are. concerned, transi- 
 tory in some sense. Thus, after the ingestion of a large amount 
 of glucose, after intoxication, cold, starvation, fatigue, or violent 
 emotion, the sugar appears in the urine only for a short while, — 
 sometimes only for hours, — and then generally disappears, never to 
 return. After infections, childbirth, etc., sugar may appear in the 
 urine for a number of days, but rarely persists for more than a 
 few weeks. In cases of neurasthenia, gout, and obesity, or in 
 senility and other more permanent states, the glycosuria may reach 
 measurable amounts for only a short while some time after meals, 
 and it may remain stationary at this point for years ; though every 
 now and then, as sometimes happens also after transitory influences, 
 it may be converted into true diabetes. 
 
GLYCOSURIAS. 29 
 
 Glycosuria is in most cases an immediate effect of hypergly- 
 cemia, or the presence of an increased amount of sugar in the 
 blood, though the relation between the blood-sugar and the urine- 
 sugar is not a perfectly fixed one, and some influence on the part 
 of the kidneys must be accepted. (See below.) Claude Bernard 
 found that the dog, whose blood contains normally about from 
 o. 10 to 0.15 per cent, of sugar, begins to exhibit glycosuria when 
 the hyperglycemia reaches from 0.25 to 0.30 percent. I accept 
 the normal glycemia in man as vaiying between o. 10 and 0.15 per 
 cent., and from the figures of Seegen and others it must be con- 
 cluded that glycosuria may appear when the amount of sugar in 
 the blood is only slightly above the last-named figures (even below 
 0.20 per cent.). 
 
 Hyperglycemia is, however, not a necessary prerequisite for gly- 
 cosuria. The quantity of sugar in the blood is abnormally low in 
 phloridzin-glycosuria. The same condition exists, according to 
 Dastre, in the glycosuria due to slozv asphyxiation. Hibernating 
 animals, according to some observations, exhibit glycosuria ; 
 although the quantity of sugar in the blood diminishes during 
 hibernation, and increases rapidly as the animals resume their 
 accustomed activity (Claude Bernard), and their glycosuria disap- 
 pears. According to Bernard, the amniotic fluid of the fetus (its 
 urine) often contains sugar. The normal glycemia of the fetus is, 
 so far as I know, not yet satisfactorily determined, but it seems to 
 me possible that we might have here another example of hypo- 
 glycemia with glycosuria.* 
 
 Aliineiitary glycosuria occurs normally after the ingestion of 
 large quantities of glucose, and it is of great importance to remem- 
 ber that, so far as human beings are concerned, this is the sole 
 physiologic variety of purely "alimentary" glycosuria — which ex- 
 pression is often incorrectly applied. The largest possible quan- 
 tities of ingested starch cause no glycosuria in healthy persons. 
 After the ingestion of large quantities of sugars other than glucose 
 
 *0n the other hand, Naunyn mentions cases in which the amniotic fluid of the fetus 
 contained no sugar, even when the mother suffered from diabetes; this fluid, in other 
 cases of diabetes, may contain quite a considerable quantity of glucose (0.7 per cent., 
 Husband). 
 
30 DIABETES MELLITUS AND GLYCOSURIA. 
 
 the urine will be found to contain normally only a small part of 
 the same kind of sugar ; we thus may have a physiologic saccha- 
 rosuria, a lactosuria, laevulosuria, etc. (see below). 
 
 Alimentary glycosuria evidently is caused by failure on the part 
 of the liver to transform into glycogen very large quantities of glu- 
 cose entering into that organ through the portal vein. The excess 
 that is not transformed or is not stored or consumed in other 
 organs (muscles) passes into the urine. 
 
 Numerous experiments of my own with glucose in normal and 
 diabetic individuals have confirmed essentially several facts pre- 
 viously observed by Worm-Miiller, Kiilz, and others, and have 
 taught me : (i) That normal individuals can take, some hours after 
 a light breakfast, and before the second meal of the day, generally 
 lOO, often 200, grams of glucose without excreting a measurable 
 amount in the urine. The maximum average amount that can be 
 taken under such circumstances is probably below 150 grams of 
 glucose. (2) That this maximum amount — or, in other words, the 
 limit of assimilation (Hofmeister) — varies vastly, even in normal in- 
 dividuals, under different, and sometimes even under apparently 
 similar, conditions. (3) That the capacity for taking glucose with- 
 out the development of glycosuria is often greater earlier than later 
 in the day. (4) That a healthy individual excretes, as a rule, far 
 less after the same amount of glucose than does a diabetic ; but (5) 
 that a diabetic in the mild stage of the disease may, by prolonged 
 abstinence from carbohydrates for the time being, attain an equally 
 high power of assimilation as a normal individual ; and (6) that, 
 consequently, a simple ingestion of glucose can not, for more than 
 the time being, determine the limit of assimilation, and can not 
 always establish the absence or presence of diabetes. 
 
 Under organic nervous glycosuria are included those cases of 
 slight excretion of sugar in the urine that occur in conjunction with 
 known lesions of the cerebrospinal and sympathetic nervous system. 
 Experimental pathology has evolved some valuable contributions 
 to our knowledge of central action in this connection ; but this 
 knowledge, however, is very imperfect.* Clinical experience 
 
 *The technical difficulties in the way of full and exhaustive investigation are scarcely 
 to be overcome. Kahler's experiments, which, unfortunately, only concerned polyuria, 
 
GLYCOSURIAS. 3 1 
 
 throws but a faint light on the subject, which is somewhat increased 
 by pathologic anatomy, (See below.) 
 
 Though isolated observations as to the connection between cer- 
 tain lesions of the nervous system and glycosuria (or diabetes) had 
 previously been made, it was Claude Bernard who, in 1849, ^^^t 
 demonstrated this relation by his celebrated "piqiire" in the floor 
 of the fourth ventricle between the centers of the pneumogastric and 
 acoustic nerves. This lesion causes a transitory hyperglycemia, 
 coupled with polyuria, and the presence in the urine of glucose to 
 the amount of several parts to the hundred for from five to six hours 
 in the rabbit and about forty-eight hours in the dog.* Puncture a 
 little higher, in a frontal direction, causes albuminuria, while another 
 somewhat lower causes simple polyuria. Bernard and many others 
 have considered these phenomena symptoms of irritation, not of 
 paralysis. As irritation of the chorda tympani causes increased 
 functional activity (and hyperemia) of the submaxillary gland 
 through the influence of sympathetic fibers, which preside over the 
 vessels and lead to their distention, so is a vasomotor center in the 
 brain irritated by Bernard's puncture. The stimulation is then 
 transmitted through the upper part of the spine, and afterward 
 through the splanchnic nerves to the vessels of the abdominal 
 organs in which hyperemia plainly manifests itself By the in- 
 creased flow of blood to the liver its glycogen is attacked more act- 
 ively than usual by the diastatic ferment in the blood, and the pro- 
 duction of sugar is increased, according to Claude Bernard. The 
 great physiologist undertook the experiment for the purpose of irri- 
 tating the center of the pneumogastric nerve, and expected glyco- 
 suria from this excitation. He discovered, however, that glycosuria 
 appeared after the puncture even if both pneumogastric nerves were 
 
 seem to have given technically the best results. He injected a concentrated solution of silver 
 nitrate through a fine cannula, and thereby caused circumscribed destruction in different 
 parts of the brain of the rabbit. Lesions of Eckhard's " lobus hydruricus et diabeticus " 
 caused transitory and inconstant polyuria, which also resulted from a lesion of Deiter's 
 nucleus and adjacent parts of the crura cerebelli. A lesion of the acoustic tubercle 
 and acoustic stride caused polyuria within forty-eight hours. Although these results 
 hold good for rabbits, they can not be applied without further experiment to other 
 animals. Kahler favored the theory of stimulation. 
 
 * Bernard's puncture also caused glycosuria in pigeons (Bernard) and in frogs (Schiff, 
 Kiihne). 
 
32 DIABETES MELLITUS AND GLYCOSURIA. 
 
 cut ; that no glycosuria followed irritation of the peripheral stump ; 
 that glycosuria may be caused by reflex action, if the central stump 
 is irritated, but that no glycosuria follows the puncture if previously 
 both splanchnic nerves are cut or if the pancreas and the liver are 
 separated from the nervous system. The puncture is now known 
 to have the usual effect even if the pancreas is extirpated, and then 
 increases the hyperglycemia (Kaufmann) and the glycosuria 
 (Hedon), but it does not have that effect if the celiac plexus is 
 extirpated (Schiff). After the glycosuria is over, the glycogen of 
 the liver has mostly disappeared. If this has been previously re- 
 moved by starvation, no glycosuria follows the puncture. If a 
 certain quantity of glucose is injected into the mesenteric veins of 
 an animal that has lost its glycogen through starvation, a slight 
 glycosuria follows. A much more pronounced glycosuria follows, 
 under otherwise the same circumstances, if the injection is preceded 
 by Bernard's puncture (Naunyn), and it is thus evident that the 
 capacity of the hver for storing glucose as glycogen is diminished 
 by the puncture. Though the glycosuria following Bernard's 
 puncture is transitory, and not very considerable, postmortem 
 observations (see below) indicate that permanent changes in the 
 floor of the fourth ventricle cause real diabetes, and Bernard's punc- 
 ture has been a factor of great importance in our comprehension of 
 diabetes mellitus. 
 
 Eckhard found that stimulation of a part of the vermis ("lobus 
 hydruricus et diabeticus ") is followed by polyuria and glycosuria. 
 
 Lesions of various parts of the brain may cause glycosuria, as 
 Schiff saw after section of the optic lobes, the pedunculi cerebri, 
 and the central and posterior parts of the pedunculi cerebelli. 
 
 Glycosuria often occurs after trauma of the brain. Higgins and 
 Ogden found it in 20 out of 212 cases. This glycosuria generally 
 passes off" in a few days ; now and then true diabetes mellitus or 
 insipidus remains. Though Asher has collected 124 cases of trau- 
 matic diabetes mellitus, I repeat that trauma is a rare cause of 
 diabetes mellitus in adults. 
 
 Section of the spinal cord down to the fourth cervical vertebra 
 is followed in the dog by glycosuria (Pavy, Chauveau, and Kauf- 
 mann). 
 
 Section of the spinal cord between the fourth cervical and the 
 
GLYCOSURIAS. 33 
 
 sixth thoracic vertebra is at first followed by slight and transitory 
 hyperglycemia, but subsequently by hypoglycemia. Incisions 
 below the sixth thoracic vertebra cause no alteration in the quan- 
 tity of the sugar in the blood (Chauveau and Kaufmann). 
 
 Claude Bernard severed the spinal cord of a rabbit between the last cervical 
 and the first dorsal vertebra. The animal became paralyzed below the divi- 
 sion, and respiration became slower, and the temperature sank. The quantity 
 of sugar in the blood also diminished, — as Chauveau and Kaufmann found 
 also subsequently, — and the amount of glycogen in the liver increased. This 
 last fact is denied by Chauveau and Kaufmann, who aver that though the 
 liver, after this operation, certainly gives off less glucose to the blood, it instead 
 discharges more glycogen (?). 
 
 If the pneumogastric of one side is cut and the central stump is 
 irritated, glycosuria follows, and persists for a few hours. Some- 
 times it arises merely in consequence of the section (Bernard, 
 Eckhard, Kiilz). Arthaud and Butte caused a more continuous 
 glycosuria (amounting almost to 2 per cent.) by maintaining an 
 inflammatory process in the central stump. Couvreur, after sever- 
 ing both pneumogastric nerves, saw glycosuria develop in the 
 rabbit, and found, after the same experiment in the pigeon, that the 
 amount of sugar in the blood first rises above, but afterward falls 
 below, the normal. 
 
 Filehne saw glycosuria appear on irritation of the depressor branch of the 
 pneumogastric nerve, perhaps from the passage of the stimulus to the latter. 
 
 Claude Bernard and others have found that irritation of the 
 peripheral stump of the divided pneumogastric nerve does not 
 cause any change in the amount of sugar in the blood under the 
 same conditions. Arthaud and Butte and Lepine observed hyper- 
 glycemia, and Morat hypoglycemia. These differences in results 
 may possibly be explained by differences in division of the nerve- 
 fibers in the trunks of the pneumogastric. 
 
 Niedieck caused inflammation of the sciatic nerve in the rabbit, 
 and found glycosuria develop. The neuritis had spread to the 
 spinal cord, and at times it had passed over to the sciatic nerve of 
 the other side. Niedieck considers that changes in the spinal cord 
 cause the glycosuria, either by directly modifying the abdominal 
 circulation or by transmitting the irritation to the floor of the fourth 
 ventricle. 
 
34 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Schiff also found that irritation of the sciatic nerve caused glyco- 
 suria, which might last for several days and reach two per cent. 
 This was afterward observed also by Ryndsjun, Bohm and Hoff- 
 mann, and others. The expeiiment does not always succeed in 
 inducing glycosuria, although Kiilz obtained it in nine of ten 
 cases. 
 
 Butte saw glycosuria after irritation of the first pair of dorsal 
 nerves. Frerichs, Frazer, and others have observed glycosuria in 
 the course of rheumatic inflammation of different nerves, and it is 
 probable that irritation of any nerve, if sufficiently intense, may 
 bring about such a result. 
 
 """^ K number of observations illustrate the influence of the sympa- 
 thetic nervous system on the sugar in the blood. 
 
 As early as 1859 Pavy found sugar in the urine after section of 
 the nerves that proceed from the superior cervical ganglion, or after 
 extirpation of the ganglion. 
 
 Cyon and Aladoff observed glycosuria after section of the inferior 
 cervical ganglion, of the superior thoracic ganglion, and of annulus 
 Vieusseni. 
 
 Kiilz found section of the cervical sympathetic trunk to cause 
 slight glycosuria in four of ten cases ; while irritation of the cen- 
 tral stump several hours later was followed by glycosuria in six of 
 the ten cases. 
 
 Irritation of the thoracic division of the sympathetic nerve also 
 causes glycosuria (Pavy). 
 
 Morat and Duponc observed an increased production of sugar in 
 the liver as a result of irritation of the splanchnic nerve. 
 
 Section of the splanchnic nerves often causes glycosuria. Hans 
 Voit, however, failed recently to obtain this result in the majority 
 of cases. 
 
 Pincus, Budge, and Lamanski saw dogs, rabbits, and cats die with 
 profuse diarrhea and a violent gastro-enteritis about twenty-four 
 hours after extirpation of the celiac plexus. By means of the same 
 operation Munck and Klebs induced atrophy of the pancreas and 
 glycosuria ; while Lustig observed neither diarrhea nor atrophy 
 of the pancreas, but considerable glycosuria (with polyuria), ace- 
 tonuria, albuminuria, and death in coma. Peiper had a similar ex- 
 perience with rabbits, the glycosuria reaching from 2.5 to 4 per 
 
GLYCOSURIAS. 3 5 
 
 cent., but neither it nor the acetonuria nor the albuminuria was 
 constant. 
 
 A. and E. Cavazzani found a great increase in the quantity of sugar 
 in the blood in the hepatic veins after mechanic and electric stimu- 
 lation of the celiac plexus. 
 
 A. Cavazzani and G. Soldani, who consider the production of 
 sugar in the liver to be a secretion, like all other secretions, found 
 that atropin, which paralyzes the sympathetic centers and diminishes 
 secretion, also diminishes the amount of sugar in the hepatic veins, 
 probably by paralyzing the celiac plexus. 
 
 Clinical experience affords numerous illustrations of the depend- 
 ence of the assimilation of carbohydrates on the nervous system. 
 Sugar has been found in the urine in cases of general progressive 
 paralysis (Lallier, Bequerel, Bond, Strauss), of tabes dorsalis (Smith, 
 Oppenheim, Eulenburg, and others), of multiple sclerosis (Weich- 
 selbaum, Mile. Blaine Edwards, Richardiere), of paralysis agitans 
 (Huchard, Topinard, Naunyn), of chorea minor (Demme, and 
 others), of epidemic cerebrospinal meningitis (Mannkopf), and of 
 cerebral meningitis (Naunyn), of syphilis (Leudet, Frerichs, and 
 others), of aneurysm and of new growths (v. Recklingshausen, 
 Frerichs, Seegen, Richardson, Spitzka, De Jonge, and others), of 
 cerebral softening (Naunyn, and many others) and cerebral hemor- 
 rhage (Frerichs, Olivier, Schiitz, Jacques Meyer, and others). 
 Michael also found a cysticercus embedded in granulations in the 
 floor of the fourth ventricle in a case of diabetes. 
 
 The numerous cases of disease of the brain, attended with the 
 presence of pathologic quantities of sugar in the urine, permit us 
 to conclude with certainty that a causal connection exists between 
 lesions of different parts of the brain and glycosuria ; but the 
 statistics on the subject are of little value, on account of the great 
 frequency of glycosuria independently of brain disease, the small 
 number of cases, and the want of uniformity in investigation and of 
 exact expression for the normal power of assimilation. It must be 
 acknowledged that in a large number of cases of brain disease there 
 is only an insignificant decrease, if any, in the power of assimilating 
 carbohydrates. In only four of Kahler's twenty-three cases of 
 organic disease of the central nervous system was there a distinct 
 diminution in that power. Van Oordt ( 1 898) found enfeebled power 
 
36 DIABETES MELLITUS AND GLYCOSURIA. 
 
 of assimilating carbohydrates in 25 of 178 cases of diseases of the 
 central nervous system. Several of the cases were neuroses (neu- 
 rasthenia, hysteria, traumatic neurosis). Epilepsy and diseases of 
 the spinal cord seemed to cause a diminution in the power of assimi- 
 lation. Van Oordt's twenty-five cases, however, do not seem to me 
 to make up a greater percentage with decreased power of assimilation 
 than is found, on the average, among brain-workers. Glycosuria 
 seems to be most frequent in cases of tumor of the brain, of 
 general progressive paralysis, and of cerebral hemorrhage. The 
 intensity of the glycosuria is generally slight, and does not amount 
 to a real diabetes. Still, in cases of general paralysis, the amount 
 of sugar often reaches one per cent, or more, and in cases of 
 tumor and hemorrhage as much as four per cent, has been ob- 
 served. If the patient survive, the glycosuria following apoplexy 
 generally is transitory ; sometimes true diabetes may develop 
 (Jacques Meyer). (For a consideration of glycosuria complicating 
 tabes dorsalis and multiple sclerosis I refer to chapter II.) 
 
 Cerebral softening, or encephalomalacia, is much more commonly 
 an effect than a cause of diabetes (Naunyn). 
 
 Exophthalmic goiter is sometimes attended with glycosuria 
 (Chvostek, Dumontpellier, Panas, Pavy, Blocq, Kraus, Ludwig, and 
 others), and sometimes with true diabetes (Bettman, Laache). I 
 have at present under observation a case of diabetes with struma, 
 tachycardia, and nervous symptoms, but without exophthalmos. 
 
 A diminished power of assimilation of carbohydrates in different 
 degrees has often been observed in cases of akromegaly also 
 (Pierre-Marie, Cunningham, Lancereaux, and others). Marinesco 
 has recorded a case of akromegaly with diabetes mellitus, epilepsy, 
 and bilateral hemianopsia. 
 
 Epilepsy is at times, especially after attacks, attended Avith gly- 
 cosuria (Goolden, Griesinger, Lallier, Ringer, Barlow, and others). 
 " Mais elle (la glycosurie) reste en somme une manifestation excep- 
 tionelle " (" Les Epilepsies, " Ch. Fere, Paris, 1890). 
 
 Pathologic quantities of sugar have also been discovered in the 
 urine in cases of meningomyelitis (Kunkler), of myelitis (Bequerel), 
 of spinal hemorrhage (Siebert, Scharlau, Vogler), of fracture and 
 contusion of the cervical and dorsal vertebrae (Schiff, Frerichs, 
 
GLYCOSURIAS. 37 
 
 Fischer), and of spondylitis (Baum). May found glycosuria and 
 levulosuria in a case of transverse myelitis. 
 
 Traumatic neuroses are often accompanied by glycosuria (Brou- 
 ardel, Richardiere, Strauss, von Striimpell, Ebstein, Naunyn, and 
 others). 
 
 Simple neuralgias also — especially of the fifth pair — and sciatica 
 are often complicated by glycosuria. I recently found one per 
 cent, of sugar in the urine in a case of violent sciatica without any 
 other symptoms of diabetes. 
 
 I consider it one of my most important tasks to emphasize the 
 glycosuria so often found in cases of acute or chronic " functional " 
 nervous disturbances, and for which there is no better name than 
 functional nervous glycosuria. 
 
 Such a pathologic excretion of sugar may be the effect of an 
 entirely transitory nervous disturbance, and may appear in other- 
 wise healthy individuals for only a few hours after some powerful 
 emotion (as of fear or anger), such as in a case of more permanent 
 glycosuria, or in one of true diabetes, may for a short while greatly 
 increase the quantity of sugar in the urine. Almost every physi- 
 cian who has given much attention to a study of the urine will have 
 encountered instances of such transitory glycosuria, of which a 
 large number are recorded in literature. Many facts tend to show 
 that a similar condition occurs not rarely in animals, especially 
 among the higher classes of vertebrates. Paul Gib has recently 
 given the account of a bitch that always objected strongly to being 
 shut up, and was greatly agitated during her seclusion, and that 
 constantly after such treatment, but never otherwise, presented 
 small quantities of glucose (up to 0.55 per cent.) in the urine. 
 
 Such an effect of transitory emotions makes it difficult in many 
 cases to determine the nature of an excretion of sugar both in man 
 and in animals. Glycosuria following an attack of gall-stones (as 
 observed by Finkler and Gans) may be caused by the simple irrita- 
 tion of peripheral nerves, or by hyperemia of the liver ; but it may 
 also be the effect of the mere mental anguish of the patient during 
 the painful, and possibly dangerous, passage of a gall-stone. Stu- 
 dents of experimental pathology should bear in mind this possible 
 cause of a transitory glycosuria of doubtful origin, and there is 
 
38 DIABETES MELLITUS AND GLYCOSURIA. 
 
 abundant evidence that it often occurs in laboratories, where the 
 infliction of pain on animals is not always avoidable. Minkowski 
 discovered glycosuria in 1 5 of 32 animals subjected to operative 
 experiments, in which this phenomenon probably must be attrib- 
 uted to mental influences. Examination of the figures given by 
 Pavy, McDonnel, Seegen, Abeles, and others, for the quantity of 
 sugar in the blood of the hepatic veins during experiments on ani- 
 mals leads to the conclusion that the experiment increases the pro- 
 duction of sugar in the hver through the mere suffering it causes. 
 It is not at all improbable that the glycosuria that follows extirpa- 
 tion of the salivary glands, so much expatiated upon by Reale and 
 Rienzi, or that observed by Schiff after the ligation of the femoral 
 artery, or by Minkowski after resection of the duodenum, as well 
 as other slight and inconstant varieties of excretion of sugar in the 
 urine, are to be referred to this category.* 
 
 Bohm's and Hoffmann's " Fesselungsglycosurie " in the cat, sub- 
 sequent to its being tied experimentally, is well known, and can be 
 explained most easily by the mental state and emotion produced 
 by such treatment, though asphyxia may also be operative in this 
 instance. The same may be said of Velisch's observation of gly- 
 cosuria in the frog after tying it on its back, or after keeping it on 
 its head in a narrow cylinder. 
 
 In some cases nervous glycosuria may last for some length of 
 time, but finally disappears. 
 
 L, a medical student, works^hard at his books, and is alarmed now and 
 then to find distinct reactions with the ordinary tests for sugar in his urine, 
 which after rest and a trip to a warmer climate becomes normal. 
 
 X, a youth of nineteen, was for several years addicted to masturbation, and 
 every evening after dinner presented about o.i per cent, of sugar, which dis- 
 appeared some time after he reformed his ways. 
 
 Mrs. T, now seventy-six years old, during middle age and after a period of 
 great anxiety, excreted daily more or less than a gram of glucose with the 
 urine. This caused her family some uneasiness, especially as a daughter 
 had died of diabetes ; but at present the old lady's urine exhibits no trace of 
 reaction two hours after an abundant mixed meal. 
 
 * Falkenberg and Kulz observed, after extiipation of the thyroid gland, glycosuria 
 that was not constant, though it sometimes lasted for weeks. Naunyn, in his recently 
 published monograph, probably coiTectly explains this glycosuria by the starvation con- 
 sequent upon the operation. 
 
GLYCOSURIAS. 39 
 
 Count X Y Z, in a scientific controversy, both made and committed to paper 
 a number of most absurd statements, for which he was subjected to severe 
 but well-deserved criticism, by which he was greatly affected. During this 
 time he availed himself of the opportunity to make some interesting investi- 
 gations concerning the influence of emotion on metabolism, and on various 
 occasions he found as much as 0.3 per cent, of glucose in his urine. After he 
 had returned to the intellectual passivity for which nature evidently intended 
 him, and time had consoled him for his disappointments, his urine returned to 
 its natural condition. 
 
 If, on the other hand, the nervous causes of glycosuria are pro- 
 longed or become permanent, so will also the excretion of sugar 
 with the urine, and this may continue for many years, and often for 
 the rest of life. These habitual glycosurias have exactly the same 
 etiology as true diabetes ; and there will be found to exist heredi- 
 tary influences of a diabetic, a nervous, or a gouty nature, and the 
 usual accidental influences : viz., painful emotions, intellectual 
 overwork, sexual excesses, etc. 
 
 Habitual glycosuria is found especially in persons suffering from 
 those common functional disorders grouped under the name of 
 neurasthenia, which disorders, when once they have appeared, 
 seldom entirely leave the patient. 
 
 Among neurasthenic patients, again, we may expect to find 
 pathologic quantities of sugar in the urine, especially in cases com- 
 plicated by gout or obesity ; and it is a matter of choice whether 
 we ascribe the glycosuria to the neurasthenia or consider it a col- 
 lateral symptom of the obesity or gout, which latter dystrophy, by 
 the way, is accompanied with marvelous constant nervous symp- 
 toms. Among obese persons we also not rarely find glycosuria, 
 especially in those that exhibit neurasthenic stigmata. There is 
 among the upper social classes a not rare type of middle-aged man, 
 with a bodily weight as often above as below 200 pounds, with 
 ruddy cheeks and a general appearance of health, but with high- 
 strung nerves, great sensitiveness, and often with some slight gouty 
 trouble.* If we adopt the rule of testing our patients' urine an 
 
 * As has already been mentioned, diabetes insipidus, like obesity and gout, may be 
 converted into diabetes raellitus or it may be attended with the excretion of a small 
 amount of sugar in the urine (Senator, Legroux). Such cases, however, seem to be quite 
 rare, even comparatively. In the rare cases of recovery from diabetes mellitus a distinct 
 diabetes insipidus sometimes remains. 
 
40 DIABETES MELLITUS AND GLYCOSURIA. 
 
 hour after dinner, we shall find in a large proportion of the repre- 
 sentatives of the type described at least distinctly pathologic traces 
 of sugar — simple glycosuria. In other cases we shall find a true, 
 though mild, diabetes. 
 
 Wherever we turn we often see in practice illustrations of the 
 close relationship between all stages of the glycosuric dystrophy. 
 
 In a family of eight children one sister died at twenty-nine in diabetic coma ; 
 another, who subsequently died of carcinoma, developed the mild type of dia- 
 betes when about fifty years of age ; in a third, somewhat corpulent, but other- 
 wise healthy, sister, I have, in the course of many years, found several times 
 after meals from o. i to 0.2 per cent, of sugar in the urine. With the exception 
 of the sister that died in coma, none of the family presents any nervous dis- 
 order, but on the father's side there are neuropathic individuals of closest 
 relationship. 
 
 In different branches of another well-known and widely spread family I 
 have seen simple glycosuria, mild and severe diabetes, gout, and obesity, with 
 or without traces of sugar. The psychopathic element in this in part highly 
 intellectual family has manifested itself in fully developed psychoneuroses, in 
 dipsomania, in perverted sexual desires, and in eccentricity. 
 
 The son of a man who met his death by diabetic coma discovered in late 
 middle age that he was excreting sugar, the condition being found to be one of 
 slight simple glycosuria. The daughter of a woman who had presented slight 
 glycosuria died in early life of severe diabetes, and so on. 
 
 The daily excretion of sugar in the urine in cases of simple glyco- 
 suria is always insignificant, and the amount is frequently so small 
 that it can not with certainty be demonstrated in larger quantities 
 of urine, even after abundant ingestion of carbohydrates. If in a 
 sample of the urine collected during twenty-four hours a percentage 
 of, for instance, 0.5 be found, the case can no longer be classed as 
 one of simple glycosuria, unless special causes — such as excessive 
 indulgence in alcohol, an acute infection, powerful emotion, and the 
 like — have contributed to the condition. The quantity in small 
 samples voided a certain time (from one to two hours) after meals 
 varies from hundredths to tenths of a per cent., and may for a little 
 while, under the influence of agencies that increase the secretion, 
 reach a somewhat higher figure. A percentage of 1.5, even in 
 small quantities of urine, is rare in cases of simple glycosuria ; more 
 than 2 per cent, scarcely occurs at all in an anomaly of this kind. 
 
 Simple glycosuria causes of itself — /. c, by hyperglycemia and by 
 loss of sugar — no symptoms at all or only ill-defined and transitory 
 
GLYCOSURIAS. 4 1 
 
 symptoms. We find in these cases, beyond the small quantities of 
 glucose in the urine, usually no pathologic manifestations except 
 the various neurasthenic stigmata and symptoms in lesser or greater 
 number, and these can not possibly be ascribed to the insignificant 
 deficiency in the power of assimilating carbohydrates or to the small 
 addition to the normal quantity of sugar in the blood, which addition 
 probably amounts to determinable quantities only for a compara- 
 tively short part of the twenty -four hours. To avoid unnecessary 
 repetitions, I refer to chapter iv for a consideration of those neuras- 
 thenic symptoms, of which the most frequent and the most distress- 
 ing are an excessive emotional irritability, insomnia, and enfeebled 
 virility. I wish here only to remark that the glycosuria stands in 
 no fixed relation to the intensity of the neurasthenic neurosis. We 
 may find glycosuria present in casQS of but slightly developed neu- 
 rasthenia, and we may look in vain for it in cases in which many 
 stigmata and symptoms combine to bring out in strong relief the 
 neurasthenic picture which is scarcely ever complete in the indi- 
 vidual case. 
 
 The symptoms that may be caused by hyperglycemia and glycosuria in 
 these cases are so vague that even a considerable experience and much atten- 
 tion have not enabled me to arrive at definite conclusions with regard to some 
 points. PoUakiuria, or increased frequency of micturition, even though the 
 quantity of urine expelled at each voidance be small, is a usual, though not 
 constant, symptom in cases of simple glycosuria. It is, however, common also 
 in " nervous " patients without glycosuria, and it is often noticeable whenever 
 the urine contains any great amount of crystals of calcium oxalate, which is 
 often the case in the presence of simple glycosuria. 
 
 I have found furunculosis in quite a number of cases, with such an insig- 
 nificant excretion of sugar that I could not possibly class them among diabetics. 
 Furunculosis is also one of the earliest symptoms of mild diabetes. With 
 regard to furunculosis, also, we must remember the oxaluria so common in 
 neurasthenic patients, and especially in those that show glycosuria. In the 
 "idiopathic oxaluria" of Begbie, Cantani, and others, the clinical picture is 
 made up of slight nervous and dystrophic symptoms, and among the latter the 
 authors also name furunculosis. It is not improbable that other causes than 
 hyperglycemia are here active, especially in view of the fact that furunculosis is 
 much more frequent in mild than in severe cases of diabetes. 
 
 Other cutaneous eruptions, especially eczema, are sometimes found in cases 
 of simple glycosuria, which, like diabetes, frequently arise in persons with 
 vasomotor irregularities of different kinds. It is difficult to assert any direct 
 connection between these cutaneous troubles and glycosuria ; they are both 
 often found in cases of gout — a frequent disease in glycosuric individuals. 
 4 
 
42 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Patients aware of the presence of slight quantities of sugar in their urine 
 sometimes mention dryness of the mouth or increased thirst, but the quantity 
 of urine rarely exceeds 20 cu. cm. to the kilogram of body weight. 
 
 The teeth, which in true diabetes are pretty certain to be carious and defec- 
 tive after some years, are often in most excellent condition after decades of 
 simple glycosuria. 
 
 When the physician wishes to determine by careful investigation 
 as far as possible the nature of a slight glycosuria, and to give it a 
 name, he must fully understand that his task is entirely a practical 
 one, and that he must give up all attempts to draw a distinct, sci- 
 entific limitation between simple glycosuria and diabetes. While 
 bearing in mind that simple glycosuria and glycosuria in mild and 
 severe cases of diabetes represent only a dystrophic symptom of 
 various pathologic states and processes, we must remember that 
 exactly the same gradual differences are to be observed in the excre- 
 tion of sugar as in other dystrophic manifestations. What inteUi- 
 gent physician would undertake to determine where gout begins ? 
 In obesity, which reveals itself to our senses much more readily 
 than gout or diabetes, even the layman understands that the interval 
 between the normal man and the representative of the highest 
 degree of obesity may be filled by a thousand individuals in such a 
 manner that only a minute difference exists between each man and 
 his neighbor to the right and to the left in the long line. We meet 
 with exactly analogous conditions in glycosuric patients. It is im- 
 possible to decide precisely when the faint trace of sugar that, we 
 must allow, may appear in normal urine ceases to be normal and 
 passes over into simple pathologic glycosuria. It is equally im- 
 possible to find the boundary-line between the latter and mild dia- 
 betes, and in the chapter on metabolism we shall find that mild and 
 severe "forms" of diabetes are also connected by intermediate 
 stages. The individual may sometimes, by slow degrees, and dur- 
 ing a series of years, pass through all stages, from the normal state 
 to that in which he is overtaken by death from diabetic coma. 
 This, however, is not the usual course, and many patients remain 
 in the vicinity of that place in the chain that they occupied a short 
 time after the beginning of their dystrophy. Simple glycosuria, 
 as already mentioned, often shows a decided tendency to remain 
 unaltered for decades, in spite of all sorts of pernicious influences. 
 
GLYCOSURIAS. 43 
 
 Mild diabetes certainly not infrequently develops gradually from 
 simple glycosuria, but it also often appears at once or after a short 
 time as mild diabetes, and usually remains mild diabetes. If we 
 can not deny that the severe type sometimes has gradually been 
 evolved from the mild, it much more frequently shows itself in its 
 severe character a short time after a normal state. 
 
 In examining and forming an opinion on a case with a small 
 amount of sugar in the urine, the physician must further always 
 bear in mind that, as simple glycosuria may, under some temporary 
 influence, momentarily resemble mild diabetes, so also may mild 
 diabetes at times appear exactly like simple glycosuria, and that, 
 consequently, repeated examinations are always necessary. Re- 
 cently I examined two patients on the same day — Mrs. M. and 
 Mr. R., both about forty years of age. An hour after a similar 
 dinner of mixed food the urine of each contained fully o. 1 5 per 
 cent, of glucose, although in the urine collected for the twenty -four 
 hours there was a scarcely perceptible trace. The patients con- 
 sumed 200 grams of cane-sugar each ; the urine in neither case 
 afterward yielded a distinct reaction with Nylander's solution, but 
 in both cases reduced abundantly after boiling with a few drops of 
 sulphuric acid.* In short, the two cases seemed for the moment 
 to be as similar as they could be. They are, however, essentially 
 different in nature. Mr. R. for fully ten years has exhibited a sim- 
 ple, neurasthenic glycosuria, which during all this time, and with 
 ordinary food, has appeared as it does now, without ever reaching 
 considerable quantities of sugar or giving rise to diabetic symp- 
 toms ; it will in all probability remain stationary in the future. 
 Mrs. M. suffers from a true, though mild, diabetes of several years' 
 standing. A few weeks ago her urine contained over two per cent, 
 of sugar, and there was some polyuria ; she has reached her present 
 power of assimilation only after several weeks of strict diet. If she 
 should for any length of time indulge in a free diet, which now was 
 occasionally allowed for a couple of days for the sake of the experi- 
 ment, her old symptoms would be certain to reappear. 
 
 In other rare cases the same individual may, without any dififer- 
 
 * In other words, neither urine contained glucose, but both urines contained some 
 cane-sugar, which, after being inverted by boiling with acid, reduced (see below). 
 
44 DIABETES MELLITUS AND GLYCOSURIA. 
 
 ence in diet, and without any assignable cause, present a periodic 
 alternation of simple glycosuria and true, though mild, diabetes. 
 This is the condition that now and again is mentioned in medical 
 literature as periodic diabetes. In the cases of this kind that have 
 come under my observation a distinctly pathologic, though com- 
 paratively insignificant, trace of glucose is found even during the 
 " free" intervals. Such a case is that of the Countess H., who has 
 been under my observation for several years. The lady, who is 
 somewhat over forty and very corpulent, shortly after her husband's 
 death began to suffer from constant thirst. The polydipsia excited 
 the attention of the servants, and the family physician found con- 
 siderable quantities of sugar in the urine. Since then, this most 
 conscientious patient has for several years constantly adhered to 
 the same diet, with a considerable reduction of carbohydrates (lOO 
 grams of bread a day and some vegetables and animal food). Once 
 or twice a year, at intervals of varying length, diabetic symptoms 
 appear for some weeks, with the excretion of considerable amounts 
 of sugar (from 20 to 25 grams daily), but these soon disappear, 
 even if no change is made in the dietetic regimen. In the intervals 
 the urine for twenty-four hours shows, with Nylander's and 
 Fehling's solutions, just appreciable traces of sugar. At present 
 the patient has just passed through a new diabetic period, which, 
 unlike the previous attacks, continued for five months, until, when 
 she appeared again in Carlsbad, I reduced for some time the carbo- 
 hydrates to a minimum. The patient is now able to take eighty 
 grams of bread daily, together with some vegetables, without show- 
 ing more than traces of glucose in the urine, which will be ex- 
 amined more frequently in order to effect without delay any reduc- 
 tion in carbohydrates that may possibly be necessary. I consider 
 it probable that the case will develop into a common, persistent, 
 mild diabetes. 
 
 Very likely similar cases, complicated by gout, have been designated " dia- 
 betes alternans'' ever since the time of Peter Franks. By this appellation is 
 generally meant a state in which alternately sugar and uric acid in abundant 
 quantities appear in the urine. Gouty patients often present either simple glyco- 
 suria or an especially mild diabetes. With the periodic increase in the power of 
 assimilation, which may occur in such cases, the amount of sugar in the urine 
 falls to a minimum. That a real alternation occurs, so that the quantity of uric 
 acid increases as the quantity of sugar in the urine diminishes, and vice versa. 
 
GLYCOSURIAS. 
 
 45 
 
 is at any rate not proved, and among the large number of gouty and glycosuric 
 patients that I have treated I have not been able to find a single case in which, 
 as a result of the considerable analytic work necessary, the slightest evidence 
 of such an alternation was detected. It is difficult to understand how the 
 presence of uric acid in the urine should bear any fixed relation to the gly- 
 cosuria. 
 
 A connection between glycosuria and the presence of oxalic acid 
 in the urine — the molecular construction of the latter giving it a 
 position between glucose on the one hand, and water and carbonic 
 acid on the other — has a good theoretic basis, and I have seen 
 cases of simple glycosuria that, when free from glucose, have pre- 
 sented marked oxaluria. 
 
 Though no exact dividing-line can be drawn between adjacent 
 cases of the one and the other, a comparison between the typical 
 forms of simple glycosuria and of true though mild diabetes will 
 show several practically important differences : 
 
 Glycosuria. 
 Smaller quantity of glucose which, even 
 after abundant and protracted inges- 
 tion of carbohydrates, seldom rises to 
 any considerable fraction of one per 
 cent, in the urine for twenty-four 
 hours, and altogether only amounts to 
 a very small number of grams. 
 
 The excretion of glucose is in less definite 
 relation to the amount of carbohydrate 
 ingested. The patient may show 
 some glycosuria after a hearty dinner, 
 but may be capable of ingesting large 
 quantities of cane-sugar or rice with- 
 out glycosuria making its appearance, 
 Emotions, alcohol, etc., have a very 
 conspicuous influence in inducing gly- 
 cosuria. 
 
 The amount of glucose, therefore, under 
 the same dietetic conditions, though 
 always small, undergoes comparatively 
 wide variations. 
 
 Simple glycosuria gives rise to no distinct 
 diabetic symptoms, except the patho- 
 logic amount of sugar in the urine. 
 
 Mild Diabetes. 
 
 Larger quantity of glucose which, after 
 abundant and protracted ingestion of 
 carbohydrates, always reaches large 
 fractions of one per cent., and usually 
 more than one per cent, in the urine 
 for twenty-four hours, the whole ex- 
 cretion, under such circumstances, al- 
 ways amounting to several grams. 
 
 The excretion of glucose is in a more defi- 
 nite relation to the amount of carbo- 
 hydrate ingested, though it may be 
 increased by emotional and other in- 
 fluences. 
 
 The amount of glucose under the same 
 dietetic conditions usually varies less 
 than in simple glycosuria. 
 
 True diabetes, though mild, generally upon 
 a free, mixed diet gives rise to other 
 symptoms than glycosuria, especially 
 to polydipsia and polyuria. 
 
46 
 
 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Glycosuria. — {^Continued.') 
 
 Simple glycosuria has a more stationary 
 tendency, and is often attended for 
 decades with the same power of as- 
 similating carbohydrates. 
 
 After the ingestion of a large dose of some 
 other saccharid than glucose, a certain 
 amount of that saccharid appears in 
 the urine, accompanied by no glucose 
 or by a relatively small amount of it. 
 
 Mild Diabetes. — [Contimied.) 
 
 True diabetes, even in its mild stage, has 
 a more progressive tendency. The 
 power of assimilating carbohydrates 
 often gradually diminishes, and the 
 mild stage not very rarely passes over 
 into the severe stage. 
 
 After a large dose of some other saccharid 
 than glucose, a certain amount of glu- 
 cose appears in the urine accompa- 
 nied by no other saccharid or by a 
 comparatively small amount of the 
 ingested saccharid. 
 
 The late excellent Norwegian physiologist and speciaUst in 
 diabetes, Worm-Mviller, considered that he had discovered a dis- 
 tinct difference between glycosuria and diabetes in their different 
 behavior after the ingestion of large amounts of other saccharids 
 than glucose. In simple glycosuria, according to this observer, 
 some part of a large amount of another saccharid ingested would 
 pass unaltered in the urine, while in diabetes every trace of sac- 
 charid found in this secretion appears in the form of glucose. 
 Thus, in a case presenting pathologic excretion of glucose after the 
 ingestion of from 200 to 300 grams of cane-sugar, one of three 
 different conditions of the urine would arise : 
 
 If cane-sugar only is found in the urine, the urine reduc- 
 ing Fehling's or Nylander's solution not previously, 
 but only subsequently, to boiling with dilute sulphuric 
 acid, 
 
 If both cane-sugar and glucose are found in the urine, 
 greater reduction taking place after than before boiling 
 with dilute sulphuric acid,* 
 
 If the urine contains only glucose, and the reduction is 
 as marked before as after boiling with dilute sulphuric 
 acid. 
 
 diagnosis of glycosuria 
 must be made. 
 
 a diagnosis of glycosuria 
 must be made. 
 
 a diagnosis of diabetes must 
 be made. 
 
 * I would remind the reader that in this experiment titration and not polarization 
 must be used before and after boiling with dilute sulphuric acid. Before the boiling, 
 the glucose alone reduces ; the cane-sugar does not. Both saccharids turn the polarized 
 light to the right. By boiling, the cane-sugar is changed into " invert sugar," a mixture 
 of levulose and glucose, of which the former turns the polarized ray of light to the left, 
 while the latter turns it to the right, but both have about the same capacity for reduction 
 (see below). 
 
GLYCOSURIAS. 47 
 
 This mode of distinguishing between diabetes and simple glyco- 
 suria has, however, only relative value, and we find also in this 
 respect only a gradual difference. In diabetes (except in some 
 cases after long periods of abstinence from carbohydrates) glucose 
 is far more easily made to appear in the urine after ingestion of 
 cane-sugar than in simple glycosuria, and after certain amounts in 
 the former only glucose may be found in the urine ; but after large 
 amounts of cane-sugar even the diabetic patient of the most aggra- 
 vated type may pass, in addition to large quantities of glucose, 
 small quantities of unaltered cane-sugar. Minkowski found this 
 to be the case even in diabetic dogs after the extirpation of the 
 pancreas, though the dog — judging from many experiments re- 
 corded in literature — is more prone than man to develop glycosuria 
 after ingestion of cane-sugar. In several cases of slight simple 
 glycosuria I have found the proportion between the amounts of 
 cane-sugar and glucose excreted after the ingestion of large 
 amounts of the former to vary greatly from one day to another in 
 the same individual. In one case of simple glycosuria of long and 
 stationary standing in a gouty and neurasthenic individual, the 
 patient, to overcome his dread of diabetes, used once every year 
 to take 300 grams of cane-sugar. The urine, which some time 
 after every rich dinner contained, for a while, a small amount of 
 glucose, after this enormous dose of cane-sugar yielded no distinct 
 reaction with Nylander's solution, although it contained a few 
 grams of unaltered cane-sugar. One day, however, just after 
 taking the 300 grams of cane-sugar, the patient got into a violent 
 passion, and an hour afterward a small amount of urine contained 
 1.3 per cent, of glucose, but only a small, doubtful amount of 
 cane-sugar. The test being repeated some few days later, yielded 
 the former usual result ; the urine contained no definite amount of 
 glucose, but a few grams of cane-sugar. 
 
 Simple glycosuria does not perceptibly alter the " patient's " state 
 of nutrition, and generally shows a strong tendency to remain sta- 
 tionary, even under the influence of deleterious circumstances. The 
 later in life it appears, and the longer it has remained unaltered, the 
 smaller is the danger of its development into true diabetes. When- 
 ever gout exists as a complication, the probability of the glycosuria 
 
48 DIABETES MELLITUS AND GLYCOSURIA. 
 
 remaining unaltered is exceedingly great, and I consider such ex- 
 cretions of sugar in the urine in elderly, gouty persons to be of 
 small clinical importance ; but even an inconsiderable glycosuria, 
 after having shown itself for a greater length of time, is most likely 
 to continue through the patient's whole life, and a development into 
 true diabetes is not with certainty excluded. 
 
 Hepatogenous Glycosuria. — The liver is the organ in which gly- 
 cogen is stored as a reserve force, and the organ in which this 
 glycogen is again converted into glucose and yielded up to the 
 circulation for the purpose of generating energy by oxidation. It 
 is evident, therefore, that certain disturbances in the activity of the 
 liver may cause disturbances in the metabolism of the sugar of the 
 blood, and occasion hyperglycemia and glycosuria. Though it 
 involves some repetition, I consider it best, for the purpose of gain- 
 ing a clear view of the subject, to make a summary of the different 
 ways in which this may occur. 
 
 The supply of glucose to the liver through the portal vein may 
 be so large and so sudden that even a normal capacity of the liver 
 to convert the surplus into glycogen is overtaxed, and the glucose 
 over and above that which can be stored in the muscles and else- 
 where, or be consumed in the tissues, enters the circulation. This 
 is evidently the case in what we call alimentary glycosuria after 
 very large amounts of glucose have been taken. Another instance 
 of a similar form of glycosuria — which with Claude Bernard, who 
 first demonstrated it, we may call alimentary, as its origin is essen- 
 tially the same — is that produced by the injection into the mesen- 
 teric veins or into the portal vein of glucose or glycogen (which is 
 transformed into glucose in the blood). 
 
 When hyperemia of the liver occurs, hyperglycemia may result 
 from an increased production of sugar, either in consequence of the 
 diastatic ferment of the blood attacking the glycogen more vigor- 
 ously or of the liver-cells becoming more pronounced in their 
 specific activity, including the secretion of sugar. It is certain that 
 Bernard's "piqure," many kinds of poison, and most of those other 
 conditions that induce glycosuria have been shown to be the cause 
 also of hyperemia of the liver ; and that which directly causes hyper- 
 emia of the liver, often causes also glycosuria. Arthaud and Butte 
 
GLYCOSURIAS. 49 
 
 have recently shown that after Hgation of the splenic artery and the 
 right gastro-epiploic artery, which considerably increases the supply 
 of arterial blood of the liver, glycosuria arises. The finding by 
 Exner (1898) of glycosuria in each of forty cases of gall-stones 
 leads me to believe that the glycosuria also in these cases is due 
 to the congestion of the liver. Trauma of the liver sometimes 
 causes glycosuria — if through congestion or through nervous influ- 
 ences is uncertain. Hyperglycemia and glycosuria also follow if 
 arterial blood is injected into the hepatic artery (Pavy) or if the vaso- 
 constrictor nerves of the liver are divided (Chauveau and Kauf- 
 mann). On the other hand, anemia of the liver seems to induce 
 hypoglycemia. After ligation of the hepatic artery Arthaud and 
 Butte found at first hyperglycemia, probably brought on by the 
 struggles of the animal during the experiment or by the loss of 100 
 grams of blood taken before the application of the ligature for the 
 sake of determining the quantity of sugar (see below) ; but after 
 this transitory hyperglycemia, the ligation was followed by distinct 
 hypoglycemia. Tangl and Harley also found hypoglycemia after 
 ligation of the hepatic artery. 
 
 Furthermore, glycosuria may arise from such disorders of circu- 
 lation as prevent the blood in the abdominal vessels from passing in 
 the portal vein through the liver in normal quantities, so that a 
 large part of this blood escapes the customary regulating influence 
 of the liver by being made to pass through the other otherwise com- 
 paratively unimportant channels outside the liver. Claude Bernard 
 thus caused glycosuria in the dog by ligation of the portal vein. 
 Andral, as early as 1856, found sugar in the urine in a case of pyle- 
 thrombosis, and Colrat and Couturier, in the seventies, confirmed 
 this observation. 
 
 Finally, we may not unreasonably assume that such processes 
 as directly decrease the power of the liver to store the glycogen 
 may tend to produce glycosuria, and some facts seem to corrobo- 
 rate this. The retention of bile speedily empties the liver-cells of 
 their glycogen (Dastre and Arthur, Hergenhahn), and Golowin 
 found glycosuria after closure of biliary fistulae, v. Wittisch after 
 ligation of the bile-ducts. Tscherinow observed glycosuria in asso- 
 ciation with acute yellow atrophy of the liver, Schmitz with amyloid 
 degeneration of the liver, Neusser with poisoning by phosphorus. 
 
50 DIABETES MELLITUS AND GLYCOSURIA. 
 
 (This effect of phosphorus, however, seems, according to BolHnger, 
 Huber, and Miinzer, to be rather the exception than the rule.) 
 Cirrhosis of the hver has been the subject of many investigations in 
 this connection, but in default of an exact expression for the normal 
 power of assimilation and of any considerable number of perfectly 
 uniform researches, and on account of the frequency of excretion 
 in the urine of small, pathologic amounts of glucose, apart from dis- 
 ease of the liver, it is difficult to arrive at definite conclusions. I 
 have in this connection observed a large number of patients with 
 simple atrophic cirrhosis and some with hypertrophic cirrhosis of 
 the liver, and repeatedly have found glycosuria, and sometimes true 
 diabetes. On the other hand, I have seen quite a considerable 
 number of patients in a far-advanced state of cirrhosis of the liver 
 that were able to take large amounts of carbohydrates without de- 
 veloping glycosuria, and I was for a long time unable to make up 
 my mind as to the supposed intimate connections between cirrhosis 
 of the liver and glycosuria. Even now I am able to accept such a 
 connection rather on account of Naunyn's figures of about sixteen 
 per cent, of cirrhosis of the liver among diabetic patients than from 
 my own experience. 
 
 Naunyn's observations seem to confirm Claude Bernard's opin- 
 ion as to the greater frequency of glycosuria in cases of incipient 
 than in those of advanced cirrhosis. One sometimes, however, finds 
 glycosuria in patients with most pronounced cirrhosis of the liver. 
 
 Toxic glycosuria arises from the ingestion of various substances, 
 and many experiments that have recently been made seem to indi- 
 cate that almost any poisonous substance may increase the amount 
 of sugar in the blood and cause glycosuria, and that this may even 
 result through substances that are normally present in the blood, if 
 they be injected or ingested in abnormally large amounts. 
 
 Except in the cases in which phloridzin has been given, and in 
 those of slow asphyxiation, the glycosuria that results from poison- 
 ing is always caused by hyperglycemia, which may be the result of a 
 toxic influence exerted in various ways. Such an occurrence may be 
 brought about by a direct effect on the nervous centers, and through 
 them on the vasomotor nerves, with hyperemia of the liver and in- 
 creased production of sugar ; or by a paresis of the muscles, with 
 
GLYCOSURIAS. 5 1 
 
 decreased consumption of the sugar of the blood, either in conse- 
 quence of metabolic changes in the muscles themselves, or in con- 
 sequence of disturbances of respiration and want of oxidation ; or 
 of an influence on the tissues and on cellular vitality, with deteriora- 
 tion of the general metabolism ; or of some influence on the Hver- 
 cells, with a weakening of their power to store glycogen ; or of a 
 change in the epithelial elements of the kidneys, in consequence of 
 which they permit the escape of the sugar of the blood with the 
 urine (phloridzin). We have as yet on this subject only hypotheses 
 that are analogous to the theories concerning diabetes. An enor- 
 mous amount of experimental work will be required to put us in 
 possession of all the knowledge that is to be gained from a 
 study of the glycosuria due to various forms of poisoning. 
 
 In all of the glycosurias of this group, with the exception of 
 that due to phloridzin, the amount of sugar in the urine keeps at a 
 moderate level* and constitutes only an unimportant feature of the 
 entire clinical picture. Having made its appearance with the other 
 symptoms, the glycosuria generally persists for some time after the 
 elimination of the poison. The glucose is often accompanied by 
 other pathologic substances. One of these is lactic acid, which is 
 considered to represent a station in the combustion of carbohy- 
 drates on their way to complete oxidation and to the formation of 
 carbonic acid and water. After the ingestion of chloralf or chloral- 
 amid (Manchot), of nitrobenzol and nitrotoluol (Ewald, v. Mering, 
 Magnus-Levy), of orthonitrophenyl-propionic acid (Hoppe-Seyler), 
 side by side with the glucose we find the combined glycuronic 
 acids, which reduce solutions of copper and bismuth and deflect 
 the polarized light to the left, but do not undergo fermentation 
 (see below). 
 
 Acids, both without and within the organism, seem to favor the 
 
 * Araki has recently induced glycosuria by the administration of veratrin, morphin, 
 cocain, strychnin, amyl nitrate, and carbon dioxid, the amount of sugar in the urine 
 reaching four per cent. There was often albuminuria. The lactic acid in the urine 
 reached two per cent. 
 
 f Ewald first saw reduction after ingestion of chloral, and attributed it to glucose. 
 Von Mering, however, by the absence of fermentation, demonstrated the reducing sub- 
 stance to be something else than glucose. It was found to be a combined glycuronic 
 acid (urochloralic acid). In some cases both substances are present. 
 
52 DIABETES MELLITUS AND GLYCOSURIA. 
 
 molecular construction of sugar and to facilitate the transmutation 
 of glycogen into glucose, just as alkalies seem to have the opposite 
 effect.* If acids are introduced into the blood for some time and 
 in sufficient quantities, they cause emaciation, anemia, lowering of 
 temperature, neuralgia, paresis and paralysis, and, finally, a state 
 that greatly resembles diabetic coma (Rolf, Walter, Hugonenq, 
 Stadelmann, Kiilz, and others). Moreover, there may or may not 
 be albuminuria. The glycosuria also is not constant, and when it 
 follows, it is slight. It has been observed in cases of poisoning 
 with sulphuric acid (Pavy), lactic acid (Golz, Naunyn), hydrochloric 
 acid (Naunyn and others), salicylic acid (PoUatschek), prussic acid 
 (Geppert), oxalic acid, orthonitrophenyl-propionic acid (Hoppe- 
 Seyler), and the lower fatty acids (Mayer). 
 
 Frerichs reports some cases of poisoning with sulphuric acid, in which he 
 found sugar in the urine only exceptionally, though reducing substances, 
 which do not undergo fermentation (combined glycuronic acids), are not 
 rarely present. 
 
 I. B. L., a healthy servant-girl of twenty-two, took a large quantity of con- 
 centrated sulphuric acid and excreted as much as 0.5 per cent, of glucose 
 (reduction, rotation, fermentation). The ^specific gravity of the urine was 
 1.043, ^'^d rio albumin was present. 
 
 2. M. S., in the fifth month of pregnancy, drank, on May 26th, concentrated 
 sulphuric acid ; was given calcined magnesia in milk, but vomited blood ; 
 had violent pains in the mouth and throat, hoarse voice, and pain in the epi- 
 
 * Acids cause saccharification of glycogen and starch, while alkalies do not. Coignard 
 watered radishes, Martin-Damourette a vine, with alkaline water, and thus obtained a 
 much smaller amount of sugar in the roots of the former and in the fruits of the latter, 
 than by using ordinary water. Ehrlich found that frogs living in a solution of glucose 
 stored a good deal of glycogen in their livers when sodium bicarbonate was added to the 
 solution of glucose, but a comparatively small amount when acetic acid was added, Pavy 
 assumes that sulphuric acid injected into the blood favors the transmutation of glycogen 
 in the liver into sugar, but that injections of sodium bicarbonate favor its transmutation 
 into something else. His opinion that the latter-named injections decrease the hepatic 
 glycogen was not borne out by the experiments of Kiilz, which yielded exactly opposite 
 results. In cases of severe diabetes with large quantities of (diacetic and /3-oxybutyric) 
 acids in the blood the hepatic glycogen is distinctly diminished (Frerichs, v. Mering and 
 Mmkowski, Stadelmann). As a result of his experiments Kulz reached the somewhat 
 uncertain conclusion that dextronic acid, sugar acid, and mucous acid contribute to the 
 formation of glycogen in the liver. This seemed certainly to be the case with the an- 
 hydrid of glycuronic acid, which is molecularly closely related to glucose. Even if all 
 these weak acids should in some way contribute to the formation of glycogen in the liver, 
 it can scarcely be doubted that stronger acids in the blood are decidedly antagonistic to 
 such a result. 
 
GLYCOSURIAS. 53 
 
 gastrium. She voided 700 cu. cm. urine of a specific gravity of 1.045 (■)> ^^^^ 
 from albumin, sugar, and other reducing substances. On May 28th the spe- 
 cific gravity was 1.039, ^^^ '^^^'^ ^^Y ^-^S^' ^^'^ ^^^^ from abnormal substances. 
 On June 1st the urine had a specific gravity of 1.034, was dark, smelt of ace- 
 tone, and yielded a wine-red reaction with ferric chlorid (diacetic acid from 
 inanition). There was no reduction, no rotation of the polarized light, no 
 albumin. The sulphuric acid present in the urine equaled 1.68 grams, of which 
 1.43 were mineral sulphates and 0.25 aromatic sulphates. Thus, the latter 
 were increased, although the whole amount was not abnormal. The vomit- 
 ing and the pains continued, so that only small quantities of liquid food 
 could be taken during the first few days. On June 3d the patient was able 
 to take more food; on June 5th the wine-red reaction of the urine had dis- 
 appeared, while the specific gravity was i.oio, and the sulphuric acid equaled 
 1. 1 8 grams. 
 
 It has been proved that a large number of partly indifferent, 
 partly poisonous, metals and metallic salts, when injected into the 
 blood or taken by the mouth, are capable of causing glycosuria. 
 This is the case with injections into the blood of ordinary sea-salt 
 (Bock and Hoffmann, see below), sodium bicarbonate (Kiilz, Kess- 
 ler), sodium acetate, sodium valerianate, sodium succinate, sodium 
 phosphate, and sodium sulphate (Kiilz, Kuntzel), as well as with 
 sodium salicylate taken by the mouth (Burton). 
 
 Phosphorus (Bollinger, Huber, v. Jaksch), arsenic (Bernard, 
 Quinquaud, Saikowski, Masoin), mercury (Reynoso, Rosenbach, 
 Bouchard, Cartier, v. Mering), lead (Brunelle, Strauss), uranium 
 (Cartier), also cause glycosuria more or less constantly. 
 
 At least under some of the conditions named the hypergly- 
 cemia is induced through the agency of the nerves, as glycosuria 
 does not follow the injection of sea-salt if the splanchnic nerves are 
 divided (Kiilz). 
 
 Phosphorus causes glycosuria, lactaciduria, and peptonuria, but none of these 
 is constant. Von Jaksch observed glycosuria in 15 of 43 cases of phosphorus- 
 poisoning. Of Miinzer's ten cases, of which several terminated fatally, it is in 
 most cases especially stated that the urine contained no sugar, and in no single 
 case is it mentioned that there was any. Laub in two cases noted 0.15-0.7 per 
 cent, of glucose. Von Jaksch mentions that glycosuria is common in such 
 cases when icterus is present. 
 
 Arsenic, which has the power of preventing glycosuria after Bernard's punc- 
 ture, and is used therapeutically because of its property of diminishing the ex- 
 cretion of sugar in the urine, in toxic doses sometimes causes glycosuria. 
 Whether this is a consequence of the glycogen being driven out of the liver 
 and the muscles being unable to consume the increased sugar in the blood 
 
54 DIABETES MELLITUS AND GLYCOSURIA. 
 
 (Zimmer), or the effect of the accumulation of arsenic in the brain (Scolozoboff ), 
 has not been decided. 
 
 Feilchenfeld has described a case of acute arsenical poisoning with an ex- 
 tensive, fully developed, multiple neuritis. The case, which first seemed to be 
 one of true diabetes (4.7 per cent, of sugar), soon settled down to an insignifi- 
 cant glycosuria. 
 
 Both sugar and albumin are sometimes found in the urine of persons under- 
 going antisyphilitic mercurial treatment, but only when the mercurial poisoning 
 is pronounced (Frerichs, Kussmaul, Lewin). Graf noticed in rabbits constant 
 glycosuria after doses of mercuric chlorid. 
 
 Brunelle found from 0.2 to i per cent, of glucose in the urine after 
 administration of 200 grams of syrup in more than half of a number of cases 
 of lead-poisoning. 
 
 Uranium and its salts constantly cause glycosuria and albuminuria.* 
 Those that, not very wisely, have introduced uranium nitrate into therapeutics 
 for the purpose of diminishing glycosuria, should have first considered its 
 poisonous properties. Cartier found subcutaneous injections of from _^ to 2 
 milligrams per kilo of body weight to be fatal, the animals (rabbits) mani- 
 festing thirst, diarrhea or constipation, loss'of appetite, somnolence, torpor, 
 paresis or paralysis, retarded respiration, emaciation, lowering of temperature, 
 and death in coma, with or without convulsions. The glycosuria appeared about 
 twenty minutes after the injection, reached its maximum in a day or two, seldom 
 exceeded more than i per cent, of sugar, and then decreased. The urine first 
 increased, then decreased, anuria finally setting in. Acetone was present, 
 probably from inanition. The autopsy disclosed a severe congestion of the 
 whole gastrointestinal tract, with ulcerations in the stomach and the duodenum. 
 The liver was intensely hyperemic ; large amounts of the drug caused cellular 
 necrosis. The kidneys were also markedly congested, and the seat of diffuse 
 parenchymatous inflammation, often with cellular necrosis. The heart pre- 
 sented subendocardial ecchymoses. Neither the nervous system nor the pan- 
 creas nor the lungs presented noticeable changes. 
 
 Alcohol, which in small amounts increases the power of assimilat- 
 ing carbohydrates, has in large amounts the opposite effect. Thus, 
 the diabetic is, after generous indulgence in alcohol, found to 
 excrete far more sugar than he does otherwise with the same 
 allowance of carbohydrates in his diet. Simple glycosuria may, 
 under the same influence, be attended with such quantities of sugar 
 in the urine as are common in diabetes ; while a normal individual 
 may, after excesses "in Baccho," present gl)xosuria. This effect 
 is more easily brought about in some persons than in others, but 
 
 * Glycosuria following the ingestion of uranium was first observed by Leconte in the 
 beginning of the fifties; then by Gmelin, Bernard, Blake, Rabuteau, Curee, Chittenden, 
 Kowalewski, Whitehouse, Lambert, Woroschilski, and Cartier. 
 
GLYCOSURIAS. 5 5 
 
 probably may be caused in any individual — a fact well worth know- 
 ing and remembering, to avoid false diagnoses of diabetes. Bever- 
 ages that contain large quantities of both alcohol and carbohy- 
 drates are especially efficient in causing glycosuria, which is often 
 observed after indulgence in champagne and beer and also in that 
 disgusting mixture of arrack, sugar, and water, which is called 
 Swedish punch, and often flows too freely in my native country. 
 The glycosuria following the use of alcohol is generally moderate, 
 and the sugar in the urine keeps within one per cent., but after 
 excessive indulgence may continue for several days, especially 
 appearing after meals. 
 
 In cases of chronic alcoholism one also sometimes finds a small 
 amount of sugar in the urine. I have, however, seen a consider- 
 able number of such persons with a normal power of assimilating 
 carbohydrates. 
 
 Ether, now and again, causes glycosuria, whether injected in the veins 
 (especially the portal vein, Harley), inhaled, or taken by the mouth. There 
 are, however, individuals that, in spite of long and great abuse of ether, 
 exhibit no glycosuria (Frerichs). Andral observed diabetes in such a case, but 
 the question whether ^^j/ or ^r^//<?^ remains undecided. 
 
 Chloroform often causes the excretion of small amounts of sugar (Eulen- 
 burg and others). 
 
 Chloral csMse.?, the appearance in the urine of urochloralic acid, belonging to 
 the group of combined glycuronic acids (v. Mering) ; on account of its reducing 
 properties this acid has often been mistaken for glucose. Chloral, however, 
 now and again also causes true glycosuria (Telz, Ritter, Eckhard). Manchot 
 observed slight glycosuria in about one-fourth of a number of cases in which 
 chloralamid was being administered. 
 
 Amyl nitrite^ causes glycosuria more surely than alcohol, ether, chloroform, 
 or chloral, the sugar in the urine rising at times above two per cent., and 
 appearing for twenty-four hours after inhalation (Fr, A. Hoffmann). Bouchard 
 thinks this due to the transmutation of the oxyhemoglobin into methemoglobin 
 and to deficient oxidation; others lay stress on the vasoparalytic influence and 
 the congestion of the liver. 
 
 Lactic acid is under these circumstances, as under others, sometimes found 
 in the urine in association with glucose. 
 
 Ammonia, when injected into the portal vein, causes glycosuria, which also 
 Bouchard ascribes to the decreased capacity of the blood to absorb oxygen. 
 
 Glycosuria from Asphyxia. — As early as 1868 Senator, in the 
 course of his investigations on the effects of disturbed respiration, 
 
 *Siebold, " Ueber d. Amylnitrit-Diabetes," Diss., Marburg, 1S74. 
 
56 DIABETES MELLITUS AND GLYCOSURIA. 
 
 found glycosuria to be one of these effects, although it proved 
 subsequently, after continued clinical observation, to be the excep- 
 tion rather than the rule. 
 
 Senff in 1869 observed that dogs, after inhaling carbonic acid, 
 constantly exhibited glycosuria, sometimes accompanied by albumi- 
 nuria. He found hyperglycemia, but a normal capacity on the 
 part of the muscles to consume sugar, and he therefore attributed 
 the hyperglycemia to an increased production of sugar in the 
 liver. 
 
 Dastre in 1879, i^ ^i^ thesis " Sur la Glycaemie Asphyctique," 
 made a distinction between slow and rapid asphyxiation : the former 
 causing hypoglycemia, the latter hyperglycemia, and both, glycosu- 
 ria. In slow asphyxiation, when the animals breathed in closed 
 compartments or in rarefied air, the amount of sugar in the blood 
 was distinctly diminished, and Dastre attributes the glycosuria 
 under these conditions to the want of oxygen and the greatly re- 
 duced oxidation, in consequence of which even the decreased 
 amount of sugar in the blood is not consumed. 
 
 In the nineties Hoppe-Seyler's pupils— Araki, Zillesen, and 
 Irisawa — proved that different conditions and circumstances that 
 induce dyspnea or are attended with a deficiency in the supply 
 of oxygen (agony, severe anemia, etc.), often also cause glucose 
 and lactic acid to appear in the urine, though neither the one nor 
 the other is always present. 
 
 Hoppe-Seyler's pupils consider the glycosuria attending the col- 
 lapse due to many poisons (curare, delphinin, strychnin, morphin, 
 chloroform, ether, sulphonal, carbonic acid, hydrocyanic acid, etc.), 
 as well as that appearing during tetanus, after epileptic attacks and 
 other similar states, as being of asphyctic type. Schiff, Sauer, and 
 others also insist that the glycosuria does not appear, or that it 
 disappears, if asphyxia is prevented by proper artificial respiration. 
 Still there are other plausible explanations : Dastre is of opinion 
 that asphyctic blood excites the liver to increased production 
 of sugar, and remarks that the glycosuria due to many poisons 
 appears before any deficiency of oxidation could be effective. 
 
 Glycosuria due to carbon monoxid was mentioned by Bernard 
 (1857), investigated by Senff (1869), and afterward studied by 
 Richardson, Ollivier, Biefel and Pollek, Frerichs, Hasse, Kahler, 
 
GLYCOSURIAS. 57 
 
 V, Jaksch, Araki, Garofalo, Rosenstein, Walter Straub, Vamossy, 
 and others. It is caused by hyperglycemia ; the sugar in the urine 
 may reach 1.5 per cent, in man (Frerichs) and 4 per cent, in the 
 dog (Senff). Lactic acid injected subcutaneously reappears almost 
 entirely in the urine, but sugar injected does not. In fact, Walter 
 Straub, Rosenstein, and Vamossy all have arrived at the conclusion 
 that the amount of glucose in the urine in this most remarkable 
 kind of glycosuria is not increased by the ingestion of sugar, and 
 that the glucose is not derived from carbohydrates, but from pro- 
 teids, especially fibrin (Vamossy). 
 
 Curare causes glycosuria, as was known to Bernard, and the condition 
 has since been made the subject of many investigations.* The glycosuria 
 appears quickly, and is associated not only with polyuria, but also with hyper- 
 secretion of the sudoriparous, salivary, lacrimal, and intestinal glands. The 
 abdominal organs, especially the liver, are intensely hyperemic. Langendorff 
 maintains that extirpation of the liver does not prevent the glycosuria due to 
 curare, although starvation does. Unlike what takes place in the glycosuria 
 due to strychnin, the liver afterward may contain a considerable amount of 
 glycogen. Schiff, Penzoldt, Fleischer, Zuntz, and Sauer agree as to the free- 
 dom of the urine from sugar, if artificial respiration is properly maintained. 
 As long as this is successful, the urine contains a reducing, but not a ferment- 
 ing, substance (probably pyrocatechin, Sauer), but as soon as respiration begins 
 to fail sugar appears.* The glycosuria due to methyl delphinin seems to be 
 very like that due to curare. 
 
 Glycosuria due to strychnin was observed in the fifties by Claude Bernard 
 and by Schiff; it was afterward studied by Langendorff and by Giirtler. It is 
 most easily induced in frogs in the autumn, when their livers are well stored 
 with glycogen. The sugar is somewhat slow to appear, and may not do so for 
 a whole day. It may then persist for several days, although at a low figure. 
 The liver is emptied of its glycogen (the "paraplasma" or substratum, for it is 
 diminished), and the hepatic cells are reduced in size and become polygonal 
 in shape (Langendorff). Extirpation of the liver prevents the development of 
 the glycosuria, as does also destruction of the spinal cord, while severance of 
 the head from the body does not (Claude Bernard). The glycosuria does not 
 depend on the tetanus, as it appears also if the muscles are entirely paralyzed. 
 There is sortie polyuria and lactaciduria. 
 
 Morphin gives rise to glycosuria, as is well known from Eckhard's work, and 
 as can easily be demonstrated by injecting from three to five centigrams 
 of the sulphate or hydrochlorate subcutaneously in a rabbit. The sugar ap- 
 pears in small quantities as early as the second hour after the injection, and 
 often persists only for a i^^N hours ; the condition is the result of hyperglyce- 
 
 * Winogradoff, Casal, Lionville, Langendorff, Voisin, Saikowski, Schiff, Doch, Gag- 
 lio, Demant, Penzoldt and Fleischer, Zuntz, Sauer (" Pfliiger's Archiv," 1S91). 
 5 
 
58 DIABETES MELLITUS AND GLYCOSURIA. 
 
 mia (Seegen). Like the glycosuria after Bernard's puncture, that due to mor- 
 phin is prevented not by section of the pneumogastric, but by that of the 
 splanchnic nerves or of the spinal cord above the roots of these nerves. After 
 large doses the transitory polyuria is followed by a decreased secretion or even 
 by anuria. An injection of glycerin prevents the glycosuria (Luchsinger), or 
 at least has an effect in that direction (Eckhard). 
 
 Sugar is sometimes found in the urine of morphinists and sometimes not 
 (Pichon). I have found only slight traces in a few cases of this kind. In these, 
 as in other cases of poisoning, the acute state is attended with more pro- 
 nounced glycosuria, and more frequently, than the chronic state. 
 
 Veratrin causes slight glycosuria and lactaciduria (Araki) — not in conse- 
 quence of diminished " glycolytic power " on the part of the blood, but on ac- 
 count of an increased production of sugar, according to Lepine. 
 
 Von Noorden observed glycosuria after the use of ergotin. 
 
 Many diuretics cause glycosuria. This and some other facts have of late led 
 some observers to the conclusion that there is a glycosuria due to polyuria. 
 When Bock and Hoffmann injected a one per cent, solution of sodium 
 chlorid into the veins of the rabbit, the animals first presented distinct poly- 
 uria and later glycosuria.* Jacoby (Strassburg) found that sulphocaffeinic 
 acid, sodium caffein, benzoate, and theobromin-sodium salicylate (" diuretin "), 
 all diuretics, caused glycosuria.! 
 
 Klemperer, who strongly maintains that glycosuria may result from poly- 
 uria, found sugar after administration of digitalis. We often find inosite ac- 
 companying polyuria — why not also glucose ? There are also, at times, cases 
 of diabetes insipidus with traces of glucose in the urine — though this does not 
 at all seem to be a common occurrence. It is not easy to make up one's mind 
 definitely as to the glycosuria resulting from polyuria. The facts already 
 mentioned may be explained in different ways, and there is one important and 
 well-known fact that denotes that polyuria does not always produce glycosu- 
 ria. Cirrhosis of the kidneys is attended with polyuria, but not with glycosu- 
 ria, and in case of diabetes it has a decided influence in decreasing the 
 glycosuria. 
 
 Some animal poisons cause glycosuria. Ewald, and afterward Strauss, found 
 as much as six per cent, of glucose in the urine after administration of thy- 
 roidin ; when the thyroidin ceased, the glycosuria also ceased. 
 
 Teschemacher noted glycosuria after injections of Koch's tuberculin; 
 Dufresne, after injections oi pancreatin. 
 
 Toepfer and Freund observed glucose after injections of a dialysate of 
 feces. The fact that the glycosuria reached a greater intensity and was of 
 
 * This experiment, however, has many other effects than polyuria, and especially a 
 decrease in the glycogen in the liver, and hyperglycemia. In some cases there was also 
 albumin and even blood in the urine, denoting a condition of the kidneys that by some 
 persons is considered conducive to glycosuria. 
 
 •f- Neumann administered " diuretin " in a case of insufficiency of the aortic valve, and 
 observed polyuria and glycosuria, which he ascribes to the heart-disease. The glyco- 
 suria may as well have been caused by the "diuretin." 
 
GLYCOSURIAS. 59 
 
 longer duration when feces from diabetics were used than when the feces were 
 derived from healthy individuals, may, if not dependent on mere chance, be 
 explained by the customary greater abundance of the products of the putre- 
 faction of proteids in the intestines of diabetics. The theory advanced by 
 Toepfer belongs, in my opinion, to what Punch calls "things one would 
 rather have left unsaid." 
 
 As is well known, the liver is supposed, among other functions, to have that 
 of retaining poisonous substances absorbed from the alimentary canal and of 
 preventing their entrance into the blood. On the other hand, the toxicity of 
 the urine is an index of the amount of such substances in the blood. Roger 
 ("Action d. Foie sur les Poisons," Paris, 1887) observed that patients suffering 
 from various hepatic disorders and secreting a highly poisonous urine readily 
 developed glycosuria after the ingestion of considerable amounts of sugar; and 
 he expresses the opinion that the liver has in those cases lost in part its capacity 
 for retaining the poisons and for converting alimentary sugar into glycogen. 
 
 Phloridsin-glycosiiria. — Scarcely had Koninck (1885) discovered 
 phloridzin when v. Mering (1886) observed that this substance 
 causes an exceedingly peculiar form of glycosuria. 
 
 Phloridzin is a glucosid obtained from the bark of the root of 
 certain species of Pyrus and Prunus. It crystallizes in glistening 
 silky crystals and is easily soluble in warm water, but requires 1000 
 parts of cold water for its solution. Phloridzin is levogyrate. It is 
 decomposed by boiling with diluted acids : 
 
 Phloridzin X Water = Plilorose + Phloretin. 
 
 Phlorose, as will be seen, is a hexose, has the same molecular 
 construction as glucose, which it resembles greatly, is dextrogyrate, 
 and reduces, though in less degree than glucose. 
 
 Phloretin, though less efficient in this respect than phloridzin, also 
 causes abundant glycosuria. Treated with caustic alkali, it forms 
 phloretic acid (an aromatic alcoholic acid) and phloroglucin (a tri- 
 atomic aromatic alcohol), both of which are probably also formed 
 in the organisms ; they do not cause glycosuria, but increase the 
 combined aromatic sulphatic acids in the urine (Moritz and Prauss- 
 nitz). In the course of the intoxication, and as long as the glyco- 
 suria lasts, there appears in the urine a brownish-violet coloration 
 on addition of ferric perchlorid (due to phloridzin). With phlore- 
 tin a similar, but more deeply violet, reaction is obtained. The 
 urine, especially if the animal has been kept fasting, becomes 
 shghtly albuminous. 
 
60 DIABETES MELLITUS AND GLYCOSURIA. 
 
 The glycosuria commences after a couple of hours, after o.oi 
 gram per kilo of body weight has been given by subcutaneous injec- 
 tion, and after double that dose by the mouth in dogs. After large 
 doses the amount of sugar may rise to more than thirteen per 
 cent. (Moritz and Praussnitz), or even to more than eighteen per 
 cent. (v. Mering) in dogs, and it may persist for several days or a 
 week (Coolen). The quantity of urine is not increased, but the 
 specific gravity may rise to 1.070. In rabbits the glycosuria is 
 less marked and more transitory, but it appears regularly after 
 subcutaneous injections ; after injection of two grams it persists for 
 from seven to twenty hours (Lusk). It is also observed in the 
 hen, the goose, and the frog (Ritter and Cremer). It has been 
 observed in the goose after extirpation of the liver (v. Mering, 
 Thiel). 
 
 The organism, even under the influence of phloridzin, assimilates 
 a considerable part of the ingested carbohydrates. The larger the 
 dose of phloridzin, the greater the absolute value of the sugar in 
 the urine, but the smaller its value in relation to the dose. 
 
 Klemperer, and recently (1899) Achard and Delamare, have 
 found phloridzin to give rise to much less marked glycosuria in 
 cases of chronic nephritis than otherwise. 
 
 Phloridzin, as may be understood from the relation between the 
 quantity ingested and the amount of sugar in the urine, acts in a 
 " specific " manner, and not by reason of being a glucosid, as other 
 glucosids do not cause glycosuria (v. Mering, Gley, Germain See). 
 Thus, 6 grams of phloridzin, containing 2.5 grams of phlorose, 
 may cause glycosuria with 41.7 grams of sugar in the urine. 
 
 An abundant mixed diet, including a great deal of sugar and 
 starch, causes the glycosuria to reach its maximum ; but it continues 
 during starvation and even after extirpation of the liver. Von Mering 
 found glycosuria in the dog when the liver and the muscles were 
 almost, but, as Kiilz remarks, not completely, emptied of glycogen. 
 
 When the food is made up exclusively of fat, the glycosuria falls 
 as low as in starvation (v. Mering, Moritz, and Praussnitz) — a most 
 remarkable circumstance, which speaks against the opinion of those 
 who think that fat may, with a deficiency of carbohydrates and 
 of albumin, form glucose in the organism. 
 
 As long as the food is abundant enough to cover the heat-wants 
 
GLYCOSURIAS. 6 1 
 
 of the organism and the loss of sugar in the urine, even large doses 
 of phloridzin do not cause any general disturbances ; but during 
 starvation and poisoning with phloridzin inanition speedily develops ; 
 the animals quickly lose weight ; the proteids of the organism are 
 decomposed; acetone, diacetic acid, and /'J-oxybutyric acid show them- 
 selves in the urine, while the ammonia increases, and weakness and 
 somnolence become manifest. If the animals are then killed, the 
 liver and the muscles are found in a state of fatty degeneration. 
 [Rosenfeld is of the opinion that the fat in the liver in these cases 
 is derived from an infiltration of fat from other parts than the liver, 
 and not from fatty degeneration of proteids in the liver-cells.] If 
 the animals are given food and the phloridzin is withheld, they 
 speedily return to health. The liver is said to store more glycogen 
 from meat under the influence of phloridzin than if the animals 
 receive only sugar. 
 
 The most peculiar feature of the phloridzin glycosuria, however, 
 is the presence of a decreased percentage of sugar in the blood. 
 Von Mering and almost all other observers agree on this point.* 
 
 Von Mering found from 0.075 to 0.09 per cent, of sugar in the 
 blood with from 6.5 to 9.2 per cent, of sugar in the urine of the 
 dog, the blood normally containing about o. 10 per cent. Gabrit- 
 schewski found that, while the white corpuscles of hyperglycemic 
 (diabetic) blood contain an abnormally large quantity of glycogen, 
 they contain an unusually small amount thereof in phloridzin cases. 
 
 There are only two ways of explaining phloridzin-glycosuria — it 
 may arise in consequence of some alteration in the epithelial ele- 
 ments of the kidneys (v. Mering), or it may be the result of some 
 combination of phloridzin or one of its derivatives with glucose 
 (Graham, Lusk). In either case the passage of the latter into the 
 urine is facilitated, and the blood, the liver, the muscles, and the 
 whole organism are thus deprived of both sugar and glycogen, 
 which are constantly renewed, though not at the same rate as they 
 are lost. 
 
 After extirpation of the kidneys the hypoglycemia ceases, but 
 
 * Pavy, whose researches on blood-sugar have led him to such curious conclusions, 
 has not found any hypoglycemia during phloridzin-glycosuria (" Journ. of Physiol.," 
 London, 1894). Coolen also found no decrease of blood-sugar, and Levene found a 
 somewhat higher figure for the sugar in the renal vein than in the arterial system. 
 
62 DIABETES MELLITUS AND GLYCOSURIA. 
 
 hyperglycemia does not arise. Zuntz took the urine from both 
 ureters of the dog immediately after an injection of phloridzin into 
 one of the renal arteries, and found that the urine on this side 
 immediately became sacchariferous, while that on the other side 
 became so only when the phloridzin had reached the kidney on 
 this latter side through the entire circulatory system. 
 
 According to Cornevin, phloridzin has an analogous influence on 
 the lactogenous glands and increases the lactose in the milk. 
 
 Antipyrin (See and Gley) and syzygium jambolanum (Graser) 
 act in a manner opposite to phloridzin, and diminish the glycosuria. 
 
 Phloridzin and phloretin are sometimes used for the purpose of 
 simulating diabetes. 
 
 The glycosuria due to infectious diseases is generally attended with 
 the presence of insignificant quantities of sugar in the urine, and 
 occurs very inconstantly in the course of acute exanthematous and 
 other infections. It is not yet known under what conditions and 
 during which period the sugar appears. On the one hand, we 
 know positively that the sugar in the urine in diabetes or glyco- 
 suria decreases and sometimes disappears during the febrile state, 
 while, on the other hand, the infectious diseases attended with fever 
 often induce glycosuria. Poli recently, after the administration of 
 glucose in cases of scarlet fever, diphtheria, septicemia, tonsillitis, 
 and pneumonia, found a decreased power of assimilation and a 
 much greater portion of the ingested glucose in the urine than 
 would have appeared in normal individuals. In cases of malignant 
 pustule Roger found the sugar in the blood in the beginning of the 
 disease normal, or even somewhat below the customar)^ amount ; 
 then a moderate hyperglycemia, with from 0.22 to 0.30 per cent, of 
 sugar in the blood appeared, and after death the liver contained no 
 glycogen. In other cases of febrile disease the glycosuria appears 
 during the period of defervescence and the beginning of the con- 
 valescence. I have also seen it during the prodromal stage, and it 
 does not seem to be excluded from any stage of febrile infections. 
 
 Glycosuria is often found in the course of, and after, influenza 
 and malaria ; and it is also observed in the course of typhoid fever 
 (Seyfert, Bordier), diphtheria (Frerichs), scarlet fever (Redon, 
 Zinn), measles (Fischer, Bouchut, Bordier, Barlow, Gelmo), dysen- 
 
GLYCOSURIAS. 63 
 
 tery (Anstoots), cholera (Heintz, Samoje, Huppert, Gubler, v. 
 Terray, Vas, and Gara), croup, pertussis, pneumonia (Bordier, 
 Semmola, Stern, Beale, Reynoso), erythema nodosum (Bordier), 
 variola, and vaccinia (during the florid stage, Gueneau, Prevost), 
 anthrax (Proust, Philipeaux, Vulpian, Charcot, Frerichs, Goolden), 
 lyssa (Eichhorst), lymphangitis, and erysipelas (Redard), and septic 
 processes (Poli). 
 
 It would seem as if all suppurative processes might induce glyco- 
 suria, which has several times been observed in association with 
 gangrene, phlegmon, noma, and especially with furunculosis and 
 carbuncle. Wagner was, I believe, the first to mention glycosuria as 
 complicating these two latter skin diseases. Still, as is well known, 
 furuncles and carbuncles are common manifestations of diabetes. 
 Furuncles especially appear at an early stage of the dystrophy, and 
 there still remains some doubt if, in the cases in which they have 
 been considered to be the cause of glycosuria, they have not really 
 been the effect of a mild diabetes. 
 
 In rare cases syphilis causes glycosuria or real diabetes by attack- 
 ing either of the organs that preside over the metabolism of carbo- 
 hydrates. In most such cases arteriosclerosis, cerebral softening, 
 hemorrhage, or gummata in the brain precede the appearance of 
 the glycosuria. The few cases that I have seen were examples of 
 glycosuria or mild diabetes. Sometimes their syphilitic nature be- 
 comes apparent e jjivantibtis, and quite a number are recorded of 
 cure by antisyphilitic treatment. Decker has reported such a case 
 in which the sugar appeared a little more than a year after the in- 
 fection. Whether syphilis can cause glycosuria in any other way 
 than through lesions of the brain, the liver, or the pancreas, is not 
 known.* 
 
 The prognosis of glycosuria (or diabetes) due to infectious dis- 
 ease is decidedly more favorable than that due to any other cause — 
 the sugar generally disappearing from the urine after or during con- 
 valescence. On the other hand, some infections undoubtedly may 
 lead to true diabetes ; but even in such cases one may sometimes 
 
 * One writer has affirmed — in a book and in advertisements on the walls in Carlsbad — 
 that he acres diabetes, which he considers almost always to be an effect of syphilitic in- 
 fection, either acquired or inherited, perhaps from some ancestor of the dark ages. Such 
 a statement must not be taken too seriously — quid verbis affirtnat satis est verbis negare. 
 
64 DIABETES MELLITUS AND GLYCOSURIA. 
 
 observe instances of perfect recovery. I have seen this take place 
 after typhoid fever and after influenza, and Zinn mentions a similar 
 occurrence after scarlet fever, and Burdel in three cases after 
 malarial fever. 
 
 In cases of cholera the sugar appears chiefly in the abundant urine follow- 
 ing the anuria ; it is often accompanied by indoxyl and albumin ; the sugar 
 rarely amounts to one per cent, and disappears during the first days of conva- 
 lescence. Cases of true and even of severe diabetes are also observed in con- 
 nection with cholera (Frerichs) ; but sugar is far from being found in all cases. 
 Von Terray, Vas, and Gara found it only in one case of sixteen ; the glyco- 
 suria began twelve days after the end of the anuria ; the sugar rose to 0.5 per 
 cent, and persisted for three days. The urine of several other patients 
 strongly reduced copper, but did not deflect the ray of polarized light, and did 
 not undergo fermentation. 
 
 In cases of typhoid fever'xi seems that sugar may appear in the urine as early 
 as during the prodromal period. A clergyman came to Carlsbad for some dys- 
 peptic trouble, and presented slight evening elevation of temperature and felt 
 generally ill. A dull note on percussion over the apex of the left lung led me to 
 suspect an incipient tuberculosis. A large specimen of urine was found to 
 contain i.i per cent, of glucose. I quickly sent the patient to his home, where 
 the typical temperature-curve of typhoid fever developed. After the end of 
 the typhoid (or before) the glycosuria disappeared. 
 
 Malaria is not rarely accompanied by transitory glycosuria, which comes 
 on after every paroxysm and sometimes, though rarely, may develop into true 
 diabetes.* The glycosuria diminishes or disappears under the influence of 
 quinin. Burdel found sugar in 14 per cent, of cases of quartan or tertian 
 type, in 22 per cent, of cases of quotidian type, in 28 per cent, of cases of per- 
 nicious malaria, and in 80 per cent, of cases of malarial cachexia. He has 
 recorded three cases of a distinctly diabetic nature, in which perfect recovery 
 ensued after the use of quinin. 
 
 Since influenza, in the beginning of the nineties, again invaded the civilized 
 world there have been published many observations of glycosuria or diabetes 
 arising in the course of this disease, really much more dreadful than dreaded, 
 I have myself seen all forms of defective power of assimilating carbohydrates 
 during and after an attack of influenza, most of the cases presenting slight 
 degrees of glycosuria. In other cases of simple glycosuria that I have had 
 under observation for many years, repeated and severe attacks of influenza 
 have been without any effect whatever on the glycosuria. I have seen several 
 cases of diabetes following influenza improve greatly after convalescence from 
 
 * Peter Frank and Sydenham, more than a century ago, mentioned diabetes in con- 
 nection with malaria. Burdel, in 1859, directed the attention of the profession to the 
 small quantities of sugar in the urine of patients suffering from malaria. Several French 
 physicians in North Africa (Calmette, Rang6, Duponchet) have contributed to the litera- 
 ture on this subject. In " Malaria and Diabetes," Diss., Rostock, 1896, Otto Jacobson 
 gives the bibliography. 
 
GLYCOSURIAS. 65 
 
 the causal disease, and I have seen at least one case in which perfect recovery- 
 ensued. 
 
 Mr. X., a Finlander, some thirty years old, came in June, 1890, to Carls- 
 bad, having had his first attack of influenza half a year before. In February 
 he had had another severe attack, with high fever, violent pains in the back 
 and legs, and great prostration. Early during convalescence the patient began 
 all at once, on a certain day, to drink and to urinate freely, and an apothecary 
 found in the urine a large amount of glucose, which by a specialist was esti- 
 mated at 8.8 per cent. Unfortunately, I could obtain no information as to 
 whether any diacetic acid had been present. The patient consulted Prof. 
 Holsti, who affirmed the existence of diabetes mellitus, prescribed a strict diet, 
 and after some time sent the patient to me in Carlsbad. The general state of 
 health was then much improved, and there were no diabetic symptoms. A gen- 
 erous amount of carbohydrates was allowed and, no glycosuria appearing, 
 the amount was slowly increased until it reached at least 300 grams a day. 
 The urine remained free from glucose, nor could that substance be found after 
 administration of 200 grams of cane-sugar. For some time after the patient's 
 arrival at home he continued to be free from glycosuria upon ordinary diet, 
 but I know nothing of his subsequent fate. 
 
 In this, as in some other cases, I have no doubt the glycosuria was due to 
 the influenza. 
 
 Blot, in 1850, found in the urine of pregnant women a variety of 
 sugar that Hofmeister afterward proved to be lactose. This puer- 
 peral lactosima begins during the last months of pregnancy and 
 persists throughout the whole period of lactation, during the begin- 
 ning of which it seems to be most pronounced, so that it may reach 
 two per cent. Abeles found lactose in every one of 30 cases ; Ney 
 observed it exceptionally before parturition, but in 80 per cent, of 
 the cases he detected it from two to four days after parturition.* 
 Lemaire found in the urine quite small quantities of glucose and 
 isomaltose before parturition, and lactose only after parturition, but 
 in large quantities. 
 
 There is no doubt that pregnancy and childbirth sometimes give 
 rise to true glycosuria. Puerperal glycosuria is much rarer than 
 puerperal lactosuria. I have seen one patient who, after some 
 months following parturition, was sent to Carlsbad with a diagnosis 
 of diabetes. The urine contained small quantities of a dextrogy- 
 rate-reducing substance, which readily underwent fermentation and 
 disappeared in the presence of common yeast. I am unable to 
 
 *See, besides, the treatises of Sinety, Kirsten, Spiegelberg, Johannowski, Hofmeister, 
 Kaltenbach, and others. 
 
66 DIABETES MELLITUS AND GLYCOSURIA. 
 
 State how long this glycosuria lasted, but after two years the urine, 
 with an ordinary free diet, contained no glucose. Marcus men- 
 tions glycosuria up to 0.7 per cent, during pregnancy; Rossa 
 found glucose during the seventh month, and Lang found that 
 pregnancy is quite often attended with some loss of the power of 
 assimilating carbohydrates. 
 
 Sometimes parturition is followed by true diabetes. 
 
 The saccharid often found in the urine of nursing infants is lac- 
 tose (Pollak, Eichhorst), which passes into the urine more easily than 
 other kinds of sugar. 
 
 CI. Bernard found sugar in the amniotic liquor in animals, observed later also 
 by Moriggia and by Cramer. The amniotic fluid contains the urine of the 
 fetus, and \.\ns fetal glycosuria, like the , glycosuria of hibernating animals, 
 constitutes one of the best arguments of those who see in hyperglycemia and 
 glycosuria the effect of deficient combustion in the muscles ; but sugar in the 
 amniotic liquor does not seem to be at all a constant phenomenon in normal 
 women, and it is sometimes absent even when diabetes exists in the mother 
 (Williams, Naunyn), though, like other liquids of the organism, it may in other 
 cases of diabetes contain quite considerable (up to 0.7 per cent.) quantities of 
 glucose (Husband). Fetal glycosuria and the glycosuria of hibernates deserve 
 further investigation. 
 
 Obesity and Glycosuria. — About one-third of all diabetic patients 
 are corpulent ; and very fat persons, according to several observers, 
 present more frequently than others pathologic traces of sugar in 
 their urine. I have, in several instances, found that persons who 
 in early middle age suddenly grew corpulent at the same time be- 
 gan to exhibit distinct traces of sugar for a short while after 
 meals, the urine having previously, under similar circumstances and 
 with the same tests, proved to be normal. Almost all fat people 
 with glycosuria present also neurasthenic symptoms. Some of 
 these patients eventually develop true diabetes, but generally 
 remain in the mild stage. Still, obesity is no safeguard against 
 severe diabetes even exclusive of pancreatic cases ; the severe dys- 
 trophy, however, within a short time puts an end to the obesity, 
 Kisch beheves that in about fifty per cent, of cases of hereditary, 
 and in about fifteen per cent, of acquired, obesity pathologic excre- 
 tion of sugar takes place sooner or later. The first of these 
 figures appears to me somewhat too high. 
 
GLYCOSURIAS. 6/ 
 
 Gout and Glycosuria. — Gout is more often than any other disease 
 associated with glycosuria or diabetes. Any physician with many 
 gouty patients under his care will, if he adopt the practice of testing 
 at least once the after-dinner urine of every patient for sugar, 
 find that a large percentage of gouty individuals excrete for some 
 time every day distinctly pathologic quantities of glucose. This 
 glycosuria may set in before the appearance of gouty symptoms, 
 which when mild are often for years overlooked both by patient 
 and physician ; in other cases the urine remains normal for some 
 time after the appearance of distinct gouty symptoms. In all such 
 cases neurasthenic symptoms seem to be present. Whether gout 
 or glycosuria has been first to make its appearance, no fact is of 
 better prognostic import in a case of glycosuria than its association 
 with gout. In almost all of the many cases of this kind that I have 
 seen the glycosuric dystrophy has shown a strong tendency to 
 remain stationary, and often, for the important purpose of encour- 
 agement, I tell such patients that they will never die until somebody 
 clubs them, which rarely fails to make their faces brighten with the 
 most intense satisfaction. 
 
 Diabetes Insipidus and Glycosuria. — Over and above polydipsia and poly- 
 uria as effects of hyperglycemia, we may explain a connection between dia- 
 betes mellitus and diabetes insipidus by the close proximity of the centers for 
 glycosuria and polyuria on the floor of the fourth ventricle. The existence of a 
 separate center for polyuria (and polydipsia) — i. e., diabetes insipidus — also ex- 
 plains why neither the intensity nor the degree of the glycosuria has any fixed re- 
 lation to the degree of the polyuria. One patient may pass in the twenty-four hours 
 1.5 liters of urine containing forty grams of glucose, while another may with the 
 same amount of carbohydrates and other food pass in the same time three liters 
 of urine with twenty grams of glucose. Many think, with Klemperer, that poly- 
 uria /^r se, by its influence on the kidneys, favors the elimination of glucose 
 with the urine, as it favors the elimination of inosite. Sometimes, though 
 rarely, one therefore finds small quantities of sugar, which are too insignificant 
 to constitute diabetes mellitus in a case of distinct diabetes insipidus (Mann- 
 kopff. Senator). 
 
 Starvation and Glycosuria. — Claude Bernard observed that dogs, 
 after having been subjected to starvation, on again receiving carbo- 
 hydrates presented glycosuria. Lehman (1873) and Hofmeister 
 (" Arch, f exp. Path.," 1887) have made investigations in this field. 
 A dog, weighing two kilos, showed, after some days of abstinence 
 
68 DIABETES MELLITUS AND GLYCOSURIA. 
 
 from food, distinct glycosuria after the ingestion of as little as ten 
 grams of starch. The sugar under such conditions appeared one 
 to two hours after meals, and generally persisted for only a kw 
 hours in small quantities, although sometimes it reached nearly four 
 per cent. In their normal state the animals generally were able to 
 receive about five grams of glucose per kilo of body weight with- 
 out presenting glycosuria ; after starvation the sugar appeared in the 
 urine after less than two grams per kilo of body weight, the rapidity 
 of absorption from the alimentary canal being, in the latter case, 
 rather diminished than increased. It is to be remembered that 
 starvation undoubtedly plays some part in the etiology of true 
 diabetes. 
 
 Fatigue and Glycosjiria. — Zimmer and others have observed that 
 muscular exercises up to a certain point, in addition to their cus- 
 tomary healthful influence on diabetic patients, also have a tendency 
 to diminish existing glycosuria ; but too long walks, too much phy- 
 sical effort of any kind has a contrary effect ; and sometimes severe 
 fatigue is followed by a considerable increase in the amount of sugar 
 in the urine. The same influences will sometimes show themselves 
 in normal persons, so that after muscular excesses glycosuria may 
 appear for a short while and quickly disappear after rest. 
 
 Cold and Glycosuria. — Bohm was, I think, the first to mention 
 the slight glycosuria that may come on after exposure to cold ; it 
 has since been observed by Araki and others in rabbits and dogs 
 after application of ice around the body. Exposure to severe cold 
 is not rarely mentioned by diabetic patients themselves as a proba- 
 ble cause of their dystrophy. 
 
 Senility and Glycosuria. — Small quantities of sugar often appear 
 in the urine of old persons. This senile glycosuria is of no clinical 
 importance, and entails upon the physician no other duty than to 
 withhold the fact from the "patient," who might be unnecessarily 
 alarmed by such an information. 
 
 Cachexia or Marasmus and Glycosuria. — In cases of carcinoma, 
 tuberculosis, Addison's disease (Burghardt), leukemia (Rebitzer), and 
 in other diseases that are accompanied by marked cachexia or maras- 
 
GLYCOSURIAS. 69 
 
 mus, slight traces of glucose are often found in the urine (Zimmer and 
 others). On the other hand, it is often observed that the glyco- 
 suria perceptibly diminishes in cases of diabetes as a cachectic or 
 marantic state develops (Naunyn and others). 
 
 The Kidneys and Glycosuria. — It is well known that the same 
 amount of hyperglycemia may cause in different persons a widely 
 different degree of glycosuria (see Seegen's figures), and there is a 
 wide -spread opinion that the kidneys have an influence on the latter 
 (Lepine and others). This opinion seems corroborated by several 
 recently acquired facts, which I recapitulate here. 
 
 The glycosuria due to phloridzin seems to depend upon changes 
 in the kidneys. We know that after extirpation of the pancreas in 
 birds, whose normal glycemia is about 0.14 or 0.15 per cent. 
 (Kausch), the hyperglycemia reaches a higher figure than in mam- 
 mals before glycosuria sets in ; or, in other terms, that the kidneys 
 of birds have a greater power of preventing the sugar of the blood 
 from passing over into the urine (Kausch). Klemperer found, in 
 nephritis, glycosuria (of 0.35 per cent.) with a normal quantity of 
 sugar in the blood. Other changes in the kidneys seem also to 
 bring about a diminished power of retaining the sugar of the blood. 
 Frerichs, Morison, Habershon, and Pavy (cited by Naunyn) saw 
 chyluria associated with glycosuria. Naunyn found sugar in con- 
 junction with hemorrhages from the kidneys. Jacobi found that 
 diuretics (theobromin, sulphocaffeinic acid, " diuretin ") cause gly- 
 cosuria, which seems easily brought about in traces when polyuria 
 exists from any cause whatever — e.g., diabetes insipidus. Most of 
 these facts, however, may be explained in other ways, and "renal 
 glycosuria" at the present moment represents scarcely more than 
 a hypothesis. 
 
70 DIABETES MELLITUS AND GLYCOSURIA. 
 
 CHAPTER IV.— SYMPTOMS AND COMPLICATIONS OF 
 MILD AND SEVERE DIABETES. 
 
 Diabetes mellitus is, as already mentioned, not a disease or a 
 clinical entity, but a syndrome that may arise from a number of 
 quite different processes in the organism. The glycosuria is not 
 necessarily the first in the series of manifestations that mark the 
 change in the patient's state of health. 
 
 In the great majority of cases the precursory signs that are not 
 rarely observed are referable to the nervous system and belong to 
 the neurasthenic group. When a patient, with a urine still free 
 from sugar and with nothing more abnormal than perhaps the 
 presence of a rather large quantity of crystals of calcium oxalate, 
 has for some time complained of insomnia, irritability, enfeebled 
 sexual power, neuralgia, etc., glycosuria may appear and slowly 
 progress. In other less frequent cases changes in the vessels, new- 
 growths, cerebral softening, hemorrhages, parasites, or traumatic 
 influences may cause cerebral symptoms before glycosuria makes 
 itself manifest. 
 
 In still other cases, and especially in persons that are approach- 
 ing middle age, I have several times found that the first appearance 
 of sugar in the urine was preceded by a tendency to corpulence, 
 whereupon a simple glycosuria or a mild diabetes has set in. 
 
 In rare cases it is possible, before glycosuria begins, to diagnos- 
 ticate disease of the pancreas, then generally of carcinomatous 
 nature. 
 
 Upon the whole, a rule prevails — though one with many excep- 
 tions — that a diabetes that afterward pursues a mild course quite 
 imperceptibly invades the patient, and years may pass after the first 
 appearance of sugar in the urine before an accidental analysis, a 
 slowly increasing polydipsia, a poor and complicated healing- 
 process, or some local complication direct the patient's or the phy- 
 sician's suspicions on the right track. Many physicians omit the 
 important investigation of the urine, and it often happens that the 
 specialist — e. g., the ophthalmologist or the dermatologist — fore- 
 stalls the family physician in discovering the existence of diabetes. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. /I 
 
 In other cases, especially in such as prove to be of a severe kind, 
 diabetes sets in suddenly with marked glycosuria and specific 
 diabetic symptoms, without any prodromal manifestations. 
 
 Mild, slowly developing diabetes is much more common than 
 severe diabetes. 
 
 When the secondary dystrophy, the general disturbance of nutri- 
 tion, has developed in consequence of the primary lesion of the 
 nervous system, or the pancreas, etc., the effects may be induced 
 in any organ as a result of either the deficiency on the part of the 
 organism to fully utilize its carbohydrates and its consequent inani- 
 tion, or of the action of certain toxins, or from defective central or 
 peripheral nervous influences. 
 
 Among the toxins in the blood we include the superfluous amount 
 of sugar contained therein. In mild cases this probably is the only 
 toxin, and one whose deleterious influence has been enormously 
 overrated. A glycemia of 0.15 per cent, may still be considered 
 not in excess of the normal ; above 0.4 per cent, is found only in a 
 small minority of cases of diabetes (Seegen, Naunyn, and others). 
 Persons suffering from true diabetes, who can not be persuaded to 
 adhere strictly to a proper diet and who constantly present glyco- 
 suria (and hyperglycemia) may live in fairly good health for more 
 than twenty years. This single id^cX. proves that hyperglycemia /^r 5^ 
 can not possibly be a very powerful nocens. Its worst effect is prob- 
 ably the retaining firmer than is the normal the water in the blood- 
 vessels, and thus, to a certain extent, desiccating the tissues. This 
 causes some disturbance in the nutritive state and the functional 
 power of the organs ; it may, e. g., bring about cataract and con- 
 tribute to the development of gangrene, suppuration, and other dis- 
 integrating processes, or of neuritis and other "parenchymatous" 
 changes. The hyperglycemia may also be in part responsible for 
 the diabetic endarteritis and the arteriosclerosis. The hyperglyce- 
 mia, however, which in most cases is quite moderate, generally 
 takes a very long time to bring about these changes. 
 
 A much more deleterious effect is attributable to the acid toxins, 
 the free fatty acids, the diacetic acid, and the /5-oxybutyric acid. 
 When the physician sees for the first time a diabetic patient, the 
 quickest and best way of determining approximately the stage of 
 the diabetic dystrophy is to make use of Gerhardt's test, which 
 
72 DIABETES MELLITUS AND GLYCOSURIA. 
 
 consists in pouring a few drops of ferric chlorid in a tube nearly 
 filled with the patient's urine. The appearance of a beautiful wine- 
 purple color denotes directly the presence in the urine of diacetic 
 acid, and indirectly often the presence of that most ominous sub- 
 stance, /5-oxybutyric acid (see below). It may then be concluded 
 that the patient is in the severe stage of diabetes, that he has at 
 the utmost only a few years of life left, which will pass in a struggle 
 with the autophagy and the acid diathesis ("acidosis "), with all its 
 manifold dangers, and that death will probably be caused by the 
 blood-toxins. 
 
 What role each of the different pathologic factors — the toxins 
 and the deficient nervous influences, etc. — play in the production 
 of anatomic lesions is only imperfectly known. A good deal of 
 mystery surrounds especially the purely nervous "trophic" influ- 
 ence and its anomalies in diabetes as in other dystrophies. 
 
 In this chapter will be considered dystrophic general changes 
 and those that occur in each of the different organs. However 
 wide a clinical difference may exist between a diabetic patient in 
 the mild and one in the severe stage, there is no distinct scientific 
 demarcation separating these two stages, and it is injudicious to 
 contribute to the idea prevailing in some quarters of two entirely 
 different "forms" of diabetes. I give, therefore, no separate 
 description of mild and severe diabetes, but only point out the toxic 
 and cachectic nature, and the autophagy of the latter, and describe 
 its usual final scene — diabetic coma. 
 
 In connection with the clinical symptoms, we must consider the 
 pathologic anatomic lesions of diabetes. These are often but Httle 
 marked, both macroscopically and microscopically. After the 
 existence of mild diabetes, which is not pei' sc fatal, changes of a 
 purely diabetic character are generally overshadowed at the autopsy 
 by alterations due to the intercurrent or complicating disease. 
 After diabetes in the severe stage or of long standing, the autopsy 
 is certainly very likely to reveal characteristic changes. These, 
 however, even when found in those organs that play a role in the 
 pathogenesis of diabetes, — the nervous system, the pancreas, and 
 the liver, — are far more frequently an effect than a cause of the 
 diabetes, and represent retrogressive and degenerative processes 
 due to the marasmus and the cachexia. The alterations in the 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 73 
 
 kidneys, the most frequent of all, have no connection with the 
 
 origin of the dystrophy, but are the results of its effects on the 
 renal functions. 
 
 SPECIFIC DIABETIC AND DYSTROPHIC SYMPTOMS. 
 
 The sugar that appears m the urine in cases of simple glycosuria 
 is present in determinable quantities only for some time after meals, 
 while in cases of true diabetes, however mild, it is present under 
 continued ordinary diet throughout the whole or, at least, the 
 greater part of the twenty-four hours, being absent only when the 
 patient's stomach is empty just before meals, and especially in the 
 morning before breakfast. With restriction of the carbohydrates 
 to a quantity below the patient's power of assimilation, the sugar 
 in the mild stage of the dystrophy disappears from the urine. In 
 the severe stage, when glycosuria is derived at least partly from 
 proteids, the urine constantly contains glucose — except, perhaps, 
 just before death, when the entire metabolism fails. 
 
 After carbohydrates have been taken glycosuria begins in about 
 half an hour, and so quickly reaches its maximum that the greater 
 part of the sugar in the urine may have been excreted during the 
 first hour. The whole excretion generally does not last more than 
 five or six hours, and often a shorter time. In rare cases one some- 
 times finds a distinct postponement of the whole excretion. 
 
 The glycosuria following proteids in the severe stage of the dys- 
 trophy is attended with the excretion of less sugar, and reaches 
 its maximum later than after ingestion of carbohydrates ; or, in 
 other words, the glycosuric curve due to proteids shows a lower 
 wave. 
 
 The intensity of the glycosuria — i. e., the amount of glucose ex- 
 creted in twenty-four hours — varies greatly, and depends on the 
 power of assimilation and on the quality and quantity of the food 
 ingested. In cases of true diabetes, however, after prolonged free 
 diet it generally reaches a considerable degree and always some 
 number of grams. Anything below one, or even two, grams under 
 such circumstances is properly considered simple glycosuria. 
 Sometimes the glycosuria reaches quite extraordinary figures, and 
 it may reach one kilo, in twenty-four hours. Dickinson found in 
 6 
 
74 DIABETES MELLITUS AND GLYCOSURIA. 
 
 one case 1500 grams, and some French observers have noted still 
 higher figures. 
 
 The mtensity of the glycosuria — /. e. , the percentage of glucose — 
 varies exceedingly during the twenty-four hours. The minimum is 
 always found in the morning before the patient's first meal, and a 
 large number of diabetics present at this time of day no glycosuria 
 that is discoverable with our ordinary tests. The maximum is 
 generally reached between one and two hours after meals, and there 
 are usually three distinct waves during the twenty-four hours, their 
 height depending on the nature of the food. With a strict diet no 
 reaction may be observed in mild cases or only a slight one. 
 In advanced cases, with a liberal supply of carbohydrates we some- 
 times find ten per cent, of sugar. Naunyn noted eleven per 
 cent. Higgins and Ogden speak of twenty per cent. (?) Urine 
 containing more than six per cent, of sugar is rare. In the course 
 of an enormous number of analyses I have found some few show 
 more than nine per cent., but only one reaching ten per cent. 
 The percentage of glucose, depending under all circumstances 
 largely on the quantity and quality of the food, forms in itself only 
 a vague expression of the intensity of the diabetic dystrophy.* 
 
 A patient living exclusively on meat and fat (water and salts), 
 with 0.3 per cent, of glucose in his urine, is much worse off than 
 another living on an abundant ordinary mixed diet, with three per 
 cent, of glucose in his urine. The same patient who, one or two 
 hours after dinner, exhibits three per cent, of sugar in his urine, 
 may early the next morning exhibit only 0.05 per cent. When I 
 hear of any one whose urine contains from three to five or seven 
 per cent, of glucose, I conclude that he is diabetic — nothing more ; 
 but if I hear of some one whose urine contains 0.5 per cent, of glu- 
 cose, I gain scarcely any information at all about his case — it may be 
 one of simple glycosuria, or of mild or severe diabetes. When I 
 hear of any one whose urine contains 0.5 per cent, of glucose. 
 
 * Bouchard unconditionally and sans phrase proposes to designate as severe every case 
 of diabetes with an excretion of over fifty grains of glucose in the twenty-four hours ; and 
 as mild, every case with less than this amount. This is for me a most striking illustration 
 of the possibility of complete absences intellectuelles, even in men of genius. Many a 
 diabetic patient may, according to this most extraordinary classification, repeatedly be a 
 severe case on Mondays and a mild one on Tuesdays, and vice versa. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 75 
 
 with Strict diet, this at once tells me that he is in the severe stage. 
 It is useless to give figures of the glycosuria without some infor- 
 mation as to the diet. 
 
 With an exclusive diet of meat and fat, glycosuria, which dis- 
 appears entirely in the mild diabetic stage, rarely reaches above 
 two or three per cent, in the severe stage. 
 
 In severe cases the patient often passes a clear, pale, greenish- 
 yellow urine with a specific gravity that often is nearer 1.040 than 
 1.030, and that sometimes may reach far above the first figure. 
 Several observers mention 1.070; Proust and Bouchard, 1.074. 
 Diabetic urine, however, especially in mild cases, varies enor- 
 mously in appearance, specific gravity, and other qualities. A dia- 
 betic in the mild stage, when he has not received carbohydrates 
 beyond his limit of assimilation, passes urine that, besides being 
 free from glucose, is otherwise scarcely different from that which 
 a healthy person passes under the same dietetic conditions. We 
 quite frequently find, even in severe cases, a urine of perfectly nor- 
 mal, sometimes even a somewhat high, yellow color, and in mild 
 cases not rarely a strong sediment of uric acid. Under the micro- 
 scope the conditions often are normal, although sometimes there 
 may be a rather large amount of the small crystals of calcium oxal- 
 ate and sometimes also occasionally hyaline and more rarely 
 granular casts. The nitric-acid test not uncommonly discloses 
 the presence of albumin, and the colored zone above the acid 
 is frequently pronounced. By reason of the abundance of animal 
 food the urea and other derivatives of proteids are generally pres- 
 ent in rather large quantities, and the specific gravity, therefore, is 
 often high, even when no sugar is present. In many cases in the 
 mild stage, however, the specific gravity is below 1.030, and not 
 only within normal but within very common limits.* One may 
 find urines of a specific gravity of 1.020 that contain quite a con- 
 siderable amount (above one per cent.) of glucose. Sometimes 
 one may even find distinctly pathologic, though small, quantities 
 of glucose in urine of an exceptionally low specific gravity. Some 
 
 * A normal middle-aged man, who eats much meat, often passes urine of a specific 
 gravity nearer 1.030 than 1.020. One may sometimes, apart from diabetes, even find 
 the urine of comparatively normal persons with quite a high specific gravity. Only re- 
 cently I encountered a specific gravity of 1.034 in such a case. 
 
■j6 DIABETES MELLITUS AND GLYCOSURIA. 
 
 time ago I saw a urine of 1.005 specific gravity undergo a beauti- 
 ful reduction with Nylander's and Fehling's solutions before, but 
 not after, fermentation. It came from a gouty patient with simple 
 glycosuria, who had been on a spree and had drunk two quarts of 
 beer. True, though mild, diabetes may give rise to exactly such a 
 urine either after prolonged abstinence from carbohydrates or dur- 
 ing one of those periods, sometimes observed in mild cases, when 
 the power of assimilation becomes very high or, finally, when some 
 care in diet has been observed, but much water has been drunk. 
 
 It is interesting to note the differences in view as to the fre- 
 quency of albuminuria in association with diabetes. Schmitz noted 
 albuminuria in 68.6 per cent. (!?),* Bouchard in 43 per cent., 
 V. Dusch in 25 per cent., Garrod in 10 per cent, of their cases of 
 diabetes. Grube (1878) states that he found albumin in the urine 
 in 191 of 473 cases of diabetes, or in 40 per cent. In the severe 
 stage of the disease albuminuria is much more frequent than in the 
 mild stage. Including all cases of true diabetes in private practice, 
 it will be found that Grube's figures, which certainly are rather too 
 high than too low, best represent the truth, while in hospitals, 
 where chiefly severe cases are found, the figures will be consider- 
 ably higher (see below). 
 
 In some cases the solution of ferric chlorid shows the presence 
 oi diacetic acid (Gerhardt's most important reaction), which, except 
 with inanition, is absent in mild cases. 
 
 For the other changes in diabetic urine I refer the reader to the 
 chapter on Metabolism. 
 
 hicrcased thirst, polydipsia, and polyuria are, as is well known, 
 frequent symptoms of diabetes, and hold a causal relation with 
 each other, which is still far from perfectly understood. Thirst 
 and polydipsia are certainly causes of polyuria, and any one, 
 whether diabetic or not, who drinks much, will pass a large quan- 
 tity of urine. The increased thirst of diabetes must arise from the 
 increased amount of sugar in the blood, which keeps the water in 
 the vessels firmer than normal, and dries the tissues, which still are 
 thirsting when a normal quantity of water is ingested, just as they 
 
 * These figures can scarcely be explained in any otherJway than by the zone of urates 
 (with Heller's test) having been mistaken for one of albumin. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. // 
 
 may hunger from the loss of glucose and from the protoplasmic 
 disintegration (see below) with a normal supply of food. Hyper- 
 glycemia in itself acts on the kidneys as a diuretic. When enor- 
 mous doses of saccharids are given, the urine always suddenly 
 increases.* To some extent an increased want of water arises 
 within the organism merely in consequence of the carbohydrates 
 passing off as glucose instead of being oxidized into water and car- 
 bonic acid. If the supply of carbohydrates in the food is restricted 
 and hyperglycemia and glycosuria cease, polydipsia and polyuria 
 often also cease. 
 
 Polyuria may, however, arise also in consequence of direct vaso- 
 motor influences, and not be the effect but the cause of increased 
 thirst and polydipsia. Thus, lesion of the " lobus hydruricus " in 
 the vermis, near the seat for Bernard's puncture, causes diabetes 
 insipidus, as does also lesion of Kahler's centers. Further, the in- 
 creased excretion of urine is observed in progressive paralysis. 
 These facts suffice to explain, easily, cases of diabetes mellitus with 
 slight glycosuria and marked polyuria, and cases of diabetes insipi- 
 dus with slight traces of sugar, and the circumstance that the poly- 
 uria sometimes remains after the disappearance of the glycosuria in 
 the rare cases of incomplete recovery from diabetes mellitus. 
 
 Sometimes cirrhosis of the kidneys contributes to the polyuria 
 and polydipsia of diabetes mellitus ; in these cases, often of a gouty 
 nature, the sugar in the urine, from some unknown cause, usually 
 decreases as the cirrhosis advances. 
 
 Pick mentions that ingested water passes through the kidneys in 
 a shorter time in diabetics than in normal persons. 
 
 The quantity of urine is generally increased only moderately — to 
 two or three liters. More than five hters is rare, except in hospital 
 practice with almost exclusively severe cases. Sometimes enormous 
 quantities are observed. Dobson noted 14, Cantani also 14, Fiir- 
 bringer 17 liters ; Schindler mentions 16 liters in a child, etc. 
 Such quantities always belong to the most severe cases. 
 
 Increased thirst, polydipsia and polyuria do not, however, consti- 
 tute such constant symptoms as many members of the medical pro- 
 
 * The frequency of the pulse decreases, but the systolic and diastolic excursions of 
 the heart become greater (Vespa). 
 
yS DIABETES MELLITUS AND GLYCOSURIA. 
 
 fession seem to think. In the severe stage, especially regardless 
 of diet, this group of symptoms is certainly, as a general thing, 
 quite pronounced. In the mild stage, even apart from diet, the 
 quantity of urine often keeps within the normal, and the condition 
 corresponds with what already Peter Frank has called diabetes decip- 
 iens. Even a moderate restriction of carbohydrates \\'\\\ in this 
 stage keep the quantity of urine within normal limits in about 
 fifty per cent, of the cases. Sometimes diabetic patients may pass 
 even an exceptionally small quantity of urine in the tw^enty-four 
 hours. I have observed cases in which only 900, 800, and 700 
 cu. cm. were passed. 
 
 I have records of 65 diabetic patients, whose urine has been measured 
 for the twenty-four hours during a somewhat considerable time, and find 
 that of 27 in the severe stage, 22 have generally passed more, and 5 less, 
 than 1600 cu. cm. ; and that of 38 mild cases, half the number have passed 
 less, the other half more, than this quantity. All of these patients were of high 
 stature, and include Scandinavians, Britons, Germans, and Americans. On 
 the other hand, it may be conceded that almost all the possible errors in meas- 
 uring have contributed to malce the figures too low ; and that in many cases 
 the diet has corrected a preexisting polyuria. 
 
 As the quantity of glucose, so also the quantity of urine, is gen- 
 erally larger during the day than during the night ; but the rule 
 has many exceptions, both glycosuria and polyuria depending on 
 the character of the food. Thus, when the largest meal, dinner, is 
 taken late in the evening, the urine and the glucose often reach 
 higher figures during the night than during the day. Increased 
 intensity of glycosuria is, as a rule, accompanied by increased 
 intensity of polyuria. 
 
 Pollakiuria, or abnormally frequent passing of urine, is a com- 
 mon symptom, but stands in no distinct relation with the intensity 
 of either the glycosuria or the polyuria. Sometimes there is dis- 
 tinct pollakiuria without any polyuria, and the patient passes urine 
 a dozen times a day, although the whole quantity may not exceed 
 the normal. In other cases, sometimes even in severe cases, there 
 is no pollakiuria, but a decided polyuria. One of my patients, who 
 died in coma, used, with great regularity, to pass urine only four 
 times in twenty -four hours, but each time the quantity approached 
 a liter. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 79 
 
 Among symptoms of diabetes may be mentioned the diminution 
 in the secretions and excretions other than the urine, although exact 
 investigations are still scanty. Of the saliva this has been long known, 
 and dryness of mouth is one of the most common complaints of dia- 
 betics. In mild cases one often finds perspiration normal, some- 
 times abundant, even to hyperidrosis ; but in advanced cases a 
 decrease in the secretion of the glands of the skin is generally mani- 
 fest, with asteatosis and anhidrosis and an extreme dryness of the 
 skin. Gall-stones are more common among diabetics than among 
 other persons, and this I consider probably the result of a decrease 
 in the secretion of bile, and chiefly the water thereof.* Young 
 diabetic men with undiminished sexual vigor sometimes mention 
 symptoms indicative of a diminished secretion of spermatic fluid. 
 The decrease in the secretions is doubtless due in part to the des- 
 iccating influence of the hyperglycemia on the glands as well as on 
 other tissues. In severe cases, however, with marasmus, atrophic 
 and degenerative changes of the different glandular elements surely 
 contribute largely to this result. 
 
 Excessive hunger — bulimia — is a common symptom in the severe 
 stage of diabetes. In the mild stage it appears only in compara- 
 tively advanced cases with a low power of assimilation and a diet 
 too rich in carbohydrates, when a considerable part of the food 
 passes off in the urine as glucose. 
 
 In the severe stage the increased hunger is so far a favorable 
 manifestation, as it alone enables the patient to make good the loss 
 of glucose and to mitigate the consequences of the protoplasmic 
 disintegration taking place in the tissues. The ingested proteids 
 under such circumstances sometimes develop enormous values, and 
 I have more than once seen patients who for a short time, in addi- 
 tion to large quantities of butter and moderate portions of carbohy- 
 drates, were able to take considerably over one kilogram of cooked 
 beef a day. In far advanced cases the patient may even, with such 
 food and with an excellent digestion, present a clinical picture that 
 
 * Bouchard states that ten per cent, of all diabetics suffer from gall-stones. Even if 
 this figure should be somewhat exaggerated, there can scarcely be any doubt about the 
 increased frequency of gall-stones in diabetics. All other explanations than the one given 
 here of the connection betvi^een diabetes and gall-stones (by I. Kraus) seem to me to 
 lack any rational basis. 
 
80 DIABETES MELLITUS AND GLYCOSURIA. 
 
 strongly resembles that presented by starvation. In both instances 
 there are observed constant loss of weight, utter prostration, low- 
 bodily temperature, decrease in the secretions, and the presence 
 in the urine of acetone, diacetic acid, /3-oxybutyric acid, and increased 
 ammonia. The final scene increases the similarity, for death from 
 starvation is partly due to the acid toxins in the blood already men- 
 tioned, and is, so far, death from poisoning, with a clinical picture 
 that strongly resembles diabetic coma. 
 
 Instead of bulimia, anorexia is sometimes observed in cases of 
 diabetes of all stages. This is a most ominous manifestation in the 
 severe stage of the dystrophy, and I shall return later on to this 
 subject. 
 
 Loss of weight belongs essentially to the severe stage, but it may 
 occur under varying circumstances, and it can as little as the gly- 
 cosuria or other manifestations of derangement of metabolism be 
 rightly considered clinically without reference to the food. 
 
 During periods of great restriction or even exclusion of carbohy- 
 drates every one, whether diabetic or not, is likely to lose in weight, 
 because it is generally difficult without carbohydrates to supply the 
 organism with the necessary amount of heat-units. Loss of flesh 
 of this purely "alimentary" kind is of no clinical importance at all, 
 and does not constitute a contraindication against a rational, periodic, 
 rigid restriction of carbohydrates. The patient will afterward, under 
 a somewhat freer diet, easily recover his loss. 
 
 Then we sometimes find loss of weight, even in the mild stage, 
 before the patient has been put upon a restricted diet, and before his 
 dystrophy has been discovered. Such a loss of flesh is of greater 
 importance, and generally takes place when the power of assimi- 
 lating carbohydrates is considerably impaired and they constitute a 
 large part of the food. Still, it is usually no very difficult task in 
 the milder stage to check the loss of weight, or even to make it 
 good, by increasing the proteids and fat of the food (and duly 
 reducing the carbohydrates). 
 
 Finally, the most marked and the most important loss of weight 
 takes place in the severe stage. When the patient's power of 
 assimilating carbohydrates has reached a very low point ; when he 
 loses in the form of glucose even a considerable part of the ingested 
 proteids ; when the toxic protoplasmic disintegration of tissues 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 61 
 
 entails a greater nitrogenous expenditure than income, and a daily 
 deficit under any dietetic conditions ; when the tissues are still 
 insufficiently supplied, although the digestive apparatus has been 
 satiated, then appears the terrible diabetic autophagia. The loss of 
 weight under these circumstances is, in spite of all dietetic measures, 
 often exceedingly rapid, and affects not only the fat and the carbo- 
 hydrates of the organism, but also the proteids, and probably often 
 the bones, and a fatal issue may be looked for in the immediate 
 future. 
 
 The great vtdnerability and diminished recuperative power of the 
 diabetic have been long known. They are due to the hypergly- 
 cemia and the toxins in the blood and to the dryness of the tissues, 
 probably also to defective nervous influences. The changes in the 
 vessels, especially the diabetic endarteritis in the smaller vessels, 
 must also have a marked influence in this direction. This weak- 
 ness is found not only in the severe stage, but it is often quite 
 extreme in patients who, with restricted diet, are free from glyco- 
 suria, but who have suffered from diabetes during many years. In 
 such persons wounds remain open for a long time, heal less often 
 without suppuration, and have pigmented cicatrices. The impaired 
 healing power in cases of diabetes has restrained surgeons from 
 many a necessary operation, and does so sometimes even yet, 
 although the diabetic patient has profited still more than others by 
 aseptic and antiseptic prophylaxis. Inflammatory and suppurative 
 processes, especially in inveterate cases of diabetes, are much to be 
 dreaded, and a carbuncle is a far more serious matter in a diabetic 
 than in a nondiabetic person. 
 
 The dry tissues, the hyperglycemia, the toxins, the defective ner- 
 vous influences, the arteriosclerosis, and the peculiar changes in 
 the small vessels of the diabetic render him more susceptible to 
 gangrene than others. 
 
 Diabetic gangrene,"^ which sometimes develops in the sequence of 
 traumatism or other accidental agency, and sometimes appears spon- 
 taneously, is comparable to senile gangrene ; in fact, it is usually the 
 
 * Marechal de Calvi and Hodgkin (1864) were the first to point out a causal connec- 
 tion between diabetes and gangrene. Peyrot (1878), Giron (1881), W. Hunt (if 
 Heidenhain (i89l),N. S. Davis (1898), and others, have since treated of the subject. 
 
82 DIABETES MELLITUS AND GLYCOSURIA. 
 
 expression of both diabetes and senility. Of 38 cases of diabetic 
 gangrene in the city of Philadelphia, the age in i case was between 
 thirty and forty ; in 2 cases, between forty and fifty ; in 11 
 cases, between fifty and sixty ; in 1 2 cases, between sixty and 
 seventy ; in 10 cases, between seventy and eighty ; and in 2 cases, 
 between eighty and ninety years (Hunt). It is thus seen that the 
 cases are rare before fifty, begin to be more frequent with advancing 
 years, and are relatively more frequent late in life. Diabetic gan- 
 grene is almost always of the moist variety, and is generally with- 
 out a sharp line of demarcation. It usually attacks the lower ex- 
 tremities, especially the feet, but it may occur almost anywhere — 
 on the body, in the lungs, on the arms, the nose, the penis, etc. 
 Sometimes the gangrene develops in several places simultaneously 
 in smaller or larger patches. Settenbom has recently described a 
 case presenting such patches with a circumference of from 10 to 15 
 cm., distributed over the whole body except the head. Kaposi 
 mentions a case with " gangrena bullosa serpiginosa " ; and Pitres, 
 Rosenblath, Blau, and others have also described cases with multi- 
 ple gangrene of the skin. Diabetic gangrene, chiefly a manifesta- 
 tion of old age, does not usually occur in the severe stage, which is 
 rare late in life and of comparatively short duration, but in cases in 
 which the exclusion of carbohydrates leads to disappearance of the 
 glycosuria, though many years of diabetes have had time, in 
 combination with senility, to bring about the changes already 
 mentioned. I have myself seen several cases in which the power 
 of assimilation was comparatively quite considerable, although the 
 dystrophy had existed for between fifteen and eighteen years. In 
 one of the cases there was marked arteriosclerosis and atrophy of 
 the kidneys. 
 
 The prognosis of diabetic gangrene is always dubious, but even 
 pulmonary gangrene is not necessarily fatal. One of my patients 
 has successfully passed through this complication. In the lower 
 extremities gangrene may often, under rational treatment, general 
 and local, result in recovery. I have seen one case in which an 
 enormous scar on the calf of the left leg reminded the patient dur- 
 ing the last three years of his life that he had undergone such a 
 process. 
 
 The variety of gangrene due to pressure, and usually designated 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 83 
 
 decubitus (bed-sore), is more easily acquired in diabetes than in 
 other conditions, and one has to be especially on his guard against 
 such a complication in the course of intercurrent diseases or other 
 states that are likely to cause it. 
 
 Among complications of diabetes with gangrene, suppuration, 
 and disintegration of tissues, must be mentioned the common 
 furuncle and the carbuncle, 3Md the two rare disorders, '' le mal 
 perforant" and "Raynaud's disease.'' 
 
 The furuncle is exceedingly common, and is especially to be 
 found in the mild stage in fat patients ; the thin, severely ill diabetic 
 usually have had no furuncle. The complication is generally not a 
 dangerous one. 
 
 The carbuncle, which generally appears on the neck or on the 
 back, belongs to advanced cases, is, when associated with diabetes, 
 quite a formidable disorder, and manifests a marked tendency to 
 spread and to give rise to general septic infection. It causes death 
 in a not inconsiderable number of cases of diabetes. " Le inal per- 
 forant" (Kirmisson, Gascuel) is, as is well known, generally a 
 symptom of tabes dorsalis ; if it is found in other cases one must 
 suspect diabetes mellitus. It is sometimes found together with 
 diabetic gangrene of the ordinary form. I have seen it several 
 times, and I suppose that it occurs in at least two or three percent, 
 of all cases. The small, sharp-edged, perfectly round, torpid ulcers 
 may occur on one or both sides, generally on the hands or feet, and 
 mostly over a joint. The innocent-looking ulcer then advances 
 into the joint, and may cause extensive destruction of both the soft 
 tissues and the bones and necessitate amputation. It sometimes 
 leads to death. The cases of " mal perforant " that I have seen 
 have presented typical symptoms of neuritis in the affected area, 
 and neuritis has been repeatedly found postmortem. 
 
 That most interesting of all forms of gangrene, Raynaud's disease, 
 is rare both in association with and independently of diabetes ; but 
 the considerable number of cases of diabetes thus complicated leave 
 no doubt that diabetes is a predisposing cause. " Raynaud's dis- 
 ease " is a vasomotor disorder, and neuritis has several times been 
 demonstrated postmortem. As is well known, the disease often 
 attacks peripheral parts symmetrically, as the feet, the hands, or 
 the ears. It begins with strong vasomotor spasm, giving rise to 
 
84 DIABETES MELLITUS AND GLYCOSURIA. 
 
 ischemia, pallor, coldness, and some loss of sensibility in the affected 
 region. I presume it is this "local syncope" that under some con- 
 ditions may lead to scleroderma. After some time, however, — hours 
 or days or weeks, — dilatation of the vessels usually follows, with 
 hyperemia, cyanosis, and excruciating pains, — whether from active 
 vasodilator influence or from vasoconstrictor paralysis, has not yet 
 been agreed upon. We have then the " local asphyxia," which 
 some consider identical with erythromelalgia as described by Weir 
 Mitchell. After this, gangrene may set in. 
 
 Lymphangitis and erysipelatous and p]ilegnio7ious processes threaten 
 the diabetic much more frequently than healthy persons, probably 
 on account of the better conditions for vegetation that he presents 
 to microorganisms. Senator and Rovere have described cases of 
 suppurative polymyositis with multiple abscesses in the muscles. I 
 am unable to understand in what respect such a process differs 
 essentially from some cases of pyemia. 
 
 Tlie cavity of the mouth often presents characteristic changes, 
 which are of serious import to the patient and of practical signifi- 
 cance to the physician, because they stand in a certain relation to 
 the duration and the intensity of the glycosuric dystrophy. The 
 breath gives at once important information, its strong odor of acetone, 
 which is much like that of chloroform, denoting the severe stage 
 of the dystrophy. This odor may diffuse itself throughout the 
 patient's room, often suggesting the diagnosis immediately, and 
 sometimes revealing to a physician the state and the impending 
 fate of some stranger passing on the street. One may sometimes 
 perceive a slight uncertain odor of acetone from the mouth of a 
 person in the mild stage of diabetes, as one always does from the 
 mouth of anybody in a state of severe inanition and sometimes 
 does from the mouths of quite healthy children. If there is no 
 odor of acetone from the mouth of a diabetic patient, he is pretty 
 certain to be in the mild stage. Inspection of the mouth also very 
 often affords valuable information. The tongiie is often somewhat 
 dry in mild cases of diabetes, but otherwise it is usually little 
 changed. In severe or advanced cases it is dry and marked off 
 into rectangular areas by deep furrows, like the hide of an alligator ; 
 the base is often covered by a brown, sometimes almost black, coat- 
 ing, while the apex is abnormally red, with hyperemic papillae. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 85 
 
 Here and there one sometimes finds glossy, fleshy looking patches, 
 where the mucous membrane has undergone atrophic changes. 
 The teeth also undergo changes after true diabetes has existed for 
 any great length of time. If I find a complete and normal set of 
 teeth, I know at once that the glycosuria (and hyperglycemia) is 
 either of recent date or does not amount to a true diabetes. In 
 diabetics, even in the mild stage, the teeth are, as a rule, cariotis ; a 
 smaller or greater number of them, besides, have fallen out. In- 
 spection of the gums often leads to discovery of the causes of loss 
 of teeth. A distinct gingivitis is often present, exhibiting tender, 
 swollen, red areas. Here and there a drop of pus may be made to 
 appear on pressure ; the bistoury may empty a little pocket of pus ; 
 and the probe may, through a fistula, reach bone. These features 
 belong to the common condition of alveola}'- pyorrhea. Sometimes 
 the patient presents the ordinary symptoms arising from a more or 
 less pronounced periostitis, or a pericementitis, as, I believe, the 
 dentists call the process when it affects the periosteum surrounding 
 the roots of the teeth. In some cases, even independently of 
 senility, teeth are missing without any evidence of an inflammatory 
 process and without the patient ever having suffered from symp- 
 toms of that condition. This is in great probability the result of 
 retrogression and atrophic changes in the periosteum and in the 
 maxillary bones. The latter process leads to osteoporosis, which, 
 there is good reason to believe, occurs in severe marantic cases 
 of diabetes (see below), and which is known to occur in other 
 disorders of the central nervous system {c. g., progressive par- 
 alysis). 
 
 Diabetes mellitus does not per se cause any elevation of tempera- 
 ture. Whenever fever takes place we have to do with some com- 
 plication and must make a careful investigation for it, especially in 
 the lungs. In mild cases without complications the temperature is 
 normal. In severe marantic cases the temperature is below the 
 normal ; but, apart from coma, it is rarely below 36° C. (96.8° F.). 
 In the presence of coma it sometimes sinks several hours, or even 
 several days, before death to between 25° and 30° C. {j'j'^ and 
 86° R). 
 
86 DIABETES MELLITUS AND GLYCOSURIA. 
 
 The Nervous System. 
 
 The diabetic patient is, as I have mentioned, often a member of 
 a nervous or even of a neurotic family in which, according to the 
 two laws of heredity and transmutation, may be found most of the 
 diseases that thrive on neurotic soil. We may thus find in different 
 generations of the same family slight mental disturbances, developed 
 psychoses, diseases of the brain and spinal cord alternating with ex- 
 ophthalmic goiter, diabetes, gout, and other morbid processes, whose 
 dependence upon the nervous system, though not perfectly estab- 
 lished, is yet beyond doubt. 
 
 Then it has been ascertained that certain lesions of the nervous 
 system directly cause diabetes, the symptoms of which develop 
 simultaneously with the nervous symptoms. 
 
 Finally, it has been learned in the last few decades that diabetes 
 per se may cause changes in the nervous elements, partly directly, 
 partly through some of its complications, and especially through its 
 influence on the vessels of the brain and consequent hemorrhage, as 
 well as other circulatory disturbances. 
 
 Thus, nervous disorders — central and peripheral, acute and 
 chronic — are exceedingly common in conjunction with diabetes. 
 Among these disorders, however, neither the severe neuroses nor 
 the systematic diseases of the brain and spinal cord are at all fre- 
 quent. Jacoby, of New York, observed three cases of epilepsy 
 complicated by diabetes mellitus, and admits the possibility of a 
 connection between the epileptic attacks and the diabetic toxins in 
 the blood. Finlayson, Ebstein, and others also mention such cases ; 
 but among nearly 200 diabetics seen in the course of the last few 
 years I have not encountered one complicated by epilepsy.* Tabes 
 dorsalis and diabetes mellitus have been observed in the same per- 
 son in a number of instances ; but these and other cases of diabetes 
 occurring in conjunction with organic, systematic, central nervous 
 diseases constitute but a small proportion among the large number 
 of diabetics, even if such complications are found somewhat more 
 frequently in association with than independently of the glycosuric 
 dystrophy. 
 
 *In a male child and in some few cases in womeo I have seen general convulsions, 
 with complete preservation of consciousness; these I considered to be hysteric. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 8/ 
 
 A far less rare, but still not very common, expression of the 
 neurotic tendency and of a depraved state of nutrition is a more or 
 less well developed psychoneurosis. In Europeans and their de- 
 scendants * this generally goes no further than hypochondriasis. 
 Sometimes, however, the patient presents a somewhat more pro- 
 found mental change, and the clinical picture of simple melancholia 
 appears. We then generally find only the mild, active form of the 
 disease, with only moderate impairment of intellectual activity, 
 though a certain degree of lack of energy is found in these as in all 
 cases of melancholia. Pronounced apathy, hebetude, or even 
 stupor is exceedingly rare, and the same may be said of hallucina- 
 tions. The false ideas are rarely without some real objective cause, 
 and generally only represent the hypochondriacal state already 
 mentioned. Sometimes, however, one finds entirely unfounded 
 fixed ideas, such as are observed in developed melancholia — e. g., 
 a delusion of poverty in the face of excellent material circumstances, 
 etc. I have also seen instances of fully developed melancholy 
 raptus with strong terror and violent tendencies. Suicide is rare, 
 even among diabetics, although somewhat more frequent than 
 among other persons. 
 
 The nervous centers that preside over the metabolism of carbohydrates are 
 not the same as those that perform the highest mental functions, and the con- 
 nection between diabetes and the disturbances of these functions is most vague. 
 Mild diabetes may be complicated by a true psychosis, and severe diabetes 
 may leave the mental state almost intact. On the other hand, an influence on 
 the mind by the diathesis can not be denied, and in diabetics of a psychopathic 
 constitution hyperglycemia may contribute to the development of mental dis- 
 ease. An analogous influence is exerted by gout (Berthier, Raynor, Savage, 
 Chrichton-Browne). In a mild but fully developed case of melancholia I dis- 
 covered also mild diabetes, with 1,3 per cent, of glucose in the twenty-four 
 hours' urine under ordinary diet. A moderate restriction of the carbohydrates 
 stopped the glycosuria and was followed by immediate improvement in the 
 mental state, obvious to the patient's family. In another case of melancholia 
 associated with diabetes restriction of the carbohydrates, with diminished 
 hyperglycemia, did not seem to influence the melancholia at all, the patient 
 eventually committing suicide. 
 
 Other pure neuroses than hypochondriasis and melancholia are 
 
 *In the East Indian medical literature we find statements from which we may con- 
 clude that severe mental diseases are more frequent among diabetic Hindoos than among 
 diabetic Europeans. 
 
88 DIABETES MELLITUS AND GLYCOSURIA. 
 
 rare in association with diabetes. Hysteria — if properly distin- 
 guished from purely neurasthenic neuroses — is sometimes, but not 
 often, found in cases of diabetes (Gumpertz, Toralbi, Kleen, and 
 others'). 
 
 Neiirastlienic symptoms, both cerebral and spinal, are exceedingly 
 common in diabetics, and it is rare to find such a patient entirely 
 free from them. The diabetic is almost always a wretched sleeper, 
 even if polyuria does not disturb him. During the day he suffers 
 from another neurasthenic symptom — namely, drowsiness, which 
 prevents intellectual activity without inducing sleep.* The slight 
 neurasthenic headache, almost continuous, sometimes only felt as a 
 sense of " emptiness " or of pressure, is frequent. The capacity 
 for assiduous intellectual work is almost always diminished and 
 memory is often distinctly impaired. Irritability is increased, as 
 any physician having much to do with diabetes has learned at his 
 own expense. In cases on the psychoneurotic border-Hne this may 
 amount to a true " iracundia morbosa," with an unbearable temper 
 and impulsive, violent acts. Spontaneous vertigo is not common, 
 but vertigo at heights is present in about two-thirds of all cases 
 with diminished power of assimilating carbohydrates. I have also, 
 though rarely, observed agoraphobia. A host of less important 
 neurasthenic sensory disturbances, in the form of hyperesthesia, 
 paresthesia, and vague pains, annoy the diabetic patient. Feelings 
 of cold or of heat, of the hair standing on end or being absent, of a 
 more or less distinct "casque neurasthenique," of pressure, of creep- 
 mg, of " plaque sacree " or other rhachialgic manifestations, of 
 shooting-pains in the limbs, etc., add to the patient's distress. 
 Pains in the epigastrium are not uncommon in diabetes, and have 
 been compared to the "crises gastriques " of tabes dorsalis, but 
 they seem hardly to be distinguishable from analogous complaints 
 often made by neurasthenic patients that are not diabetic. 
 
 Among neiivalgias in diabetes, sciatica is the most common. 
 Next in frequency come neuralgias of the fifth pair of nerves 
 (trigeminus), especially of the inferior maxillary division. Supra- 
 orbital neuralgia, aS in other conditions, is sometimes accompanied 
 
 * An American neurasthenic (nondiabetic) lady aptly described this condition by say- 
 ing : "I suffer from insomnia all night and from somnia all day." 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 89 
 
 by the vasomotor disturbances that constitute migraine.* All of 
 these neuralgias, while generally not very intense, are quite obsti- 
 nate, and are often bilateral. 
 
 In 1887 I treated at Carlsbad a case of one of those curious forms of aber- 
 rant vasomotor neurosis that are called equivalents of migraine. The patient, 
 fifty-three years old, was the principal of a school. His father, an uncle, and 
 at least one cousin had suffered from diabetes. The patient himself had suf- 
 fered from the glycosuric dystrophy for at least fifteen, probably for nineteen, 
 years, and he had reached the boundary between the mild and the severe 
 stage. He had not had syphilis, presented no distinct rigidity of the arteries, 
 and no other ocular disorder than moderate myopia. From time to time he 
 felt a sense of rigidity in the left side of the face, and at the same time paresis 
 in the left arm. I saw the man during one of these attacks, which had begun 
 at 2 p. M. He presented marked paresis of the left facial nerve and of the 
 whole left arm ; at 5 p. M. his condition again was perfectly normal. Some 
 months afterward the patient suddenly suffered a cerebral hemorrhage and in 
 one of these attacks died " apoplectico modo." I presume that vasomotor 
 neurosis in a case of long-standing diabetes, with brittleness in the vessels 
 from diabetic endarteritis, is rather likely to end this way. 
 
 Sometimes there occur functional disturbances of the secretory nerves, and 
 instead of the customary decrease of secretion there may be an abundance, as 
 manifested by local sialorrhea, hyperidrosis, etc. 
 
 The muscular neurasthenia — not to be confused with the func- 
 tional disturbances resulting from marantic and other changes in 
 the muscles in the severe cases — is often marked, and even 
 in a mild case the patient has often much less muscular en- 
 durance than his general robust appearance would seem to indi- 
 cate. Among other muscular neurasthenic symptoms there have 
 also been observed, generally at night, cramp in the calves of the 
 legs, which sometimes, however, is not merely functional, but a 
 symptom of beginning inflammation of the posterior tibial nerve. 
 The fine, fibrillary, clonic spasm is not uncommon, especially in 
 the orbicularis. 
 
 Sexual potency is generally weakened, but the degree of failure 
 varies greatly and has no fixed relation to the intensity of the dia- 
 betes. This symptom often is but little influenced by hypergly- 
 cemia, and is often found, together with other neurasthenic dis- 
 turbances, in mild cases, as in cases of simple glycosuria or of 
 
 * That terrible cousin of the comparatively innocent migraine — epilepsy — is, in spite 
 of their angioneurotic tendencies, rare among diabetics. 
 7 
 
90 DIABETES MELLITUS AND GLYCOSURIA. 
 
 neurasthenia without glycosuria. In some cases, on the other hand, 
 the patient is conscious of a decided improvement after restric- 
 tion of carbohydrates and the disappearance of glycosuria. In mild 
 cases of diabetes the potency sometimes remains normal or nearly 
 normal for many years ; in a small number of cases apparently trust- 
 worthy patients make statements of virile power that painfully strain 
 credulity. Sterility in diabetes will be considered later. 
 
 Diabetic neuritis ajtd poly7ieuritis * are often detected, but still 
 more often exist and escape detection. They certainly do not de- 
 pend exclusively on the acetone and the acid toxins in the blood, — 
 the " acidosis," as Naunyn terms the condition, — as they are much 
 more common in mild cases (without acidosis) of long standing than 
 among cases in the severe stage (with acidosis), which generally are 
 severe from an early period of their existence and rarely last many 
 years. In fact, the one feature common to all cases of diabetes with 
 neuritis I have found to be the long duration of the dystrophy. If 
 an accessory influence is present, one may find distinct neuritis in 
 cases with an only shghtly impaired power of assimilating carbohy- 
 drates. The most frequent of these accessory influences are gout 
 and alcoholism. Even in cases of purely diabetic neuritis (without 
 gout or alcohol) the symptoms are closely similar to those of gouty 
 neuritis. By this I mean that diabetic neuritis, though sometimes 
 isolated and circumscribed and sometimes unilateral, is far more 
 often multiple and bilateral ; that it involves especially the lower 
 extremities, though I presume it may attack any nerve ; and, finally, 
 that it is of a pronounced torpid character. Only rarely does the 
 process set in with active symptoms, acute pains, and sensations of 
 " tingling." Usually its onset is so insidious that the patient is 
 virtually unconscious of his sensory disturbance until it is disclosed 
 by the physician's investigation. Sometimes, however, the patient 
 complains of a feeling of burning or of prickling, and hyperesthetic 
 areas may be found upon the skin. One must not expect often to 
 find distinct tenderness of the nerves on pressure. Diffuse muscular 
 sensitiveness, like that due to rheumatic infiltration, is much more 
 
 * Von Ziemssen was, so far as I know, the first to point out tlie occurrence of 
 diabetic neuritis (1885). Thomas, Leyden, Althans, v. Striimpell, Buzzard, Charcot, 
 Bury and Ross, and many others have since contributed to our knowledge of this 
 subject. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 9 1 
 
 common. Diminished sensibility to pin-prick, or the esthesimeter, 
 or to a tube filled with hot water is frequently present. Complete 
 analgesia and anesthesia are exceedingly rare ; I have not seen a 
 single instance of either, though cases so complicated are recorded 
 in literature. In rare instances I have observed retarded sensibility. 
 
 Apart from the frequent spasm of the muscles of the calf, which 
 probably is caused by neuritis only in rare cases, motor disturbances 
 are much rarer than sensory. If the neuritis is intense, and there is 
 also general debility and marasmus, marked reaction of degeneration 
 to the electric current is sometimes present, and in rare cases pro- 
 found functional disturbance. Foot-drop and complete paraplegia 
 have been observed in some cases, and many instances of paresis or 
 paralysis of single muscles or of groups of muscles are recorded 
 (Charcot, Buzzard, and others). 
 
 The neuritis often causes trophic changes within the distribution 
 of the nerve or nerves affected. Among such manifestations are 
 local hyperidrosis or anhidrosis; atrophic, thin, "glossy" skin; 
 cutaneous eruptions, as urticaria, eczema, herpes zoster, etc. (see 
 below) ; discolored, thick, brittle nails, which readily fall out, etc. 
 The " mal perforant " and "Raynaud's disease" are undoubtedly 
 manifestations of neuritis, which probably also contribute to the 
 development of other gangrenous processes, whether occurring as 
 a single area of sphacelus or disseminated in patches. 
 
 Absence or weakening of the knee-jerk (and other tendinous and 
 cutaneous reflexes) is a frequent symptom of diabetes.* The ex- 
 planation for the disappearance of the tendinous and other reflexes 
 is to be sought in changes in both peripheral and central nervous 
 elements (see below). Inflammation of the crural nerve has been 
 found in cases with absence of knee-jerk. According to Erlen- 
 meyer, the cause is generally to be found in changes in the " ban- 
 delettes externes " of Burdach's tracts in the posterior columns of 
 the spinal cord. In other cases postmortem investigation has failed 
 to disclose any nervous change whatever (Nonne, Rosenstein), and 
 
 * Absence of the knee-jerk was noted by Marinian and by Bouchard in 1884. It 
 occurs also in tabes dorsalis and sometimes in apparently normal individuals. This lat- 
 ter occurrence seems to be much more frequent in some races than in others. Prof. H. 
 C. Wood, of Philadelphia, has told me that he has found it strikingly often in South 
 Americans. 
 
92 DIABETES MELLITUS AND GLYCOSURIA. 
 
 it seems possible that the absence of the knee-jerk may sometimes 
 be the result of a purely functional disorder, i. e., a change with- 
 out discernible anatomic basis. 
 
 The knee-jerk is found absent in both the mild and the severe 
 stage, but much more frequently in the latter than in the former. 
 Apart from this fact, absence of the knee-jerk has no distinct prog- 
 nostic significance, and it is sometimes found in cases in which 
 the diabetic syndrome has remained stationary in a mild form for 
 many years. Often the knee-jerk is weakened. Sometimes it re- 
 mains distinct for a long time on one side after having disappeared 
 from the other. In some few cases I have observed that one or 
 both knee-jerks have reappeared after having been absent for some 
 time.* 
 
 Statistics show that the knee-jerk is absent in from j.G to 50 per cent, of 
 all cases of diabetes. The former figure is much nearer the truth than the 
 latter. Tests even of the almost exclusively severe cases seen in hospitals will 
 show that the knee-jerk, at least among Anglo-Saxon or Teutonic diabetics, 
 though often weakened, is still distinct in the majority of cases. As I write this, 
 an analysis of 100 cases of diminished power of assimilating carbohydrates, 
 taken at random from my records of private practice, shows that the knee-jerk 
 was absent in 7 of 39 severe cases, in 7 of 51 cases of true though mild diabetes, 
 and in i case of simple glycosuria of many years' standing from among 10 
 similar cases. Of the 85 cases in which the knee-jerk remained distinctly, it 
 was weakened in many and in several it was absent on one side. When the 
 result of the investigation was at all uncertain, the knee-jerk has always been 
 recorded as absent. 
 
 The Other tendinous reflexes and the cutaneous reflexes may also 
 be weakened or lost. It is important, however, to remember that 
 the reflex contraction of the pupil on exposure to light is not lost 
 in uncomplicated cases of diabetes, and the Argyll- Robertson pupil 
 (contracting in accommodation, but not on exposure to light) points 
 to a complication with central nervous diseases of organic origin. 
 
 In causing changes not only in the peripheral nerves, but also 
 in the spinal cord, especially its posterior columns, diabetes mellitus 
 sometimes presents an anatomic similarity to tabes. Diabetes also 
 
 * This may or may not be a favorable sign. We know that removal of the influence 
 of higher centers is capable of heightening a reflex dependent on lower centers. In a 
 case of diabetes it may happen that an absent knee-jerk reappears after acute cerebral 
 disturbances of paralytic character. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 93 
 
 is almost always associated with more or less pronounced neuras- 
 thenia or a group of symptoms sometimes attended with functional 
 disturbances similar to those that occur in tabes. It is, therefore, 
 not astonishing to encounter cases of diabetes presenting a cHnical 
 picture that resembles more or less closely that of true tabes. This 
 '^pseudotabes diabetica,'' like all other forms of pseudotabes, may be 
 attended with more or less hyperesthesia, paralysis, or ataxia. The 
 individual case, however, rarely comports with the somewhat arti- 
 ficial division of Leyden, but presents symptoms of each kind. 
 Sometimes, apart from true tabes, diabetic patients present hyper- 
 esthetic or anesthetic areas, with peripheral neurasthenic pains, 
 which, though less violent, may resemble the lancinating pains of 
 tabes, and be associated with epigastric pains that may be mistaken 
 for " crises gastriques " ; we further find absence of tendinous 
 reflexes, sexual impotence, a neurasthenic, tired, gait, or — if the 
 multiple neuritis is pronounced in the lower extremities — high- 
 stepping, uncertain, ataxic movements of the legs in walking and 
 an unsteadiness in standing with closed eyes, much like Romberg's 
 symptom, etc. In short, diabetic cases of long standing may ex- 
 hibit sensory, motor, secretory, and trophic changes of various 
 kinds, that cause difficulty in distinguishing this "pseudotabes peri- 
 pherica diabetica" from true tabes, especially from " neurotabes 
 peripherica." The absence or the presence of tabetic ocular symp- 
 toms, which usually appear early in true tabes, especially reflex im- 
 mobility of the pupils, may sometimes govern the decision, while in 
 other cases it may be necessary to reserve the diagnosis for a 
 time. 
 
 A combination of diabetes mellitus and true tabes is rare, but, apart from 
 being merely accidental, it may be brought about by the sclerotic process of 
 tabes attacking the diabetic center in the floor of the fourth ventricle of the 
 brain. Under such circumstances there will (always ?), according to Guinon and 
 Souques, be found : (i) anesthesia within the distribution of the trigeminus, in 
 consequence of destruction of the center for that nerve, and (2) increased 
 frequency of the pulse, in consequence of destruction of the center for the 
 pneumogastric nerve. 
 
 The question of a connection between tabes dorsalis and diabetes has been 
 most elaborately discussed in recent years. Frerichs, in 1863, reported a case 
 of tabes associated with diabetes ; Smith, in 1883, had a patient with tabes asso- 
 ciated with glycosuria; and Oppenheim, in 1885, presented a similar case to 
 the Society of Physicians of Berlin. Absence of knee-jerk, one of the earliest 
 
94 DIABETES MELLITUS AND GLYCOSURIA. 
 
 symptoms of tabes, has since 1884 been noted in many cases of diabetes, while 
 from the eighties the expression "pseudotabes" of Leval-Piquechef became 
 current, and our knowledge of the polyneuritis of diabetes and of "pseudo- 
 tabes peripherica diabetica " on the one hand, and of " neurotabes peripherica " 
 in true tabes on the other hand, developed. A vast literature has grown, from 
 which I select especially the names of v. Ziemssen, Rosenstein, Lecorche, 
 Eichhorst, Marie and Guinon, v. Hoesslin, Price, Auerbach, Buzzard, Leyden, 
 Althans, Charcot, Auch6, Burns, Vergely, Ross and Bury, Naunyn. 
 
 In true tabes one rarely finds glycosuria. Eulenburg observed one such 
 instance among 125 cases of tabes, and Gilles de la Tourette, 3 among 100 
 cases, while Marie and Guinon found no case of glycosuria among 50 of tabes. 
 These figures illustrate the superficial character of the investigations, and 
 it is certain that one would find pathologic quantities of glucose in the urine in 
 a much larger percentage of average individuals ; but, on the other hand, 
 these figures permit us to draw the conclusion that the combination of tabes 
 and diabetes mellitus is a rare one. 
 
 I have seen a number of, in part merely neurasthenic, in part really 
 neuritic, cases of " pseudotabes," but only one case of true tabes complicat- 
 ing diabetes. This case occurred in a clergyman, sixty-two years of age, who 
 somewhat feebly denied a history of syphilis, but who was well known in his 
 younger days to have sinned much and indiscriminately against sexual morality. 
 This somewhat unfaithful servant of the Church later in life, after marriage, 
 ^and especially after becoming completely impotent, — turned his iniquitous 
 ways from the temple of Venus to that of Bacchus, and sometimes shocked his 
 flock by being terribly drunk. Still, these triumphs of the flesh, thanks to the 
 careful control of his strong-minded wife, caused such rare interruptions in an 
 otherwise exceedingly moderate mode of life, that an alcoholic basis for neu- 
 ritis could be excluded. But there was distinct, though not pronounced, locomo- 
 tor ataxia, with Romberg's symptom, a feeling as if cotton were under the feet, 
 lancinating pains in the upper part of the legs, absence of tendinous reflexes, 
 Argyll-Robertson pupil, an unreliable sphincter ani, and a quick pulse. The 
 urine, of normal quantity, generally contained, with a free diet, somewhat more 
 than I per cent, of glucose. Not then having in view the publication of any 
 article on diabetes, I made no more careful investigation than that indicated 
 by the facts recorded. 
 
 In advanced stages of diabetes, or, rather, in cases of long stand- 
 ing, when diabetic endarteritis has had time to render the vessels 
 brittle, accidents from intracranial hemorrhage are not uncommon. 
 I believe that small hemorrhages often take place under such con- 
 ditions without causing symptoms sufficiently pronounced to attract 
 the notice of either the patient or the physician, and especially that 
 a number of such hemorrhages may take place simultaneously 
 with similar small ecchymoses that occur in conjunction with hem- 
 orrhagic diabetic retinitis. In some cases the patient may com- 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 95 
 
 plain of deep-seated pains in the head, nausea, ocular disturbance, 
 etc., but the condition often remains so vague and indistinct that 
 the physician is easily misled to consider it an insignificant vaso- 
 motor disorder, until some serious accident directs attention to the 
 warnings. The patient may suddenly exhibit apoplectic symptoms, 
 and subsequently become monoplegic or hemiplegic, with hemian- 
 opsia, diplopia, amblyopia, strabismus, ptosis, etc. The nervous 
 symptoms included in Weber's syndrome have several times been 
 observed in cases of diabetes. The oculomotor nerve of one side is 
 paralyzed, with resulting divergent strabismus, crossed diplopia, 
 dilatation of the pupils, paresis of accom.modation, and ptosis ; while 
 on the other side the lower branch of the facial nerve, the arm, and 
 the tongue are paretic or paralytic. In other cases the abducens or 
 trochlear nerve is paralyzed. The paralysis of the facial nerve in 
 diabetes is often central, but not rarely is it peripheral. 
 
 There is one thing to be said about these diabetic hemorrhages 
 — they indicate a more favorable prognosis than any other kind 
 of cerebral hemorrhage, except, perhaps, the syphilitic ; I pre- 
 sume because the bleeding often takes place from quite small ves- 
 sels. Even when the hemorrhage has left the patient unconscious, 
 the symptoms sometimes quickly disappear. The patient, how- 
 ever, is in constant danger, and a new attack may bring life to an 
 end. 
 
 In some cases, when a chronic nephritis is present, intracranial 
 hemorrhage may have to be diagnosticated from uremia. 
 
 In autopsies after diabetes, whether of the mild or the severe 
 stage, it often happens that both the naked-eye and microscopic 
 examination fail to disclose any change in the nervous system. 
 This may be so even when neither the liver nor the pancreas is 
 materially altered, and when clinical observation has given reason 
 to beheve that the glycosuric dystrophy has, as usual, been depend- 
 ent upon nervous disturbances. 
 
 It is proper to point out that, on the other hand, it is not rare to 
 find postmortem tumors and other changes in the brain, which 
 must have affected decidedly the fourth ventricle, without glycos- 
 uria ever having been observed during life (Verron, Lepine). 
 
 In autopsies in other cases of diabetes there are found in the 
 
96 DIABETES MELLITUS AND GLYCOSURIA. 
 
 central nervous system changes that there is good reason to con- 
 sider as either the cause or the effect of diabetes. From what has 
 already been said, it is generally easy to form an idea as to which 
 of the two one has to deal with, and it seems worthy of remark 
 that, in order to cause glycosuria, brain-disease need not necessarily 
 directly affect Bernard's center in the floor of the fourth ventricle. 
 
 In chapter iii it was mentioned that there have been observed in 
 the brain after diabetes extravasation of blood, atheromatous pro- 
 cesses, aneurysm, softening, sclerosis, colloid or fatty degeneration, 
 new growths (fibroids, gliomata, sarcomata, osteomata), and the 
 cysticercus racemosus, through which Michael's name has become 
 familiar to all students of diabetes. It was also pointed out that 
 general paralysis and akromegaly have often, and multiple sclerosis, 
 tabes dorsalis, paralysis agitans, meningitis, and syphilitic disease of 
 the brain have sometimes, been seen in association with either simple 
 glycosuria or diabetes. 
 
 A common condition found after diabetes is dilatation of the 
 smaller blood-vessels, with small hemorrhages into the brain 
 (Frerichs), probably as a result of changes due to diabetes endar- 
 teritis (see below). The small cysts mentioned by Saundby and 
 others are probably the residual products of such hemorrhages. 
 
 Dickinson, in 1870, described perivascular spaces filled with detri- 
 tus occurring throughout the whole cerebrospinal system in cases of 
 diabetes. It is a seductive theory to consider vasomotor paralysis, 
 or paresis, strong dilatation of the vessels of more or less transitory 
 character, and pressure with retrogressive metamorphosis of the 
 surrounding central nervous elements in the floor of the fourth 
 ventricle, as a cause of diabetes ; but the perivascular spaces de- 
 scribed by Dickinson often occur independently of diabetes, and 
 neither German (Frerichs) nor English (Taylor and Goodhart) 
 observers are inclined to ascribe any such significance to the con- 
 dition named. 
 
 Glycogen, which seems, in severe causes of diabetes, to be in- 
 creased in other organs as it is decreased in the liver, has been 
 found in much greater quantity than normal in the brain after dia- 
 betes (Futterer). 
 
 It seems that diabetes not rarely causes certain changes in the 
 spinal cord, the most common of which is sclerosis of the posterior 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 9/ 
 
 columns, especially Goll's and Burdach's tracts, more rarely of the 
 lateral columns (Williamson, Leyden, Minor, Sandmeyer, Leich- 
 tentritt, Kalmus, Hensay). 
 
 Boccardi's studies of the spinal cords in dogs made diabetic by 
 extirpation of the pancreas have yielded valuable information. The 
 degeneration is not symmetric and has no systematic character. It 
 was found essentially in Goll's and Burdach's tracts and in the zone 
 external to them (Lissauer's tracts), close to the posterior nerve- 
 roots. Sometimes it encroached almost upon the whole of the 
 posterior columns, so that only the posterior parts of Goll's tracts 
 and a thin zone of Burdach's tracts remained free. Changes in the 
 lateral columns were much less common, and, when present, were 
 found in Gowers' tracts and in the crossed pyramidal tracts. 
 Alterations in the sheath and in the axis-cylinders of the nerves, — 
 the former being thinner and the latter having a lacerated appear- 
 ance — were found even a short time after the onset of severe dia- 
 betes. The proliferation of the areolar tissue and the process of 
 sclerosis began subsequently. The gray substance also was 
 changed ; degenerated, enlarged, hyaline cells being found in the 
 anterior and posterior cornua and in Clark's columns, and the nuclei 
 of these cells staining with difficulty or not at all. Here and there 
 were observed lacunae, Hke those described by Charcot and Joffroy. 
 Sometimes the endarteritis with endothelial desquamation, described 
 by Ferraro, was noted ; according to Boccardi, it was rather the 
 exception than the rule. 
 
 Nonne observed {in vivo and postmortem) chronic anterior polio- 
 myelitis as a complication in a case of severe pancreatic diabetes. 
 
 Toward the close of the eighties. Price, Eichhorst, and Auche 
 described diabetic neuritis, all three finding parenchymatous degen- 
 erative neuritis with uneven, vacuolar sheath, with the axis-cylinder 
 segmented or absent. It seems that these alterations are present 
 most frequently in the anterior and posterior tibial nerves. Hensay 
 noted similar changes in the facial and spinal accessory nerves. 
 The crural nerve also has been found in this condition.* 
 
 * The knee-jerk in this case had been absent during life. Changes in the peripheral 
 nerves, however, unless sufficiently far advanced to destroy conductivity, could not alone 
 cause loss of the knee-jerk. Even though our present means of investigation are in- 
 capable of detecting changes in the cellular nervous centers, such changes may exist, and 
 
98 DIABETES MELLITUS AND GLYCOSURIA. 
 
 The pneumogastric 7ierve has several times been found abnormal, 
 sometimes sclerotic and thickened (Percy, Fleury), sometimes com- 
 pressed by tumors (Anger, Frerichs, Henrat, Neumann), sometimes 
 atrophic from other influences than tumors (Lubinoff). Eichhorst 
 found it the seat of a parenchymatous neuritis. 
 
 The sympathetic nervous system, which has been studied care- 
 fully, since it has been known that lesions of different parts 
 thereof may give rise to glycosuria, has often been found in a 
 pathologic condition. The changes have generally been found in 
 the celiac ganglion, and have usually been of a sclerotic, more 
 rarely of a simply atrophic, nature. 
 
 Circulatory System. 
 
 In inveterate cases of diabetes the heart is never very 
 strong. The sounds are often weak and distant, the systolic 
 elevation in the sphygmogram being often low and the pulse 
 uneven, while the patient complains of the usual symptoms 
 of weak heart if great demands are made on the circulatory 
 apparatus. This deficiency is usually present in only a moderate 
 degree, and the pronounced fatty heart is comparatively rare. 
 Still, the fatal issue from this cause, by its similarity to sudden 
 death in some cases of coma, has several times contributed to the 
 number of false reports of death in coma apart from the severe 
 stage and without " acidosis." 
 
 The pulse varies exceedingly in diabetes. Its frequency, how- 
 ever, is distinctly increased in about 75 per cent, of all cases of 
 severe diabetes, and it is not rare in such cases, apart from 
 complications and from diabetic coma, to find a pulse of 100 or 
 more. I think this must be caused by the irritating influence of 
 the toxins on the heart's own sympathetic centers more often than 
 by any paralyzing action on the center for the pneumogastric 
 nerve. If one should speak of a diabetic type of pulse, it would be 
 the small, feeble pulse of great frequency. 
 
 Organic changes in the valves of the heart are generally brought 
 
 may be expected after the operation of marantic and toxic influences of long standing. 
 To such changes may be ascribed both the absence of the knee-jerk and an important 
 role in the production of peripheral nervous disturbances. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 99 
 
 about by chronic endarteritic processes and the aortic valves are 
 most commonly attacked. Changes in the mitral valves do not seem 
 to me to be much more common in association with diabetes than 
 independently thereof, and Lecorche's statistics showing such 
 changes in 12.3 per cent, of all cases of diabetes are to me inex- 
 plicable. 
 
 The most frequent macroscopic alteration in the circulatory sys- 
 tem in diabetes consists in atheromatous processes iQr\(Xmg to ai'terio- 
 sclerosis which, excluding the juvenile cases, may be detected by 
 palpation during life in about 20 per cent, of all cases. It is a 
 feature essentially of inveterate cases, and is thus much more com- 
 mon in those of long standing, though in what I persist in calling 
 the mild stage, than in cases that belong to the severe stage and 
 rarely persist for any considerable number of years. I should 
 think that the glycemia and other blood-toxins are responsible for 
 the condition ; but an influence arising from enfeebled vasomotor 
 activity may possibly also contribute to the result. In the presence 
 of pronounced arteriosclerosis one often finds alcoholic or syphilitic 
 complications. In rare cases the atheromatous and consequent 
 conditions of the arteries of the brain are not the effect but the 
 cause of diabetes. 
 
 Atrophic ajid degenerative conditions of the mj/ocardizim sometimes 
 attend diabetes, though they are much more rarely detected during 
 life than after death. 
 
 Much has been said and written about angina pectoris compli- 
 cating diabetes. The attacks of pain and the asthmatic disturb- 
 ances that sometimes occur in cases of diabetes — more often during 
 the night than by day, like all sensations called angina pectoris — 
 are either the expression of organic disease of the heart, usually 
 resulting from changes in the coronary arteries and in the myo- 
 cardium, or they are manifestations of less important neuralgic or 
 rheumatic conditions in the chest-wall, which, especially in "ner- 
 vous " persons, may cause great momentary suffering. Both the 
 first kind, the true, dangerous, "organic" form of angina pectoris, 
 and the latter kind, the comparatively insignificant, "nervous" 
 form of pseudo angina pectoris, are more common among diabetics 
 than among other individuals. In most cases of diabetes present- 
 ing such disturbances that I have seen, the attacks recurring at 
 
lOO DIABETES MELLITUS AND GLYCOSURIA. 
 
 long intervals for years, the failure to detect symptoms of organic 
 disease on careful physical examination, the presence of rheumatic 
 infiltrations or of neuralgic symptoms in the chest-walls, the differ- 
 ence in the radiation of the pains from what usually takes place 
 in true angina, and the manifest influence of purely rheumatic and 
 nervous causes, have led me to attribute the symptoms to the 
 " nervous " form, pseudo angina, which seems to me decidedly 
 more common than the true angina. 
 
 Among the rarer complications of diabetes there occur sometimes, 
 though only in advanced cases, numbers of petechias, due to stnall 
 subaitaneous hemorrhages, most frequently on the lower extremities, 
 and probably dependent on brittleness of the small vessels caused by 
 the diabetic endarteritis described by Ferraro. 
 
 The heart, in autopsies of cases in which there has been pro- 
 nounced marasmus, often appears in a state of brown atrophy. In 
 other cases the organ shows no distinct alteration. In at least 1 5 
 per cent, of all cases some enlargement, which usually affects the 
 whole organ, is manifest. Pronounced fatty degeneration is rare. 
 Atheromatous changes in varying degree are common, but other 
 endocarditis or valvular alterations are not. 
 
 Dr. Jaques Mayer found, clinically, enlargement of the heart in 21.6 per 
 cent, of cases of diabetes in a first series ; and in a later series 27 per cent. 
 The latter figure is nearly twice as high as the 15 per cent, at which I arrived 
 in the same manner — a difference that, as I have found after consultations 
 with my esteemed colleague, depends upon differences in opinion concerning 
 the physical basis for the diagnosis. Dr. Mayer himself, in an investigation of 
 the postmortem records of the city of Berlin, did not obtain a higher figure 
 than 13 per cent. He mentions the chemic irritation of the increased amount 
 of sugar and urea in the blood as a cause 'of the hypertrophy without further 
 explanation. O. Israel has shown experimentally that in extreme cases the 
 kidneys become unable to fulfil their function of eliminating urea and that the 
 heart attempts to make good this deficiency by hypertrophy of its left ventricle 
 (injections of sodium nitrate and of urea in horses and dogs). For my part, I 
 am inclined to ascribe the rather large percentage of cases in which hyper- 
 trophy of the heart attends diabetes to (i) the adiposity which is common in 
 diabetes, and which often per se causes enlargement of the heart; (2) the 
 atheromatous changes in the vessels and the obliterating and desquamative 
 endarteritis of the small vessels (Lecorche, Ferraro) ; (3) the polydipsia and 
 the increased quantity of water passing through the system. The last two 
 influences must increase the burden of the heart and tend to produce a work- 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. lOI 
 
 ing hypertrophy. In some cases there coexist the causes of hypertrophy 
 resulting from cirrhosis of the kidney, which, according to the prevaihng views 
 of trustworthy investigators, consist in more than the narrowing of the blood- 
 current. An irritating action of the blood-toxins on the vasoconstrictors might 
 especially be thought of. The mesenteric vessels, however, which exert so 
 important an influence on the arterial pressure, are in diabetic patients prob- 
 ably much oftener dilated than constricted. 
 
 Diabetic endarteritis of the small vessels (Ferraro, Strauss, Boc- 
 cardi) seems to be very common and may exert an important influ- 
 ence in the causation of hemorrhages and of degenerative pro- 
 cesses in the tissues. It generally causes desquamation of the 
 endothelium (Ferarro), and sometimes obliteration of the vascular 
 lumen (Lecorche). The brittleness of the small vessels in cases of 
 inveterate diabetes is manifest, and finds expression in the extrava- 
 sations into the brain, the retina, and the cutaneous and other 
 tissues.* 
 
 Diabetic blood presents distinct changes of a physical anatomic 
 and chemic nature. To the last I shall return later. The per- 
 centage of water has been found both increased and diminished. 
 Von Jaksch found it diminished in every one of lo cases, in which it 
 ranked from 66.46 per cent, upward, but never reached the normal, 
 72.28 per cent. The specific gravity was found by Hammerschlag 
 to be increased to 1.064; by Davy, to be 1.061 ; by Nasse, to be 
 diminished to 1.048. The number of red blood-corpuscles is 
 usually high (A. James and others), except in bronze-colored dia- 
 betes (see below), in which the number is much diminished, and 
 marked hemosiderosis, due to the products of disintegrated red 
 blood-corpuscles, is found in almost all of the organs. Bremer, 
 Williamson, and others have found that the red corpuscles in dia- 
 betic blood are stained in a different way by methylene-blue and 
 other dyes than those in normal blood (see below). Habershon 
 found marked leukocytosis in diabetic blood, the number of white 
 
 * Rosenblath, as early as 1888, saw the walls of the small vessels thickened in an 
 advanced case of diabetes. The case is surrounded with some interest on account of 
 the presence of numerous small hemorrhages or ecchymoses strewn over the skin of the 
 legs. Above the ecchymoses the skin in many places presented necrotic areas, which 
 invaded the papillary body and about half the depth of the entire cutis. The lungs con- 
 tained circumscribed gangrenous areas, and the tongue and the esophagus were the seat 
 of numerous ulcers. 
 
I02 DIABETES MELLITUS AND GLYCOSURIA. 
 
 blood-corpuscles diminishing with restriction of carbohydrates and 
 increasing during coma. Bettman, in a case of diabetes compli- 
 cated by exophthalmic goiter, observed the number of white blood- 
 corpuscles undergo diminution with a free supply of carbohydrates. 
 Neusser found around the nuclei of the leukocytes in diabetic 
 blood small particles that stained black with a modification of Ehr- 
 lich's solution ("perinuclear basophilia"). 
 
 It has been known since the end of the eighteenth century that 
 the blood of diabetics sometimes exhibits a peculiar whitish color, 
 owing to the numerous particles of fat present, — diabetic lipemia, — 
 which may reach ii or 12 per cent. (Lecanu, D. Gerhardt, after 
 Naunyn). After a rich meal the percentage of fat in the blood 
 may reach high figures in healthy persons ; but the lipemia in 
 diabetics, like that which attends some other pathologic conditions, 
 may occur on an empty stomach (Naunyn). The intimate causes 
 of the condition are unknown.* 
 
 Respiratory Organs. 
 
 The most common pulmonary complication of severe diabetes 
 mellitus is htberculosis. While this pulmonary disease ordinarily 
 causes the sacrifice of from one-seventh to one-fifth of mankind, it 
 attacks, according to Griesinger, 72 per cent, of diabetics in the 
 severe stage and destroys 39 per cent. These figures apply only 
 to severe cases, and are never reached outside of hospitals. 
 
 In private practice, especially in watering-places such as Carlsbad, 
 the proportion of patients with tuberculosis of the lungs is a low 
 one and the patients are usually in a Hght stage and in fairly good 
 nutritive state. This observation would seem to show that hyper- 
 glycemia predisposes less to pulmonary tuberculosis than does 
 marasmus. It is often said that tuberculosis of the lungs is much 
 more quickly fatal when associated with, than when independent of, 
 diabetes ; but any practitioner with a large number of diabetic 
 patients knows that the difference in this respect between diabetic 
 and nondiabetic patients with the same degree of marasmus is but 
 
 * Our knowledge of changes of the blood in different diseases is only developing, and 
 some of these observed in diabetic blood apparently do not belong exclusively to 
 diabetes. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. IO3 
 
 slight. The results in cases of pulmonary tuberculosis complicating 
 diabetes is not rarely that usual with the condition first named ; 
 but in many of these cases, however, the termination is that com- 
 mon with severe diabetes, namely, diabetic coma. 
 
 Diabetes mellitus seems to some extent to predispose to acute 
 croupous and lobular pneumonia, which, by reason of the tendency 
 to severe complications, the weak heart, and the generally low con- 
 dition, makes the prognosis worse than it would otherwise be. 
 Still, one ought not to despair of a favorable issue, and I have had 
 several diabetic patients that have passed through acute pneumonia 
 — in one both lungs being attacked. When acute pneumonia occurs, 
 the glycosuria is generally diminished in a marked degree ; in rare 
 cases the reverse effect has been observed (Naunyn). 
 
 Inflammatory processes in the lungs in diabetic patients, espe- 
 cially in inveterate or advanced cases, are much more likely to 
 induce gangrene than in nondiabetics. In Naunyn's work, pub- 
 lished after the Swedish edition of this book had appeared, the 
 great German clinician distinguishes between two forms of pul- 
 monary gangrene : the acute and the chronic. I have seen only 
 instances of the first, but Naunyn considers one about as frequent 
 as the other. 
 
 The acute form generally begins as a croupous pneumonia, and 
 is often attended with hemoptysis and abundant bloody and puru- 
 lent sputa, which generally lack the customary odor of gangrene. 
 This disorder lasts at the longest for a few weeks. After death 
 one finds in the lungs gangrenous and purulent cavities, which 
 usually contain bacilli or other fungi (Zenker, Fiirbringer), but 
 which often are not very offensive to the sense of smell. One of 
 my diabetic patients, who is still alive, recovered some years ago 
 from this complication. Marklen has observed a similar case. A 
 fatal issue is naturally the more common termination. 
 
 The other chronic form of pulmonary gangrene complicating 
 diabetes begins as a catarrhal condition, with fever and bloody or 
 purulent, often offensive, sputa, and may last for years, until hemop- 
 tysis or marasmus brings about a fatal issue. Naunyn observed 
 this complication only in elderly patients. 
 
I04 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Digestive Organs. 
 
 I have already mentioned the diabetic changes that take place in 
 the cavity of the mouth. I would here refer only to the important 
 circumstance that in the diabetic the power of viastication is likely 
 to be much impaired, on account of caries or loss of the teeth. 
 
 The saliva is often distinctly diminished, and dryness of the 
 mouth is a common complaint. Besides, the saliva, particularly in 
 certain cases, is often acid ; but, apart from the predisposing influ- 
 ence this may have with regard to caries, it is rather of theoretic 
 than practical interest. 
 
 The g astro -intestinal tract in diabetic patients generally fulfils its 
 functions quite well so far as digestion and absorption are concerned, 
 and advanced changes are exceptional. 
 
 A most remarkable circumstance is the rarity of distinct dilata- 
 tion of the stomach. One certainly finds often, clinically and post- 
 mortem, that the Hmits of the stomach are rather extended, but not 
 beyond what may be considered normal ; and clinically pronounced 
 dilatation certainly does not occur in one per cent, of all cases of 
 diabetes. 
 
 The diminution in all of the secretions (except the urine), which 
 there is reason to believe occurs in diabetes, is not sufficient to 
 impair digestion, and may, in many cases, be made good in the 
 stomach and the remainder of the digestive tract by a hypertrophy of 
 the secretory glands (see below). When I began to make analyses 
 of the gastric juice, I made examinations in a considerable number 
 of cases of diabetes, but only rarely found anomalies of composi- 
 tion or of digestive power. This experience is in accord with the 
 results obtained by Honigmann, Rosenstein, Gans, and others. 
 Numerous and exact investigations into the absorption of various 
 foods, as well as careful fecal analyses, also have demonstrated that 
 absorption from the gastro-intestinal tract is, as a rule, normal or 
 nearly normal.* 
 
 Slight dyspeptic and catarrhal troubles are, of course, quite 
 common among diabetics as among other persons. During periods 
 in which the use of bread and vegetables is interdicted or rigidly 
 restricted, manifest gastro-intestinal catarrh, with diarrhea and 
 
 *See Weintraud's masterly treatise in " Bibliotheca medica," i, Cassel, 1893. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. IO5 
 
 sometimes with fetid stools, is especially prone to occur, and not 
 rarely necessitates a greater allowance of carbohydrates. 
 
 Then there is a small class of diabetic patients who exhibit a 
 digestive deficiency of a grave nature. These cases generally belong 
 to the severe, or at least to a very advanced, stage of diabetes, and 
 depend upon primary or secondary degenerative processes in the 
 pancreas or in other glandular elements of the digestive apparatus. 
 
 Hirschfeld * has published seven such cases from his own and from 
 Frerichs' and Kiilz's experience. In these, from 29.4 to 47.2 per 
 cent, of the ingested fat and from 30 to 45 per cent, of the ingested 
 proteids were found in the feces. Even in these cases the car- 
 bohydrates were fairly well digested and absorbed. This certainly 
 does not occur when the pancreas is in an advanced abnormal con- 
 dition, and Abelmann found in the feces of Minkowski's dogs, after 
 extirpation of the pancreas, almost the whole quantity of ingested 
 carbohydrates, upward of 43 per cent, of the emulsified and nearly 
 the whole of nonemulsified fat, and as much as 56 per cent, of the 
 proteids. As a rule, the fat is the kind of food that most fre- 
 quently and to the greatest extent remains undigested and unab- 
 sorbed, even independently of the great variations that occur in 
 each individual case (Sandmeyer). 
 
 The deficient absorption of fat, which is apparent without closer investiga- 
 tion from the hght color of the feces, has long been observed in diabetes, 
 and has been ascribed to disease of the pancreas. Bright, Eliotson, Frerichs, 
 Fles, and Silver observed fatty stools in diabetes, but their patients also suf- 
 fered from retention of bile and icterus. Le Nobel noticed similar stools in 
 diabetes without biliary retention. Claude Bernard, by experiment, came to 
 the conclusion that the pancreatic juice is necessary for the absorption of fat. 
 Senn observed fatty stools after extirpation of the pancreas. William T. Bull 
 and Hartsen mark a like observation in patients with pancreatic cysts, and the 
 latter found the extract with ether from pigeons' stools three times the normal 
 after extirpation of the pancreas. Von Mering, Minkowski, and Abelmann, 
 
 *See Hirschfeld's interesting paper in " Zeitschrift f. klin. Med.," Berlin, 1891. It 
 is difficult to understand why these cases should be described as ' ' eine neue klinische 
 Form von Diabetes." The absence of polyuria is not rare in diabetes, and in most 
 of the seven cases the polyuria, according to Hirschfeld's own figures, was manifest. 
 The cases present no peculiarity beyond the deficient digestion, and the establishment of 
 artificial clinical forms is undesirable. In one of the cases, which ended fatally from 
 marasmus, the glycosuria ceased with a strict diet. The pancreas was either carcino- 
 matous or atrophic or not distinctly changed. 
 
I06 DIABETES MELLITUS AND GLYCOSURIA. 
 
 finally, have observed analogous conditions after extirpation of the pancreas in 
 dogs. Thus, it is finally established that pancreatic juice plays an important 
 role in the absorption of fat. It is also known that the pancreas is in some 
 way necessary to prevent hyperglycemia, and that the destruction of this organ 
 is followed by glycosuria. It has, however, not been shown that every diabetic 
 patient who, apart from retention of bile, does not digest fat suffers also from 
 disease of the pancreas ; while, on the other hand, it is positively known that 
 this organ may be greatly changed without noteworthy impairment in the ab- 
 sorption of fat (Hartsen, Fr. Miiller) and without diabetes resulting (Minkowski). 
 It is known, further, that there are sometimes in cases of diabetes reasons un- 
 connected with the pancreas for digestive deficiency. 
 
 Habitual constipation is, in consequence of marasmus, and an 
 atonic state of the bowels, deficient innervation, etc., still more 
 common among diabetics than among other individuals, and any 
 tendency in that direction is likely to become manifest with rigid 
 restriction of carbohydrates. 
 
 In connection with a consideration of the digestive apparatus in 
 diabetics illustrations are not wanting of the great frequency of 
 purely nervous symptoms in association with the diabetic syn- 
 drome. Gastro-intestinal 7ieuroses are exceedingly common among 
 diabetic patients. It would carry me far beyond my purpose — as 
 it would be beyond my power — to describe here all of the different 
 neuroses of this kind that may occur in diabetes. The most fre- 
 quent of these belong to that group of which a part generally is 
 called nervous dyspepsia or gastric neurasthenia, but which, on 
 account of its manifold sensory and motor disturbances, referred to 
 different parts of the digestive tract, I prefer to designate gastro- 
 intestinal neurasthenia. The patient often suffers from inexplicable 
 variations in appetite, — which may one day be excellent and the 
 next fail entirely, — from eructations, a sense of pressure, of tension, 
 or of pain in the epigastrium, or of nausea, etc. Sometimes flatu- 
 lence is the chief complaint. Easily aroused and excessive peris- 
 taltic activity may cause attacks of diarrhea on slight provocation ; 
 spastic disturbances of stomach and intestines may cause severe 
 pains, and, especially in the latter, may give rise to what Kussmaul 
 calls " tormina ventosa." One sometimes may find a part of the 
 alimentary canal distended by gas and giving for the moment the 
 impression of a tumor. I believe that the much-talked-of diabetic 
 crises gastriques usually are of spastic nature. They may be quite 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. lO/ 
 
 painful and be followed by diarrhea, and in rare cases by vomiting. 
 I can not find that they differ from similar manifestations in purely 
 neurasthenic cases, and they certainly resemble these more nearly 
 than the tabetic " crises gastriques," to which they have been com- 
 pared. 
 
 Secretory neuroses certainly exist much oftener than they are 
 noted, being sometimes difficult of detection, even on elaborate in- 
 vestigation. I have twice seen in diabetic patients what I believed 
 to be an excessive secretion of gastric juice, a condition that is sel- 
 dom mentioned. The glycosuric dystrophy is rather hkely to 
 diminish the secretions, but an exception in the other direction may 
 occur with the gastric juice, just as sometimes hyperhidrosis is 
 observed instead of the customary anhidrosis. Hyperacidity (from 
 hydrochloric acid) has sometimes been noted (Riegel, Naunyn). I 
 believe that it is not uncommon. 
 
 The most serious of all gastric neuroses that can attack the dia- 
 betic patient is nervous anorexia (Gull, Lasegue), which is some- 
 times found in neuropathic persons, but which, happily, is rare both 
 in association with and independently of diabetes. In the few 
 cases other than of diabetes in which I have encountered this 
 curious affection — which has Kttle in common with the refusal to 
 eat in developed mental diseases — the course has been favorable, 
 and the patients, after a few weeks of marked inanition, have been 
 restored to normal appetite and health. This seems also to have 
 been the almost universal rule in recorded cases. In diabetic 
 patients, however, the prognosis appears to be much less favorable. 
 The anorexia is sometimes particularly obstinate, and is especially 
 pronounced with regard to meat and fat, and even if the patient is 
 allowed a completely unrestricted diet, — which, I think, is to be 
 recommended, — all remedies may fail to secure the ingestion of 
 more than a small part of the food required for the genera- 
 tion of the necessary number of calories. Most of these patients 
 are women. The last one under my care exhibited after the begin- 
 ning of the anorexia no glycosuria, but pronounced diaceturia 
 from the inanition, and died after several months of marasmus. 
 
 Gastro-intestinal changes have often been found after death, 
 though they are rarely of a marked nature. The increased diges- 
 
I08 DIABETES MELLITUS AND GLYCOSURIA. 
 
 tive demand causes at first functional hypertrophy in different 
 structures. Dittrich, Frerichs, Lancereaux, Rosenstein, and others 
 found hypertrophy of the muscular layers in the stomach. Boccardi 
 saw (in diabetic dogs) enlargement of the gastric glands and their 
 ducts, and dilatation of the lymphatic vessels. [Hyperacidity of the 
 gastric juice — 0.4 per cent. — is not rare (Riegel).] Boccardi also 
 found Brunner's glands and Lieberkiihn's crypts hypertrophied. 
 I have generally found, both clinically and after death, a rather 
 large, but never decidedly dilated, stomach. I have several times 
 on postmortem examination seen enlargement of the mesenteric 
 glands, as first pointed out by Frerichs. 
 
 In advanced cases there is atrophy both of the muscular (Fre- 
 richs) and of the glandular elements (Ferraro, Boccardi). Armanni 
 found in one of Cantani's patients pronounced atrophy of the 
 peptic glands. Rosenstein mentions a decreased amount of hydro- 
 chloric acid. These changes and those that sometimes occur in the 
 pancreas suffice to explain the severe digestive troubles in Hirsch- 
 feld's cases, previously mentioned. Catarrhal changes are exceed- 
 ingly common. 
 
 Hemorrhage and ulceration are mentioned as occurring in 
 different parts of the gastro-intestinal tract (Frerichs, Ferraro, and 
 others). 
 
 The pancreas plays a most important part in the pathogenesis 
 of diabetes mellitus, and I propose further on to describe pan- 
 creatic diabetes and to give a summary of v. Mering's and Mink- 
 owski's discovery of the results of extirpation or resection of the 
 pancreas. 
 
 Clinically, anything noteworthy with regard to the pancreas is 
 found with comparative rarity among diabetic patients. As I 
 write, it happens that I have under observation such a case, in which 
 the rapid development from day to day is striking. The patient, a 
 Jewess, sixty-seven years old, has had upward of six per cent, of 
 glucose in her urine, the sugar disappearing entirely with restriction 
 of diet. In the beginning of the diabetes, which set in quite sud- 
 denly, there was no diacetic acid in the urine. Now, Gerhardt's 
 reaction is pronounced as a result of inanition. The patient is 
 often ravenously hungry, but can scarcely take any food when it 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. IO9 
 
 is brought to her. She sometimes vomits, and complains often of 
 severe pains in the epigastrium and in the back. Palpation raises a 
 suspicion of increased resistance over the head of the pancreas. 
 No icterus is present, but a decided cachectic hue. The feces some- 
 times contain large quantities of fat. Unfortunately, I shall not 
 be able to be present at the postmortem examination, which is cer- 
 tain to take place within a few weeks, and which probably will 
 reveal a carcinoma of the pancreas.* 
 
 Since the connection between diabetes and disease of the pan- 
 creas was pointed out that organ is as much studied in diabetic 
 patients after death as it was neglected in the past. Such changes 
 in the pancreas as can be reasonably considered to have caused the 
 diabetes are, however, found comparatively rarely — certainly not in 
 more than ten per cent, of all autopsies after diabetes. In fully 
 ninety per cent, or more of such cases the pancreas is either normal 
 or diminished in size and flabby in consistence, with small but 
 otherwise normal acini ; it presents a condition of simple atrophy, 
 which may with much better reason be considered an effect than a 
 cause of the glycosuric dystrophy, f 
 
 Among the comparatively few cases in which disease of the pan- 
 creas may be considered as a cause of the diabetes the most com- 
 mon are atrophy and cirrhosis from the presence of calculi in the 
 ducts, which may, in consequence, be much enlarged. 
 
 Cirrhosis of the pancreas, interstitial pancreatitis, may also exist 
 without the presence of calculi (Heinemann), and in exceptional 
 cases may cause diabetes. 
 
 Sometimes the pancreas is the seat of more or less fatty necrosis, 
 as I have seen in cases in which the whole clinical picture has been 
 that of fat, constitutional, gouty, nonpancreatic diabetes. Seyler 
 recently recorded a case of ischemic fatty necrosis, which he con- 
 sidered due to atheromatous processes that were exceedingly pro- 
 nounced in the celiac axis and its branches, with diabetes as a 
 remote sequel. 
 
 * Since this was written the diagnosis has been found to be correct. It is a curious 
 fact that the woman's father also died of carcinoma of the pancreas. 
 
 f My opinion in this respect is based upon not a few personal autopsies and on infor- 
 mation gained in Carlsbad, where a considerable number of postmortem examinations 
 after diabetes are made. 
 
no DIABETES MELLITUS AND GLYCOSURIA. 
 
 Some observers mention interstitial lipoma of the pancreas 
 (Hansemann, Naunyn). 
 
 Hyaline necrosis, with homogeneous, transparent contents in the 
 enlarged, glandular cells, such as has been described by Armanni 
 in the kidneys (see below), seems also sometimes to occur in the 
 pancreas (Saundby). 
 
 Carcinoma of the pancreas has several times been found after 
 diabetes, and is now and then diagnosticated during life. It may 
 exist without diabetes, partly because a sufficient amount of the 
 glandular tissue is left intact, partly, as Hansemann points out, 
 because of the retention by the degenerated cells of some of their 
 functional capability. 
 
 Other changes in the pancreas are rare. Abscess has been 
 found, but seems only exceptionally to have time before death to 
 cause diabetes. Cysts generally leave enough of normal tissue to 
 prevent the development of diabetes. Frerichs has reported a case 
 in which the postmortem findings seem to indicate the development 
 of diabetes as a result of (Fitz's) hemorrhagic acute pancreatitis ; 
 Benda and Stadelmann have reported a similar case. The majority 
 of instances of acute hemorrhagic pancreatitis are unattended with 
 glycosuria (Seitz). 
 
 Hansemann * has recently published an excellent paper on the relations of 
 the pancreas to diabetes. He believes — on insufficient grounds, it seems to 
 me — in the occurrence of a specific variety of diabetic atrophy of the pancreas, 
 and maintains that there exist anatomic difTerences between this and a simi- 
 lar state after nondiabetic cachexia or marasmus. 
 
 The liver is the organ in which one must look for the immediate 
 cause of diabetes if, with Bernard and his many adherents, one 
 considers the condition to depend upon an excessive production 
 of sugar. We have already seen that a number of affections of 
 the liver are sometimes, though inconstantly, accompanied by 
 glycosuria, which may or may not be found after ligation of the 
 gall-ducts, or, together with biliary fistulse, after attacks of gall- 
 stones, after trauma over the liver in association with pylethrom- 
 bosis, organic heart-disease and a consequent stasis in the liver, 
 acute yellow atrophy, phosphorus-poisoning, amyloid degeneration, 
 
 *"Zeitschr. f. klin. Med.," 1894. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. I I I 
 
 and, above all, cirrhosis. I consider the frequency of the associa- 
 tion of cirrhosis of the liver and glycosuria fully demonstrated since 
 Naunyn, in his excellent work recently published, mentions 22 
 cases of incipient and 2 cases of advanced cirrhosis of the liver 
 among 152 diabetics. 
 
 Still, it must not be expected that some distinct abnormity of 
 the liver will be found clinically in a large percentage of diabetic 
 patients. The character of Naunyn's figures depends on the 
 enormous frequency of cirrhosis of the liver in and around Stras- 
 burg, where his observations were made ; his earlier figures are 
 much lower. The usual state of the liver is, so far as clinical 
 investigation goes, a normal one. On percussion the size of the 
 organ is found to be within the normal limits, and palpation yields 
 no information of any change in form, consistency, or sensibility. 
 In other cases, fewer though not very rare, there is some enlarge- 
 ment and perhaps some tenderness on pressure.* 
 
 Now and then any one who sees many diabetic patients will find 
 one with a cirrhotic liver — generally of the usual atrophic variety. 
 I will cite two cases under observation within the last few years : 
 
 Dr. , a Scandinavian, is an unmarried physician, fifty-four years old, 
 
 who has a great aversion to pure water. He does me the honor to consult me in 
 Carlsbad, where he appears in my office with watery eyes, a rough voice, trem- 
 bling hands, and a flabby panniculus, and complains bitterly of loss of appetite 
 and nausea, especially in the mornings, etc. When he discovers that I have, 
 without asking any unpleasant questions or making further investigation, 
 booked him as a case of chronic alcoholism, he indignantly protests, exclaim- 
 ing that he has drunk " only " a bottle of claret and half a bottle of whisky a 
 
 *Glenard, of Vichy, has arrived at other conclusions in his " Resultats Objectifs 
 d'Exploration du foie chez les Diabetiques," Paris, 1890. Among 324 diabetics he found, 
 on palpation, by a method that he designates " precede du pouce," a distinct change in 
 60 per cent. , and these cases he classifies under 8 varieties and 42 subvarieties, which 
 he illustrates by diagrams. So far as both classification and palpation go, this is entirely 
 beyond me, as well as some others. The last medical friend to whom I showed Glenard's 
 plate did as Voltaire's governor — " il releva sa moustache et sourit am^rement," but said 
 nothing. Neither will I concede, without all reservation, the truth of Glenard's state- 
 ment : tout foie percu par la palpation chez le vivant est un foie anormal. Glenard con- 
 siders hypertrophy of the liver to be present in 34.5 per cent, of all cases of diabetes, 
 and usually limited to the right lobe ; the consistency to be increased in one-third and 
 sensitiveness in one-fourth of all cases ; and nontender induration to be present in 23 per 
 cent, of all cases and in 40 per cent, of those in which the liver can be felt by palpa- 
 tion. 
 
112 DIABETES MELLITUS AND GLYCOSURIA. 
 
 day. Even this concession probably represents only a part of the truth. 
 Syphilis was denied. 
 
 The radial and the temporal arteries were sclerotic. The heart was 
 somewhat enlarged in all directions ; the second aortic sound somewhat accent- 
 uated. On percussion the right lobe of the liver appeared to be distinctly 
 diminished in size, but there was no tenderness. The spleen was a little 
 enlarged. There was no icterus, no bile in the urine, and no manifestations 
 of stasis. The tongue and the breath were fairly normal ; only a few teeth 
 remained, and those were carious. 
 
 The patient was irritable, slept badly, and could not approach steep declivi- 
 ties. Sexual power was " highly satisfactory." The knee-jerks were normal. 
 
 When the patient received about 120 grams of starch with his food, he 
 passed 1700 cu. cm. of urine of a specific gravity of 1.019 and containing a 
 trace of albumin and about 0.05 per cent, of glucose. On microscopic exami- 
 nation quite a remarkable number of calcium-oxalate crystals were found, and 
 only a few hyaline casts. Single samples of the urine contained as much as 
 0.5 per cent, of glucose. Glycosuria was first observed fourteen years ago. 
 
 The patient died about a year after my examination, and I received word 
 that the liver was fairly well advanced in cirrhosis. 
 
 Mr. , a Jewish Bavarian brewer, thirty-nine years old, whose father had 
 
 been a diabetic and who himself had always been " nervous," forgot the law 
 and the prophets and the usually temperate Jewish customs, drank for many 
 years much " Kornbranntwein " and beer, smoked ten cigars a day, and was 
 far from moderate "in puncto sexus." He insists that he never had syphilis. 
 Two years ago he began, from mere thirst, to attack the beer-casks even more 
 energetically than before, and his physician found four per cent, of glucose 
 in the urine. Since then the patient has lived under a moderate restriction of 
 carbohydrates. 
 
 The man was exceedingly neurasthenic, and had a " smoker's heart." The 
 reflexes were normal. The breath was natural ; one tooth was missing, and the 
 remainder presented very little caries. The liver was somewhat reduced in size. 
 The left lobe was distinctly palpable. The spleen extended a little beyond the 
 anterior axillary line. Slight icterus existed. About 120 grams of carbo- 
 hydrates caused scarcely 0.5 per cent, of glucose to appear in the daily 2500 
 cu. cm. of urine, with a specific gravity of 1.016 and containing a trace of 
 albumin. 
 
 I have already mentioned the frequency with which gall-stones 
 complicate diabetes mellitus. 
 
 On postmortem examination the liver often appears normal to 
 the naked eye and on microscopic examination. In other numer- 
 ous cases the liver is slightly enlarged, probably as a result exclu- 
 sively of dilatation of the vessels. The hyperemia is of the active 
 kind. The veins usually are not distended, but the arteries and 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. I 1 3 
 
 capillaries are distinctly so, and the organ presents a more or less 
 rosy color, often limited to certain parts. In some cases the vessels 
 may be dilated " ex vacuo " as a result of atrophy of the Hver-cells 
 (Armanni). Now and then one finds what Hanot has described as 
 a liver " couleur chamois," with a reddish-yellow color, and the 
 intralobular veins distended. Simple atrophy, with diminution in 
 size and a brownish-yellow color, is not rare. The same can be 
 said of the typical fatty liver. Under these conditions the gly- 
 cogen, which is always likely to be diminished, especially in cases 
 of severe glycosuric dystrophy, reaches its lowest figures (Boc- 
 cardi). Cirrhosis, moderately developed, is not rare, but rarer than 
 any of the other states mentioned. Abscess, probably somewhat 
 more frequent in association with than independently of diabetes, 
 is, nevertheless, quite exceptional. When the fatal issue has been 
 immediately preceded by high fever, the parenchymatous change 
 designated by the Germans as cloudy swelling is found in cases of 
 diabetes, as under other conditions. 
 
 Boccardi observed in dogs, after extirpation of the pancreas, 
 hyperemia of the liver, but no true hypertrophy. Atrophy or 
 fatty degeneration quickly came on. While the nucleus remains 
 perfectly visible, vacuoles are discernible in the protoplasm, as after 
 arsenical poisoning (Steinhaus, Gianturco, Sampacchia). The vessels 
 become markedly dilated, partly, at least, in consequence of an in- 
 fluence " ex vacuo "; and small hemorrhages occur, especially near 
 the surface. Boccardi found also in the liver diabetic desquamative 
 endarteritis, but not the hyaline necrosis observed in the spinal cord 
 (Boccardi), in the kidneys (Armanni), in the pancreas (Saundby), 
 and in the liver (Ferraro). 
 
 Roque, Devie, and Hugonenq found here and there among the liver-cells 
 crystals which they believed to be leucin or tyrosin. 
 
 Bonome,* after extirpation of the celiac ganglion, noted neuro- 
 paralytic dilatation of the vessels and hemorrhage and atrophy of 
 the lobules ; i. e., a state similar to which Boccardi found in the 
 liver of dogs after extirpation of the pancreas. 
 
 The spleen may be mentioned here on account of its relation to 
 
 * " Riforma Med.," 1842. 
 
I 1 4 DIABETES MELLITUS AND GLYCOSURIA. 
 
 the liver. It is, like all the abdominal organs, often hyperemic and 
 somewhat enlarged. Clinically, distinct enlargement is of import- 
 ance, as it may strengthen a doubtful diagnosis of incipient cirrhosis 
 of the liver. In advanced diabetic marasmus the spleen is often small 
 and flabby, and it participates in the general atrophy. 
 
 Urinary Organs. 
 
 The kidneys are often slightly changed in diabetes, but compara- 
 tively rarely show excessive alterations. 
 
 Fully a third, perhaps more, of all diabetic patients show albu- 
 minuria. The albumin in most cases is present only in traces, or 
 at least in small quantities, and it usually does not reach so much 
 as one part in a thousand. Almost all patients, who have lived 
 for some time within the severe stage, present some albumin- 
 uria, which in the mild stage occurs only in a small minority of 
 cases. 
 
 Slight albuminuria in a diabetic patient is usually considered of 
 less clinical and prognostic significance than under other conditions; 
 and in the presence of conflicting therapeutic indications, as between 
 the kidneys and the glycosuric dystrophy, physicians generally 
 regard chiefly the latter. In some cases the albuminuria is an 
 effect of stasis in the kidneys from the weakness of the heart that 
 is common among diabetics. In cases that have reached the severe 
 stage it is often undoubtedly of toxic origin, resulting from the 
 irritation of the kidneys in consequence of the " acidosis." Arterio- 
 sclerosis per se also not rarely causes some degree of albuminuria 
 without the presence in the urine of epithelial elements from the 
 kidneys ; such vascular changes are likely to be found earlier in 
 life in diabetics than is usual in others. Further, true nephritis is 
 not rare in diabetes. As Grube correctly remarks, it is usually a 
 form of mixed parenchymatous and interstitial character ; casts can 
 then usually be found without difficulty in the urine. (From the 
 presence in the urine of hyaline casts no conclusions as to more 
 profound alterations are to be reached, as such formations are 
 extremely common, especially in senile individuals, in connection 
 with or independently of true nephritis.) The typical gouty 
 kidney is occasionally found. It sometimes causes no albuminuria, 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. II 5 
 
 but only polyuria, the urine being of low specific gravity, and 
 containing only small quantities of glucose. 
 
 Like almost all writers on diabetes, I have a number of times 
 observed the curious change in the glycosuria that takes place in 
 cases with cirrhotic processes in the kidneys. As the arterial 
 pressure and the quantity of the urine increase and the specific 
 gravity falls with the advancing cirrhosis, the glycosuria ceteris 
 paribus slowly but quite considerably grows less marked. The 
 same patient that in the incipient stage of interstitial nephritis with 
 a fixed supply of carbohydrates excreted twenty grams of glucose 
 in the twenty -four hours, may five years afterward, under the same 
 conditions, excrete only one gram of glucose. Such cases may 
 finally resemble the rare combination of diabetes insipidus with 
 insignificant but pathologic traces of glucose in the light, abundant 
 urine. The state of the glycemia in these cases can not at present 
 be considered settled, and the result of injections of phloridzin 
 in patients with interstitial nephritis is still uncertain (Klemperer 
 versus Magnus-Levy, Naunyn, and others). Naunyn, in his recent 
 work, expresses the opinion that the curious increased tolerance 
 for carbohydrates in cases of diabetes complicated with chronic 
 interstitial nephritis is only an analog to the same tolerance 
 observed in all cases in which diabetes is associated with some 
 other severe organic disease attended with cachexia and marasmus. 
 Still, I have seen cases in which the cirrhotic process in the kidneys, 
 though developed, has left a fairly good general state of health, 
 and in which this increased tolerance has been perfectly evident. 
 Concerning the influence of the kidneys on glycosuria, reference is 
 made for further particulars to what is said in chapter iii on renal 
 glycosuria. 
 
 Diabetics are often gouty, and gouty patients often suffer from 
 renal calculi, which are not rare in diabetes of the mild "lithemic " 
 type. Budde found 28 cases of nephrolithiasis among 256 
 diabetics. 
 
 Otherwise, diseases of the urinary organs do not occur much 
 more frequently among diabetic patients than among others. 
 Schmitz, who sometimes gathered amazing statistics, quite in- 
 correctly mentions cystitis as a common complication. Senator, 
 Fr. Miiller, Guiard, and others have seen pneumaturia ; Ernst, 
 
Il6 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Naunyn, and Hartge have found microorganisms (leptothrix, sar- 
 cina) in different parts of the urinary tract. Such vegetations easily 
 occur in places in which the sweet urine comes in contact with the 
 air, but the germs do not, as a rule, spontaneously ascend the 
 urethra, and complications of this kind are comparatively rare. 
 
 The kidneys show after death distinct and frequent, but not con- 
 stant and not marked, changes. With the naked eye generally 
 some enlargement and hyperemia of the whole organ is appreciable. 
 On section the cortex often presents some slight fatty and opaque 
 change of color ; and the glomeruli are enlarged, while the 
 medulla is distinctly hyperemic. Next in frequency to these con- 
 ditions the kidney is found without distinct changes. Advanced 
 parenchymatous or interstitial alterations are exceptional. The 
 nephritis of diabetics usually represents a slight development of 
 morbid processes both in the interstitial and in the parenchymatous 
 (epithelial) tissue. Sometimes changes like those of the large 
 white kidney are seen, but I know of no typical case of this kind. 
 
 Under the microscope some degree of fatty degeneration may be 
 found, especially marked in the convoluted tubules, but only rarely 
 developed to such a degree as to obliterate the nuclei or other- 
 wise to compromise the integrity of the cells. 
 
 Fichtner, in 1888, described the curious appearance of a trans- 
 verse section of the convoluted tubules showing large particles of fat, 
 arranged like a string of pearls, in the degenerated epithelial cells 
 along the basement membrane. Besides, fatty particles are found 
 strewn all over the section of the cells, which, however, almost 
 always retain their structure. 
 
 The most characteristic (frequent, but not constant) microscopic 
 change is represented by what Armanni * designates hyaline meta- 
 morphosis, Ebstein hyaline necrosis, and Straus vitreous degenera- 
 tion. I believe that all these designations denote the same thing, 
 
 * Armanni was the first to describe this curious change, which he considered a meta- 
 morphosis of leukocytes that had entered the tubes : " II est peu probable qu'il s'agisse 
 d'une metamorphose speciale des Elements epitheliaux," he says in the French edition of 
 Cantani's work. The Germans were the first to interpret correctly the change as one of the 
 epithelial cells. See the works of Frerichs, Straus, Marthen, Albertoni and Pisenti, 
 Trambusti and Nesbi, Ferraro, Obici, Boccardi. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 11/ 
 
 which also is identical with what Frerichs and Ehrlich described as 
 enlarged, polygonal, hyaline, epithelial cells, as found in Henle's 
 tubes. Frerichs and Ehrlich did not, however, consider the change 
 a necrosis, the nuclei in their cases always retaining the property of 
 taking the stains distinctly. They laid especial stress on the brown 
 reaction with Lugol's solution, distinct even to the naked eye, 
 especially in the limiting zone, in the section of the kidney, and de- 
 noting marked infiltration with glycogen. Later investigations leave 
 scarcely any doubt that the hyaline metamorphosis that is probably 
 found in several organs besides the kidneys, and perhaps even apart 
 from diabetes, is an independent occurrence, and may exist without 
 any infiltration with glycogen, which substance, however, seems to 
 have a predilection for the altered cells in the loops of Henle. 
 
 Marthen * noted that van Gieson's stain (hematoxylin and picric acid) col- 
 ored the hyaline contents of the enlarged polygonal cells a vivid red. Alber- 
 toni and Pisenti observed hyaline metamorphosis in dogs, both in the straight 
 tubes and in the convoluted tubules, after large doses of acetone (?) ; and Tram- 
 busti and Nesbi noted the same conditions after continued large doses of 
 phloridzin, Pisenti and Acri, according to my opinion without sufficient rea- 
 son, distinguish between Armanni's hyaline metamorphosis, which they con- 
 sider identical with Frerichs' and Ehrlich's cells with intact nuclei in the isth- 
 mus of Henle's loops, and Ebstein's hyaline necrosis in the convoluted tubules, 
 which disintegrates the nuclei of the cells. 
 
 Boccardi often found the kidneys normal in dogs that became 
 diabetic after extirpation of the pancreas, but sometimes found the 
 vessels and the tubules dilated ; the interstitial tissue somewhat in- 
 creased, least in the cortex, most in the limiting zone ; Bowman's cap- 
 sules with thickened epithelium, desquamation of the endothelium, 
 and immigrated white blood-corpuscles ; glomeruli either enlarged 
 or atrophic ; epithelial cells in a state of fatty degeneration, which 
 sometimes went so far as to disintegrate ; hyaline degeneration with- 
 out any glycogenic infiltration in 3 of 40 cases ; in the arteries 
 the adventitia thickened and the intima exfoliated. 
 
 The sexual organs in cases of diabetes often undergo functional 
 and other changes. 
 
 Impotence has already been mentioned among the nervous symp- 
 
 *" Arch. f. path. Anat.," 1895. 
 
I 1 8 DIABETES MELLITUS AND GLYCOSURIA. 
 
 toms. It is rarely absolute, apart from advanced senility ; but 
 " facultas coeundi " is often distinctly weakened from the moment 
 the glycosuric dystrophy, however mild, makes its appearance. In 
 rare cases sexual vigor remains normal. 
 
 Sterility is common and does not depend on " impotentia coeundi," 
 as it exists also in women. The cause must rather be looked for 
 in some influence exerted by the excess of sugar or by toxins in 
 the blood, on the sperm and on the ova, or in atrophy of the testi- 
 cles, or the ovaries, or in the diabetic metritis of which Lecorche 
 speaks. Still, both diabetic men and women may produce chil- 
 dren, and sometimes conception takes place even in the severe 
 stage. Pregnancy in a diabetic woman is often interrupted by mis- 
 carriage in the fourth or fifth, or as late as the seventh, month 
 (Seegen, Gaudard). Further, pregnancy, which sometimes per se 
 causes glycosuria or true diabetes, often accelerates the progress of 
 an existing diabetes. The mortality among both mothers and new- 
 born children is very great. Of the latter, 41 in every 100 die soon 
 after birth (Gaudard). 
 
 I have seen two cases of diabetes in which orchitis appeared as 
 a complication without obvious cause. 
 
 Those parts of the diabetic patient's skin that often are moist- 
 ened by the sacchariferous urine readily become the seat of vege- 
 tation for a small flora of low fungi, which cause eczema, excori- 
 ations, pruritus, and, especially in the labia majora, sometimes a 
 series of furuncles. Vulvitis in women, balanitis, balanoposthitis, 
 and sometimes phimosis in men, are induced, and recur readily if 
 not restrained by the use of antiseptic lotions. Both in men and 
 in women the irritation thus caused gives rise to the development 
 of papillomatous excrescences, which are known to have changed 
 into epitheliomata (Naunyn). 
 
 Straynowski mentions atrophy of the uterus and of the ovaries 
 as occurring in diabetic women. Analogous changes in the testicles 
 may be quite distinct in marantic cases in men. 
 
 Organs of Special Sense. 
 
 Diseases of the eyes are extremely common in diabetics, and there 
 is no part of these organs that has not been named as the seat of 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. II9 
 
 pathologic processes caused by the glycosuric dystrophy. Though 
 most of these diseases develop only after the diabetes has existed 
 for a long time, they not rarely constitute the primary reason for 
 the patient's seeking medical aid, and they thus lead to the dis- 
 covery of the dystrophy. It has been said that two-thirds of all 
 diabetic patients suffer from some affection of the eye. This esti- 
 mate must certainly be based upon hospital statistics and upon 
 observations among severe cases, as in private practice, with its 
 large number of mild cases, the proportion is much smaller. All 
 the deleterious influences already named as belonging to the gly- 
 cosuric dystrophy are efficient with regard to the eye, but the 
 toxins in the blood in many cases play the most important role ; 
 and some of the diabetic affections of the eye are very similar to 
 those that occur during long-continued poisoning with alcohol or 
 tobacco, or to those that may be produced in quite a short time by 
 injections into the blood of common salt, sugar, naphthalin, and 
 other substances. 
 
 The most frequent diabetic affections of the eye are cataract^ 
 anomalies of accommodation (especially premature presbyopicL), retin- 
 itis, and inflammation of the optic nerve. 
 
 Diabetic amblyopia or amaurosis, iritis and iridocyclitis, opacities 
 in the vitreous body, processes in the cornea and sclera, paralysis of 
 the muscles, and some other dystrophic troubles are less common.* 
 
 Diabetic cataract generally develops after the dystrophy has been 
 present for many years, but in exceptional cases and in the specific 
 soft form it may appear after a few weeks ; this happens especially 
 in children. The affection is almost always bilateral, and is found 
 in both stages of diabetes, although it is more frequent in severe 
 cases, without bearing any fixed relation to the intensity of the 
 diabetes. 
 
 Weir Mitchell caused cataract in frogs by subcutaneous injections 
 
 * For more extensive information on diabetic affections of the eye, reference may be 
 made to the works of Leber, Grsefe, Foerster, Jacobson, Wiesinger, Bouchard, Schirmer, 
 Knies, Hirschberg, Schmidt-Rimpler, O. Becker, Deutschmann, Berger, Papanikolau, 
 and others. The essential facts can be found in the " Archiv fiir Ophthalmologie. " The 
 notes of my own cases are incomplete with regard to the ocular state, as I always refer 
 the patient for this information to the best specialist at hand. 
 
I20 DIABETES MELLITUS AND GLYCOSURIA. 
 
 of sugar ; Richardson noted the same result in frogs and fishes by- 
 keeping them in a dilute solution of sugar ; and cataracts have 
 since been induced in rabbits and frogs by introducing sugar into 
 the fold of the conjunctiva. Thus, there can be no doubt as to 
 the efficiency of the hyperglycemia to bring about cataract, 
 whether it be due to direct irritation of the tissues of the lens or 
 to their desiccation. The cataracts induced artificially begin by 
 the formation of vacuoles in the cells ; and this may also be the 
 case with diabetic cataract before proliferation and disintegration 
 of the cells take place. The diabetic changes in the vessels, with 
 local nutritive disturbances, the marasmus, and other common 
 influences, may contribute to the result, and may in many cases, 
 especially in those not representing the typical diabetic soft cataract, 
 be the chief etiologic factors. The hypothesis of the formation 
 of lactic acid in the aqueous humor of the eye has been abandoned, 
 since investigations have proved this liquid always to be alkaline. 
 In the liquids of the eye, in the lens, and in the vitreous body, 
 where glucose also has been found apart from diabetes, this sub- 
 stance seems to be increased when diabetes develops (Deutsch- 
 mann, Gorlitz, Hedon and True). 
 
 Typical diabetic cataract, which is the customary variety in 
 young persons with severe diabetes, is of the soft kind. The 
 process begins, according to Knies, in the small polygonal cells on 
 the posterior aspect of the anterior part of the capsule of the 
 lens ; the adjacent cellular elements of the lens next begin to 
 undergo changes. Becker states that opacities appear at first in 
 the equatorial zone, then in the posterior, and afterward in the 
 anterior, cortical substance. Whether the first change begins 
 behind or in front, it is certain that, contrary to what takes place 
 in the common senile cataract, the most superficial parts of the 
 cortical substance are the first to undergo change in the develop- 
 ment of the typical diabetic cataract. The first macroscopic mani- 
 festation of this is the appearance of a milky layer in the field of 
 the pupil ; then the whole mass of the lens whitens, and mother-of- 
 pearl-like patches become visible therein. The entire development 
 and appearance of this typical, soft, diabetic cataract strongly 
 resemble what Bouchard has described in speaking of the experi- 
 mental cataract caused by naphthalin. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 121 
 
 The soft cataract is, however, by no means the only variety 
 found in diabetic patients, and so far as my experience goes, it is 
 not even the most frequent. In elderly diabetics one often finds 
 the usual variety of senile cataract, with central, yellowish sclerosis, 
 and bluish-gray, radial streaks between this and the still normal 
 peripheral parts of the lens and (before the maturity of the cataract) 
 the shadow of the iris, etc. There is good reason to believe that 
 these changes are favored by the glycosuric dystrophy, and that 
 they, hke diabetic gangrene, are an expression at the same time of 
 diabetes and of senility. 
 
 Konig found among 500 diabetic patients only 10 cases of cata- 
 ract. Most other writers made the proportion higher. I have 
 certainly seen more than 10 cases of cataract in association with 
 diabetes, though I have not yet reached 500 cases of the latter. 
 This may be due partly to the fact that several cases from Dr. 
 Nordenson's extensive clinical material have been referred to me in 
 Stockholm. I suppose that among diabetic patients in Carlsbad 
 from three to four per cent, exhibit cataractous changes. 
 
 Sometimes, and especially in severe cases of diabetes, one finds' 
 that the visual near-point, even in young persons, grows more and 
 more remote, and that premature p7'esbyopia develops. This con- 
 dition has been attributed to marasmus, with its weakening influ- 
 ence on the muscles of accommodation, to alterations in the vessels, 
 to neuritic processes, and to hemorrhages. Diminished elasticity 
 of the lens may also be a contributing cause. 
 
 Mydriasis may arise from toxic influences. In the presence of coma the 
 sphincter of the pupil may be seen to resist and to react in quick succession to 
 the paralyzing influence of the poisons in the system. Still, the pupils in dia- 
 betic persons may be large altogether independently of diabetes— " Cette dilata- 
 tion des pupilles, associee le plus souvent aux symptomes de depression est un 
 bon signe des etats neurastheniques," says Bouveret (" La Neurasthenie "). 
 
 Myopia from the tumefaction of the lens is the most frequent anomaly of 
 accommodation in cases of diabetes, if it develops in middle age or later. This 
 fact should be borne in mind, and the urine in such cases of myopia should 
 always be examined for glucose. 
 
 Hypermetropia is mentioned by Horner as occurring in associa- 
 tion with diabetes. 
 9 
 
122 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Diabetic retinitis (elaborately described by Hirschberg) belongs 
 in general to one of two groups, and may be either exudative or 
 hemorrhagic. 
 
 Exudative diabetic retinitis — retinitis diabetica centralis punctata — 
 presents small, glossy, nonpigmented exudations around the 
 central portion of the retina. The exudates have uneven borders 
 without being so distinctly stellate as the exudates of albu- 
 minuric retinitis ; here and there a small point of blood may be 
 visible. There is no discoloration of the papilla ; if there is, a 
 renal complication and albuminuric retinitis should be suspected. 
 
 Hemorrhagic diabetic retinitis is characterized by the presence of 
 a number of ecchymoses of varying size distributed over the retina. 
 They sometimes cause amblyopia and occasion quite a dubious 
 prognosis, as they often represent only a part of hemorrhages 
 extended over different regions of the central nervous system. I 
 have seen them attended with serious symptoms, sometimes even 
 with perfect loss of consciousness. They often occur successively 
 over some length of time, and they may be found in all stages in the 
 same eye, as recent hemorrhages and as whitish residual patches. 
 I consider these small retinal hemorrhages as analogous in type to 
 the small hemorrhages in the brain, which I suspect to be frequent 
 in inveterate cases of diabetes, and which often may be unattended 
 with manifest symptoms. 
 
 Diabetic optic neuritis is so much like the neuritis due to alcohol 
 or tobacco that its diabetic nature has been called in question even 
 in recent times {e.g., by Mauthner). Still, Schmidt-Rimpler found 
 this complication in 34 among 140 cases, and Leber in 14 among 
 50 cases of diabetic disorders of the eye, and it can not be doubted 
 that inflammation of the optic nerve is not uncommon in inveterate 
 cases of diabetes independently of both alcohol and tobacco, 
 though it often escapes detection. When developed, it presents a 
 central scotoma, with deficient color-perception, corresponding to 
 the macular part of the optic nerve, and a whitish discoloration 
 of the temporal part of the papilla. The differentiation from 
 neuritis due to alcohol or tobacco can be made only from the his- 
 tory ; in some cases all three causes may contribute to the result. 
 Peripheral contraction of the field of vision and atrophy and dis- 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 23 
 
 coloration of the entire papilla may ensue. Diabetic optic neuritis, 
 though it often exhibits temporary improvement, has a worse prog- 
 nosis than the analogous affections caused by alcohol or tobacco, 
 which, as is well known, are themselves quite obstinate, even after 
 the removal of their causes. 
 
 Amblyopia and amaurosis may arise in the course of diabetes 
 from such alterations within or without the eye as ordinarily give 
 rise to them, but they may also result from the action of diabetic 
 toxins (Leber). In the latter event the danger of corna is never to 
 be lost sight of. In the last case of this kind that I have treated 
 exceedingly elaborate investigation by Dr. Nordenson failed to dis- 
 close any other than a toxic cause ; the deflection of the ray of 
 polarized light to the left, due to /5-oxybutyric acid in the urine, 
 equaled a little more than 0.5 degree with Hoppe-Seyler's instru- 
 ment. The patient died about two months afterward in coma. 
 
 Diabetic iritis * is a torpid, suppurative process without ulceration 
 of the cornea ; it usually appears in both eyes, and is observed in 
 advanced cases. Leber noted hypopyon in two among nine cases. 
 A fibrinous deposit over the whole pupil was present in several 
 cases, but disappeared quickly and completely under the influence 
 of sodium salicylate. In some cases only an adhesive iritis is 
 found, with synechiae. Finally, there seems to exist exceedingly 
 torpid forms of the disease, which develop almost imperceptibly 
 until they cause a change in the color of the iris. The whole pro- 
 cess may lead to atrophy of the iris, sometimes to glaucoma. 
 
 The choroid may participate in the process and cause opaci- 
 ties in the vitreous body. Leber observed detachment of the 
 choroid. 
 
 Hemorrhages and opacities in the vitreous body have their origin 
 in the retina or in the choroid. 
 
 Diabetic keratitis presents itself as a parenchymatous inflammation 
 of neuroparalytic character, and may lead to ulceration and 
 suppuration. 
 
 * Leber, " Arch. f. Ophthal.," 1885. 
 
124 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Scleritis and episcleritis are also mentioned, but their relation to diabetes 
 seems undecided. 
 
 The eyelids may become the seat of Jiordeobnn, cJialazion, 
 eczema, or herpes. HeviorrJiages in the conjunctiva are considered 
 to be an effect of diabetes and a special reason for analysis of the 
 urine. 
 
 The intracranial hemorrhages that are likely to complicate dia- 
 betes of long standing sometimes cause paralysis of the muscles of 
 the eye, and any one that has seen a large number of diabetic 
 patients must also have seen such disturbances of function on the 
 part of the abducens, the oculomotor, the trochlear, or the facial 
 nerve, with strabismus, lagophthalmos, ptosis, etc. In some cases 
 rapid absorption and complete restitution take place. I have also 
 seen paretic symptoms remain for several years and for the re- 
 mainder of the patient's life. 
 
 Being constantly on the alert for the many severe diseases of the 
 eye that threaten the diabetic patient, one is likely to overlook 
 symptoms of a purely neurotic and less dangerous nature. If, how- 
 ever, the physician makes it his custom to ask concerning such 
 symptoms, and sometimes even if he does not, he will gain infor- 
 mation indicating the frequency, also in this field, of neurasthenic 
 symptoms in cases of diabetes. The practitioner who is not well 
 versed in the use of the ophthalmoscope will often find difficulty 
 in excluding organic disease. Sometimes neurasthenic asthenopia, 
 with local subjective sensations and deficiency of endurance in the 
 use of the eyes, is observed. Many diabetics display marked hyper- 
 esthesia for light. 
 
 Diseases of the ears'^ are much rarer complications of diabetes than 
 diseases of the eyes. Central disturbances of the acoustic nerve, 
 whose center is quite near to the situation of Bernard's puncture, 
 are exceedingly rare. 
 
 Otitis follicularis externa, or furuncle of the external auditory 
 
 *See Kuhn, " Archiv f. Ohrenkr.," Bd. xix ; Kirchner, " Deutsche med. Wochen- 
 schr.," 1887 ; Korner and v. Wildt, " Zeitschr. f. Ohrenheilk.," Bd. xxiii. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 125 . 
 
 canal, is undoubtedly more common in diabetics than in other indi- 
 viduals. 
 
 Otitis media diabetica sometimes leads to suppuration of the 
 internal ear and its osseous parts, and one now and then sees 
 patients with scars after operations in the mastoid region. Inflam- 
 mation of the middle and internal parts of the ear may cause 
 meningitis, but few such cases are recorded ; and these processes in 
 the ear, which owe their origin to bacteria (streptococcus, staphylo- 
 coccus, etc.), scarcely occur in more than one per cent, of all cases 
 of diabetes. 
 
 I have had under observation a rare and interesting case of trauma of the 
 inner ear in a case of diabetes. Mr. , a Scandinavian merchant, sixty- 
 six years old, had suffered from diabetes for about eighteen years. He was in 
 the mild stage of the dystrophy, and the glycosuria disappeared when the car- 
 bohydrates were restricted to about thirty-five grams. I was called early one 
 morning to the patient, who had fallen out of bed during the night, and somehow 
 had been struck on the left side of the head by a basin filled with water that 
 had fallen over him. The left tympanic membrane had ruptured and the 
 pillow was stained with serous liquid slightly mixed with blood. The pulse 
 was at least normal in frequency, and thus indicated no irritation of the pneu- 
 mogastric nerve. There were no symptoms referable to the eyes, but the 
 patient presented a cotnplete inability to maintain equilibriutn. I supposed a 
 fissure through the labyrinth and the semicircular ducts had taken place. 
 During proper local and general treatment the patient otherwise recovered in 
 the course of some weeks, but the inability to maintain equilibrium, subsiding 
 very slowly, remained for several months. 
 
 Ordinary functional nervous troubles of auditory character are 
 not absent. The diabetic patient often exhibits a marked acoustic 
 hyperesthesia, which sometimes causes him to make elaborate ar- 
 rangements to avoid noise. Subjective acoustic perceptions, espe- 
 cially during the night (tinnitus aurium, etc.), are not rare. Otalgia 
 is sometimes complained of The cause may then be looked for in 
 the teeth, which are so commonly carious in diabetes. In other 
 cases the otalgia is only a secondary manifestation of an extensive 
 neuralgia in the distribution of the fifth pair of nerves (auriculo- 
 temporal branch), or of neuralgia in the distribution of the occipital 
 'or the auricularis magnus nerve. The differentiation must then be 
 made between a merely nervous and a rheumatic affection. Rheu- 
 matic infiltrations in the soft parts of the head, which constitute one 
 
126 DIABETES MELLITUS AND GLYCOSURIA. 
 
 of the most attractive hobbies of the professional masseur, may be 
 the cause. Sometimes pruritus or hyperesthesia or paresthesia of 
 the outer ear is spoken of 
 
 The skin often presents local or general changes. 
 
 General changes are observed in the severe stage or in advanced 
 cases in the mild stage. I have already mentioned the diminished 
 secretion of the sebaceous and the sudoriferous glands — the astea- 
 tosis and the anhidrosis — and the resulting marked dryness of the 
 skin. The cause of this condition resides not only in the more 
 tenacious retention of the water of the blood within the vessels by 
 reason of the hyperglycemia, but also in the atrophy of the skin, not 
 rarely found in the severe stage, especially on the hands, and still 
 more often in the face, where one observes the change that, in its 
 fully developed state, is called " glossy skin." The skin is mani- 
 festly thin, and there is a marked, circumscribed, cyanotic redness 
 of the cheeks. 
 
 It is in such cases that diabetic pruritus is best marked. It is 
 usually much less intense than in cases of icterus, for instance, and 
 it rarely constitutes a serious annoyance. 
 
 I have already mentioned the furuncle, the carbuncle, the " mal 
 perforant" and Raynaud's disease, the different forms of diabetic 
 gangrene and the different forms of eczema, and other changes that 
 result when the skin is often moistened by the urine. It is chiefly 
 these latter eruptions that the French call " diabetides," which 
 appellation should not suggest an idea of anything pathognomonic. 
 
 So far as I know, there is not a single change in the skin in 
 diabetes that may not occur apart from this dystrophy. This is 
 true even of the rare " xanthoma tuberosum diabeticum," observed 
 hitherto, in all, in about thirty cases. The one case that I have 
 seen presented the customary solid, yellowish-red excrescences, as 
 large as peas, distributed in considerable numbers chiefly on the 
 extremities. They were most numerous over the triceps muscle on 
 the upper part of the arms and over the extensors on the lower 
 part. A few were to be seen on the flexor aspect. On the legs 
 they were exceedingly numerous over the quadriceps femoris, 
 especially in the vicinity of the knee-joint. A few were to be 
 seen on the outer sides of the calves and on the dorsal aspect of the 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 12/ 
 
 tibiotarsal joint. There were a few on the shoulders and on the 
 neck, and one in the left external auditory canal. Neither in 
 their distribution * nor in any other feature could I discover any 
 difference from what I have seen of " xanthoma tuberosum " 
 attending icterus. The patient was a man twenty-eight years old, 
 suffering from severe diabetes, without icterus. 
 
 The formations that Kaposi calls " dermatitis papulosa diabetica^ with ex- 
 crescences in patches on an inflamed base, may probably also be seen inde- 
 pendently of diabetes, in association with which they are extremely rare. 
 
 Besides the skin-diseases already mentioned, diabetic patients 
 frequently yield the dermatologist varied clinical material. I have 
 seen erythema, urticaria, lichen, acne, impetigo, rupia, herpes (in- 
 cluding herpes zoster^, pemphigus, pityriasis, ichthyosis, psoriasis, all 
 sorts of eczema, petechice. Purpura hemorrhagica (Dujardin-Beau- 
 metz) and pityriasis rubra (Harden) have been mentioned. For 
 some of these affections we may look to the marasmus as the chief 
 cause. In other cases the hyperglycemia may be efficient. In a 
 great many instances the connection with diabetes may consist only 
 in the angioneurotic constitution common in diabetic patients, who, 
 in fact, often mention that they suffered from their cutaneous 
 troubles long before glycosuria arose. 
 
 The hair of diabetic patients offers two peculiarities : in conse- 
 quence of the asteatosis and anhidrosis it is often dry, and therefore 
 presents a ragged appearance; and it is" often prematurely gray, f 
 Diabetes may have some influence in causing baldness, and " de- 
 fluvium capillorum " is mentioned by more than one writer on 
 this subject. Marked effects of this kind are not conspicuous, and I 
 
 * The distinction between diabetic and icteric xanthoma is said to be that the former 
 is equally spread over the whole body, while the latter is distributed as in my diabetic 
 patient. Kaposi does not acknowledge the existence of a specific diabetic xanthoma. 
 
 t Susruta, about 1200 years ago, mentioned a peculiar, wild appearance of the diabetic 
 patient's hair. I suppose that the gray hair has no direct connection with diabetes, but 
 depends on the great emotional sensitiveness common among diabetic patients. The 
 curious and sometimes remarkably sudden influence depressing emotions have in this 
 respect is well known. Thus, it is related that a Hindu suddenly turned gray just 
 before his execution during the great mutiny (" Ind. Med. Times and Gazette," 1859) ; 
 as did also Ludovico Sforza when he was taken prisoner, and Guarini da Verona when 
 he lost his Greek manuscripts. (See H. C. Wood, "Nervous Diseases," Philadelphia, 
 1887.) 
 
128 DIABETES MELLITUS AND GLYCOSURIA. 
 
 know many patients who, after long years of abundant glycosuria, 
 still keep a luxuriant growth of hair on their heads. 
 
 The nails sometimes show distinct alterations. Paronychia is not 
 rare and sometimes causes the nails to fall out. In other cases the 
 nails change without any cause whatever discoverable to the naked 
 eye. They become thick, brittle, discolored and brownish, markedly 
 curved in both directions, and may then fall out. It seems to 
 me that this occurs chiefly in inveterate cases complicated with 
 gout, and in cases with distinct neuritis. It is certain that such 
 changes are not related to the intensity of the diabetes, and one 
 often finds the nails on the hands and feet perfect in patients toward 
 the close of life after years of the dystrophy in its severe stage. 
 
 Organs of Locomotion. 
 
 The patient in the mild stage of diabetes is generally an indolent 
 person, of sedentary habits, to whom the physician must preach 
 long sermons as to the utility and the necessity of bodily exercise, 
 and whose muscular strength and endurance usually are much 
 smaller than seems indicated by his often robust appearance. The 
 diabetic patient in the severe stage often drags himself along with 
 an unsteady gait, and is made excessively tired by exercise that con- 
 stitutes a daily salutary habit in healthy persons, but which in some 
 cases of diabetes may be sufficient to cause coma. A patient of 
 this kind will rise late and go early to bed, and his lassitude, his 
 feeling of excessive muscular weakness, will sometimes even keep 
 him in bed throughout the twenty-four hours. 
 
 The muscular neurasthenia is partly the cause of the diabetic's 
 constant feeling of tiredness. The dryness of the muscular tissues 
 — much dwelt upon by Dieulafoi — probably is an important causa- 
 tive factor in cases of marked hyperglycemia. The excessive 
 amount of sugar in the blood in a similar manner also directly 
 affects the motor nerves. In marantic cases the vmscles often are 
 extremely atrophic and reduced to ribbon-like proportions, of 
 which no great mechanical effects can be expected. 
 
 The bones in cases of severe diabetes have been found remarkably 
 light and porous, and fractures often heal slowly and imperfectly. 
 The enormous amount of those salts that enter into the constitution 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 29 
 
 of the bones sometimes found in severe cases (v. Ackeren, Fodor) in 
 the urine seems also to denote disintegration in those structures. So 
 far as I know, there have been no systematic investigations of these 
 processes and of the consequent osteoporosis in diabetes. Charrin 
 and Guignard, with many others, accept the existence of this dia- 
 betic osteoporosis and believe it due to the acidosis. Considering 
 that the acids only diminish, but never entirely neutralize, the alka- 
 linity of the blood, I am more inclined to believe in a general mar- 
 antic or in a purely trophic influence, analogous to that observed 
 by Kassowitz in the bones of rabbits' legs after section of the sciatic 
 nerve. 
 
 As there are to be found all stages between a normal power of 
 assimilating carbohydrates and the greatest possible reduction of 
 that power, so also, with regard to the general clinical picture, there 
 are all possible intermediate gradations between the healthy indi- 
 vidual and the patient approaching diabetic coma. There are, 
 especially, many persons who live on the border-land between what 
 may still appropriately be called the mild and the severe stage, 
 and there may be only a slight clinical difference between a patient 
 who is free from glycosuria during abstinence from carbohydrates 
 and one who even under such dietetic conditions excretes a few 
 grams of glucose in the course of the twenty -four hours. If, however, 
 a patient is selected from the middle of each of the two stages, quite 
 marked clinical differences will generally be found between these 
 two representatives of the glycosuric dystrophy. 
 
 The history often presents remarkable points of difference. Mild 
 diabetes is often discovered by mere accident ; e.g., on examination 
 for life-insurance. In other cases neurasthenic symptoms, or some 
 local trouble, or some slight signs of dystrophy guide the sus- 
 picions of the physician in the right direction. The diabetic 
 symptoms, if there are any at all apart from the glycosuria, have 
 developed gradually, and the dystrophy has only slightly affected the 
 patient, who often is unable to give any definite information as to the 
 time of the beginning of the diabetes. Severe diabetes — often in a 
 short while — changes a state of health into one of marked ill-health, 
 and the patient is often able to name at least the month, and some- 
 times the day, of appearance of the first symptoms. Even in such 
 
130 DIABETES MELLITUS AND GLYCOSURIA. 
 
 cases, in which at first restriction of carbohydrates suppresses the 
 glycosuria, sudden appearance of diabetic symptoms is an unfavor- 
 able sign, and makes probable the future development of the severe 
 stage of the disease. 
 
 The actual state of the representatives of the two classes men- 
 tioned usually presents a number of salient points of difference. 
 The patient with mild diabetes may, even after years, appear as a 
 man of quite fair, sometimes even of florid, health, with a normal 
 complexion, a robust form, and active habits. He is sometimes 
 troubled with adiposity or with gout, almost always with " ner- 
 vousness." He may, however, perform quite important duties in a 
 private or a public capacity, and can easily conceal his diabetes, 
 with its insignificant and vague symptoms, from the world. The 
 severely affected patient, with acid toxins in the blood, — the " acid- 
 osis," — often manifestly presents evidence of that marasmus which 
 constitutes the most essential distinction between severe and mild 
 cases. He is generally thin, often extremely so ; his movements 
 are weak ; his gait uncertain ; the expression of his face either lan- 
 guid and drowsy or uneasy, sometimes desperate ; the complexion 
 either of a cachectic pallor or marked by an unhealthy cyanotic red- 
 ness of the cheeks. His mere aspect reveals his serious state, and 
 his family and friends, even without recognizing the nature of his 
 disease, often realize that his days are numbered. 
 
 Then, the issue in the two stages of glycosuric dystrophy is dif- 
 ferent. Mild diabetes is in no specific way fatal ; if it does not 
 develop into a severe diabetes, the patient will live until stricken 
 by some accidental intercurrent or complicating affection, which, 
 though perhaps less frequently, may occur apart from diabetes, 
 such as acute pneumonia, carbuncle, cerebral hemorrhage, heart- 
 failure, etc. Severe diabetes, however, leads to death in most 
 cases through a specific complication caused by the presence of 
 toxins in the blood. Acetone may exert some slight contributory 
 influence ; the diacetic acid and the low fatty acids, by reason of 
 their small amounts, can not per se bring about the result. The 
 /9-oxybutyric acid, which may be formed in large quantities, is the 
 chief factor in the production of the acid diathesis, the "acidosis," 
 and of the final acute poisoning, which, when once begun, gener- 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. I3I 
 
 ally in a short time leads to paralysis of the nervous centers, and is 
 known as — 
 
 Diabetic Coma.* 
 
 The development of diabetic coma may be excited by some in- 
 considerable depressing incident, such as emotion, fatigue, or a 
 slight indisposition. A common cause, or, perhaps better, a com- 
 mon forerunner, of coma is obstinate constipation, which, after coma 
 has set in, may give way to profuse fetid diarrhea. Coma is, how- 
 ever, promoted not only by all depressing influences, but by any 
 cause that increases the acid diathesis, the acidosis. Every agency 
 that has both these effects is especially dangerous, and I believe 
 that the most frequent immediate cause of coma arises from a too 
 rigid restriction of carbohydrates, with consequent inanition and in- 
 crease of diacetic acid and of /?-oxybutyric acid in the blood. 
 
 A feeling of extreme weakness, of drowsiness, and of headache 
 generally precedes the attack. Sometimes there is complete loss 
 of appetite. Severe epigastric pains, sometimes accompanied by 
 vomiting, are not rare, and may continue for some time before the 
 paralytic stage develops. 
 
 The first manifest, and the most characteristic, symptom of coma 
 is a sudden dyspneic frequency and depth of respiration ; at the 
 same time the frequency of the pulse increases. Respiration fol- 
 lows no distinct type, — especially not the Cheyne-Stokes, — inspira- 
 tion taking place forcibly and deeply twenty or thirty times a 
 minute in a blowing manner, even in cases in which postmortem 
 examination subsequently shows a normal state of the lungs. The 
 pulse runs up to from 1 30 to i 50 or more, becomes extremely small, 
 and can soon be no longer counted. The pupils may be strongly con- 
 tracted. Mental excitation, often of great terror, may precede the 
 depressing symptoms. Sometimes the dyspneic respiration and the 
 
 * Diabetic coma was first described, in 1854, by v. Dusch, but it was little known in the 
 profession until described twenty-one years later by Kussmaul. The majority of my 
 diabetic patients in the severe stage have died in coma. Frerichs, among 250 patients, 
 diabetic at the time of their death, found 150 cases of coma. A. James, of Edinburgh, 
 however, encountered only 24 instances of coma among 50 fatal diabetic cases. In the 
 other 26 cases death was due to pulmonary tuberculosis in 16 and to acute pneumonia or 
 gangrene of the lungs in 8 cases. 
 
132 DIABETES MELLITUS AND GLYCOSURIA. 
 
 quick, small pulse may continue for many hours, or even for days, 
 before paralytic symptoms set in. Sometimes the first stage of ex- 
 citation may pass so quickly and be so little marked, and the par- 
 alytic stage set in so suddenly, that the condition can hardly be dis- 
 tinguished from apoplexy or primary paralysis of the heart. Sooner 
 or later the sensorium becomes clouded ; but even before this is 
 manifest, the speech may denote incipient motor disturbance. The 
 depression is generally supreme, signs of excitation being only 
 slight and of short duration, and spasm being sometimes scarcely 
 perceptible. The extremities become icy cold ; the temperature, 
 which often before the attack was below the normal, now sinks still 
 further. During this period the glucose, the urea, the toxic acids, 
 and the other products of metabolism in the urine may be dimin- 
 ished.* I may refer also to the small casts from the kidneys that 
 Kiilz, among others, found to be numerous and constant (?) during 
 coma. The comatose state may last for days, rarely for weeks, 
 and sometimes only for hours. The average duration of life after 
 the first manifest symptoms have appeared may be estimated at two 
 or three days. Even if the patient, as sometimes happens, almost 
 completely regains consciousness, and all symptoms of comatose 
 depression recede, restitution to the preexisting state — though it is 
 mentioned in literature by trustworthy observers — is extremely rare. 
 When the nervous centers have once been attacked, all treatment, 
 however energetic and quickly applied, almost always fails to bring 
 about permanent recovery, and the physician does well not to let 
 transitory improvement deceive him as to the approaching fatal 
 issue. The last hours are generally quiet, with scarcely any other 
 signs of life than the respiration and the pulse, and dilatation and 
 contraction of the pupils, the latter often asynchronous. 
 
 Diabetic coma is a state of poisoning — there is no doubt about that in the 
 mind of any physician who has once seen it ; but opinions as to the kind of 
 poison differ greatly. At one time the hyperglycemia was suspected as a 
 cause, but I consider this view to have only historic interest. The increased 
 amount of sugar in the blood may reach higher figures in mild cases of diabetes 
 with a free diet than in severe cases with restriction of the carbohydrates ; but 
 mild cases of diabetes — i. e., cases in which glycosuria disappears when caibo- 
 
 * Munzer and Strasser, however, have found the nitrogen in the urine increased dur- 
 ing coma ; the excess may, however, have been produced before. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 33 
 
 hydrates are excluded — do not develop coma. I consider that all reports of 
 such an occurrence are the result of mistake, and represent cases of uremia or 
 of primary heart-failure, etc. Complete exclusion of carbohydrates causes 
 diminution in the hyperglycemia, but notoriously increases (the acidosis and) 
 the danger of coma. Diabetic coma is sometimes not unlike uremia, from 
 which it differs in several respects, and especially in the marked dyspneic 
 respiration, though this may to some extent be present in the final stages of a 
 number of different diseases. Besides, patients die in diabetic coma in the 
 absence of serious changes in the kidneys. The Scotch theory as to fat- 
 embolism in the brain has scarcely any basis at all, and has not survived. 
 From 1857, when Fetters, in a case of coma, found acetone in the blood and 
 in the urine, the theory of acetonemia as the cause of diabetic coma was 
 widely accepted ; but Kussmaul refutes this theory, and Frerichs, in the 
 seventies, Albertoni, in 1884, and others proved that the toxicity of acetone, 
 especially in view of the small quantity produced in diabetes, is insufficient to 
 be considered a cause of death. Fere, in fact, does not consider acetone much 
 more poisonous than ethylic alcohol, which is drunk in such quantities by 
 millions of human beings. 
 
 Gerhardt, in 1865, discovered his most important reaction ; and when Deich- 
 miiller, Tollens, and v. Jaksch had found it to be due to diacetic acid, suspicion 
 fell on this substance; but here, again, the toxicity and the quantity were too 
 small. When acetone and diacetic acid both pass over during distillation as 
 acetone, scarcely ten grams of the latter can be obtained from the daily 
 urine ; and Brieger showed that injection into the blood of twenty grams of 
 diacetic acid left the nervous system perfectly intact. 
 
 Hallervorden had found the quantity of ammonia excreted in severe cases of 
 diabetes enormously increased, and he and Coranda found that this increased 
 ammonia corresponded to an increased excretion of acid. Walther, in 1877, 
 showed that injection of acids into dogs produced a state quite similar to 
 diabetic coma. On this basis Stadelmann, in 1883, made further investigations 
 in cases of severe diabetes, and found what he first considered as a-crotonic 
 acid, but what Minkowski and Kiilz later proved to be /3-oxybutyric acid. 
 Since Kiilz afterward found that the excretion of /?-oxybutyric acid may amount 
 to more than 200 (226.5) grams in twenty-four hours, this acid, not with- 
 out good reason, has been considered to be the principal cause of diabetic 
 coma, though the other acids (diacetic acid and fatty acids of low order), the 
 acetone, and perhaps other still unknown toxins* may exercise a contributory 
 influence. 
 
 In this book I have adhered to the old division of diabetes into 
 a mild and a severe stage, and this I beheve to be the best and 
 most practical, founded, as it is, on the absence or presence of gly- 
 cosuria with abstinence from carbohydrates. Of late, however. 
 
 * Ammonia may be present in increased quantity through the influences of other acids 
 than /3-oxybutyric acid (Rumpf, Strasser, and Miinzer). 
 
134 DIABETES MELLITUS AND GLYCOSURIA. 
 
 another classification has been made, namely, pancreatic, neurogenic, 
 and constitutional diabetes. 
 
 The pancreatic and the neurogenic varieties are considered, as a 
 rule, to form together what I have called severe diabetes, character- 
 ized by its sudden, comparatively acute appearance, its rapid de- 
 velopment, the autophagy, the acidosis, and the frequency of death 
 in diabetic coma. Pancreatic diabetes is distinguished from neuro- 
 genic diabetes by (i) the absence of a nervous, etiologic factor ; (2) 
 the presence of local symptoms referable to the pancreas ; (3) pecu- 
 liar qualities of the feces. 
 
 The absence of a nervous etiologic factor only rarely helps in the 
 differentiation, because almost all human beings have been subjected 
 to such nervous influences as may cause diabetes, and because 
 nothing is more common than an hereditary neurotic predisposition. 
 In rare cases a tumor may be felt in the pancreas during life. 
 Icterus also, when there are no other distinct causes for it, speaks 
 for disease of the pancreas, which per se often causes icterus. Then 
 there are sometimes colicky pains referable to the pancreas (not 
 rarely accompanied by vomiting or by diarrhea) (Fleiner, Licht- 
 heim, Naunyn). These pains may increase in severity for hours, 
 are felt in the epigastrium, and radiate to the back. Sometimes 
 they are observed in cases of calculi in the pancreatic ducts, and 
 the stones, consisting chiefly of phosphates and calcium carbonate, 
 may be passed with the stools (Minnich). Often, when the func- 
 tions of the pancreas are impaired, the feces contain abnormal 
 quantities of fat. Such stools, conspicuous by their light color, 
 strongly suggest a pancreatic origin. Le Nobel also considers the 
 absence of salts of the fatty acids simultaneously with the presence 
 of large quantities of fat as characteristic of the feces in cases of 
 pancreatic diabetes. As the pancreas is important in the assimila- 
 tion both of proteids and of carbohydrates, the presence in the feces 
 of abnormal quantities of undigested remains of both of these kinds 
 of food also speaks for pancreatic diabetes. Finally, Le Nobel lays 
 stress on the decrease in or absence from the feces and the urine 
 of indol and skatol, and of the corresponding series of products of 
 decomposition, with their combined sulphuric acid, in pancreatic 
 diabetes. Naunyn, in his recent work, also mentions the late 
 appearance in the urine, in cases of pancreatic diabetes, of the 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 35 
 
 reaction for salicylic acid after administration of salol, which sub- 
 stance, under the influence of the pancreatic juice, is quickly de- 
 composed into salicylic acid and phenol. Otherwise the urine 
 affords no information concerning the pancreas. The glycosuria, 
 the phosphaturia, the azoturia, and the amounts in the urine 
 of all products of metabolism are exactly the same in pancreatic 
 as in other forms of diabetes. Von Ackeren's and Le Nobel's 
 maltosuria seems to represent a mistake, as the sugar in the urine 
 in dogs after extirpation of the pancreas is found to be glucose 
 (v. Mering, Minkowski), and as many other pancreatic cases 
 afterward observed constantly presented glucose in the urine. The 
 liver, which Lancereaux first described as unduly large in neuro- 
 genic, but as of normal size in pancreatic, diabetes, may, as he now 
 acknowledges, be equally large in both conditions. It must further 
 be remembered that symptoms referable to the pancreas need 
 not be present in all cases of pancreatic diabetes. Neither need 
 pancreatic or neurogenic diabetes always be the severe type ; it has 
 been proved that severe lesions of the pancreas, as of the nervous 
 system, may cause mild diabetes. In practice, many cases are en- 
 countered in which it is quite impossible to decide between pan- 
 creatic and neurogenic diabetes. 
 
 Fully two hundred years elapsed between Brunner's original 
 attempt at extirpation of the pancreas (1686) and Minkowski's and 
 v. Mering's discovery of the glycosuria resulting from that opera- 
 tion. Yet Cowley, in 1788, noted atrophy of the pancreas due to 
 concretions in a case of diabetes, and Haller observed intense 
 hunger after extirpation of the pancreas. Within more recent 
 tirnes Bouchard, in 185 1, expressed his opinion of a causal con- 
 nection between diseases of the pancreas and diabetes, and Lance- 
 reaux's three cases (1877) established the matter in the mind of the 
 profession. Later, N. Senn observed several symptoms of dia- 
 betes in dogs after extirpation of the pancreas, and William T. 
 Bull, after such an operation on a patient, observed diabetes. Both 
 of these distinguished American surgeons, however, were con- 
 cerned chiefly with the surgical features of their work, and they just 
 missed adding a great discovery in experimental pathology to their 
 other successes. The same fate befell Finkler and Orth, who had 
 undertaken extirpation of the pancreas in dogs in order to observe 
 
136 DIABETES MELLITUS AND GLYCOSURIA. 
 
 any possible diabetic effect. They evidently failed in their purpose 
 by not effecting complete extirpation.* Finally, v. Mering and 
 Minkowski, in 1889, announced their great discovery at Strasburg. 
 If we have been rather slow in acquiring facts, some of us, how- 
 ever, are really much too quick in drawing conclusions, and there are 
 some, especially in France, who consider that all cases of diabetes are 
 of pancreatic origin, and who, as soon as glycosuria is mentioned, at 
 once think of the pancreas, as quickly as they do of alcohol when 
 delirium tremens is referred to. The clinician, however, who learns 
 that a broker was attacked by diabetes after great losses, a statesman 
 after a political failure, a woman after the loss of her husband, and 
 any one after a severe blow on the neck, will scarcely believe that this 
 effect has been brought about by the pancreas ; and when one finds 
 postmortem that the pancreas, in fully nine out of ten cases, after 
 diabetes is either normal, macroscopically and microscopically, or 
 presents no greater change than a slight degree of atrophy, such as 
 is found in many other organs, he does not gain the impression that 
 the cause of diabetes is constantly to be found in the pancreas. 
 Whatever information the future may bring, it is to-day absurd to 
 insist upon a primary pancreatic cause for every case of diabetes, 
 and facts rather point to the conclusion that pancreatic diabetes 
 represents only a small minority of all cases of diabetes. 
 
 Then there is the "constitutional," "fat," "gouty," or "her- 
 petic " diabetes, which often seems to be a distinct type. These 
 designations are used to indicate the mild cases with a course cov- 
 ering many years, which develop slowly in middle age or in senility, 
 and which often constitute rather a weakness than a disease. This 
 condition is found almost exclusively among the upper classes, and 
 usually among brain-workers. A diabetic of this kind generally 
 has some hereditary neurotic, gouty, or adipose predisposition, 
 which may have developed in several directions. He has usually 
 been " nervous " throughout his whole life, and he has often suf- 
 fered in youth from cutaneous eruptions (eczema, Hchen, psoriasis). 
 In middle -age he becomes sedentary, delights in the pleasures of 
 the table (which often have to make up for a somewhat lowered 
 virility), suffers from neuralgic, rheumatic, and gouty troubles, 
 
 * Medical Congress at Wiesbaden, »i 886. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 3/ 
 
 and begins to show glycosuria, which may amount to a mild dia- 
 betes, with slight dystrophic troubles, cutaneous eruptions, fur- 
 uncles, neuritis, brittle nails, defective teeth, etc. With many of 
 these patients, especially those that suffer from gout, the chances 
 of reaching advanced age are almost as good as with the average 
 man, and their diabetes continues to be slight. An affection that 
 begins as a "constitutional" diabetes may, however, in rare cases, 
 later appear as a neurogenic one ; neither is it perfectly certain that 
 such an affection does not depend upon changes in the pancreas. 
 
 It is impossible at present to decide what is hepatogenic diabetes ; 
 it is not even quite certain that this designation may not be applica- 
 ble to all varieties of diabetes. In equal degree muscular diabetes 
 is a mystery. Gastro-intestinal diabetes — with all respect to the 
 honored name that first advocated this designation — according to 
 all evidence does not exist at all. Renal diabetes is not deserving 
 of the name diabetes, and has been mentioned among the glyco- 
 surias. 
 
 Bronze-colored Diabetes.* 
 
 Since 1882, when a treatise by Hanot and Chaufifard appeared,t 
 about a dozen cases of a most peculiar form of diabetes have 
 been described, almost all of which have occurred in France. 
 This form of diabetes offers, cHnically, a good deal of resem- 
 blance to pancreatic diabetes, but it is apparently a disease sui 
 generis, and is called " le diabete bronzee," from the color of the 
 patient's skin. Bronze-colored diabetes generally appears in men 
 between forty and sixty years old ; in most cases there has 
 been a previous history of alcoholism or malaria. It presents the 
 clinical picture of a severe diabetic syndrome, and is usually com- 
 plicated with tuberculosis. In addition, there may be marked 
 dyspeptic symptoms, considerable swelling of the abdomen, with a 
 small amount of ascites, a hypertrophic, hard, and sensitive liver, 
 some dilatation of the abdominal veins (rarely a distinct " caput 
 
 *"La Cachexie Bronzee dans le Diabete," Gonsalez Hernandez, Th6se, Mont- 
 pellier, 1892. Pierre-Marie, " Sem. Med.," 1895. Brault and Gallard, Letulle, and 
 others. 
 
 t "Revue de Med." 
 10 
 
138 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Medusae " around the umbilicus), high-colored urine, and pro- 
 nounced cachexia. The most conspicuous symptom of all, how- 
 ever, is a dark brownish-gray color of the whole skin, most pro- 
 nounced in the face, on the extremities, and on the genitals. 
 
 The disease invariably leads to death — usually in marasmus or 
 coma — in about a year's time. 
 
 Besides the usual diabetic changes, almost all of the organs, but 
 chiefly the liver, the pancreas, the walls of the alimentary canal, and 
 the mesenteric glands, are found the seat of an abundant ocher- 
 colored deposit, derived from the hemoglobin of the blood. This 
 substance increases up to several thousand per cent, the amount of 
 iron of the tissues (Hanot, Lapique, Parmentier and Carrion). 
 (The same pigment is present in the malarial cachexia, in hyper- 
 trophic cirrhosis of the liver, and in Addison's disease.) The liver 
 is found in a state of diffuse hypertrophic cirrhosis with pigmented 
 cells. Its arteries are almost occluded as a result of endarteritis 
 (Triboulet), and the portal system is remarkably dilated. Other 
 organs also are often more or less cirrhotic. The red blood- 
 corpuscles are diminished in number ; Parmentier and Carrion 
 found about 3,500,000 to the cubic millimeter. Several observers — 
 e. g., Anselme — consider the disintegration of the red blood- 
 corpuscles from some unknown cause responsible for the diabetes 
 by invading the pancreas and inducing cirrhosis. 
 
 I have already mentioned that habitual excretion of glucose, 
 however inconsiderable, generally becomes permanent, in so far that 
 it occurs daily for some time after meals ; and that simple glyco- 
 suria usually remains unchanged, though there are exceptions to this 
 rule. 
 
 In cases of true diabetes definitive cessation of glycosuria with a 
 free diet is still rarer, and such complete and permanent restoration 
 to health certainly does not occur in more than about one per cent, 
 of all cases. I think it likely that this occurs chiefly in cases in 
 which the diabetes has been caused by trauma or by infection, and 
 that, when it takes place, the restoration is effected within a com- 
 paratively short time. 
 
 One often hears patients, and sometimes physicians, speak of 
 recovery from diabetes and restoration to complete health. Almost 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 39 
 
 all such reports will be found incorrect on careful investigation. 
 Sometimes the glucose has disappeared with a restriction of carbo- 
 hydrates and reappears with a free ordinary diet. In other cases 
 transitory or periodic increase in the power of assimilation is re- 
 sponsible for the mistake (see Periodic Diabetes). Other reports of 
 like character refer to simple transitory glycosuria from some acci- 
 dental cause, or even to the casual occurrence in the urine of 
 reducing-substances other than glucose. 
 
 I have, in practice, seen disappearance of glucose from the urine 
 with a free diet only in three cases in which sugar had appeared * 
 in diabetic quantities. In one of these cases there remained a dis- 
 tinct polyuria, — i. e., diabetes insipidus, — as has happened in several 
 reported cases. 
 
 My first case of recovery from diabetes was the one following 
 influenza mentioned under glycosuria due to infection. Both the 
 fully developed diabetes and the restoration of normal conditions 
 for at least several months appear to me to be certain. 
 
 The second case was that of a Scandinavian lady, fifty-one years 
 old, who, after a violent blow on the forehead, felt exceedingly 
 weak, and lost in weight for a considerable time. She did not 
 remember any symptoms of diabetes other than pruritus vulvae. 
 After a year and a half she at last consulted a physician, who found 
 the urine to have a specific gravity of 1.037, and to contain a large 
 amount of glucose ; the presence of the latter was ascertained by a 
 fully reliable investigation. When I saw the patient, half a year 
 later, there was nothing noteworthy beyond some neurasthenic 
 symptoms and a cataract in drop-form, which probably had nothing 
 to do with diabetes. After five days of free diet with a consider- 
 able amount of carbohydrate the urine did not contain glucose ; 
 nor was there any pathologic trace of it in the urine collected for 
 six hours after ingestion of 120 grams of glucose. Some time 
 before this was written, three and a half years after her accident, 
 the patient appeared to tell me of her complete recovery. She has 
 observed no dietetic rules, but the urine has always been found free 
 from sugar, and is so at present. 
 
 * I have seen rather large quantities of glucose (for simple glycosuria) in typhoid 
 fever disappear after the end of the fever, and I have seen diabetic quantities of glucose 
 after influenza dwindle to simple glycosuria. 
 
140 DIABETES MELLITUS AND GLYCOSURIA. 
 
 The third case was Mr. F. D., a teacher from Boston, forty-five 
 years old, who had, five months previously, without manifest cause, 
 been seized with symptoms of diabetes ; a chemist of Harvard Uni- 
 versity had found 7.5 per cent, of glucose in a specimen of his 
 urine. The patient had for three months before arriving at Carls- 
 bad observed a most rigorous diet. Under my care he gradually 
 received an increased supply of carbohydrates, until more than two 
 hundred grams a day were given. The urine, which contained no 
 albumin, remained free from glucose during his four weeks' stay in 
 Carlsbad ; but the quantity reached three liters a day, and the 
 specific gravity was about 1.012. 
 
 Thus, it sometimes, though rarely, happens that a true diabetic 
 may be restored to health. Whether this ever happened in a case 
 of severe diabetes is another matter ; so far as I know, not one cer- 
 tain instance of this kind has been recorded. In my own experi- 
 ence, I have never seen any case with diacetic acid (apart from 
 inanition and in association with a full supply of food) in which this 
 acid has disappeared.* 
 
 Mild diabetes is compatible with long life, and I know of cases 
 that in all probability have lasted forty years, and with certainty 
 more than thirty years. A duration of twenty years is by no means 
 rare. The outlook is the better, the later in Hfe the disease sets in, 
 the greater the power of assimilating carbohydrates, and the better 
 the general somatic and mental state. A strong digestion is of very 
 favorable moment. Trauma and infection as causes afford a better 
 prognosis with regard to both complete recovery and a mild course. 
 Gout and adiposity as complications are favorable signs, especially 
 gout. Heredity does not seem to me so pernicious an influence as 
 some authorities would make it. I have at least several times seen 
 sons of diabetic fathers or mothers present through many years 
 mild diabetes or simple glycosuria. Independent pecuniary re- 
 sources and the ability to live without care in a suitable climate, 
 and to afford a generous diet, are highly advantageous to the dia- 
 betic patient. 
 
 *Dr. Toepfer, of Carlsbad, has told me of such a case in a young diabetic girl, who 
 one summer presented a distinct Gerhardt's reaction, even while increasing in weight, 
 and who the following summer exhibited no diaceturia. Such an occurrence is certainly 
 exceedingly rare. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. I4I 
 
 Mild diabetes more commonly remains mild diabetes than it 
 develops into severe diabetes. On the other hand, a transition 
 from the mild into the severe stage is no very rare occurrence, and 
 it is difficult to understand how even specialists of wide experience 
 can have failed to observe it. 
 
 Severe diabetes rarely lasts more than four or five years ; the 
 average duration can not be much above three years. In very 
 severe cases, and especially in young persons (see below), the 
 dystrophy may lead to death in a few weeks. 
 
 I make the following twenty-four extracts from my records of diabetic 
 patients. The cases are related as briefly as possible, and they are intended 
 only to convey an impression of the general clinical picture of the diabetic 
 syndrome and its common complications. The cases are arranged so as to 
 represent different stages and to illustrate the gradual failure of the power of 
 assimilation and the development of the glycosuric dystrophy. If one is 
 anxious for appellations, he may call the first 8 cases simple glycosuria, the next 
 8 cases mild diabetes, and the last 8 severe^diabetes, at the time when last in- 
 vestigated. Matters of local significance, of nationality, of treatment, etc., are 
 here omitted. The patients include Scandinavians, Americans, Germans, and 
 Englishmen ; the first alone belonged to the Semitic race. 
 
 1. Mr. , thirty -two years old, came to Carlsbad with dyspeptic troubles, 
 
 which showed themselves, however, to be only the gastric manifestations 
 of a pronounced neurasthenia, partly inherited and partly acquired, chiefly 
 through sexual excesses. The patient had of late years grown exceedingly 
 " nervous." His restless sleep was of the usual neurasthenic type, with an in- 
 terruption of complete wakefulness from i to 4 or 5 A. m. The man was 
 irritable, often giddy, had a " casque neurasthenique," a beautifully pro- 
 nounced "plaque sacree " and other rhachialgic manifestations, shooting-pains 
 in the legs after standing for some minutes, etc. The usual fear of suspected 
 tabes was (as always) entirely unfounded ; thorough investigation demon- 
 strated, even to the patient's satisfaction, the absence of all symptoms of that 
 disease, and, rather strangely, he had escaped syphilis. The man declared 
 somewhat mournfully that coitus was no longer " what it had been, what it 
 could be, and what it ought to be"; besides, the act had been of late suc- 
 ceeded by a feeling of extreme weakness. 
 
 The urine obtained one hour after the end of dinner constantly underwent 
 reduction, which disappeared after fermentation. When reduction was most 
 marked, the urine caused a slight deflection of the ray of polarized light to the 
 right instead of the customary deflection to the left (from combined glycuronic 
 acid). 
 
 2. Miss , twenty years old, had been informed by her physician, eight 
 
 years previously, that her urine contained sugar. There was no direct hereditary 
 
142 DIABETES MELLITUS AND GLYCOSURIA. 
 
 cause and no etiologic point other than some intellectual overwork and a dis- 
 appointment in love just before the discovery of the glycosuria. 
 
 At sixteen the patient had hysteric attacks and several stigmata. She was 
 of a marked nervous temperament, and suffered still from periods of sleepless- 
 ness, "terreur nocturne," and other manifestations of similar character. 
 Sometimes during nervous exacerbations the patient herself was cognizant of 
 polyuria and pollakiuria, with the almost colorless (" spastic ") urine secreted 
 periodically by " nervous " persons. 
 
 When the young woman consulted me she was at her best, and made the 
 impression of a lively, fairly healthy individual, with no distinct hysteric* 
 and only moderate neurasthenic symptoms, and presenting nothing remarka- 
 ble apart from the urine, which repeatedly, in samples obtained an hour after 
 meals, contained from 0.05 to 0.2 per cent, of glucose. On a perfectly free 
 mixed diet the tall young woman passed 1850 cu. cm. of urine, with a specific 
 gravity of 1.021 and a faint trace of glucose. Eight years after the discovery 
 of the glycosuria I learn that the state has not changed, and that the general 
 health is fairly good. 
 
 3. Mr. J., fifty-nine years old, had a diabetic father, had himself worked 
 hard intellectually for a large part of his life, felt a strong attraction to the fair 
 sex, and thought American whisky a most delightful and wholesome bev- 
 erage. He had been a hard smoker. The still deeply affected father was 
 scarcely able to mention the terrible loss of a daughter two and a half years 
 before. 
 
 The patient came to Carlsbad for adiposity and gout (in the big toe !). Sleep 
 was fairly good ; sexual power, considering age, likewise ; and the knee-jerk 
 present. The heart was somewhat weak, with distant sounds ; the organ was 
 somewhat enlarged, the pulse small and weak, but fairly regular. The func- 
 tions in general were tolerably well performed, and after a mild dietetic course 
 and systematic exercises the patient took quite long walks in the hills around 
 Carlsbad. The teeth were partly absent and partly affected with caries. 
 
 On the back a gouty eczema existed. 
 
 The ophthalmoscope disclosed a distinct picture of optic neuritis, chiefly 
 marked on the right side (from tobacco and whisky). 
 
 The patient assured me that his urine, recently analyzed, was normal. 
 Finding him a sensible and not at all a hypochondriac person, I told him that, 
 from his "tout ensemble," I was quite certain that during some parts of the 
 day it would contain small, clinically insignificant, but abnormal quantities 
 of glucose — and a specimen obtained after dinner contained about 0.25 per 
 cent. 
 
 4. Dr. X, a physician, was descended from families both of which were free 
 from developed psychoses, but which, together with some instances of great in- 
 tellectual capacity, included others of " eccentricity " and extremely choleric 
 temperament. 
 
 * The field of vision was not examined. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 43 
 
 The patient himself was strong, but sensitive and lively as a child. He had 
 suffered now and then from eczema, and had worked hard and participated a 
 good deal in the customary dissipations at the university. At the age of twenty- 
 three he was subjected to a powerful depressing emotion, and some weeks 
 afterward a series of furuncles appeared. The patient at this time worked 
 hard for academic honors, and a year later began to suffer from sleeplessness ; 
 diminution in sexual desire and other neurasthenic symptoms developed. At 
 twenty-five the patient for the first time accidentally found a distinct trace of 
 sugar in his urine ; this again happened when he had reached his thirty-second 
 year. He then alsb found distinct oxaluria. Shortly afterward the patient, at 
 a postmortem examination, contracted a severe pyemia, which wrecked him 
 somatically and depressed him mentally for some time. At the age of thirty- 
 eight the patient again accidentally found sugar in his urine, and in view of 
 the two previous observations of the same kind, subjected himself to a thorough 
 investigation. It was then found that a liberal supply of carbohydrates (sev- 
 eral hundred grams) did not cause sufficient glycosuria to permit a distinct 
 reaction with Nylander's solution of the urine for the twenty-four hours, which 
 amounted to between 1500 and 1800 cu. cm. ; that the first specimen obtained 
 an hour after dinner usually contained between o.i and 0.2 per cent, of glu- 
 cose ; that the patient generally could take a large amount of rice or 300 grams 
 of cane-sugar without the development of glycosuria ; and that the slight amount 
 of glucose that appeared in the urine after mixed meals with some wine could 
 temporarily be increased quite considerably under the influence of emotional 
 disturbances. On one occasion the patient, immediately after a rather sump- 
 tuous dinner, was seized with an intense fit of anger ; a specimen of urine 
 passed shortly afterward contained 1.4 percent, of glucose, the largest quantity 
 observed among more than 100 analyses, of which only one other had yielded 
 so much as 0.4 per cent. The patient now for three days lived chiefly on carbo- 
 hydrates ; then collected the urine for twenty-four hours, and to his delight saw 
 the phosphates form a beautifully white precipitate on boiling with Nylander's 
 solution. But few analyses have since been made, and these showed speci- 
 mens of the urine collected for twenty-four hours to be practically free from 
 glucose. The patient has presented gouty symptoms from his thirty-third year. 
 The joints of the fingers from time to time suddenly swell and become tender. 
 The great toe of the right foot also has been involved. Dr. X is now (1899) 
 in his fifty-second year, and is rather healthier than twenty years ago. He is 
 unwilling to permit further analysis, which formerly kept him in a hypochon- 
 driac state. His weight keeps at the level of 95 kilograms. The patient was 
 married eighteen years ago, and has six mostly strong and healthy children. 
 One otherwise healthy child suffered for a long time from nocturnal enuresis 
 and from psoriasis. 
 
 Another physician, an apparently healthy, hard-working man, on hearing 
 of Dr. X's glycosuria, mentioned the fact that he had himself accidentally 
 found sugar in his own urine sixteen years ago. An hour had just passed since 
 his frugal dinner when this was mentioned. I expressed my opinion that the 
 urine probably still contained glucose, and we found fully 0.2 per cent, of it in 
 the specimen. 
 
144 DIABETES MELLITUS AND GLYCOSURIA. 
 
 5. An apothecary, forty-eight years old, whose father had suffered for 
 many years in old age from diabetes, was terrified by finding sugar in his own 
 urine. 
 
 The patient presented the outward appearance of an unusually healthy, 
 powerful man. During the preceding ten years his weight has kept at about 
 107 kilograms, and his height was about six feet. Investigation failed to dis- 
 close anything abnormal. Even most of the usual neurasthenic symptoms 
 were absent, except a fear of approaching great depths and slight weakening of 
 sexual power. 
 
 The urine was collected several times for twenty-four hours, with an allow- 
 ance of 120 grams of white bread and some green vegetables in the diet. The 
 secretion varied from 870 to 1200 cu. cm. in amount, and from 1.033 ^o '^•023 
 in specific gravity. A specimen of the twenty-four hours' urine contained 
 scarcely so much as 0.05 per cent, of glucose. 
 
 The patient took 300 grams of cane-sugar in one liter of Giesshiibler water, 
 and after four and a half hours the urine was found free from glucose. The 
 amount collected equaled 500 cu. cm., with a specific gravity of 1.016, and it 
 contained about 0.05 per cent, of glucose. After being boiled with sulphuric 
 acid the urine reduced as a solution of 0.24 per cent, of glucose. 
 
 6. Mr. G. W., a bank clerk, fifty-six years old, was free from known 
 hereditary predisposition or other etiologic influence worthy of mention other 
 than a severe malaria thirty years before. He came to Carlsbad on account 
 of constipation, which, together with flatulence, constitutes his chief complaint. 
 He was a fat, exceedingly "nervous" man, with a melancholy, "fussy" tem- 
 per ; had a pronounced " casque neurasthenique " ; slept badly ; did not like 
 to go out on a balcony ; had weak sexual power ; and was easily made tired by 
 physical or intellectual exertions. 
 
 I found glucose in the urine, which contained, besides, many crystals of 
 calcium oxalate. The patient ate nearly 300 grams of bread a day, and what- 
 ever he liked besides. A specimen of urine an hour after dinner contained 
 I.I per cent, of glucose ; but the mixed total quantity for twenty-four hours, — 
 1500 cu. cm., with a specific gravity of 1.024, — not quite o.i per cent. 
 
 The patient told me five years afterward (in Stockholm) that he went to 
 Lindewiese, in Silesia, and lived exclusively on white bread, and that the 
 sugar then disappeared from his urine. Investigation, however, proved the 
 state to be exactly what it had been in Carlsbad. 
 
 7. Mr. , forty-six years old, a noted barrister, came to Carlsbad on ac- 
 count of dyspeptic troubles and not excessive adiposity — he weighed 94 kilo- 
 grams. The condition was much like that described in case 3. The patient 
 had hereditary adipose and gouty tendencies ; had worked hard and smoked 
 hard; had led a sedentary life and greatly enjoyed a good table. He was 
 quite irritable, slept badly, and had incipient symptoms of smoker's heart. 
 I found 0.4 per cent, of glucose in a specimen of urine after dinner. Free 
 diet is attended with the elimination of a normal quantity of a somewhat 
 " lithemic " urine, containing a distinct trace of sugar. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 45 
 
 Seven years afterward I saw the patient in his home. He was very active in 
 his profession, had made a large fortune by speculation, and did not know 
 anything about his glycosuria, suffering only from slight neurasthenic symp- 
 toms. 
 
 Nine years after our first acquaintance I again saw the patient. He had 
 worked and speculated a great deal, had twice made and lost a large fortune, 
 and had, still more than before, led a life of constant emotional activity. The 
 former simple glycosuria now sometimes reached diabetic figures (two per 
 cent.) in large specimens, and occasionally slight symptoms of diabetes mani- 
 fested themselves. 
 
 8. Professor , fifty-eight years old, a distinguished surgeon, had had a 
 
 rheumatic and gouty father, and had himself, eleven years before, discovered 
 two per cent, of glucose in a specimen of his urine, having for some time pre- 
 viously felt tired and worn out. 
 
 A specimen of urine after a dinner with a moderate supply of carbohydrates 
 had a specific gravity of 1.037, but was found (by titration and polarization) to 
 contain only 0.25 per cent, of glucose. With a customary diet and some re- 
 striction of carbohydrates the urine amounted only to somewhat more than a 
 liter, with a specific gravity of 1.024 and somewhat more than o.i per cent, of 
 glucose. 
 
 The patient was slightly neurasthenic and distinctly "lithemic." Some 
 trouble with the toes, especially the great toes, probably was of a gouty 
 nature. 
 
 9. Mr. E., judge, forty-seven years old, belonged to a family with strong 
 neurotic tendencies, including several instances of diabetes. The patient had 
 in his youth been addicted to masturbation, and several years afterward suf- 
 fered from neurasthenia. Six years before coming under observation he had 
 applied for life-insurance, but was refused on account of the presence of 
 glucose in the urine. Shortly afterward he was seized with a violent attack of 
 influenza, and during convalescence a specimen of urine obtained after dinner 
 contained 3.2 per cent, of glucose. 
 
 The patient was a heavily built man, who had recently, with rigorous dietetic 
 restrictions, lost in weight. Finding that this regime affected his general 
 health badly, he returned to a somewhat more liberal diet, with a moderate 
 allowance of carbohydrates, felt considerably better, and regained his previous 
 weight. There were no distinct diabetic symptoms except the glycosuria. Even 
 the teeth were normal. There was a moderate degree of neurasthenia, with 
 some disturbance of sleep, and other cerebrasthenic symptoms. The sexual 
 power was somewhat impaired. There were five healthy children in the 
 family. 
 
 A perfectly free diet without any restriction whatever, and with quite a large 
 quantity of carbohydrates, was attended with the secretion of 1300 cu. cm., 
 with a specific gravity of 1.025 ^^d 0.28 per cent, of glucose. A specimen 
 obtained after dinner contained 1.34 per cent, of glucose. The patient was 
 again put on a systematically but moderately restricted diet, and the urine con- 
 
146 DIABETES MELLITUS AND GLYCOSURIA. 
 
 tained only traces of glucose. Ten years after the discovery of the mild dia- 
 betes I again met the patient and found the general state unchanged. 
 
 10. Dr. H., a widely known physician, at the age of twenty-seven years acci- 
 dentally discovered over two per cent, of glucose in a specimen of his urine. 
 There was no hereditary influence, but a history of much intellectual effort. Nor 
 were there other symptoms of diabetes. The quantity of urine had always 
 been rather large, though it had never amounted to distinct polyuria. The 
 patient kept himself under some dietetic restriction, and the glycosuria disap- 
 peared for several years and did not reappear even upon a free diet. Six years 
 after its first discovery the glycosuria again appeared, following an attack of 
 typhoid fever, and sometimes reaching considerable proportions. 
 
 Fourteen years have now elapsed since the sugar first appeared in the urine. 
 The patient, a man of iron will, adheres constantly to a diet with an allow- 
 ance of about seventy grams of carbohydrate a day, and is free from deter- 
 minable glycosuria. When for experimental purposes a greater allowance is 
 made, the sugar again appears in moderate but quite determinable quantities. 
 This most valued friend of mine, who is a hard worker, suffers from no other 
 symptom than periodic insomnia. 
 
 11. Lieutenant-Colonel R., a retired officer, eighty-one years old, has no 
 knowledge of hereditary or other morbid predisposition. Thirty-nine years 
 before coming under observation the man suddenly had a succession of fur- 
 uncles, and he dates his diabetes from this time ; the glycosuria, however, was 
 not discovered until sixteen years later. 
 
 The patient, who has been under my care for many years, is at the present 
 time (1899) a lively old gentleman, with a healthy appearance. Only during 
 the last two years has he observed any failure of memory ; he has also pru- 
 dently left off playing whist, in which pastime he was, up to his eightieth year, 
 considered to have few equals. The patient suffers from insomnia. Some- 
 times there is giddiness. The reflexes, especially the knee-jerks, are weakened. 
 Most of the teeth are absent, but the cavity of the mouth is otherwise normal. 
 There is no odor of acetone from the breath. The patient is presbyopic, but 
 the visual acuity is fairly good. Gerontoxon is not very strongly developed. 
 There is some slight rigidity of the radial and temporal arteries. 
 
 When the patient partakes of a moderate but undetermined quantity of 
 bread and green vegetables, he passes about two liters of urine containing 
 about two per cent, of glucose or a little more. There is no albuminuria. 
 One hundred grams of Graham bread (about forty grams of carbohydrate) and 
 some green vegetables yield 1750 cu. cm. of urine, with a specific gravity of 
 1.025 and containing 0.8 per cent, of glucose. 
 
 The patient's wife also suffers from mild diabetes. 
 
 12. Baron X, fifty-eight years old, a statesman, had a gouty inheritance; 
 his mother also probably suffered for many years from diabetes. The patient 
 has for forty years been a heavy smoker, and had been much interested in his 
 good table. His restless spirit, quarrelsome temper, and heavy responsibilities 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 14/ 
 
 had caused him a life full of emotions. In early manhood he suddenly in- 
 creased considerably in weight. Twenty-six years before coming under obser- 
 vation he had several furuncles. Already at this period his teeth began to show 
 caries, and they successively fell out ; the patient had often suffered from gin- 
 givitis. The last molar tooth was sneezed out two years before my first inves- 
 tigation. The glycosuria, which in small specimens of urine has reached over 
 six per cent,, was discovered only a year before the patient came to me. There 
 was no albuminuria and no diaceturia. 
 
 The patient had a weak nervous system, and periodically suffered from vio- 
 lent supraorbital neuralgia. Some years previously he was troubled with 
 agoraphobia ; he always carefully shunned steep declivities. Creeping sensa- 
 tions in the legs and nocturnal cramps in the calves caused annoyance. 
 There was no distinct neuritis. The left knee-jerk was weakened. 
 
 The spleen was somewhat enlarged (the patient had had malaria eleven 
 years before). The liver appeared of normal size on percussion and palpation. 
 The heart was somewhat large and not powerful. 
 
 During two seasons in Carlsbad I found that the patient, who was a little 
 less unreliable during his "cure" than at home, when taking 120 grams of 
 white bread and some green vegetables with his food, presented a gradual 
 diminution in his glycosuria, until in the third week he was passing about 1800 
 cu. cm. of urine containing only a trace of sugar. 
 
 13. Herr S,, forty years old, an engineer, had some months previously 
 suffered from a remarkably obstinate ulcer on his leg, and his physician found 
 six per cent, of glucose in the urine. 
 
 The patient was free from neurotic or diabetic inheritance. He had rarely 
 neglected free libations of strong grog in the evening and had smoked im- 
 moderately. During the preceding few years he had suffered from gouty 
 troubles. Four years before he had passed through a violent attack of influ- 
 enza. The patient denied syphilis, but his wife had twice miscarried in the 
 sixth month. 
 
 The patient is a robust man, without obvious manifestations of theglycosuric 
 dystrophy. Even the cavity of the mouth exhibited nothing abnormal beyond 
 caries of two teeth. Sexual power was rather weak. The knee-jerks were 
 just perceptible. The patient now and then felt pain " deep in the head." 
 
 His heart was somewhat enlarged, the sounds weak and distant, the impulse 
 not perceptible; the pulse 76, not quite regular, and weak. The temporal 
 arteries were unduly distinct on palpation. 
 
 One hundred grams of white bread and some green vegetables with the 
 food yielded regularly about 2100 cu. cm. of urine, with a specific gravity of 
 1.027 3.nd containing 0.9 per cent, of glucose, a trace of albumin, and some 
 granulated tube-casts. After two days of abstinence from carbohydrates the 
 patient was able to take regularly sixty grams of white bread a day with green 
 vegetables, without any determinable glycosuria. 
 
 Nearly three years after this the patient again consulted me. He had, two 
 weeks before, while driving about in a cab, suddenly lost first his sight and 
 shortly afterward consciousness, having previously suffered from acute, deep- 
 
148 DIABETES MELLITUS AND GLYCOSURIA. 
 
 seated pains in his head. Consciousness returned after some hours. There 
 were no distinct paretic symptoms, but amblyopia persisted for several weeks. 
 The patient could at first only count fingers, but not read. Vision gradually 
 returned to the previous state. The patient's physician believes the symptoms 
 to have been due to uremia, while I attribute them to cerebral hemorrhage. 
 The ophthalmoscope disclosed a hemorrhagic retinitis, with ecchymoses in dif- 
 ferent stages. The glycosuria was now, probably in consequence of the cirrho- 
 sis of the kidneys, slighter than it had been three years before ; 120 grams of 
 white bread and some green vegetables causing only faint traces of glucose to 
 appear in the urine, of which abouftwo liters were excreted in the twenty-four 
 hours, and which had a specific gravity of 1.021 and contained a trace of 
 albumin. 
 
 14. A., a restaurateur, forty-seven years old, developed three " maux per- 
 forants " on the right foot, and consulted Dr. H. Toll, who found a large 
 quantity of glucose in the urine and called me in consultation. The patient 
 admitted having "wet his tongue now and then," which means in Sweden 
 that he has drunk enormously. 
 
 The man was somewhat maudlin, slept badly, presented no knee-jerks, 
 had weakened sexual power, and complained of right genitocrural neuralgia. 
 The pupils differed distinctly in size. The patient denied all history of syphilis. 
 His heart was somewhat large, his pulse small and weak, but regular. Pro- 
 nounced arteriosclerosis was obvious in the radial, temporal, and femoral 
 arteries. There were no appreciable signs of cirrhosis of the liver. 
 
 Restriction of the diet caused disappearance of the glycosuria and of the 
 distinct polyuria, and the patient excreted in twenty-four hours 1500 cu. cm. 
 of urine of a specific gravity of 1.035 ^"d, rather remarkably, free from al- 
 bumin. 
 
 The three " maux perforants " had made terrible ravages in the foot, which 
 was already resected through Chopart's joint ; the process now continued 
 chiefly along the tendons of the peroneal muscles. Sensibility was distinctly 
 diminished on this leg, and there was a distinct retardation of the perception 
 of needle-puncture. There being no indication of a clot in the popliteal artery, 
 I proposed amputation below the knee, which was effected, with an excellent 
 result after a few weeks of dietetic and restorative treatment. Nearly three 
 years later I learned that the patient was still alive and in possession of a 
 good stump. 
 
 15. E., fifty-four years old, manager of a factory, ten years ago sought 
 life-insurance, but was not accepted on account of the existence of glyco- 
 suria. The history gave no clue to the origin of the diabetes. 
 
 The patient one night awoke with an attack of serious indisposition, felt a 
 sensation of pressure or weight in the occiput, and vomited profusely. The 
 next day the lower branch of the facial and the abducens nerve on the right 
 side were paralyzed. The patient now consulted Dr. Nordenson, who made 
 the following note : " In both eyes numerous small hemorrhages in the retina ; 
 around the macula lutea round whitish patches, with small points of blood. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 49 
 
 Field of vision, normal extent; normal color-perception. Left eye: hyperme- 
 tropia, I D. ; visual power, 0.3. Right eye: hypermetropia, 1.50 D. ; visual 
 power, 0.3. 
 
 Seven weeks later ,the patient came to Carlsbad. I then found the lower 
 branch of the right facial nerve and both abducens nerves paralyzed — the 
 right eye alone seemed to be used. Other symptoms referable to the nervous 
 system, besides the usual neurasthenic symptoms, included a feeling of heavi- 
 ness in the occiput and some giddiness. The knee-jerk was absent on the 
 left and barely appreciable on the right. A large specimen of the urine con- 
 tained about three per cent, of glucose, but no albumin and no diacetic acid. 
 Eighty grams of Graham bread and some green vegetables a day yielded a 
 urinary secretion of from 2700 to 3000 cu. cm. a day, and, quite constantly, 
 about 26 grams of glucose. A strict diet would, beyond a doubt, have caused 
 entire disappearance of the glucose. With the use of syzygium jambolanum 
 on three different occasions the glycosuria, ceteris paribus, sank to 15 grams, 
 without any other appreciable change. In the autumn the neuroparalytic 
 symptoms had disappeared, but otherwise the state of the eyes had undergone 
 no change. 
 
 A few months after his visit to Carlsbad I was called early one morning to 
 the patient in Stockholm. He had again had at night a cerebral attack like 
 the previous one. After a rectal injection, application of an ice-bag to the 
 occiput and of hot bags to the feet, and elevation of the head, the attack was 
 soon over without leaving any noteworthy sequel. 
 
 Half a year later gangrene made its appearance in the left leg, and while 
 the patient was under treatment for this a renewed cerebral attack suddenly 
 ended his life. I was not at hand and there was, unfortunately, no postmortem 
 examination. 
 
 16. E. T. B., a farmer, seventy-two years old, was considered by his family 
 and friends to be a healthy and active old man. Apart from his eyes he had 
 suffered from no disease whatever, and he knew of no reason for believing 
 that any existed. He himself and others, however, were struck by a " pecu- 
 liarity " that had made its appearance about thirty years previously — namely, 
 that he drank more water and passed a greater quantity of urine than other 
 persons. 
 
 The patient complained that his eyes had for many years been a source of 
 trouble, and stated that he had used only the left one. Some days before 
 coming under observation this eye began to ache ; the patient obtained from a 
 neighboring physician some atropin, which made the eye ache "horribly." 
 He then consulted Dr. Nordenson, who found the cause of the " peculiarity," 
 and sent the patient to me on account of his diabetes. 
 
 The right eye presented an absolute glaucoma. The upper lid was some- 
 what swollen, the conjunctiva of the bulb was hyperemic, and there was 
 marked pericorneal injection. The cornea was smoky, the pupil dilated, and 
 the anterior chamber was wanting. The vitreous body yielded a yellowish- 
 brown reflection (hemorrhage). 
 
 In the left eye there was found hypermetropia of 1.50 D, with a visual acuity 
 
I 50 DIABETES MELLITUS AND GLYCOSURIA. 
 
 of 0.8 ; except for a pronounced gerontoxon, the cornea was normal. The iris 
 also was normal and reacted well. At the bottom of the eye small yellowish 
 patches could be seen between the inferior temporal and the inferior nasal 
 vein. A considerable hemorrhage and some small ecchymoses were visible. 
 
 The patient did not complain of any nervous disorder ; the sensibility in the 
 left leg, however, was much impaired. The knee-jerk in the same side was 
 almost destroyed ; the toe-nails were discolored, strongly curved, thick and 
 brittle ; on the plantar aspect of the great toe, beneath the interphalangeal joint, 
 there was a circular scar attached to the bone and evidently from a " mal 
 perforant," which had healed a couple of months before, under treatment by a 
 surgeon, who, by the way, seemed to have omitted to look for diabetes.] 
 
 On the right leg there was no " mal perforant," and the nervous and dys- 
 trophic changes were much less marked than on the left leg.* 
 
 The temporal and radial arteries were somewhat rigid, pulse 104, at noon, 
 before lunch. The amount of urine secreted with free diet was 2.5 liters, with 
 a specific gravity of 1.046, and it contained eight per cent, of glucose. 
 
 A diet including an abundance of green vegetables, about 100 grams of pota- 
 toes, and 100 grams of rye-bread yielded 1600 cu. cm. of urine containing five 
 per cent, of glucose, but no diacetic acid. It is probable that with a strict diet 
 the urine would have been free from^glucose. 
 
 Three years later the patient was said to have been in about the same 
 state. 
 
 17. A judge, sixty-one years old, nine years before coming under observa- 
 tion, after some loss of weight and a sense of weakness, was discovered to be 
 diabetic. The patient himself believed the dystrophy to be due to exposure to 
 cold, and no other cause, hereditary or acquired, could be elicited. During 
 his first season at Carlsbad the patient felt fairly well, and the neurasthenic 
 symptoms, which constituted his chief complaint, subsided with the complete 
 rest of his sojourn at the spa. 
 
 The power of assimilation was quite good, and with a daily allowance of 
 some green vegetables and 150 grams of Graham bread, the patient passed 
 1600 cu. cm. of urine, with a specific gravity of 1.025, and containing only faint 
 traces of glucose. 
 
 Two years later the patient looked much less well and complained of in- 
 creasing weakness and incapability of fulfilling his public duties. Investiga- 
 tion shows, apart from the results of urine analysis, only one important change 
 from the state of two years before — namely, there was now a distinct odor of 
 acetone on the breath. The glycosuric dystrophy had made considerable prog- 
 ress, and 75 grams of Graham bread and some green vegetables yielded 1800 
 cu. cm. of urine containing 1.3 per cent, of glucose. There was then no dis- 
 tinct Gerhardt's reaction. The patient, who seemed entirely reliable, was for a 
 
 * About the same time Dr. Kinnicutt, of New York, to whom I mentioned my case, 
 had a similar one under observation, with marked neuritis, knee-jerk almost destroyed, 
 "mal perforant," and other dystrophic changes in the one leg, with a comparatively 
 normal state in the other. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. I5I 
 
 whole week put on strict diet, with exclusion of carbohydrates. He then lost 
 weight from 95.3 kilograms to 93.4 kilograms, and the urine yielded a faint 
 Gerhardt's reaction indicative of the presence of diacetic acid. There was even 
 now about o.i per cent, of glucose in the urine ; this could scarcely have been 
 derived from carbohydrates, but it seemed to be derived partly from albumin. 
 The patient undoubtedly has arrived at the boundary line between the posi- 
 tively mild and the positively severe stage, but his exact place can not be deter- 
 mined under the conditions that prevail at Carlsbad. 
 Four years later I learned that the man was still alive. 
 
 18. A merchant first became my patient in his thirty-sixth year. His father 
 had been diabetic, and a paternal uncle diabetic and insane. Seven years 
 previously the patient contracted syphilis, and he had always been a hard 
 drinker. Half a year before coming under observation the patient observed 
 that white spots were left by his urine, which was found to contain six per cent, 
 of glucose after dinner. Beyond this and moderate neurasthenia the man was, 
 during his first season in Carlsbad, fairly healthy and quite robust-looking. 
 Thirty grams of bread and some green vegetables were permitted with the 
 food, without the development of glycosuria. As the patient with this restric- 
 tion maintained his weight (92 kilograms) the diet was continued for five 
 weeks. 
 
 In the following summer the condition of affairs appeared pretty much the 
 same. Sixty grams of bread and some green vegetables caused a trace of glu- 
 cose to appear in the urine ; the bread being increased to 90 grams, the nor- 
 mal quantity of urine for twenty-four hours contained fully o.i per cent, of 
 glucose. The patient had entered into matrimonial plans, and combated ener- 
 getically my somewhat feeble opposition, asserting that Providence itself was 
 strongly interested, but promised moderation in all respects. 
 
 Two years later the man again appeared in Carlsbad, having carried out 
 his plan of marrying, but having entirely forgotten his promise of moderation. 
 Sixty grams of bread and some green vegetables now yielded 1450 cu. cm. of 
 urine in twenty-four hours, with a specific gravity of 1.032 and containing 0.2 
 per cent, of glucose and no diacetic acid. When carbohydrates were entirely 
 excluded for some days the patient lost somewhat in weight, while the glucose 
 entirely disappeared, and a faint Gerhardt's reaction developed with ferrichlo- 
 rid. As the drops of the solution fell in the urine they were, for a moment, 
 surrounded by a purple zone, the urine above the phosphates having the 
 color of sherry. In the following year the power of assimilation had 
 again decreased, and the patient was in the severe stage of the dystrophy. 
 Abstinence from carbohydrates was no longer followed by disappearance of 
 the glycosuria, though only a few grams of sugar were excreted during the 
 twenty-four hours. Gerhardt's reaction was now well pronounced. About 
 70 grams of bread and some vegetables yielded 1500 cu. cm. of urine, with a 
 specific gravity of 1.034 and containing rather more than one per cent, of glu- 
 cose. Upon this diet the patient kept his weight, but a distinct though faint 
 Gerhardt's reaction could still be elicited. 
 
 Two years again passed and the patient returned to Carlsbad. The bodily 
 
152 DIABETES MELLITUS AND GLYCOSURIA. 
 
 weight was almost the same ; the glycosuric dystrophy had again made some 
 sHght progress. Mentally the patient was an altered man. He suffered from 
 melancholia, without stupor or hallucinations, but with unfounded ideas of 
 financial ruin, many expressions of " tedium vitse " ; terrible anxiety for the 
 future mental and somatic fate of a new-born son, great restlessness, with an 
 occasional " raptus " during the nights, and general profound depression, etc. 
 The "cure" at Carlsbad somewhat improved the man's condition; but 
 during the autumn the melancholia again regained its sway over the patient, 
 who, some months after my losing sight of him, was found lying across a rail- 
 way track dead and mutilated. 
 
 19. H., a clerk, forty-six years old when I saw him for the first time at 
 Carlsbad, had known for two years that he was diabetic, but distinct polydipsia 
 and polyuria had been present for five years. 
 
 A history was obtained only with the greatest difficulty, owing to the stu- 
 pidity of the patient, who did not seem to know anything of his whole past 
 life, except that he had acquired syphilis twenty-nine years before and had 
 successively passed through five antisyphilitic cures. 
 
 The man was extremely peevish and irritable ; he slept badly. Sexual 
 power was enfeebled. Supraorbital neuralgia was present on both sides. The 
 teeth were partly carious and partly gone. 
 
 The urine, which had lately contained so much as seven per cent, of glu- 
 cose, was now found to contain three per cent. There was no odor of acetone 
 on the breath, no diaceturia, no albuminuria. A restricted diet put an end to 
 the glycosuria, which afterward did not return in determinable quantities so 
 long as the patient took no more than 60 grams of white bread and some green 
 vegetables. 
 
 Ten years afterward the man returned to Carlsbad. His breath now dis- 
 tinctly smelled of acetone ; the teeth were almost all gone ; the tongue showed 
 longitudinal and transverse furrows " a la crocodile.'" Sexual potency was 
 entirely gone. There was a suspicion of neuritis in both legs. The apex of 
 the right lung exhibited signs of tuberculosis, and in one place there was a 
 small cavity. The pulse was 84, the temperature slightly elevated. The 
 patient complained of night-sweats. 
 
 Exclusion of carbohydrates for several days reduced the glycosuria to 0.6 
 per cent., 1500 cu. cm. of urine with a specific gravity of 1.026 being secreted 
 in twenty-four hours ; and a distinct Gerhardt's reaction was present. Eighty 
 grams of bread and 100 grams of levulose and some green vegetables with the 
 food considerably increased the glycosuria, but distinctly diminished the diacet- 
 uria (which, however, still continued), caused some restoration of weight pre- 
 viously lost, and maintained the bodily weight at 77 kilograms. Syzygium 
 jambulanum, even in large doses, had no appreciable effect. 
 
 20. Mrs. L., thirty-eight years old, knew of no hereditary or other etiologic 
 causes for her condition than an excessive fondness for sweets. Her diabetes, 
 to judge from the polyuria and the polydipsia, had probably set in two years 
 before. The patient was extremely stout, and did not lose in weight until her 
 diet was restricted. 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. I 5 3 
 
 During her first season in Carlsbad the lady appeared in fairly good general 
 health. There was no smell of acetone on the breath. Some teeth were carious, 
 and now and then gingivitic troubles arose. Some of the usual neurasthenic 
 symptoms were present, and on the left side supraorbital neuralgia and sciatica. 
 Cramp occurred at night in the calves of the legs. There was a tendency to 
 profuse perspiration. Finally, the patient complained of pruritus vulvs, which 
 speedily ceased on application of a solution of mercuric chlorid (i : looo) twice 
 a day. The urine, which had contained four per cent, of glucose, became 
 normal in quantity and quality upon a restricted diet, and remained so, except 
 for small traces of sugar excreted, when 60 grams of white bread and some 
 vegetables were added to the dietary. 
 
 Eleven years after the beginning of the diabetes the patient again appeared 
 in Carlsbad in a very different state. She had diminished in weight from 86 
 to 67.15 kilograms and she felt very weak. The skin was dry and of cyanotic 
 hue upon the cheeks. The patient was no longer troubled with profuse perspira- 
 tion. The breath smelled of acetone ; the teeth were defective ; the tongue was 
 dry, partly coated, and of an angry red at the apex. Restriction of diet no 
 longer stopped the glycosuria. The weight could not be maintained with less 
 than 100 grams of Graham bread and some vegetables with the food, upon 
 which the patient passed 2500 cu. cm. of urine containing 2 per cent, of sugar 
 and with a distinct (but not marked) Gerhardt's reaction, but no albumin. 
 
 A year later small ecchymoses or petechise, sometimes observed in advanced 
 cases, began to appear. The petechiae disappeared when the patient remained 
 in bed, and reappeared as soon as she moved about. They were present 
 almost exclusively on the legs, only a few being visible on the trunk and none 
 on the arms. 
 
 Another year added iritis on both sides and cyclitis on the left side to the 
 other symptoms. The patient was then in an advanced cachectic state, and 
 died in coma a few weeks after the appearance of the ocular symptoms. 
 
 21. Captain , forty-four years old, an officer of the Guards, had in the 
 
 spring received from his physician the information that he was diabetic, and in 
 August he came to Carlsbad. 
 
 The patient had during the preceding months at home felt some increased 
 thirst and some need of passing his urine more frequently than before ; still, 
 the quantity did not distinctly exceed the normal limits. Apart from the urine — 
 which at the time of the patient's arrival contained a considerable quantity of 
 glucose — there were scarcely any symptoms at all. All carbohydrates were 
 excluded from the food, and during a week of strict diet the patient's weight 
 went down from 86.7 kilograms to 85.3 kilograms. The man now gradu- 
 ally received increased amounts of carbohydrate. The urine remained nor- 
 mal in quantity and quality until more than 90 grams of Graham bread and 
 some vegetables were given. The patient had a splendid appetite, and one 
 day passed 18 grams of nitrogen with his urine. When 120 grams of Graham 
 bread were given, the mixed urine for twenty-four hours contained fully o.i 
 per cent, of glucose. The patient maintained his weight and felt as well as 
 ever. 
 
 II 
 
154 DIABETES MELLITUS AND GLYCOSURIA. 
 
 The next year the man again appeared at Carlsbad, on May 7th, His gen- 
 eral appearance had undergone a change for the worse, and there was an omi- 
 nous smell of acetone on his breath. The bodily weight had fallen to 83 kilo- 
 grams. The urine contained much glucose, and yielded a distinct though not 
 very marked Gerhardt's reaction. After an exclusion for five days of carbo- 
 hydrates the patient passed 2200 cu. cm. of urine, of a specific gravity of 1.018, 
 with 0.5 per cent, of glucose, and yielding a somewhat more pronounced reac- 
 tion with the solution of ferric chlorid than at the patient's arrival. The 
 patient now received, daily, a large piece of Seegen's almond-bread, which, as 
 it is sold in Carlsbad, contains a not inconsiderable quantity of starch, and a 
 generous supply of fish, meat, butter, and eggs. He then excreted 19.5 grams 
 of glucose daily and Gerhardt's reaction was less pronounced, though distinct. 
 He still lost in weight, and added to his bill of fare 100 grams of levulose 
 daily. The glucose in the urine increased from 19.5 to 34 grams in the 
 twenty-four hours, but the diaceturia evidently decreased and the patient 
 maintained his weight, which now was only 82.4 kilograms. Some ordinary 
 bread was now given, and the bodily weight rose to 83.3, which it still was 
 when patient left for home, after a stay of five weeks. There had constantly 
 been some diaceturia. 
 
 The patient, whom I asked concerning the presence of fat in the feces, 
 was able to detect no difference from the ordinary ^.ppearance. 
 
 On October 17th, while upon a fair amount of carbohydrates allowed by his 
 physician at home, the man expired in diabetic coma. No autopsy was per- 
 formed. 
 
 This case represents the most rapid transition from a distinctly mild to a 
 distinctly severe diabetes that I have ever witnessed. 
 
 22. V. X., thirty-five years old, a diplomatist, belonged to a family that has 
 given me diabetic, fatty, and gouty patients. The man had been a hard 
 smoker. In the course of a diplomatic mission to Asia he had to stand a good 
 deal of fatigue and of emotion. In the south of Europe he contracted malaria. 
 A few months afterward diabetes suddenly set in, and took the patient to 
 Carlsbad during three successive seasons. 
 
 The man was exceedingly sensitive in every respect, slept badly, and a 
 steep declivity made him giddy. The knee-jerks were present and moder- 
 ately strong. The sexual power was somewhat weak, although the patient 
 begot a child about two years after the beginning of his disease. The bodily 
 weight had lately kept at about 73 kilograms. A few days after our first 
 acquaintance he invited me to breakfast, where he consumed a piece of 
 Graham bread, a large piece of butter and another of cheese, one partridge, 
 two sausages, a considerable quantity of ham, and four eggs. We often after- 
 ward took meals together, and I always found him with an enormous appe- 
 tite. 
 
 The teeth grew more and more carious, and the tongue showed more and 
 more of the customary appearance in severe diabetes. The pulse was rarely 
 below 100. The skin was dry and the patient was often troubled by itching. 
 
 The urine after a few days' absolute diet contained between 1.4 and 1.6 per 
 
SYMPTOMS AND COMPLICATIONS OF DIABETES. 1 55 
 
 cent, of glucose in about three liters. With the moderate quantity of carbohy- 
 drate necessary for the maintenance of the bodily weight and of a fairly good 
 general condition it increased to about four liters, containing between 2.6 and 
 3 per cent, of glucose. During the whole time Gerhardt's reaction was quite 
 distinct, and the urine was repeatedly found to contain some /3-oxybutyric 
 acid. A trace of albumin was always present. 
 
 When the patient arrived at Carlsbad for the third time there was no oppor- 
 tunity to analyze the urine. He was then in a state of utter exhaustion ; the 
 frequent pulse and the dyspneic respiration already foreboded coma, although 
 they were to some extent affected by a left-sided pneumonia. The patient 
 was seized with a chill on the cars. A flat sound on percussion was elicited 
 over the lower part of the upper lobe of the left lung, and in the same area 
 distinct, though distant, bronchial respiration was audible. Constipation had 
 been present for four days. 
 
 A large, tepid, rectal injection, with the addition of potassium permanganate, 
 whisky and enormous doses of sodium bicarbonate by the mouth, were imme- 
 diately given. Coma gradually overwhelmed the patient, the specific gravity 
 of the urine, which from the beginning of his disease had always been above 
 1.035, falling to 1. 019, and the glucose to 1.3. Gerhardt's reaction, which had 
 been very pronounced, became much less so ; still, there seemed to remain some 
 ^-oxybutyric acid to the end. There was some expectoration of pneumonic 
 sputa. Death took place six days after the patient's arrival. 
 
 On postmortem examination a central, small pneumonia was found in the 
 left lung. The pancreas was perhaps somewhat too soft in consistency and 
 undersized ; otherwise it was normal. The liver was in a state of pronounced 
 fatty degeneration. The spleen was hyperemic and about twice the normal 
 size. The kidneys were large, hyperemic, with the cortex slightly discolored 
 by fatty degeneration. 
 
 23. Miss B., a teacher of music, after a severe attack of influenza was seized 
 with severe diabetes. 
 
 Her general health failed rapidly, and she lost quickly in weight, in spite 
 of an enormous appetite. She passed daily about four liters of urine. 
 
 One year and a half after the beginning of the glycosuric dystrophy she 
 came to Carlsbad in a most miserable cachectic and marantic condition. 
 Eighty grams of Graham bread and some vegetables in the food yielded 2000 
 cu. cm. of urine, with a specific gravity of 1.037, containing 4.4 per cent, of 
 glucose and yielding a strongly marked Gerhardt's reaction. The day before 
 coma set in I took a specimen of the urine and found, after thorough fermenta- 
 tion and precipitation with ammonia and lead acetate, the ray of polarized light 
 deflected to the left between 0.4 and 0.5° in Hoppe-Seyler's instrument. 
 
 During her three weeks' stay at Carlsbad a most wonderful contrast was 
 evident between her miserable somatic and her splendid mental state ; her 
 courage not only keeping her in a happy frame of mind, but enabhng her con- 
 stantly and patiently to cheer another (most intractable) diabetic lady. I had 
 not omitted to warn her of the danger of any continued constipation ; never- 
 theless she remained in such a state for four days without taking the prescribed 
 
156 DIABETES MELLITUS AND GLYCOSURIA. 
 
 measures. She then, during a walk in the woods, was seized with the pro- 
 dromes of coma, and was brought back to her hotel, where I immediately 
 arrived. The brave little patient presented a pulse of 120 and the ominous 
 "blowing" respiration. An immediate purging injection was given; she 
 besides received whisky, enormous doses of sodium bicarbonate in Geisshiibler 
 water, and general massage. Being able to take no solid food, the patient 
 drank a good deal of levulose in Geisshiibler water. After a distinct but trans- 
 itory improvement the coma gradually overpowered the patient, and after 
 more vigorous clonic convulsions than I ever saw before with this kind of 
 death, the girl succumbed on the third day. 
 
 24. Augusta J., forty years old, a widow who had married again, grieved 
 greatly at the drunkenness and general moral degeneracy of her second hus- 
 band, a laborer, and was suddenly seized with symptoms of diabetes. On 
 October 29, 1891, about a year after the beginning of her diabetes, the woman 
 entered Queen Sophia's Hospital, in Stockholm, to be operated on for cata- 
 ract by Dr. Nordenson, who, previously to the operation, confided her to my 
 care for her diabetes. 
 
 The patient was very thin, with a dry, scaly skin. Her tongue was thickly 
 coated at its base, and presented the customary diabetic type, " a la peau croco- 
 dile'' with some fleshy-looking patches and an atrophic mucous membrane. 
 The teeth were carious and the breath smelled of acetone. 
 
 The patient suffered from continuous headache and slept badly. There was 
 no knee-jerk. Hearing was poor; vision, which was excellent a year before, 
 was destroyed by the soft, diabetic cataract. At the apex of the right lung there 
 was in a small area a somewhat sharp respiratory sound and a higher-pitched 
 percussion-note. The pulse was 100. 
 
 The headache might have been a precursory sign of coma ; but it had lasted 
 for a whole year, and could be more easily explained in almost any other way. 
 The urine, — which with an almost free diet amounted to about three liters, of 
 high specific gravity, and contained six per cent, of glucose and a trace of 
 albumin, — after fermentation of the glucose and precipitation of the combined 
 glycuronic acids with lead acetate and ammonia, deflected the ray of polarized 
 light to the left only slightly (0.2° with Hoppe-Seyler's instrument), and 
 yielded a moderately pronounced Gerhardt's reaction. On account of the 
 presence of but a small amount of /3-oxybutyric acid, I considered it not 
 dangerous for three days to exclude carbohydrates from the food. The patient 
 received an abundant food in eggs, fish, different meats, and butter — a seem- 
 ingly much better diet than her poor fare at home, chiefly consisting of herring 
 and potatoes. After three days, when I had found out how much glucose was 
 being excreted with the strict diet, the patient was to receive 60 grams of white 
 bread and a considerable amount of vegetables every day. 
 
 Polyuria and glycosuria quickly diminished, but Gerhardt's reaction became 
 much more marked, even comparatively, and during the night of November 
 2d-3d violent diarrhea began. When I visited the patient on the morning 
 of November 3d, coma evidently was threatening. Respiration was blowing 
 and dyspneic, the pulse 120, the temperature in the rectum 35° C. (95° F.) in 
 
DIABETES INFANTILIS. I 5/ 
 
 the morning and 34.4° C. (93.9° F.) in the afternoon. The patient was given 
 brandy in strong tea, together with eggs, biscuits, and enormous quantities of 
 sodium bicarbonate water. When she could eat no biscuits, and no levulose 
 could be had, I gave her cane-sugar in my anxiety to increase the carbo- 
 hydrates. Marked improvement followed, and when the danger of coma 
 seemed much diminished, some opium was given for the diarrhea. The 
 patient improved greatly. On November 7th the pulse was 84, the temperature 
 36.8° C. (98° F.), respiration almost normal, the sensorium and intelligence 
 seemed quite free, and I began to hope that I should escape too severe con- 
 sequences of this ill-timed dietetic system, still defended by powerful 
 authorities. Diarrhea, however, again began on November 8th, and the 
 patient became more and more comatose, and died on November i6th. Dur- 
 ing the period of coma the glucose sank to 0.7 per cent., the urea to 0.35 per 
 cent., the chlorids likewise to a minimum, and the specific gravity to 1.013. 
 The phosphoric acid decreased less, and was o.i per cent. The temperature, 
 which before had constantly been somewhat below the normal, during the last 
 days went up to 38° C. (100° F.) in consequence of the pulmonary lesion. 
 
 On postmortem examination the muscles were found dry and atrophic, the 
 dura somewhat thickened, the pia distended with edema, the heart small, 
 pale, and flabby, while the right lung contained a caseous focus. The liver 
 was partly in a state of fatty degeneration and partly exhibited rose-red spots 
 and an appearance suggestive of the nutmeg-liver. The pancreas was in 
 every respect normal. The kidneys were large, flabby, pale, with the cortex 
 somewhat discolored. The spleen was normal. A strong smell of acetone 
 filled the room. 
 
 CHAPTER V— DIABETES INFANTILIS.^ 
 
 The pathologic excretion of glucose is much rarer in children 
 than in adults, and almost always represents either a simple, trans- 
 itory glycosuria from some accidental cause, or a severe diabetes, 
 which may lead to death in the course of a few weeks, and hardly 
 ever fails to do so in the course of a few years. Still, in excep- 
 tional cases it happens that a child suffers from protracted dia- 
 betes in the mild stage. 
 
 * Niedergesass (1873), Redon (1877), Kiilz (1878), Leroux (1880), Stern (i 
 and others have written on Diabetes infantilis. 
 
158 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Simple glycosuria in children generally occurs in conjunction 
 with neuroses and with the infectious fevers, but it may arise from 
 any cause that has the same effect in adults. It has been observed 
 by a number of clinicians in cases of diphtheria, scarlet fever, and 
 measles, and also in cases of epilepsy, chorea, supraorbital neuralgia 
 (Franque, Goolden, and others). In cases of pertussis and croup 
 it may be the result of asphyxia (Laborde). Lecoq mentions the 
 appearance of from o.i to 0.2 per cent, of glucose in the urine of 
 healthy children who had eaten sweets (? ?). Parrot found glucose 
 in more than one-third of all athreptic children, especially in those 
 that were cyanotic. I have several times found distinct traces of 
 glucose in boys that had been addicted to masturbation. I believe 
 that in many such cases true diabetes may develop in middle age, 
 though one may see glycosuria disappear in other cases. Pro- 
 tracted glycosuria is much rarer, and is of much greater significance 
 in children than in adults.* 
 
 True diabetes is so rare in early childhood that many an expe- 
 rienced children's physician and many a specialist in diabetes have 
 never seen a diabetic patient under ten years of age. Romberg 
 observed among 5900 infant patients but a single case of diabetes. 
 Schmitz encountered among 21 15 cases of diabetes 10 patients in 
 the first and 75 patients in the second decad of life. 
 
 Prout saw among 700 cases of diabetes one child under five 
 years old.f It is only by mere accident that in the course of little 
 more than a year (1895- 1896) I have been consulted in four cases 
 of diabetes in children under ten years of age, while previously I 
 had seen but a single such case. On the other hand, I have seen 
 a not inconsiderable number of cases in children between ten and 
 
 * Cantani urges the necessity of looking for glucose in cases of nocturnal enuresis. 
 If one does so, and in the presence of a reducing-substance verifies it as glucose by the 
 fermentation-test, he will find that in the great majority of the common cases of nocturnal 
 enuresis the urine is free from glucose. 
 
 f I have, unfortunately, taken notes of my diabetic cases only during recent years, 
 and do not know their number ; but my 5 cases of diabetes in children under ten years 
 occurred — one in a girl six years old, in the central part of Sweden ; another in a girl four 
 years old, in Stockholm ; 2 boys of four and of nine years, respectively, in Stockholm; 
 and one boy of four years, in New York. For two of my cases in Stockholm and for 
 the case in New York I am indebted to my esteemed friends. Dr. Nettelbladt and Dr. 
 Kinnicutt, respectively. 
 
DIABETES INFANTILIS. I 59 
 
 fifteen, and some in girls and boys between fifteen and twenty years 
 old. Statistics show that the third quinquennium of life, — viz., from 
 ten to fifteen years, — of the first four quinquenniums is that in which 
 diabetes occurs most frequently. In the period from fifteen to 
 twenty years diabetes again becomes rarer, while from the latter 
 age it continues to grow more frequent. 
 
 It is of great interest to see how the total frequency increases, and how the 
 greater frequency among boys than among girls shows itself from the second 
 decad, in which both sexes begin to be somewhat strained intellectually, and 
 in which, unfortunately, sexual excesses (masturbation) among boys already 
 begin to become frequent. Among 136 cases of diabetes up to the age of fifteen 
 years, there were 27 cases during the first, 32 during the second, and ']'] during 
 the third quinquennium of life (Leroux). Pavy has observed 5 girls and 3 boys 
 in the first, and 35 boys and 22 girls in the second decad of life. 
 
 In children under ten the relative frequency in the two sexes differs from 
 the analogous figures later in life. In adults the ratio between diabetic men 
 and diabetic women is best represented by the figures 3:1. But among dia- 
 betic children under ten years of age we find at least as many girls as boys. 
 Among 102 cases at this period there were 57 girls and 45 boys. Leroux alone 
 has observed what he calls a " statistique favorable aux gargons'' : namely, 22 
 boys and 16 girls. Kiilz's and Leroux's figures from different sources and my 
 own 5 cases make up the usual small majority for the girls in early childhood : 
 75 girls and 70 boys. 
 
 The causes are, of course, the same for children as for adults, 
 but there is some difference in their relative efficiency. Hereditary 
 influence is exceedingly important in childhood. Isenflamm, as 
 early as 1784, mentions an instance of diabetes in 7 brothers, who 
 all died at the age of seven or eight years. Roberts observed 8 
 diabetic children in the same family ; Watson, Bence -Jones, and 
 West each saw 3 ; and in India such cases are common. I am in- 
 clined to believe that infectious diseases are the most frequent acci- 
 dental cause of diabetes in children ; in adults emotions and mental 
 sufferings play a much more important role. Trauma is the cause 
 of a greater percentage of infantile than of other cases. Finally, 
 both from reports in literature and from two of my own cases, I am 
 inclined to believe that starvation is a relatively more frequent cause 
 in childhood than later in life (Andral, Heine, Senator, Ingerslev, 
 and others have seen such cases). 
 
 Infantile diabetes usually is like the worst cases in adults, and 
 presents itself as a terrible dystrophy with a rapid course. It 
 
l60 DIABETES MELLITUS AND GLYCOSURIA. 
 
 is especially in these cases that one sometimes hears the date of 
 the attack named. " The 20th of April my boy was in perfect 
 health ; the 21st he was very ill, and drank as much as he could 
 the whole day," the father of a four-year-old diabetic boy told 
 me some time ago. The little victims suddenly stop playing and 
 become quiet and drowsy, irritable and peevish. The diabetic 
 symptoms rapidly reach a maximum of intensity. There are on 
 record reports of cases in which sixteen liters of urine and one kilo- 
 gram of glucose were secreted in the twenty-four hours. The 
 urine usually is pale, greenish-yellow in color, and of high specific 
 gravity. In a case seen by Redon the latter was 1.070. Ger- 
 hardt's reaction is often distinct from the beginning. In a few 
 months the cavity of the mouth may present a furrowed tongue, 
 partly with a thick, brownish covering, partly with fleshy, flayed- 
 looking patches, and carious teeth ; it often becomes the seat of a 
 luxuriant vegetation of Oidium albicans. The soft, diabetic cataract 
 may develop in an amazingly short time, and at quite an early age. 
 In one of my cases, to be related later, the patient was fourteen 
 years old. The face is either pale or it may present a circumscribed, 
 cyanotic, red discoloration on the cheeks ; the skin is dry and 
 squamous. Girls suffer from vulvitis, boys from phimosis and balano- 
 posthitis. The loss of flesh can not be checked, and the children 
 become exceedingly weak and have to keep their beds. The tem- 
 perature, apart from febrile complications, keeps below the nor- 
 mal, but even in these cases rarely below 36° C. (96.8° F.). 
 
 The prognosis is extremely bad, and I do not know that in any 
 of the typical infantile cases the patient has returned to health.* 
 
 In cases of diabetes in the first decad of life death often takes 
 place within a year ; a longer duration than two years after the 
 first appearance of symptoms at this age is rare, and the rarer, the 
 younger the patient. In some cases the dystrophy leads to death 
 
 * There are many reports of complete recovery even from infantile diabetes. Of 96 
 cases from 11 different writers I find 8;^ with a fatal issue and 13 in which recovery 
 ensued. These reports are as unreliable as the analogous ones concerning adult cases. 
 But as in cases of diabetes from infections and from trauma the prognosis is better than 
 in other cases, and as these causes are relatively frequent in infantile cases, I presume 
 that true diabetes in a child — which may be a mild diabetes — now and then has dis- 
 appeared. 
 
DIABETES INFANTILIS. l6l 
 
 in a few weeks. The fatal issue in most cases is brought about by 
 coma or marasmus.* 
 
 As infantile cases are comparatively rare, I record here one of my own from 
 each of the four first quinquenniums. 
 
 Ellen W., four years old, had an insane aunt. The father is very " reli- 
 gious." On December i6th I was called to see the child, and on asking about 
 the duration of the disease the mother answered : " She fell ill the 5th of 
 November." 
 
 The girl was pale and almost only " skin and bones." The tongue already 
 presented the diabetic type, the teeth were carious, and the breath smelled of 
 acetone. Thrush reappeared in several places constantly as quickly as it was 
 got rid of. The child was irritable, but otherwise drowsy ; a certain degree of 
 poisoning was already manifest. The reflexes were extinguished. Severe 
 epigastric pain caused the patient to cry out with anguish. The pulse was 80, 
 the temperature in the rectum 36.2° C. (97.2° F.). 
 
 The child received about 75 grams of bread with her food. The urine ex- 
 creted amounted to 2500 cu. cm., had a specific gravity of 1.040, and yielded a 
 pronounced Gerhardt's reaction, some /3-oxybutyric acid, and a large quantity of 
 glucose. The introduction of this allowance of carbohydrate after the previous 
 strong restriction was followed by decided improvement; coma, however, was 
 only put off for four weeks. No postmortem examination was held. 
 
 B., a boy nine years old, had a " nervous " mother, two insane aunts, and 
 an uncle who died by suicide. (There are, however, reasons for suspecting the 
 boy's diabetes to be of pancreatic origin. See below.) 
 
 About a year before the child came under my observation he began to wet 
 his bed, and the family physician found an abundant quantity of glucose in the 
 urine. 
 
 When I saw the boy on April i, 1896, he was in an exceedingly miserable 
 state. His appetite was voracious. He had, however, lost a great deal of 
 weight, and the outlines of the wasted muscles were distinctly to be seen 
 through the dry, atrophic skin. The mental state had lately gone from bad to 
 worse, and the boy, who had previously been of a gentle disposition and of 
 quite excellent parts, was now usually apathetic, but on the slightest provoca- 
 tion was subject to attacks of violent rage, followed by deep depression. Sleep 
 rarely came before three in the morning. After exertions attacks of general 
 clonic spasms occurred, with full consciousness. A continuous headache exacer- 
 
 * In 21 cases collected by Redon from different writers there were 9 deaths from 
 marasmus without coma, 3 from marasmus with coma, 4 from pulmonary tuberculosis, 3 
 from acute inflammation of the lungs, and 2 from cerebral affections. Concerning these 
 statistics, it may be remarked that the number of deaths attnbuted to coma is doubtless 
 much too small ; coma seems to be the most frequent mode of death in cases of infantile 
 as well as those of other severe forms of diabetes. 
 
1 62 DIABETES MELLITUS AND GLYCOSURIA, 
 
 bated in the morning and in the evening. Sciatica was present on both sides. 
 The knee-jerk was slight on the left, but almost normal on the right side. On 
 the left leg sensibility was distinctly diminished. Psoriasis was present on both 
 knees. Vision was normal. The pulse was 66, the temperature in the rectum 
 37.3° C. (99° F.). Later, the patient's mental state did not permit thorough 
 examination. 
 
 The feces consisted partly of white-colored fatty masses. (Were it not for 
 this symptom, one might be inclined, on account of the strong neurotic in- 
 heritance, to consider the case one of neurogenic diabetes.) 
 
 After considerable though not absolute restriction of carbohydrates a large 
 sample of urine was found to have a specific gravity of 1.038 and to contain 
 6.6 per cent, of glucose, some diacetic acid, but not an appreciable amount of 
 j8-oxybutyric acid. The disease, which probably for some time had kept within 
 the light stage, had lately, according to a chemist's calculation, caused a loss of 
 nearly one kilogram of glucose a day. The maximum measured quantity of 
 urine in my observation, however, did not exceed eight liters. 
 
 The boy had previously lived on a more or less rigid diet, but on account of 
 his despair with regard to his food some concessions had lately been made. 
 The state was such that none of the three physicians who saw him believed 
 that his life would be spared for more than a few weeks. The treatment now 
 was directed chiefly against the nervous symptoms. The diet was changed, 
 and the patient was allowed to eat as much bread as he wished, and green vege- 
 tables and levulose were added to his bill of fare. The polyuria and the poly- 
 dipsia, of course, increased at once, but the mental and general state improved 
 manifestly, and the hitherto continuous loss of flesh stopped. To our amaze- 
 ment the patient lived not only through the whole of 1896, but also through 
 the greater part of 1897, and died in October of that year, not from coma or 
 marasmus, but from a carbuncle on the head. I did not dare to ask for a post- 
 mortem examination. 
 
 It is my firm opinion that any considerable restriction of carbohydrates 
 would have led to a much earlier death, though I fully acknowledge the small 
 value of the patient's last year for himself and others. 
 
 Anna Charlotta J., fourteen years old, did not know much about her family, 
 but described the evident epilepsy of her sister. 
 
 At the age of twelve the girl lived for two months as a servant with some 
 poor people, and literally starved. When she again returned to the compara- 
 tively good table of her home, she became diabetic. 
 
 Somewhat more than two years afterward the child was admitted to Queen 
 Sophia's Hospital in Stockholm to be operated upon for typical, diabetic, soft 
 cataract on both eyes (Nordenson). I found her very thin, pale, and anemic, 
 with a dry, scaly skin. She was moderately depressed, somewhat irritable, 
 slept fairly well, had normal knee-jerks, and felt " creepings " in the arms and 
 legs. The teeth, though still fairly good, now began to be carious, and the 
 tongue was dry and of a vivid red, while fissures formed in both angles of the 
 mouth. The appetite was voracious. The liver was normal in size, consis- 
 tency, and sensibility. The bowels were somewhat sluggish. 
 
DIABETES INFANTILIS. I 63 
 
 Over the apex of the right lung in one place there was some flatness of the 
 percussion-note. 
 
 The pulse was 120 in the morning. The temperature was somewhat below 
 the normal during the whole time. The weight was 28!kilograms. 
 
 A sample of urine obtained when the patient, who had eaten whatever she 
 wanted, arrived had a specific gravity of 1.046, contained 9.2 per cent, of glu- 
 cose, was free from albumin, and yielded a dark bluish-purple reaction with 
 ferric chlorid. 
 
 During the first days the patient received 90 grams, and afterward 60 grams, 
 of rye-bread, some green vegetables, and four glasses of unskimmed milk a 
 day, with much butter, meat, fish, and eggs. 
 
 The bodily weight increased from 28 kilograms on December ist to 30 
 kilograms on December 23d. Then dyspeptic troubles arose, with diarrhea 
 and a loss of weight in one week of nearly two kilograms. Opium was given 
 and the patient was allowed 80 grams of white bread daily. 
 
 By January 5th -the girl had regained her bodily weight and reached her 
 maximum of 30.3 kilograms. The general state also was at its best. The 
 daily portion of bread was again reduced to 60 grams. With this diet the 
 urine amounted to from 2 to 2.5 liters and contained upward of 5 per cent, of 
 glucose. Gerhardt's reaction constantly was pronounced, as manifested by a 
 rich Burgundy color; after fermentation and precipitation with ammonia and 
 lead acetate the urine still deflected the ray of polarized light in Hoppe-Seyler's 
 instrument about 0.2 degrees to the left (/3-oxybutyric acid). The urine from 
 8 P. M. to 8 A. M. generally was a little more abundant than the urine collected 
 during the day, but not rarely the contrary happened. 
 
 On January 7th the urine for twenty-four hours amounted to 2125 cu. cm., 
 and had a specific gravity of 1.034, with 4.4 per cent, of glucose. It yielded, 
 as usual, a marked Gerhardt's reaction, and, for the first time, contained a 
 small quantity of albumin. 
 
 On January loth the patient presented the well-known prodromes of coma. 
 She had been very uneasy during the night, and was then in terrible anguish, 
 but intelligence and sensorium were still clear. The patient complained, at 
 times with loud cries, of violent epigastric pains. The pulse was nearly 150, 
 the respiration 28. The girl was given tea with brandy, liquor ammoniac, 
 anisatus, a rectal injection of tepid water, a warm bath (39° C.) (102.2° F.), and 
 general massage. The diet was unrestricted, and enormous quantities of 
 sodium bicarbonate were given in soda-water. After a marked but transitory 
 improvement the patient struggled on, with shght changes, until the 12th, when 
 drowsiness became manifest. The epigastric pains had now stopped, the res- 
 piration was 25, the pulse 132 ; the 2125 cu. cm. of urine had a specific gravity 
 of only 1. 021, with 2.7 per cent, of sugar and some diacetic acid. On January 
 13th the specific gravity was i.oig and the glucose 1.2 per cent. The patient 
 remained conscious until noon, with only slightly impaired intelligence, but 
 then became comatose and died quietly at 7 A. M. 
 
 Upon postmortem examination the dura mater was found somewhat thick- 
 ened, the pia distended by an abundant edema. The fourth ventricle and the 
 aqueduct of Sylvius and adjacent parts seemed to the naked eye normal. 
 
164 DIABETES MELLITUS AND GLYCOSURIA. 
 
 beyond some perivascular spaces, such as Dickinson has described. A large 
 part of the sympathetic nerves was carefully dissected, and seemed perfectly 
 normal. The heart was pale and small. At the apex of the right lung was a 
 caseous nucleus of the size of a pea. The pancreas was normal. The liver 
 was somewhat hyperemic. The mesenteric glands were enlarged ; one of them 
 was caseous. The kidneys were large and hyperemic. 
 
 Miss G. v., nineteen years old. with a maternal neurotic inheritance, began 
 to feel exceedingly thirsty in November, and consulted me January 28th. 
 
 There was polydipsia, polyuria, and pollakiuria. The formerly gentle dis- 
 position of the patient was changed into one of great irritability. Sleep was 
 bad, and there was constant headache. The knee-jerks were very weak. 
 The teeth were partly carious, partly absent. The gingiva around a molar 
 tooth was swollen, and an incision was followed by the escape of a drop of 
 pus ; a probe passed rather deep along the root of the tooth. The tongue 
 was coated, and with a dry, bright-red apex. A strong smell of acetone was 
 present on the breath. 
 
 The patient was exceedingly anemic, and over the jugular vein a pronounced 
 " bruit du diable " was audible. The apex of the right lung was slightly 
 infiltrated. 
 
 A specimen of urine had a specific gravity of 1.040, with 8.2 per cent, of 
 glucose, a marked Gerhardt's reaction, and a small quantity of ;8-oxybutyric 
 acid. 
 
 Sixty grams of white bread and some green vegetables in the food yielded 
 about 170 grams of glucose a day in 3000 cu. cm. of urine. 
 
 At the end of May the patient died in diabetic coma. 
 
 CHAPTER VI.— DIABETES MELLITUS FOLLOWING EXTIR- 
 PATION OF THE PANCREAS. 
 
 As I have mentioned, a connection between lesions of the pan- 
 creas and the glycosuric dystrophy had long been suspected by 
 many and accepted by some. Finally, in 1889, v. Mering and 
 Minkowski communicated to the Association for Natural Sciences 
 of Strasburg their great discovery that total extirpation of the pan- 
 creas gives rise to severe diabetes, characterized by glycosuria 
 under all dietetic conditions, polydipsia and polyuria, rapid loss of 
 weight, the presence of acetone, diacetic acid, /3-oxybutyric acid. 
 
DIABETES MELLITUS AFTER REMOVAL OF PANCREAS. 165 
 
 and an increased amount of ammonia in the urine, and death in 
 diabetic coma. These admirable and successful investigators had 
 discovered the only certain method yet known of producing " arti- 
 ficially" true severe diabetes. They had, further, studied this form 
 of diabetes conscientiously. Minkowski afterward continued the 
 researches in a careful and extensive scientific investigation. About 
 the same time De Dominicis, in Italy, independently of others, also 
 observed (in dogs) diabetes after extirpation of the pancreas. 
 
 Later, Aldehoff, Sandmeyer, Lepine, Hedon, Gley, Thiroloix, 
 Chauveau and Kaufmann, Gaglio, Caparelli, and others made re- 
 searches on diabetes after extirpation of the pancreas. Unfortu- 
 nately, these researches have on many points led to such different 
 results that definite conclusions are at present impossible, though, on 
 the other hand, many important facts have been added to our stock 
 of knowledge. 
 
 Diabetes mellitus following extirpation of the pancreas has been 
 observed in dogs, cats, and hogs (v. Mering and Minkowski), 
 hawks (Langendorf), falcons (Weintraud), geese (Kausch), turtles 
 and frogs (Aldehoff, Marcuse, Velisch). Kausch observed the 
 extremely interesting fact that in birds hyperglycemia may reach 
 much higher figures — up to 0.5 per cent. — than in mammals with- 
 out causing glycosuria. This doubtless is the reason why the 
 urine after operations on birds (pigeons and ducks) has sometimes 
 been found free from glucose. The normal glycemia in birds 
 seems to amount to only 0.14 or 0.15 per cent. (Kausch). 
 
 For the details of the operation reference may be made to the 
 special works. The technical difficulties are quite considerable, and 
 the object of the experiment is often frustrated by necrosis of the 
 duodenum and other complications. The French experimenters 
 have generally injected paraffin, asphalt, etc., into the pancreatic 
 duct, resulting in atrophy and induration of the gland, and a 
 couple of weeks afterward they have performed the operation of 
 extirpation. 
 
 I here follow chiefly Minkowski ; the facts, when no mention is 
 made to the contrary, refer to the dog. 
 
 Glycosuria generally begins a couple of hours, sometimes much 
 later, after the operation ; in 50 per cent, of the cases it appears 
 within five hours (Lepine). It generally reaches its maximum on 
 
1 66 DIABETES MELLITUS AND GLYCOSURIA. 
 
 the third day, with from lo to 12 percent.* of glucose in about 1.5 
 hters of urine. The hyperglycemia may reach 0.9 per cent., but 
 rarely exceeds 0.5 per cent. As already mentioned, the relation be- 
 tween the hyperglycemia and the glycosuria is not a fixed one, and 
 some influence on the part of the kidneys must be admitted. If the 
 animals escape other complications, the glycosuric dystrophy leads 
 in a few wrecks to diabetic coma. 
 
 If any considerable part of the pancreas — one-eighth or one- 
 twelfth — is left, diabetes does not result. Hedon found the reten- 
 tion of even about one-thirtieth sufificient to prevent the develop- 
 ment of the glycosuria. By leaving a small part of the gland one 
 may restrict the effect to a slight glycosuria or to a mild diabetes, 
 and it has been found that all the different stages of the glycosuric 
 dystrophy may be effected by resection of the pancreas. 
 
 Chauveau and Kaufmann have found that if the spinal cord is 
 divided in the lower cervical or upper thoracic region before extir- 
 pation of the pancreas, the operation is not followed by glycosuria. 
 I shall recur later to their experiments and conclusions. 
 
 Hedon and Thiroloix both are of the opinion that a gradual and 
 slow destruction of the pancreas (by injections of different sub- 
 stances into it) may take place without causing glycosuria (?). 
 
 Fever diminishes and phloridzin increases the glycosuria follow- 
 ing extirpation of the pancreas. 
 
 The sugar in the urine has been proved to be glucose, not mal- 
 tose. 
 
 When carbohydrates are excluded from the food after total 
 extirpation of the pancreas, there gradually arises a fixed relation 
 between the glucose and the nitrogen in the urine, a relation which 
 is represented by the figures 2.8:1. When carbohydrates are 
 given, it seems that during the highest intensity of the dystrophy 
 all the glucose produced is excreted, and this fact and the fixed 
 relation between the glucose and the nitrogen in the urine during 
 exclusion of carbohydrates would — if one does not accept the 
 presence in the hXoodi oi 2. ^' iiiatcria peccans'' — seem to indicate 
 that with the destruction of the pancreas something is lost to the 
 organism that is necessary for the combustion of every molecule 
 
 * Hedon, by giving only bread as food, increased the glycosuria to 22 per cent. 
 
DIABETES MELLITUS AFTER KEMOVAL OF PANCREAS. l6j 
 
 of glucose. During other periods of the diabetes following total 
 extirpation of the pancreas, however, according to all researches, a 
 certain part of the ingested glucose is used up in the organism. 
 Then, — though the conditions for the production of glucose from 
 proteids are not fully known, — theoretically, out of lOO grams of 
 proteid, minus the carbon necessary for the production of urea, 
 there might be produced 213 grams of glucose and only 16 grams 
 of nitrogen — z. e., much more than only 2.8 times as much glucose 
 as nitrogen. 
 
 It thus seems that though the pancreas is proved to have a 
 specific function in the utilization and combustion of glucose, it 
 may not be alone concerned in this phase of bodily activity. 
 
 Minkowski, after giving large amounts of levulose, observed 
 increased glycosuria, but found that a smaller part of this mono- 
 saccharid had passed unchanged into the urine. After 200 grams 
 of levulose by the mouth the urine contained 105.6 grams of 
 glucose and 15.6 grams of levulose. There were 7.8 grams of 
 nitrogen, so that 21.84 grams (7.8 X 2.8) of glucose were derived 
 from proteids. The rest — 83.76 grams of glucose — was thus 
 derived from the levulose. 
 
 Minkowski failed, after giving considerable amounts of maltose, 
 saccharose, and lactose, to find any of these disaccharids in the 
 urine unchanged, probably because the quantities were not large 
 enough ; in fact, none of them seems to have been given in as 
 large amount as the levulose. The glycosuria was increased by 
 all three of the disaccharids. 
 
 After extirpation of the pancreas the animals quickly lose flesh, 
 sometimes in the course of a fortnight losing more than one-third 
 of their bodily weight. This is a necessary effect of the deficient 
 digestion and of the enormous glycosuria. Abelmann found 43 
 per cent, of fat ingested in emulsion, almost all other fat and 56 
 per cent, of ingested proteid in the feces, which also contained 
 large quantities of undigested bread. Kaufmann found that dia- 
 betic dogs of from 8 to 15 kilograms in weight, subjected to abso- 
 lute starvation, lost from 250 to 500 grams in weight a day, while 
 normal dogs of the same size under similar circumstances lost only 
 between 160 and 175 grams. 
 
 Glycosuria and impaired digestion, according to the opinion of 
 
1 68 DIABETES MELLITUS AND GLYCOSURIA. 
 
 most investigators, are not the only causes of autophagy in these 
 and in other cases of severe diabetes. A third cause is the almost 
 universally diCCQ^ied protoplasmic, toxic disintegration of the proteid 
 cellular substances of the organism. 
 
 Minkowski failed in some cases after total extirpation of the pan- 
 creas to find diacetic acid and /S-oxybutyric acid in the urine, both 
 of which, so far as my experience goes, are constantly found in 
 equally severe cases in man. Further investigations in this respect 
 seem necessary, but it is possible that the production of these acids, 
 which certainly are in some way connected with the excretion of 
 glucose produced by proteids, is governed by other conditions in 
 the dog than in human beings. The diabetic animals completely 
 oxidize ingested acetone (Schwarz), but the ingestion of diacetic 
 acid (Schwarz) and of /5-oxybutyric acid (Minkowski) is followed 
 by acetonuria. 
 
 The lactic acid in the muscles was found to be greatly dimin- 
 ished. The glycogen was also greatly reduced in the liver and in 
 the muscles — probably on account of the acidosis, which in most 
 cases was quite pronounced. Syzygium jambulanum had no de- 
 creasing effect upon the glycosuria. 
 
 The diabetes following extirpation of the pancreas is a direct 
 effect of the removal of the gland. It does not result from the 
 absence of the pancreatic juice, for ligation of the pancreatic duct or 
 the production of a fistula through which the juice is conducted 
 outside the organism causes no diabetes. Neither does the dys- 
 trophy result from a lesion of the solar plexus, as has been sup- 
 posed. Minkowski proved this theory to be false by leaving a part 
 of the pancreas in connection with its vessels outside the perito- 
 neal cavity under the skin, without the development of diabetes, 
 while subsequent removal of this remaining piece of pancreas was 
 followed by the customary diabetes. 
 
 Either the removal of the pancreas causes something to disap- 
 pear from the blood that is necessary for the normal combustion 
 and utilization of the sugar, or it causes something to remain in the 
 blood that prevents the combustion and utilization of sugar. 
 
 It has been proved that injection of diabetic blood into the veins 
 of a healthy animal does not produce even transitory diabetes. On 
 
METABOLISM AND NUTRITIVE NEEDS. 1 69 
 
 the other hand, it was shown by Claude Bernard that the normal 
 blood contains something that causes the sugar in it to disappear 
 after it has been for some time outside the organism. These facts 
 have led many to the acceptance of a theory that extirpation of the 
 pancreas causes diabetes by removing something that is produced 
 in the pancreas as an " internal " secretion and is given up to the 
 blood, where its presence is necessary for the combustion of the 
 sugar. Lepine and his disciples, and even some of his antagonists, 
 found that the blood of dogs, diabetic after extirpation of the pan- 
 creas, both within and without the organism, loses its sugar less 
 quickly than does normal blood. Kausch saw an analogous 
 phenomenon in birds. Schwarz found that, though dogs after extir- 
 pation of the pancreas seem to oxidize as large amounts of acetone 
 as normal dogs, the former, diabetic dogs, unlike normal dogs, 
 after ingestion of diacetic acid exhibited acetonuria. All this has 
 strengthened the position of those who consider diabetes an effect 
 of decreased consumption of sugar. In the next chapter we shall 
 find that, even if these observations are correct, they alone do not 
 settle the question of the immediate causes of diabetes — a question 
 the solution of which is one of the most difficult and complicated 
 tasks that are at present engaging the attention of students of experi- 
 mental pathology. 
 
 CHAPTER VII.— METABOLISM AND NUTRITIVE NEEDS. 
 
 Notwithstanding the progressive strides that have been made 
 in recent years, the metabolic changes that take place in diabetes 
 are but imperfectly known. 
 
 By following as well as we can the carbohydrates, the fat, and 
 the proteids on their way through the organism we may, however, 
 obtain a conception of the respective processes, which is not with- 
 out considerable theoretic and practical value. In doing this we 
 must not omit to give some attention to corresponding processes in 
 normal orcranisms : neither must we lose sieht of the differences 
 
I/O DIABETES MELLITUS AND GLYCOSURIA. 
 
 between cases of mild and severe diabetes — /. e., between the patient 
 that excretes sugar only after ingestion of carbohydrates and the 
 one that exhibits glycosuria at the expense of proteids, and with a 
 diet consisting exclusively of these and of fat. 
 
 We have already seen that in the great majority of diabetic 
 cases digestion is perfectly normal. In such cases Pautz recently 
 found 7.59 per cent, loss of nitrogen and 3.54 per cent, loss of fat. 
 The maximum and minimum figures for nitrogen were 12.97 and 
 1.74 ; for fat they were 9.12 and 1.06 — i. e., just about what we are 
 accustomed to see designated as normal. As to carbohydrates, 
 Heller, as early as 1852, showed that they are, as a rule, normally 
 digested in cases of diabetes, and Hirschfeld's cases prove that this 
 often takes place, even when digestion of proteids and fat is im- 
 paired. Of ingested starch, normally from i to 7.4 per cent, 
 appears undigested in the feces. 
 
 The normal changes that carbohydrates undergo in the alimentary canal 
 must be borne in mind. Starch (or glycogen) digested by the mixed saliva (or 
 by the secretion of the parotid gland alone) yields achroodextrin and maltose* 
 and only small quantities of glucose (Musculus and v. Mering, Kiilz). The 
 diastatic ferment found in the stomach in the acid gastric juice is not very 
 active ; but in the duodenum the pancreatic juice is most efficient in the same 
 way as the saliva. The final products, however, of the digested starch, found 
 almost entirely in the portal system and only in comparatively minute quanti- 
 ties in the lymphatics, consist almost exclusively of glucose, together with some 
 traces of dextrin and maltose (C. Voit, Bleile, v. Mering), whether this result 
 has been brought about by the " invertin " from the mucous membrane of the 
 bowels (Tebb), or by the epithelium itself (Bunge), or by the blood (Bial, Roh- 
 mann). 
 
 Cane-sugar partly is decomposed into glucose and levulose, partly remains 
 unchanged in the stomach, and is so far absorbed in this state ; in the duodenum 
 this part of the disaccharid is also quickly decomposed into its monosaccharid, 
 levulose, and glucose by the pancreatic juice (Kobner). When taken in large 
 amounts like all saccharids it remains unchanged for some small part as cane- 
 sugar, not only in the bowels, but in its passage through the whole organism, 
 and it is found as such in the urine. 
 
 Maltose probably is already changed in the bowels into glucose (Voit). 
 
 Lactose, so far as it is not changed into lactic acid, etc., probably remains 
 in large part unchanged in the alimentary canal (Lusk) ; the different results 
 of numerous researches seem to me to indicate great individual and accidental 
 
 ''' Disaccharids and Monosaccharids. Maltose := glucose -}- glucose. Cane-sugar = 
 glucose -j- levulose. Lactose ^ glucose + galactose (Hammarsten). 
 
METABOLISM AND NUTRITIVE NEEDS. 
 
 171 
 
 variations. Lactose passes unchanged into the urine after smaller amounts 
 are taken than do the other saccharids (G. Voit, Bischoff, Hofmeister, and 
 others), and does often so during lactation. 
 
 In chickens and rabbits levulose seems to be absorbed in an unchanged 
 state (Fr. Voit, Lusk, Otto). Like all other saccharids, it passes partly un- 
 changed into the urine after large amounts have been taken. 
 
 Cane-sugar and maltose are in larger part (70 or 80 per cent.) absorbed 
 during the first hour after ingestion. Glucose seems to remain a little longer, 
 but lactose a less time in the stomach. 
 
 These results are gained chiefly in dogs whose food and digestion are simi- 
 lar to man's. Still, there seem to be differences, and normal dogs seem to 
 excrete glucose after the ingestion of large amounts of cane-sugar, which is not 
 the case with man. Rubner, by feeding dogs with cane-sugar exclusively, 
 found almost only this disaccharid in the urine on the first day, but afterward 
 gradually more and more glucose. Seegen found in dogs after the ingestion of 
 cane-sugar this saccharid in part in its unchanged state, in part as invert- 
 sugar (= glucose -f- levulose), while Praussnitz made the same observation in 
 chickens. 
 
 Lusk obtained the following results six and one-half hours after the inges- 
 tion of 30 grams of cane-sugar by rabbits : 
 
 
 Cane-sugar. 
 
 Glucose. 
 
 Levulose. 
 
 Stomach, 
 
 0.269 
 
 1.498 
 
 0.858 
 
 Duodenum and jejunum, . . 
 
 0.002 
 
 Traces. 
 
 Traces. 
 
 Cecum, 
 
 0. 
 
 0.846 
 
 1. 321 
 
 
 Colon and rectum, 
 
 0. 
 
 Small amounts. 
 
 Small amounts. 
 
 With regard to the digestion of fat it must be remembered that during an 
 abundant supply of easily digestible quality, often only 1.5 per cent., rarely 
 more than from 4 to 6 per cent., is lost ; that fat with a low-melting tempera- 
 ture is absorbed better and more quickly than fat with a high-melting tempera- 
 ture (Miiller and Arnschink) ; that the presence of free fatty acids facilitates 
 absorption, in which process both bile and the pancreatic juice are of great 
 importance, if the fat is not ingested in a state of emulsion (Levin, Buchheim) ; 
 that a mixed diet promotes absorption, though the most advantageous relation 
 in the quantities of the different kinds of food has not yet been determined 
 (Rosenheim, Munk). Finally, it is known that catarrhal conditions first impair 
 the absorption of fat, while proteids and carbohydrates still continue to be 
 absorbed normally (Fr. Miiller). Individual and accidental circumstances have 
 a great influence even under normal conditions. 
 
 We shall here entirely pass over the highly complicated chemic processes 
 by which the ingested proteids are converted ultimately into albumoses and 
 peptones, as well as the manner in which these substances are absorbed in con- 
 sequence of the specific cellular activity of the mucous membrane. There are 
 
1/2 DIABETES MELLITUS AND GLYCOSURIA. 
 
 in this respect no known or even suspected differences between the diabetic 
 and the normal individual, nor in the processes by which the albumoses and 
 the peptones are again changed into true albumin in its different modifications. 
 According to differences in the quality of the food, from 3 to 5, or from 6 to 10 
 per cent., or even more, of the proteids may normally remain undigested in 
 the intestines (Rubner). During the passage of proteids through the aliment- 
 ary canal there are formed, as is known, many substances that are not proteids 
 (leucin, tyrosin, tryptophan, amido-acids, asparagic acid) ; in the colon and 
 rectum are found a whole series of " aromatic " substances and other products 
 of putrefaction (indol, skatol, parakresol, phenol, phenyl-propionic acid, 
 phenyl-acetic acid, paraoxyphenyl-acetic acid, hydroparacumaric acid, free 
 fatty acids, carbonic acid, marsh-gas, hydrogen sulphid, etc.). Often secret- 
 ing a smaller amount of bile than normal, and partaking of food rich in pro- 
 teids and often suffering from habitual constipation, which allows of a longer 
 period for putrefactive process, diabetics are likely to produce large quantities 
 of the aromatic substances mentioned. In consequence their urine usually 
 contains large quantities of " ethereal " combined sulphates resulting from 
 the oxidation of the "aromatic" substances.* 
 
 When with an ordinary diet the ingested carbohydrate, changed 
 into glucose (together with some small quantities of dextrin, 
 maltose, and perhaps still other carbohydrates), is carried by the 
 blood in the portal vein to the liver, it there forms the anhydrid of 
 glucose or glycogen, f and to this most important substance we 
 must devote a good deal of attention. 
 
 It seems certain that not all the glucose carried by the portal vein 
 to the liver is, under all circumstances or at once, transformed into 
 
 * The phenols, skatol, and indol are oxidized in the organism and pass into the urine 
 as indoxyl-sulphuric and skatoxyl-sulphurlc acids. The quantity of these and other 
 ethereal sulphates normally equals about 0.25 gram a day, and bears a ratio to the sul- 
 phuric acid of the sulphates of I : lo (from I : 15 up to I : 67). 
 
 f Glycogen, as is well known, is a polysaccharid closely related to starch ; its formula 
 probably is 6(CgH,Q05) + H^O (Kiilz). Under the influence of dilute acids it is entirely 
 changed into the monosaccharid glucose ; saliva and pancreatic juice transform it into 
 achroodextrin, maltose, and small quantities of glucose. In the cells of the liver gly- 
 cogen is uniformly diffused in small granules embedded in larger granules of the so-called 
 paraplasm (Kupfer), an imperfectly known substance, probably representing a form 
 intermediate between glycogen and its mother-substances. The muscles constitute the 
 other important repository of glycogen, containing about as much as the liver; it is 
 present in the interfibrillary substance (Frerichs). From whatever substance glycogen is 
 formed it is itself completely homogeneous (Salomon, Luchsinger, Otto). Still, there 
 is some difference between the glycogen of the liver, which is colored brownish-red by 
 tincture of iodin, and the glycogen of the muscles, which with the same tincture 
 develops rather a violet color. 
 
METABOLISM AND NUTRITIVE NEEDS. 1/3 
 
 glycogen. After the ingestion of large amounts of glucose even 
 normal individuals excrete some glucose in the urine. Under ordi- 
 nary and normal circumstances a considerable part of the glucose 
 may also pass through the liver and be either used immediately in 
 the tissues or stored as glycogen in the muscles or elsewhere, or it 
 may return to the liver and be stored there after having passed 
 through the whole circulation. It is certain that the glycogen in 
 the liver continues increasing for a much longer time after the in- 
 gestion of carbohydrate than the glucose needs to pass through the 
 whole organism. After the ingestion of a large amount of glucose 
 the glycosuria appears within thirty or forty minutes ; after the in- 
 gestion of syrup the maximum amount of glycogen in the liver is 
 reached (in rabbits) only after from sixteen to twenty hours (Kiilz). 
 After the ingestion of small amounts six hours, and after the in- 
 gestion of large amounts from twelve to sixteen hours, elapse before 
 this maximum is reached in chickens (Hergenhahn). The liver 
 generally stores its maximum long before the muscles acquire 
 theirs ; after the ingestion of very large amounts, however, the 
 glycogen is stored about as quickly by the latter as by the liver 
 (Hergenhahn). 
 
 Glycogen is formed in the liver from both carbohydrates and 
 proteids, and its amount can be maintained or increased there by 
 many different substances. Glucose and levulose (or starch) yield 
 the highest values, up to 20 per cent, or even more. Those sac- 
 charids that do not ferment with yeast do not yield more than a 
 small percentage. 
 
 The researches on the formation of glycogen, since its discovery in 1857, 
 already represent an enormous amount of work, and the subject certainly will 
 be the object of further investigation. The experiments consist in subjecting 
 the animals to starvation until the glycogen is supposed to be wholly con- 
 sumed, in feeding them afterward with the substance in question, and, finally, 
 in determining the quantity of glycogen in the liver. 
 
 Bernard proved that both carbohydrates and proteids — i. <?,, meat and 
 fibrin — produce glycogen, Woroschilofif that the latter is formed from glue. 
 [That carbohydrates are formed from proteids can be demonstrated to any one 
 who does not accept their formation from fat by the fact that diabetics in the 
 severe stage continue for months to excrete more glucose than can possibly be 
 made up by the carbohydrates in their food.] Kiilz's " Beitrage zur Kenntniss 
 des Glycogens," Marburg, 1891, contains a good exposition of what has been 
 done in this connection by Bernard, Stokvis, MacDonnell, Tcherinoff, Hoppe, 
 
1/4 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Doch, Weiss, Luchsinger, Naunyn, Nencki, Wolfberg, v. Mering, Finn, 
 Pfliiger, Hergenhahn, Nebelthau, and by Kiilz himself, who fed chickens with 
 muscle, fibrin, casein, serum-albumin, and egg-albumin. The last-named thus, 
 beyond a doubt, proved that these substances yielded from i to 2.5 per cent, of 
 glycogen in the liver. Pavy (in rabbits) with starch and cane-sugar succeeded 
 in depositing 27.6 per cent, of glycogen in the liver; with starch, cane-sugar, 
 and albumin the amount was 17 per cent. Meat yielded at the utmost 7 per 
 cent., gum-arabic q per cent., gelatin traces, and olive oil also only traces 
 (probably remaining from before the experiment). MacDonnell's, Tcheri- 
 noffs, and Seegen's experiments led to similar results. Seegen besides found 
 1.67 per cent, of glycogen in the liver of dogs after eight days without food, 
 and after feeding the animals during the following eight days exclusively on 
 fat in large quantities he found 0.93 per cent. Kiilz, in chickens fed with cane- 
 sugar, found 8.24 per cent. ; with glucose 6.63 per cent. ; with levulose 6.07 per 
 cent. ; with galactose 3.28 per cent., and with lactose 2.32 per cent, of glycogen 
 in the liver. Kausch and Socin (1898) have found as much as 9 per cent, with 
 lactose. 
 
 It will thus be seen that the power of the different saccharids to 
 form glycogen in the liver in normal individuals does not bear any 
 relation to their power of causing glycosuria in diabetics. Glucose 
 and levulose normally yield about the same amount of glycogen, but 
 glucose causes much greater glycosuria in diabetes than does levu- 
 lose. The glycogen in the liver in diabetics again is increased in much 
 greater degree by levulose than by glucose (Sandmeyer) — a quality 
 of the levulose, which presumably is the cause for its producing less 
 glycosuria in such individuals. The more easily a saccharid under- 
 goes fermentation the more glycogen it forms normally, according 
 to C. Voit ; the less it normally passes into the urine, according to 
 Cremer ; and the better it forms fat, according to Liebig. 
 
 It is in many respects interesting to learn the effect of subcuta- 
 neous injections of different saccharids. Fritz Voit, in 1896, made 
 such injections (of ten per cent, solutions) of monosaccharids : levu- 
 lose, galactose, and glucose ; and of the disaccharids : maltose, lac- 
 tose, and cane-sugar. All of the monosaccharids were completely 
 consumed in the tissues even after the injections of considerable 
 amounts. After the injection of large amounts a small quantity 
 appeared unchanged in the urine. Thus, the injection of 60 grams 
 of glucose yielded a trace of glucose in the urine, while the injec- 
 tion of 100 grams yielded 2.6 grams of glucose in the urine. 
 Maltose, too, was readily consumed. The disaccharids, cane-sugar 
 and lactose, however, were not consumed, and passed almost com- 
 
METABOLISM AND NUTRITIVE NEEDS. 1/5 
 
 pletely through the organism, and appeared unchanged in the 
 urine. Only the monosaccharids and the disaccharid, maltose, 
 whose molecules are believed to consist of two molecules of 
 glucose, seem to form glycogen without being first changed. Cane- 
 sugar can be stored as glycogen in the liver only after being con- 
 verted into glucose and levulose, lactose only after being converted 
 into glucose and galactose. 
 
 Besides the substances already mentioned, Kiilz found that the following 
 substances also have some power of maintaining glycogen in the liver : Raf- 
 finose, glycerin, gum-arabic, sorbin, ethylene, glycol, erythrite, dulcite, man- 
 nite, inosite, saccharin, isosaccharin, dextronic acid, saccharic acid, mucic 
 acid, glycuronic acid, calcium dextronate, sodium tartrate, and citrate. Urea 
 also yielded glycogen. Inulin yielded small quantities and olive-oil traces. 
 Nebelthau found some power of maintaining glycogen in the liver in ammo- 
 nium citrate carbonate, lactate, and formate in benzamid and formamid, in 
 glycocoUa and asparagin, in antipyrin, cairin, quinin, and chloral, chloramid, 
 paraldehyd, and sulphonal. Ether, chloroform, and alcohol seemed somewhat 
 efficient, while urethan yielded a dubious result. Cremer found that some 
 glycogen formed after use of the pentoses * (xylose, arabinose, and rhamnose) ; 
 Salkowski also found some after use of arabinose; Fraentzel obtained a com- 
 pletely negative result from xylose. 
 
 From the foregoing it will be understood that glycogen can be 
 formed or maintained in the liver in many different ways. From 
 glucose it is formed by dehydration, a comparatively large amount 
 resulting. Lactose forms glycogen only indirectly, after having 
 been divided into its monosaccharids ; but though a large part of 
 the ingested lactose may have been changed into lactic acid before 
 this happens, the rest usually gives rise to the presence of quite 
 considerable quantities of glycogen in the liver (Kausch and Socin). 
 Olive-oil and other fatty substances, which are believed to main- 
 tain the glycogen in the liver only by undergoing oxidation them- 
 selves, seem to afford very little protection for it. As for the power 
 of antipyrin to maintain glycogen in the liver, this must be derived 
 
 * The pentoses do not seem to promise the diabetic patient anything. Ebstein found 
 arabinose and xylose unchanged in the urine after quite small doses. Lindemann and 
 May found about eight per cent, of rhamnose unchanged in the urine of normal indi- 
 viduals. Sixty-five grams of rhamnose caused some glycosuria in a diabetic patient 
 previously free from it ; besides 7.27 grams of rhamnose appeared in the urine and 2.85 
 grams in the feces. Rhamnose is suspected of having no wholesome influence on the 
 kidneys. 
 
1/6 DIABETES MELLITUS AND GLYCOSURIA. 
 
 from some specific influence, and can result neither from direct for- 
 mation nor from oxidation. 
 
 The glycogen in the muscles is formed in and by the muscles 
 themselves from the sugar of the blood. It may, perhaps, be fur- 
 nished to them also to some small extent as glycogen. Bohm and 
 Hoffmann found 0.4 per cent, in the cat ; Hasse between 0.4 and 
 0.9 per cent, in dogs, cats, and rabbits. Kiilz considered these 
 figures somewhat too small. 
 
 The glycogen in the liver and the glycogen in the muscles are, 
 under ordinary circumstances, about equal in amount, and together 
 make up the organism's whole store of this substance, except a 
 comparatively insignificant amount in other tissues. The storage 
 in the liver and the storage in the muscles depend on the same 
 influences, and are both increased or decreased by the same causes. 
 The glycogen of the muscles manifests greater stability, and is 
 slower both in increasing and in decreasing. Heat increases the 
 glycogen, and rest has the same influence. By severing the cen- 
 tral from the peripheral nervous system glycogen is stored in great 
 quantity, partly on account of the paralysis of the muscles, partly, 
 perhaps, on account of the withdrawal of other nervous influences 
 (Claude Bernard, Nebelthau). Cold diminishes the amount of glyco- 
 gen and is capable of causing its disappearance from both liver and 
 muscles in thirty hours (Bohm and Hoffmann). Mechanical work 
 is most effective in the same direction. Weiss found only about 
 half as much glycogen in tetanized muscle as in the corresponding 
 muscle at rest. Chauveau and Kaufmann had a similar experience. 
 Rosenbaum, Demant, and Hergenhahn saw the glycogen almost 
 totally disappear during the convulsions from poisoning with 
 strychnin ; and Kiilz found the glycogen in both its great store- 
 houses reduced to a minimum after a short period of starvation 
 and hard work combined. Starvation decreases the glycogen. 
 Kiilz, however, still found traces of it in the liver and somewhat 
 more in the muscles of the dog after twenty days of abstinence 
 from food. After extirpation of the liver the glycogen suddenly 
 decreases in the muscles (Laves). Acids in the blood decrease 
 and alkaline salts increase the amount of glycogen (Kiilz). After 
 ligature of the choledoch duct with biliary stasis the glycogen dis- 
 appears from the liver and is not formed again (Frerichs, Wick- 
 
METABOLISM AND NUTRITIVE NEEDS. 1/7 
 
 ham Legg). After death glycogen disappears from the Hver and 
 (somewhat more slowly) from the muscles. Praussnitz, after only 
 half an hour, found 75 per cent, of the original amount. Werther, 
 after three hours, found scarcely anything left. This change takes 
 place more quickly in a warm than in a cold room. 
 
 In the blood the glycogen is found in the leukocytes ; a liter con- 
 tains only about 0.0 1 gram (Huppert). The lymphatics also con- 
 tain a small quantity (Frerichs). Glycogen has besides been found 
 in the skin (Paschutin), in the hair-bulbs (Neisser), in the kidneys 
 (Wiersma, Paschutin, Abeles, Ehrlich), in the spleen (Hoppe- 
 Seyler), in the lungs (Abeles), in the testicles (Kiihne), and in new 
 growths (Hoppe-Seyler, Brault). It seems to occur especially in 
 inflamed tissues (Sotniskewski, Pavy, Kiihne), and during this state 
 it has also been found in the brain (Paschutin), where it does not 
 seem to be found normally (Abeles, Seegen, Kratschmer, Paschutin). 
 Finally, it is much more abundant in embryonic than in fully devel- 
 oped tissues (Bernard). In view of this fact, and of the further 
 fact that it is found especially in inflamed tissues and in tumors of 
 rapid growth, it would seem to be indicative of a condition of 
 energetic cellular life. 
 
 It may now be considered as settled that in cases of diabetes the 
 amount of glycogen is diminished both in the liver and in the 
 muscles. Frerichs, with admirable presence of mind, plunged a 
 trocar into the liver of three submissive individuals, of whom one 
 was in good health and the other two were diabetic. Although 
 the stage of diabetes is not stated, it was probably an advanced one. 
 It was found that between four and one-half and five and one-half 
 hours after an abundant mixed meal the liver-cells of the healthy 
 person contained a large amount of glycogen, while those of the 
 two diabetics contained a moderate amount and a very small 
 amount, respectively. Both the liver and the muscles of diabetic 
 dogs contain little glycogen (v. Mering, Minkowski, Sandmeyer). 
 Pieces of liver excised shortly after death in diabetic coma were 
 found to contain very little glycogen (Frerichs) ; and it could not 
 be found at all in the muscles of such patients (Abeles). The 
 diabetic liver in a state of fatty degeneration seems to contain the 
 smallest amount of glycogen (Boccardi). 
 
 I presume that if a diabetic in the mild stage and a healthy 
 
178 DIABETES MELLITUS AND GLYCOSURIA. 
 
 person receive the same food with so much carbohydrates that the 
 diabetic excretes sugar in his urine, the latter will store less glyco- 
 gen than the healthy person, and the glycogen will thus never reach 
 such high figures as are reached normally after the ingestion of 
 large amounts of carbohydrates. If, however, both the diabetic and 
 the healthy individual receive the same food with such restriction 
 of carbohydrates as to render the diabetic free from glycosuria, both 
 will probably store the same amount of glycogen. The diabetic 
 patient in the severe stage always passes in the urine glucose derived 
 from both the carbohydrates and the proteids of the food, and from 
 this cause alone he possesses but a limited power of storing glyco- 
 gen. In the severe stage, however, this power is besides weakened 
 by the acidosis, or the presence in the blood of diacetic acid and 
 y9-oxybutyric acid. 
 
 At the same time that the amount of glycogen is diminished in 
 the liver and in the muscles in cases of diabetes, it is increased in 
 other parts and elements of the organism, Gabritschewski found 
 much more marked reaction for glycogen in the leukocytes of dia- 
 betic blood than in those of normal blood ; Minkowski observed 
 the same fact in pus (0.83 per cent, in diabetics as against 0.23 per 
 cent, in nondiabetics). The leukocytes partly have their own inde- 
 pendent economy and store much glycogen from a hyperglycemic 
 medium. The brain, in which glycogen is not normally found, con- 
 tains this substance in cases of diabetes (see above). Ehrlich first 
 demonstrated the deposition of glycogen in the epithelial elements 
 of the kidneys. Leube found it twice in diabetic urine.* 
 
 The enormously important questions with regard to the meta- 
 bolism of glycogen, and with regard to the origin and significance 
 of the glucose in the liver, have given rise to a variety of opinions 
 and have been the subject of much controversy. The technical 
 difficulties in solving these problems experimentally are very great, 
 and the human obstinacy in defending per fas and nefas a position 
 once taken is still greater. Even to-day three different main cur- 
 rents of opinion may be recognized as represented by the names 
 of Claude Bernard, Pavy, and Seegen. At present we are justified 
 
 * Glycogen is besides found (in cases of diabetes) in the lungs, in the testicles (Grohe), 
 pancreas, spleen (Abeles), in the heart, and in the cartilages (v. Mering, Ewald). 
 
METABOLISM AND NUTRITIVE NEEDS. 1/9 
 
 in saying that the theory advocated by Bernard has proved to be 
 much the strongest, and that the vast amount of work performed 
 since the fundamental discoveries of this great French physiologist 
 and experimenter has tended to strengthen the opinion that if he 
 has not demonstrated the whole truth he has certainly demonstrated 
 the essential points of it. Pavy's theory, denying entirely the phys- 
 iologic formation of glucose in the liver and its presence for pur- 
 poses of vital power in the blood, almost everywhere belongs to 
 the past. Seegen, who denies that the glucose of the liver and of 
 the blood (whose vital importance for the organism he acknowl- 
 edges) is formed from glycogen, and who considers it to be formed 
 from proteids and from fat, has gained comparatively few adherents 
 to this last view, in which he deviates from Claude Bernard. 
 
 Claude Bernard, in 1877, summed up his views on these subjects, 
 his theory, confirmed and enlarged by later investigations, being as 
 follows : The liver forms glycogen from (a part of) the carbohy- 
 drates and the proteids of the food, and afterward, from this glyco- 
 gen, under the influence of a ferment and under the vasomotor regula- 
 tion of the nervous system, forms glucose, which, according to the 
 needs of the organism, it delivers to the blood, of which glucose is 
 a most important ingredient. For the production of vital force the 
 glucose is then oxidized in the tissues into carbonic acid and water. 
 Recent investigations, leaving many questions as to the fate of glu- 
 cose for solution in the future, seem to confirm Bernard's opinion 
 that the glucose is led to complete combustion through the molec- 
 ular structure of lactic acid (Kausch, Lang), and make it probable 
 that another intermediate station between the glucose and its ulti- 
 mate products, carbonic acid and water, is represented by the mole- 
 cule of glycuronic acid (Weintraud). It has been proved and is 
 universally accepted that fat is produced from the superfluous car- 
 bohydrates, and the seat of this process is believed to be the liver. 
 
 Of late, some persons, who may be considered authorities, have 
 so far adopted Seegen's theory as to believe that, with a deficiency 
 of proteids and carbohydrates, fat may give rise to the formation of 
 glucose. It seems to me that the facts that plead for such a theor}^ 
 are much weaker than those that plead against it (see below). 
 
 The diastatic ferment in the liver, like all ferments not consist- 
 ing of organisms, presents many mysterious points ; Dastre goes 
 
100 DIABETES MELLITUS AND GLYCOSURIA. 
 
 SO far as to call it hypothetic. All attempts to isolate it — chiefly 
 by precipitating it with alcohol after having extracted it from the 
 liver with glycerin — have failed. Tiegl believes that it arises from 
 the products of the disintegration of the red blood-corpuscles, while 
 many believe it to be fixed to the living liver-cells.* 
 
 In a decoction of the liver and in the precipitate thrown down by 
 absolute alcohol from such a decoction again dissolved in water, 
 glucose is formed at ordinary temperature, which is not the case 
 with a solution of pure glycogen (Schwiening). Bernard believed 
 the variations in the production of glucose to depend on variations 
 in the circulation, and these on nervous, vasomotor influences. 
 Bial, who considers the diastatic ferment of the liver identical with 
 the diastatic ferment of the muscles, believes both to belong to and 
 depend on the lymph. The diastatic ferment in the liver and in 
 the blood changes starch and dextrin and glycogen, not into mal- 
 tose, but into glucose, and also converts maltose into glucose. 
 In the embryo and in the new-born child these effects, which 
 vary in different species of animals, are quite weak. Sodium car- 
 bonate and bicarbonate retard the effect of the diastatic ferment 
 on glycogen (Gans). 
 
 The sugar in the liver has been produced in substance by Kiilz, has 
 been proved to be glucose, and is present in the liver during life to 
 the amount of from 0.2 to 0.5 per cent. (Bernard, Seegen). 
 
 After some knowledge on these subjects had been gained through earlier 
 investigations, Claude Bernard, late in the forties, proved the constant presence 
 of sugar in the blood, independently of the kind of food taken, and showed that 
 it must be looked for shortly after the blood is obtained, as it soon decomposes. 
 He showed that the sugar of the blood is formed in the liver, which always con- 
 tains some, and that a piece of liver from which the sugar has been removed 
 by washing soon again becomes sacchariferous. He explained this by the 
 continued activity of the diastatic ferment constantly producing sugar, which 
 increases when not removed by the circulation. When Pavy afterward con- 
 sidered this process to take place exclusively after death, Bernard (as Dalton, 
 Seegen, and others have done after him) showed that the liver during life also 
 contained sugar, the quantity of which he (by somewhat too low an estimate) 
 placed at 0.24 per cent. 
 
 *Arthus and Hubner, however, have shown that a solution of fluorin (l : loo), 
 which destroys cellular life, does not prevent the fern ation of glucose in pieces of liver. 
 Schwiening believes that the proteids play some special role in the formation of glucose 
 in the liver. 
 
METABOLISM AND NUTRITIVE NEEDS. 161 
 
 Nearly ten years afterward Claude Bernard and Hensen discovered the 
 glycogen, determined its nature, and proved that it could be formed both from 
 proteids and from carbohydrates. Bernard showed also that, if the liver is 
 separated from the circulation, the sugar disappears from the blood — a fact after- 
 ward corroborated by Bock and Hoffmann and by v. Mering. Bernard found, 
 moreover, that the veins issuing from the liver and the inferior vena cava 
 usually contain more sugar than the portal vein. On finding more sugar in 
 the inferior vena cava than in the carotid artery, he first concluded that the 
 sugar is consumed in the lungs, but, always ready to be corrected by facts, he, 
 after Chauveau's investigations, and after having himself found more sugar in 
 the arteries than in the collateral veins, expressed the opinion that this con- 
 sumption takes place in the tissues of the whole organism. Bernard showed 
 that the sugar of the blood usually undergoes only slight variations in quantity, 
 that it is somewhat increased after generous meals, that it gradually diminishes 
 on starvation and in the febrile state, and that it disappears from the blood 
 outside the organism in about twenty-four hours. Finally, Bernard found 
 glycosuria after lesions of the brain in the floor of the fourth ventricle, made 
 investigations concerning hyperglycemia in diabetes, and showed that glyco-, 
 suria in the dog begins when the sugar in the blood reaches from 0.25 to 0.30 
 per cent. 
 
 At about the same time Lehmann found traces of sugar in the portal vein, 
 and determinable quantities of it in the veins issuing from the liver (horse). 
 
 C. Schmidt, in 1850, without a knowledge of the results of Bernard's inves- 
 tigations, found sugar in the blood of cows, dogs, and cats. 
 
 Chauveau, partly alone and partly in conjunction with Kaufmann, has, 
 since 1856, contributed more than any one else to the confirmation of Bernard's 
 theories. After extensive and numerous experiments he came to the conclu- 
 sion that the sugar in the blood is derived from the liver, that it is always pres- 
 ent, and even after long-continued starvation does not entirely disappear ; that 
 the arteries contain more sugar than the collateral veins, and that all divisions 
 of the circulatory system contain about the same amount, except the veins 
 issuing from the liver and the inferior vena cava, which are more saccharifer- 
 ous, and the portal vein, which (except after the ingestion of large amounts 
 of carbohydrates) is less sacchariferous than other vessels. 
 
 Subsequently, Bohm and Hoffmann, Bock and Hoffmann, Bleile, Kiilz, 
 Lusk, v. Mering, Ewald, Otto, Barral, Lepine, and others made investigations 
 which have corroborated Bernard's results. 
 
 Pavy, one of Bernard's own disciples, began at the close of the fifties his 
 opposition to this greatest of French experimenters. Pavy found that the 
 blood from the right heart of a living dog contained much less sugar than after 
 death — an observation that is certainly correct, and is dependent on the fact 
 that when the circulation gradually ceases, the districts next to the liver, where 
 the formation of sugar continues even some time after death, become more 
 sacchariferous. Pavy found also that bits of liver obtained from living animals 
 and thrown into boiling water or subjected to freezing contained only small 
 quantities of sugar, while, when exposed to ordinary temperature, they con- 
 tained much larger quantities. This is also true, partly, perhaps, because the 
 
1 82 DIABETES MELLITUS AND GLYCOSURIA. 
 
 liver-cells of living animals produce, and the dead liver-cells do not produce, 
 sugar, and partly because excessive temperatures diminish the influence of the 
 diastatic ferment. Pavy concluded from these observations that the production 
 of sugar in the liver is aportmortem phenomenon, and that in life the sugar passes 
 through the liver only under pathologic conditions, as in diabetes or after cer- 
 tain lesions, probably in consequence of a vasomotor neurosis which leads to 
 congestion of the liver with blood that has not entirely lost its arterial qualities. 
 This sugar, then, may come from the glucose formed normally by ingested 
 carbohydrates or from the glycogen, which customarily produces fat. Even 
 Pavy has been forced to acknowledge the presence of sugar in the blood under 
 ordinary conditions, but he believes it to be there only in insignificant traces and 
 for no physiologic purpose, admitted, as it were, by some defect in the func- 
 tions of the liver, escaping again through the kidneys as a trace of sugar in 
 the urine. Pavy's views have now only historic and personal interest, and are 
 strenuously opposed even in Great Britain {e. g., by Dr. Noel Paton [1898] ). 
 For many years, however, they exercised considerable influence. Among 
 Pavy's adherents were Schiff, Meissner, Ritter, MacDonnell, and (as late as 
 1876) Lussanna. 
 
 Seegen also was at first an adherent of this view. Then having found 
 (with Kratschmer) that diastatic ferment in saliva and in the pancreatic juice 
 does not change glycogen into glucose, but into another saccharid, which Mus- 
 culus and v. Mering showed to be maltose, and finding in the liver no other 
 substance capable of saccharifying the glycogen, he began to doubt that it was 
 the source of the glucose. In a series of experiments he sought and believed 
 that he had found that the glucose must be derived from other substances than 
 glycogen. He found the glucose to increase in bits of liver before the glycogen 
 began to decrease. Investigations on this subject, however, by Bohm and 
 Hoffmann, Girard, Chittenden and Lambert, Bial, Butte, and Montuori have not 
 corroborated Seegen's results. Seegen, by various experiments, for which I 
 must refer to his own works, believed also that he had proved the formation of 
 glucose in the liver from peptone, a process which Lupine considers to take 
 place throughout the whole organism. Hofmeister, Chittenden, Lambert, 
 Neumeister, and Bial have also on this point arrayed themselves against Seegen, 
 and arrived at other conclusions. Seegen believed, further, that he had found 
 in 70 cases the blood of the hepatic veins always more sacchariferous than the 
 blood of the portal vein, and he somewhat irrationally considered this a proof 
 of the correctness of his views. In this also he has powerful opponents; both 
 Bernard's and v. Mering's observations tend to show that after the ingestion 
 of large amounts of carbohydrates the portal vein may contain a much higher 
 percentage (up to 0.4 percent.) than the hepatic veins or the inferior vena 
 cava. 
 
 It must be remembered that we here have usually to do with small differ- 
 ences. Max Mosse found 0.107 per cent, in the hepatic veins and 0.093 per 
 cent, in the femoral artery, which, according to Seegen, contains only slightly 
 more than the portal vein. Mosse and others are in all probability right when 
 they maintain that the high percentage of glucose sometimes found in the 
 blood just coming from the liver is partly due to the sufferings of the animal 
 
METABOLISM AND NUTRITIVE NEEDS. 1 83 
 
 during the experiment. Seegen finally remarks that, while glycogen is driven 
 out of the liver by starvation, the sugar of the blood remains in unchanged 
 quantity. This is decidedly wrong. Claude Bernard, Bohm and Hoffmann, 
 and Otto all have shown that prolonged starvation does decrease, though 
 slowly, the sugar of the blood ; and, on the other hand, Kiilz has shown that 
 even starvation for twenty days does not fully free either liver or muscles from 
 glycogen. Seegen, however, is determined to adhere to his opinion that gly- 
 cogen does not form glucose, but fat, and that the liver for purposes of vital 
 energy produces glucose from fat and proteids. At the same time that Seegen 
 denies the formation of glucose from the glycogen of the liver he accepts such 
 a formation from the glycogen of the muscles. This surely appears a rather 
 far-fetched theory, and the presumed facts on which it is based have not been 
 established, nor would they necessarily lead to Seegen's conclusions even if 
 they were so ; but, according to the strongest evidence, some of them are false. 
 Naturalists will not, without convincing proofs, believe that nature should form 
 exclusively fat from carbohydrates, and at the same time and in the same 
 organ should form carbohydrates from fat ; and even those who believe that 
 fat may form glucose under certain circumstances are far from accepting 
 Seegen's views, which now, like Pavy's, may be considered to be a matter of 
 history. 
 
 We now have acquired a right to consider the hver as the main 
 sugar-producing organ of the body, and to look upon the sugar of 
 the Hver, which is identical with the sugar of the blood, as derived 
 from the glycogen. We have seen that the sugar of the blood 
 usually is most abundant in the vessels leaving the liver, and that 
 it decreases and disappears if the liver is cut off from the circula- 
 tion. We have seen also that, when the sugar increases in portions 
 of liver, there is a corresponding decrease in glycogen. This fact 
 may be demonstrated experimentally even during life by irritation 
 of the celiac plexus or the sympathetic nerves of the liver, which 
 produces an immediate increase in the amount of sugar with a 
 corresponding decrease in the amount of glycogen (Chauveau, 
 Cavazzani and Butte, Morat and Dufour). Marcuse has lately 
 shown that the diabetes that is constantly caused also in frogs by 
 extirpation of the pancreas is prevented by previous extirpation of 
 the liver. Finally, we know that phloridzin, which causes the sugar 
 of the blood to pass into the urine without hyperglycemia in con- 
 sequence of changes in the kidneys, and causes a constant and rapid 
 reproduction of glucose, decreases the glycogen, and that diabetes 
 following the extirpation of the pancreas, with the consequent enor- 
 mous losses of glucose, has the same effect. 
 
184 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Generally, glycogen is believed to represent fixed, stored-up 
 potential energy, which, whenever it is found, may be changed into 
 glucose, representing potential energy in solution ready to be trans- 
 formed into vital force. 
 
 So far, so good ; but what about the important questions that 
 next present themselves ? 
 
 Does all transformation into vital force necessarily pass through 
 the molecular structure of glucose, or may proteids and fat be 
 used unchanged for this purpose ? 
 
 Can glucose be formed from proteids anywhere else than in the 
 liver ? 
 
 Can glucose be formed at all from fat ? 
 
 Can carbohydrates and, perhaps, fat contribute to a possible syn- 
 thetic formation of proteids ? 
 
 Where and how are the molecules of fat attacked and disinte- 
 grated ? 
 
 It appears to me, unfortunately unable to form an opinion on 
 these subjects, but, from the researches of others, that we can at 
 present not give much more definitive answers to these questions 
 than we could in the beginning of the last decad of the nineteenth 
 century. 
 
 Chauveau has recently formulated his own conclusions from 
 extensive researches on the transformation of force within the or- 
 ganism. These conclusions, in a somewhat abbreviated form, are 
 as follows : 
 
 1. All vital force within the organism is produced by oxidation. 
 
 2. The potential energy is always in the ultimate stage repre- 
 sented by carbohydrates. 
 
 3. During starvation carbohydrates are constantly formed also 
 by a rudimentary oxidation of fats. 
 
 4. Oxidation of proteids never directly contributes to the pro- 
 duction of vital force ; or, in other words, mechanical work does 
 not increase the amount of nitrogen in the urine. 
 
 Unfortunately, there are still various opinions with regard to 
 each of these conclusions. Munk, Zuntz, and others think it still 
 doubtful that all vital force is produced by oxidation. We know, 
 especially from the researches of Zuntz, that mechanical work in 
 some way may be sustained by fat and by proteids, as well as by 
 
METABOLISM AND NUTRITIVE NEEDS. 1 85 
 
 carbohydrates, and Newton Heyneman's experiments prove also, 
 by the figures of the respiratory quotient, that the kind of food 
 chiefly ingested, be it proteids, fat, or carbohydrates, is also chiefly 
 used for the production of mechanical force. 
 
 The power of the organism to produce carbohydrates from fats is 
 exceedingly doubtful. Something may be said in favor of the exist- 
 ence of such a power, but it seems to me that still much more may 
 be said against it. The chief reason — apart from the much opposed 
 results of Seegen's experiments — for believing in the formation 
 of glycogen or glucose from fats depends on the highly uncertain 
 theory that muscles can not use fats as fuel for their work. It has 
 been demonstrated that with a scanty supply of carbohydrates the 
 quantity of proteids and carbohydrates consumed does not always 
 cover the expense of the mechanical work performed. The for- 
 mation of carbohydrates from fats in vegetable cells constitutes 
 absolutely no reason for admitting such a formation in animal cells. 
 Any one who has at all occupied himself with the physiology of 
 plants knows what an enormous metabolic difference there is be- 
 tween animals and plants. The clinician, who constantly finds that 
 he may increase the butter in the food of his diabetic patients to 
 any ingestible quantity in any stage of diabetes and under any diet, 
 without any perceptible increase of the amount of glucose in the 
 urine, will have strong doubts as to the formation of carbohydrates 
 from fats even with a deficient supply of carbohydrates ; and, how- 
 ever much it may be repeated from some quarters that the sugar 
 of the blood remains at par during feeding with fats alone, Seegen's* 
 own figures show that the sugar of the blood, after having dimin- 
 ished during starvation continues to do so during subsequent feeding 
 exclusively on fats. Von Mering, Moritz and Praussnitz, Cremer 
 and Ritter, and now (1898) Kumagawa and Miura alike consider 
 that during phloridzin-poisoning, with its enormous loss of glucose, 
 fats do not give rise to carbohydrates. 
 
 Chauveau has been led to his conclusions as to the ability of the organism 
 to produce carbohydrates from fats chiefly by his own and by Regnault's and 
 
 * Among authorities now Hving, so far as I know, only Seegen, v. Noorden, Bunge, 
 Chauveau and Kaufmann, and Weiss accept the formation of carbohydrates from fats in 
 man. 
 
 13 
 
1 86 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Reiset's investigations on the marmot. This animal, when subjected to star- 
 vation in summer, dies after the loss of between 95 per cent, and 97 per cent. 
 of its fat, and then has scarcely any carbohydrate at all left in liver, muscles, 
 or blood. After hibernation the marmot has used up its fat, but the blood still 
 . contains glucose and the liver and muscles contain glycogen. Chauveau 
 asks how this could be, after such a time of continued abstinence from food, 
 with considerable expenditure for heat and circulation, if the carbohydrates 
 (glycogen and glucose) had not been formed from fat. Then Regnault and 
 Reiset had observed that the marmot may, during its sleep in hibernation, 
 increase in weight, and that it consumes considerably more oxygen than it 
 expires in carbonic acid, and Chauveau thinks that the fat has been changed 
 into glucose by oxidation according to the following equation : 
 
 2C57HJ10O6 + 670, = i6CgHi,06 + 18CO2 + I4H,0. 
 Stearin. Glucose. Carbonic Water. 
 
 Acid. 
 
 The question whether proteids directly produce vital force is not 
 to be answered at present. Voit, Brietske, Fick and Wislicenus, 
 and others found no increase in the nitrogen of the urine after 
 mechanical work. Pavy, Flint, Parkes, Argutinsky, Oppenheim, 
 and others arrived at opposite results, and Zuntz, too, after his 
 beautiful researches, has formed the opinion that proteids (and fats) 
 may directly contribute to the formation of vital force. 
 
 Finally, it is not impossible that a part of the proteids so utilized 
 is derived from carbohydrates. Pfliiger, Schenk, and others admit 
 a synthetic formation of proteids, as a station on the way to the 
 final production of vital force, to which formation carbohydrates 
 may contribute part of the nonnitrogenous constituents. So long 
 as we do not know more than we do at present of the fate of the 
 fats, we can not absolutely deny its participation in such a synthesis 
 of proteids. 
 
 Until further information is forthcoming it must be admitted that 
 proteids may form proteids, fats, and carbohydrates, that carbo- 
 hydrates may form carbohydrates and fats, but that fats are not 
 positively known to form anything but fat. On the other hand, we 
 have no right to deny positively the formation under some circum- 
 stances of carbohydrates from fat ; still less have we a right to 
 deny the synthesis of proteids, in which both carbohydrates and 
 fats may participate. 
 
 The sugar of the blood is proved to be glucose, and is found in 
 the serum. 
 
METABOLISM AND NUTRITIVE NEEDS. 1 87 
 
 The quantity of sugar in the blood varies normally from 
 0. 10 to 0.15 per cent., and it may, perhaps, sometimes slightly 
 exceed these limits in either direction. The veins contain some- 
 what less than the collateral arteries. The portal vein, except after 
 the ingestion of large amounts of carbohydrate, contains less and 
 the hepatic veins contain more than do other vascular areas. 
 Unlike the glycogen of the liver, which varies enormously under 
 different dietetic conditions, the amount of sugar in the blood nor- 
 mally undergoes but comparatively shght variations. It increases 
 somewhat after the ingestion of large amounts of carbohydrate 
 (Claude Bernard, v. Mering) and after copious hemorrhage (Edel, 
 Schenk), and decreases during continued starvation (Bernard, 
 Bock and Hoffmann, Otto, Seegen, Chauveau), during the febrile 
 state, after extirpation of the liver, and as a result of poisoning 
 with phloridzin. The quantity of sugar in the blood is about 
 half of the quantity of fibrin, and the amount is not small consid- 
 ering that the sugar is being constantly produced and constantly 
 consumed. Seegen calculates that a human being produces and 
 consumes about lo grams of glucose per kilogram of bodily 
 weight in twenty-four hours. A German, Anglo-Saxon, or Scan- 
 dinavian of ordinary size thus manufactures and uses up between 
 700 and 800 grams. 
 
 The sugar of the blood is consumed in the different tissues of 
 the organism, but chiefly in the muscles ; and by its oxidation into 
 carbonic acid and water it forms the organism's largest, but prob- 
 ably not its only, source of vital power. 
 
 The sugar of the blood causes reduction of copper- and bismuth-solutions ; 
 undergoes fermentation, with the generation of alcohol, carbonic acid, etc. ; 
 forms with potassium a combination, out of which it may be driven by car- 
 bonic acid (Seegen, Ludwig, Abeles) ; deflects the ray of polarized light to the 
 right (Ewald) ; and yields glycosazone with phenyl-hydrazin-chlorate and 
 sodium acetate (Pickhardt). Thus, there is no doubt that it is glucose. To 
 this rule there may, however, be rare exceptions ; it seems probable that in 
 cases in which the sugar in the urine is another saccharid — .?. ^., levulose — 
 the sugar of the blood is also constituted by this saccharid. 
 
 Otto proved the sugar of the blood to be contained in the serum by intro- 
 ducing in Hoppe-Seyler's equation for the valuation of blood-corpuscles from 
 the quantity of plasma and fibrin (in two cases) the figures of the sugar instead 
 of the figures of the fibrin, arriving at nearly the same figures as Hoppe- 
 Seyler's equation gave. Calculating with the aid of Hoppe-Seyler's equation, 
 
i88 
 
 DIABETES MELLITUS AND GLYCOSURIA. 
 
 he found in one case 64.65 per cent, of plasma and 35.35 per cent, of red 
 blood-corpuscles ; and with his own equation he found the corresponding 
 figures to be 64.29 and 35.71. In a second case the analogous figures were 
 67.88 and 32.12, and 67.96 and 32.04. The figures representing fibrin and 
 sugar were as follows : 
 
 
 Cases. 
 
 Blood. 
 
 Plasma. 
 
 
 Fibrin. 
 
 Sugar. 
 
 Fibrin. 
 
 Sugar. 
 
 I, 
 
 0.205 psi' cent. 
 
 O.I 16 per cent. 
 
 0.317 per cent. 
 
 0.182 per cent. 
 
 2, 
 
 
 0.311 " 
 
 0.123 
 
 0.458 " 
 
 0.181 
 
 Naunyn states the normal quantity of sugar in the blood as about o.i per cent. 
 — rather somewhat below (from 0.08 to 0.09) than above this figure ; Bernard 
 found between 0.09 and 0.117 per cent. ; Seegen, between 0.12 and 0.19, and 
 as an average in ten cases, nearly 0.17 per cent. ; Otto, nearly 0.12 per cent. ; 
 V. Mering (in the serum), between 0.13 and 0.14 per cent. ; Frerichs, between 
 0.12 and 0.30 (!!!) per cent. All of these figures refer to man. In the rab- 
 bit Otto found between 0.09 and o.ii per cent.; Barral, in the dog, between 
 0.08 and 0.17 per cent. ; Otto, in the dog, o.ii per cent. The highest of these 
 figures include not only the sugar, but all reducing-substances in the blood 
 (kreatinin, uric acid, etc.), and thus represent too high a value for the glucose. 
 Otto corrected this error, which, besides, shows a wrong relation between the 
 quantity of sugar in the arteries and that in the veins, the reducing, nonsac- 
 charine substances being present in greater quantity in the veins than in the 
 arteries. Otto found in the dog, in blood from the femoral artery, a reduction 
 before fermentation of 0.160 per cent., and after fermentation of 0.034 per cent., 
 the amount of glucose thus equaling 0.126 per cent. ; in blood from the femoral 
 vein of the same dog a reduction before fermentation of 0.158 per cent., and 
 after fermentation of 0.039 P^i" cent., the amount of glucose thus equaling 
 0.1 19 per cent. (The blood was taken simultaneously from both vessels.) 
 After hemorrhage the reduction is increased. Otto considered this to be an 
 effect of the increase of nonsaccharine reducing-substances. Bernard had 
 mentioned this increase as due to the presence of an increased amount of 
 glucose, and Schenk,* in opposition to Otto, maintains that the whole increase 
 is due to the presence of glucose. 
 
 The excess of glucose in the arteries over that in the veins is small ; accord- 
 ing to Otto, the proportion is 12 : 11; according to Barral, 100 : 92.7. As already 
 mentioned, the hepatic veins generally contain most, and the portal vein least 
 sugar of all vessels. The great difference, however, that has so often been 
 found is i7i part the effect of a marked increase in the production of sugar 
 in the liver from nervous causes during the experiment. Mosse, who arranged 
 his experiments with a view to the elimination of this influence, found only 
 
 *" Pfliiger's Archiv," 1894. 
 
METABOLISM AND NUTRITIVE NEEDS. 
 
 189 
 
 0.107 per cent, of glucose in the hepatic veins; the portal vein rarely contains 
 less than 0.08 or 0.09 per cent. After the ingestion of large amounts of carbo- 
 hydrate the portal vein may contain as much as 0.4 per cent., and much more 
 than the hepatic veins (v. Mering). 
 
 The accompanying table, showing the results of Seegen's experiments, illus- 
 trates the influence of diet on the amount of glycogen in the liver and the 
 amount of glucose in the blood. The figures representing the amount of 
 glucose in the hepatic veins probably are much too high, from the influence of 
 the experiment on the nerves ; and all the figures relating to glucose in reality 
 represent both glucose and other reducing-substances. Nevertheless, I con- 
 sider the relations of this conscientious experimenter's figures to be of great 
 value. The observations were made upon dogs that had been subjected to 
 starvation for eight days, and were then fed exclusively on one of the several 
 kinds of food named. I would call attention to the most important fact that 
 both glucose and glycogen reach their lowest figures when the period of pre- 
 liminary starvation is followed by a period in which the only food is fat. 
 
 Food. 
 
 Glucose. 
 
 Carotid. 
 
 Portal Vein. 
 
 Hepatic Vein. 
 
 Glycogen 
 
 IN 
 
 Liver. 
 
 None, 
 
 Fat, 
 
 Muscle, 
 
 Starch, . 
 
 Cane-sugar, .... 
 Cane-sugar and dex- 
 trin, 
 
 0.157 per cent. 
 0.128 " 
 
 0-I55 " 
 0.165 " 
 0.165 " 
 
 0.176 " 
 
 o. 147 per cent. 
 0.I14 " 
 o. 141 " 
 0.147 " 
 0.186 " 
 
 0.258 " 
 
 0.269 P^"" cent. 
 0.217 " 
 0.281 " 
 0.261 " 
 0.265 " 
 
 0.327 <' 
 
 1.67 per cent. 
 0.93 " 
 
 3-7 
 
 6.0 " 
 
 9.4 
 
 Chauveau and Kaufmann, in 1886, brought to light important facts in con- 
 nection with the consumption of glucose in the muscles. They determined the 
 amount ,of both carbonic acid and glucose in the blood from the masseter 
 muscle and from the parotid gland, having previously made a corresponding 
 analysis of the blood in the carotid. This artery supplies the muscle and 
 the gland with about the same amount of blood, which in both is about three 
 times as large during functional activity as during repose. During functional 
 activity the muscle consumed about 5^ times as much glucose as the gland 
 and produced about five times as much carbonic acid. The muscle in exercise 
 produced about 3^ times as much carbonic acid as in repose, and also con- 
 sumed about 3>^ times as much glucose. With the gland, the figures during 
 functional activity and in repose were as 87 : 60 with regard to the production 
 of carbonic acid, and as 90 ; 70 with regard to the consumption of glucose. 
 
 Quinquaud found from 0.12 to 0.15 per cent, of glucose in the femoral vein 
 before, but only 0.07 per cent, after strong faradization. 
 
 As soon as the sugar in the blood reaches a certain amount, 
 which Claude Bernard found to be about 0.25 per cent, in the dog, 
 
IQO DIABETES MELLITUS AND GLYCOSURIA. 
 
 it begins to pass over into the urine. Lepine, immediately after the 
 beginning of the glycosuria in diabetic dogs (following extirpation 
 of the pancreas), found between 0.19 and 0.24 per cent, of glucose 
 in the blood. Seegen's figures indicate that glycosuria in man may 
 exist with less glycemia than 0.20 per cent. Still, there seems to 
 be a certain interval between the ordinary glycemia, which only 
 rarely exceeds 0.15 per cent., and the decided hyperglycemia, in 
 connection with which glycosuria begins. Thus, we find glyco- 
 suria often absent in states that bring about hyperglycemia — £■ g-, 
 asphyxia. Carcinoma is usually (Freund), though not constantly 
 (Matrai), attended with hyperglycemia, but is often found without 
 glycosuria. In cases of simple glycosuria only the highest degrees 
 of glycemia give rise to glycosuria, which appears for only a short 
 part of the day some time after meals. In cases of diabetes there 
 is always hyperglycemia in the severe and often in the light stage. 
 It rarely exceeds 0.4 per cent., but much higher figures are occa- 
 sionally reached. Pavy found 0.57 and Hoppe-Seyler 0.9 per 
 cent, of glucose in the blood. Investigations have proved that 
 the glycosuria bears no fixed relation to hyperglycemia (Seegen, 
 Lepine, and others). Seegen found 3.8 per cent, of sugar in the 
 urine and 0.182 per cent, in the blood ; and afterward, in the same 
 (mild) case, 0.6 per cent, in the urine and o. 181 per cent, in the 
 blood. In a severe case during the observance of a strict diet he 
 found 0.6 per cent, in the urine and 0.19 per cent, in the blood. 
 We thus see that the hyperglycemia, even with considerable gly- 
 cosuria, may be quite moderate. Still, the hyperglycemia consti- 
 tutes the real '^ nocens'' — the sugar in the urine, which alone we 
 are generally able to observe, is of small account. A moderate 
 hyperglycemia, however, is certainly capable of only a moderate 
 noxious influence. We are terrified on finding a glycosuria of 3.8 
 per cent, in a patient, but should be much less alarmed if told at 
 the same time that it resulted from a hyperglycemia of only 0.18 
 per cent. Every one understands at once that if it is normal for 
 the blood to contain 0.12 per cent., or even 0.15 per cent, of glu- 
 cose, it does not constitute a very great danger for it to contain 
 0.18 per cent, of glucose. 
 
 I now arrive at that much-discussed question whether hypergly- 
 cemia and glycosuria — i. e., diabetes mellitus — arise from an in- 
 
METABOLISM AND NUTRITIVE NEEDS. I9I 
 
 creased production or from a decreased consumption of sugar, or 
 from both of these causes. 
 
 The first essential difference in metabolism between the normal 
 and the diabetic individual is met with in the liver, which exhibits 
 a decreased capability of storing glycogen. The opinion is held 
 by many that this deficiency of forming glycogen — which may 
 afterward be used for producing fat, or, in case of need, may be left 
 to the blood as glucose — is the immediate cause of diabetes. The 
 liver is incapable either of keeping the formed glycogen in that 
 state or of transforming enough of the glucose derived from the 
 food into glycogen, and thus it produces or permits too large quan- 
 tities of glucose to escape into the circulation. Claude Bernard 
 believed the increased production of sugar in the liver to be a result 
 of hyperemia and of the action of the diastatic ferment in the blood 
 in attacking the glycogen too vigorously — ^^ V augmentation de 
 rapidite de la circidation du foie accrdit la glycemie." 
 
 Others — e. g., Zimmer — sought to find the root of the evil in the 
 muscles and in an impaired consumption of the sugar of the blood. 
 When in these latter days it was discovered that extirpation of the 
 pancreas causes diabetes, and that extirpation of the thyroid gland 
 causes myxedema, Brown-Sequard formulated the theory of an 
 " internal " secretion of the glands in addition to that which had 
 hitherto alone been observed. The profession, as already men- 
 tioned, for a large part adopted the view that the pamcreas, through 
 an internal secretion, sends into the blood some substance necessary 
 to the combustion and the utilization of the sugar. 
 
 Claude Bernard was familiar with this " glycolytic ferment," or, 
 as Nommes calls it, the "glycolysine." It is this ferment that 
 drives the sugar out of the extravasated blood in about twenty- 
 four hours. Bernard used acetic acid, carbolic acid, or sodium 
 sulphate to prevent or retard this disappearance, Lepine has pro- 
 posed as a unit of glycolytic power the relative quantity of sugar 
 that disappears from the blood in one hour at a temperature of 38° 
 C. (100.4° F.). The normal unit is about twenty per cent, of the 
 whole amount. According to Lepine and Barral, the glycolytic 
 power — which seems to be subject to great variations within the 
 normal — is quite low at a temperature of 15° C. (66° F.), but it 
 increases then for a while with the higher temperature, and is very 
 
192 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Strong at 40° C. (104° F.). At 52° C. (125.6° F.) it suddenly 
 decreases, and is annihilated at 54° C. (129.2° F.). Lepine and 
 his disciples have made extensive researches upon the glycolytic 
 ferment, which, according to that observer, is partly, but not ex- 
 clusively, formed in the pancreas, and is delivered to the blood and 
 the lymph ; it is, further, chiefly, but not exclusively, fixed in the 
 Avhite blood-corpuscles. Spitzer found the glycolysis effected both 
 by the red and the white blood-corpuscles. The process is one of 
 oxidation, oxygen being taken up and carbonic acid produced (Kraus, 
 Spitzer). Barral found that oxygen and ozone slightly increase, while 
 rarefied air, carbonic acid, and carbon monoxid diminish the glyco- 
 lytic power. Acidity also lessens and finally annihilates the glyco- 
 lytic power. This is also the effect of antipyrin (Lepine and Barral, 
 Brouardel and Loye), of sodium carbonate, of morphin, and of vale- 
 rian (Butte). Colenbrander made the observation that the glyco- 
 lysis is destroyed by the extract of leeches. Curare augments it 
 somewhat (Butte). The glycolysis is about as energetic after as 
 before defibrination (Dastre). 
 
 Lepine considers that there is a certain alternation between the 
 "internal" secretion (of the glycolytic ferment) and the external 
 secretion (of the pancreatic juice) in the pancreas. By irritation of 
 the peripheral stump of the pneumogastric nerve Lepine caused 
 increased secretion of pancreatic juice, and found that at the same 
 time the blood from the pancreatic vein had almost entirely lost 
 its glycolytic power, which afterward returned, when the external 
 secretion had moderated. 
 
 After ligation of the pancreatic duct the glycolytic ferment in the 
 blood is increased, probably as a result of pressure on the glandu- 
 lar cells in consequence of stasis. 
 
 In cases of diabetes the glycolytic ferment in the blood is 
 markedly diminished, according to Lepine and many others ; there- 
 fore less sugar is consumed in the tissues, and hyperglycemia, with 
 its various consequences — /. e., diabetes — arises. 
 
 Lepine and Metroz * found that in normal blood — at 37° C. 
 (98.6° F.) — the sugar had decreased, as a result of glycolysis, 
 from 0.13 per cent, to o. 10 per cent.; i. e., the blood had lost 
 
 * " Compt. Rend.," 1893. 
 
METABOLISM AND NUTRITIVE NEEDS. 1 93 
 
 23 per cent, of its sugar. In diabetic blood under the same 
 circumstances the glycolysis may bring down the sugar from 
 0.32 to 0.29 per cent., and the loss amounts to less than 10 per 
 cent. Not only the relative, but also the absolute, loss of sugar is 
 smaller in diabetic than in normal blood ; but relative loss is the 
 one to be taken into consideration. Lepine and Metroz have found 
 that a liter of normal blood customarily loses in the course of an 
 hour about 0.20 gram of sugar, but that an addition of glucose to 
 this same blood may cause the loss, under otherwise the same cir- 
 cumstances, to amount to 0.60 gram. 
 
 Lepine observed chyle from the thoracic duct of a normal dog 
 injected in the veins of a diabetic dog diminish for a short time the 
 glycosuria. Lepine and Barral, by adding such chyle to a solution 
 of glucose in water, also produced "glycolysis," with loss of glu- 
 cose. They also found the normal difference between arterial and 
 venous blood decreased in diabetes. By driving the blood through 
 the extirpated kidney of a dog in Jacoby's apparatus they proved 
 that loss of sugar takes place in the tissues independently of ner- 
 vous influences.* For the details of the extensive researches of 
 Lepine and his disciples I must refer to his own treatises. 
 
 Hedon also, by a series of investigations, has tried to establish a 
 defective glycolysis in cases of diabetes and to exclude an increased 
 production of sugar in the liver. He maintains that on separating 
 the liver from the circulation the sugar disappears (by glycolysis) 
 from normal, but not from diabetic, blood. Minkowski submits that 
 this last fact may depend upon an abnormal transformation into 
 glucose of the glycogen of the muscles. For other results of 
 Hedon's researches also I must refer to the original communica- 
 tions. 
 
 Several experimenters, and especially Minkowski, have come to 
 other conclusions than those of Lepine. Minkowski found the 
 glycolysis in the blood of a diabetic dog to be quite normal, and he 
 was not able to reduce the glycosuria by injections of glycolytic 
 ferment or of pancreatic extract ; he points out that the experiments 
 with Jacoby's apparatus do not exclude postmortem changes — 
 Qui z'ivra, verra ! 
 
 * Barral, " Sucre du Sang," Paris, 1890. 
 
194 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Lepine also mentions a '' pouvoir saccliariferant'' of the blood. 
 While the '' pouvoir glycolytigue " ceases at 54° C. (129.2° F.), 
 the saccharification, which is effected in the serum, is at its best at 
 from 56° to 58° C. (132.8° to 136.4° F.), and gives rise to the pro- 
 duction of about one gram of sugar to the kilogram of blood. The 
 material for this production of glucose is, according to Lepine {vide 
 Seegen), left by peptones. The '^ pouvoir sacchariferant," like the 
 " potcvoir glycolytigue," is increased by acute, but reduced by slow, 
 asphyxia. 
 
 Lepine, while laying the greatest stress on reduced " glycolysis " 
 and diminished consumption of sugar as a cause of diabetes, pru- 
 dently does not deny an increased production of glucose as an addi- 
 tional cause. It is interesting to note Kaufmann's plea * for the 
 view at which he and Chauveau have arrived as a result of numerous 
 experiments. The production of sugar is, according to Kaufmann, 
 like the oxidation in the lungs, a regulative function of one organ. 
 The consumption of sugar, on the other hand, is a common quality 
 of the different tissues, which consume sugar in order to be able to 
 perform their functions, but which do not perform their functions 
 for the purpose of consuming sugar. When a deviation from the 
 normal takes place, it is more reasonable to look for the cause in the 
 organ among whose functions is the production and distribution of 
 sugar — i. e., the liver — than in those organs that have only indirectly 
 anything to do with the sugar. In hibernating animals, in spite of 
 their comparatively profound muscular repose, one does not find 
 hyperglycemia but hypoglycemia, and only when they return to 
 muscular activity does the sugar in the blood reach its full amount. 
 In this instance production is seen to depend on consumption. 
 Chauveau and Kaufmann, in 1893, demonstrated the fact that the 
 sugar increases in organs, especially in muscles, when they are 
 occupied in their functions. By administering large amounts of 
 glucose or by injections of glucose into the portal vein one may 
 induce a glycosuria that manifestly has nothing to do with 
 diminished consumption, but with the overstraining of the liver's 
 capability of transforming and storing glucose in the form of 
 glycogen. This capability is reduced in cirrhosis of the liver ; this 
 
 * " Sem. Med.," January l6, 1895. 
 
METABOLISM AND NUTRITIVE NEEDS. 1 95 
 
 is the cause of the frequency of glycosuria in connection with that 
 disease. Kaufmann further calls attention to Dastre's view that in 
 cases of asphyctic glycosuria the asphyctic blood causes an abnor- 
 mally large production of sugar in the Hver by stimulating the 
 organ to increased activity. In the course of glycosuria due to 
 other poisons (curare, morphin, and anesthetics in general) there is 
 certainly a reduction in oxidation and in consumption ; but the 
 glycosuria is not caused by this, being often developed during the 
 stage of excitement, before the decrease of oxidation and consump- 
 tion ; under these conditions also the glycosuria results from 
 increased production. After Bernard's puncture, with the develop- 
 ment of glycosuria the consumption of sugar is normal (Chauveau). 
 In the course of glycosuria from irritation of peripheral nerves the 
 animals are much excited and consumption is increased. After 
 section of the spinal cord between the last cervical and the first 
 dorsal vertebra Bernard found (after a transitory hyperglycemia 
 from the operation per se), in spite of the lameness and reduced 
 consumption, no hyperglycemia, but a decided hypoglycemia. The 
 lowered temperature in cases of severe diabetes does not depend on 
 the diabetes, but on the marasmus. 
 
 Chauveau and Kaufmann * accept a combined activity of the liver 
 and the pancreas for the regulation of the glucose — economy of 
 the organism, each organ having an inhibitory and a stimulating 
 nervous center influencing its secretion. The medulla oblongata 
 contains a stimulating center for the pancreas and an inhibitory 
 center for the liver.f When the stimulating center for the pan- 
 creas becomes active, the internal secretion of the pancreas increases 
 and stimulates the inhibitory center for the liver ; this secretion has 
 at the same time an inhibitory influence on the stimulating center 
 for the liver located in the cervical part of the spinal cord above the 
 fourth cervical vertebra. The production of glucose in the liver 
 is thus diminished by a twofold influence. 
 
 Chauveau and Kaufmann, besides, accept an inhibitory influence 
 
 * " Comptes rend., " 1 893-1 897. 
 
 f The inhibitory center for the liver transmits its impulses through the " rami com- 
 municantes " of the first four pairs of cervical nerves. Its stimulating center transmits 
 its impulses through the "rami communicantes " below the first four pairs down to the 
 sixth dorsal vertebra. 
 
196 DIABETES MELLITUS AND GLYCOSURIA. 
 
 from the stimulating center for the pancreas on the whole general 
 metabolism — the "histolysis" in the tissues."* This histolysis, 
 they further state, results in the bringing to the blood certain sub- 
 stances, which are again carried to the liver and there transformed 
 into glycogen and glucose. The same influence of the pancreas 
 that otherwise inhibits the production of glucose in the liver thus 
 also diminishes its supply of carbohydrates. 
 
 A section through the spinal cord between the atlas and the 
 occipital bone separates the liver from its inhibitory centers and 
 delivers its stimulating center in the upper cervical cord from its 
 antagonist ; at the same time it separates the pancreas from its 
 stimulating center and cuts off communication between the cere- 
 bral centers and the sympathetic nervous system (inferior cervical 
 ganglion), which executes the impulses transmitted from the cere- 
 bral centers. The internal secretion of the pancreas does not cease, 
 but it is considerably diminished, and the effect of the operation 
 is a hyperemia, quite distinct from, and less pronounced than 
 that which follows total extirpation of the pancreas. Bernard's 
 puncture on the floor. of the fourth ventricle has the same effect, in 
 consequence — according to Chauveau and Kaufmann — not of stim- 
 ulation, but of a paralyzing effect on the nervous center of excitation 
 for the internal secretion of the pancreas, f 
 
 Section through the cord below (or behind) the fourth cervical 
 vertebra, and between this and the sixth thoracic vertebra, leaves the 
 communication between the cerebral stimulating center for the pan- 
 creas and the cerebral inhibitory center for the liver, but cuts off 
 the stimulating center for the liver, and the effect is not hypergly- 
 cemia, but distinct hypoglycemia. Sections below the sixth tho- 
 racic vertebra have no influence on the amount of sugar of the 
 blood. 
 
 If the pancreas is extirpated after section of the cord between 
 
 *I fear that it is impossible to bring this part of Chauveau's and Kaufmann's theories 
 in accordance with the established facts concerning the metabolism of diabetic patients. 
 
 I Kaufmann later, after cutting all the nerves of the liver, found that hyperglycemia 
 still follows Bernard's puncture, and he therefore also accejHs a direct influence, outside 
 of the nervous system, of the internal secretion of the pancreas on the liver. This inter- 
 nal secretion and its inhibitory influence on the liver are diminished by the paralyzing 
 influence of the puncture on the stimulating center for the pancreas. 
 
METABOLISM AND NUTRITIVE NEEDS. 1 97 
 
 the fourth cervical and the sixth thoracic vertebra, diabetes does not 
 develop, but the hypoglycemia continues, the stimulating center for 
 the formation of glucose in the liver being cut off. If, however, the 
 pancreas is first extirpated, and the same section is made after the 
 beginning of the diabetes, hyperglycemia and glycosuria continue. 
 Chauveau and Kaufmann explain this by a certain autonomy on the 
 part of the sympathetic centers in the abdominal cavity, which con- 
 tinue to exercise stimulating functions after these have once been 
 assumed. 
 
 For the same reason hypoglycemia continues if the cord is first 
 severed between the fourth cervical and the sixth thoracic vertebra 
 and section of the medulla oblongata above the atlas is made after- 
 ward. For the same reason hyperglycemia continues after section 
 of the medulla above the atlas, if later the cord is severed between 
 the fourth cervical and the sixth thoracic vertebra. 
 
 After publication of the foregoing results Kaufmann * came to 
 the conclusion, from further experiments, that Lepine's observations 
 concerning diminished "glycolysis " on the part of the blood after 
 total extirpation of the pancreas are correct. Kaufmann, too, has 
 found (in dogs) diabetic after such extirpation, a reduction of "gly- 
 colysis " from I to 0.77, or even to 0.68, and a normal or even 
 slightly decreased production of sugar. He maintains his pre- 
 viously expressed views, so far as they are not directly affected by 
 Lepine's and his own observations on the effect of extirpation of 
 the pancreas on glycolysis. He accepts two secretions on the 
 part of the pancreas : one, the well-known external secretion, 
 among whose functions is the production of glucose from the in- 
 gested carbohydrates ; and the other, the recently discovered inter- 
 nal secretion, among whose functions is the production both of a 
 glycolytic ferment and of a substance possessing an inhibitory influ- 
 ence upon the production of glucose in the liver. Kaufmann thus 
 adopts at present the view that will probably in the future be uni- 
 versally accepted. He believes that diabetes mellitus may arise 
 from an increased production of glucose in the liver or from a de- 
 creased consumption of glucose in the tissues, especially in the 
 muscles, or from both of these causes in combination. 
 
 * " Comptes rend. hebd. Soc. de Biologic," 1896. 
 
I9S DIABETES MELLITUS AND GLYCOSURIA. 
 
 The results of Chauveau's and of Kaufmann's experiments tend 
 to make a pathologic unit of all varieties of decreased power of 
 assimilating carbohydrates. The hypothesis of the two distin- 
 guished French physiologists must, however, be confirmed by a 
 vast amount of experimental work before anything can be con- 
 sidered settled. For the details of Kaufmann's numerous and 
 laborious experiments I must refer to his own works. 
 
 The clinician certainly sees more manifestly the increased pro- 
 duction than the decreased consumption of glucose in cases of 
 diabetes. A child of 20 kilograms bodily weight requires 800 calo- 
 ries in twenty-four hours. A diabetic child of equal weight may pro- 
 duce one kilogram of glucose, representing 3692 calories, in the same 
 time, or so enormously much more vital force than is needed or 
 can be consumed that such a production under normal conditions is 
 not possible. 
 
 As long as we know so little of the laws governing the activity 
 of the pancreas and of the liver, or are uncertain with regard to the 
 details of the regulatory nervous influence ; as long as the formation 
 of carbohydrates from, fats is a mystery and the conditions for the 
 formation of fats from carbohydrates are unknown ; as long as the 
 molecular conditions necessary for the ultimate oxidation are not 
 clearer than they are at present, so long shall we, even if we accept 
 recent views on the increased production of sugar and on decreased 
 "glycolysis" in cases of diabetes, be unable to form any detailed 
 or clear opinions on the immediate cause or causes of diabetes, and 
 we shall do well to abstain from too much speculation on the sub- 
 ject and to wait for further conclusions until experimental pathology 
 has provided us with the necessary amount of established facts. 
 
 The normal human being after ingestion of carbohydrates other 
 than glucose excretes no glucose in determinable quantities in the 
 urine. This fact was first proved by Worm-Miiller, and I have re- 
 peatedly verified the correctness of the observation so far as starch, 
 cane-sugar, and levulose are concerned. After the ingestion of 
 enormous amounts of rice by healthy individuals the urine causes 
 no reduction that can be removed by fermentation. My own 
 experience has been only with isolated instances in which large 
 amounts of carbohydrate have been taken. But healthy Chinese, 
 who live almost exclusively on rice, exhibit no glycosuria. After 
 
METABOLISM AND NUTRITIVE NEEDS. 1 99 
 
 the ingestion of large amounts of the different disaccharids or 
 monosaccharids, a comparatively insignificant part of the ingested 
 saccharid appears in the urine in unchanged form. My own 
 numerous experiments have yielded in all essential respects the 
 same results as Worm-Miiller's. After the ingestion of 250 grams 
 of cane-sugar, Worm-Miiller found 1.8 1 grams of cane-sugar in the 
 urine ; after the ingestion of 50 grams of cane-sugar, he found o. i 
 gram of the same disaccharid in the urine, but not a trace of glu- 
 cose. The ingestion of 200 grams of lactose was followed by the 
 excretion of 1.68 grams of lactose; 100 grams of lactose by the 
 mouth yielded 0.32 gram of lactose in the urine. After the in- 
 gestion of large amounts of honey, which is a mixture of levulose 
 and glucose, Worm-Miiller found only glucose in the urine. Levu- 
 lose, however, obeys the same laws as other saccharids. After 
 the ingestion of 150 grams of crystallized levulose by a normal 
 individual, I found a small quantity of reducing and fermenting 
 substance in the urine ; and by doubling the dose I was able to dem- 
 onstrate that the urine contained no saccharid other than levulose, 
 and to observe the difference in levogyration at different tempera- 
 tures peculiar to this saccharid. 
 
 Miura has lately observed that the ingestion of large amounts of 
 different saccharids by healthy individuals is followed by the ap- 
 pearance in the urine of small quantities of these saccharids exclu- 
 sively in unchanged form. Maltose yielded maltosuria ; levulose, 
 levulosuria ; lactose, lactosuria. Miura found also that the ingestion 
 of even enormous amounts of starch by healthy persons is followed 
 by the appearance of no abnormal or unusual substance in the 
 urine. 
 
 When taken in large amounts, glucose, like other saccharids, ap- 
 pears in some degree unchanged in the urine in normal as well as 
 in diabetic persons. Normal individuals, however, are usually able 
 to assimilate considerable amounts of glucose without exhibiting 
 glycosuria. Worm-Miiller found, in the urine of a person whom 
 he accepted as normal, 0.47 gram of glucose after the ingestion of 
 only 50 grams of the same monosaccharid. I am inclined to 
 believe that in this experiment Worm-Miiller happened to come 
 across a person with the common, but decidedly pathologic, weak- 
 ening of the power of assimilation found especially often in brain- 
 
200 DIABETES MELLITUS AND GLYCOSURIA. 
 
 workers with some degree of neurasthenia. A perfectly normal 
 person can usually take, on an empty stomach or after a light 
 meal, at least lOO grams of glucose without consequent glycosuria. 
 To again assure myself of this fact, I had, shortly before this manu- 
 script left my hands, each of fifteen soldiers in Stockholm take in 
 my presence, at lo A. m., ioo grams of glucose,* a few hours 
 after a light breakfast. Not one of them afterward excreted suffi- 
 cient glucose in the urine to cause any reaction with Nylander's solu- 
 tion of bismuth. Two days afterward I gave 200 grams of glucose 
 in water to each of ten soldiers ; neither after this amount was there 
 in any case sufficient glucose in the urine to yield a distinct reaction 
 with Nylander's solution after four minutes of boiling. 
 
 In other instances 200 grams, and sometimes, though rarely, 
 even 100 grams of glucose cause, in apparently healthy persons, 
 some slight glycosuria. 
 
 Moritz mentions that large amounts of cane-sugar cause in normal indi- 
 viduals an excretion of cane-sugar and of glucose. I maintain that when glucose 
 appears in the urine after the ingestion of cane-sugar the individuals in ques- 
 tion are not normal .f 
 
 De Jong, after some experiments with lactose, came to the conclusion that 
 large amounts cause in normal men an excretion of lactose and of a compara- 
 tively small amount of fermentable saccharid. This is contrary to the obser- 
 vations of Worm-Miiller, Miura, and others, and I doubt that the individual in 
 question was normal. 
 
 A large number of observations have taught me to conclude that 
 any person who exhibits glycosuria after the ingestion of large 
 amounts of rice suffers from a deficient, distinctly pathologic power 
 
 * Five of the soldiers received loo grams of perfectly pure glucose ; all the others 
 were given "technical" glucose, which contains some dextrin. The urine was secured 
 nearly three hours after the ingestion of the sugar. The excretion of the saccharid is, in the 
 large majority of cases, ended, or nearly ended, after that length of time. The diuretic 
 influence of large amounts of glucose is often apparent, even when there is no glycosuria. 
 
 f I wish again to call attention to the fact that no conclusions can be drawn with 
 regard to the details of metabolism in one species of vertebrates from the results of 
 observations made upon another species. Seegen found cane-sugar, glucose, and 
 levulose in the urine of dogs after the ingestion of large amounts of cane-sugar, and 
 Rubner found cane-sugar and glucose. Budge also found glucose in the urine of dogs 
 after the ingestion of large amounts of cane-.'-ugar, but not in man. As to starch, Hof- 
 meister mentions that the ingestion of even enormous amounts causes no glycosuria in 
 the normal dog. 
 
METABOLISM AND NUTRITIVE NEEDS. 20I 
 
 of assimilating carbohydrates. To me, such an individual is either 
 distinctly diabetic or in danger of becoming so. The appearance of 
 glucose in the urine, together with unchanged cane-sugar, after the 
 ingestion of large amounts of cane-sugar is a less serious manifes- 
 tation, but it is not normal, and it takes place in individuals who will 
 daily, under ordinary circumstances, show some glycosuria. The 
 smaller the proportion of glucose and the greater that of cane-sugar 
 in the urine under such circumstances, the more nearly is the patient 
 in a normal condition. There are individuals who may take from 
 200 to 300 grams of cane-sugar without excreting determinable 
 quantities of glucose, — but only some cane-sugar, — and who still do 
 not possess perfectly normal powers of assimilation, but present 
 glycosuria up to 0.05 or o. i or o. 1 5 per cent, for a short while after 
 every dinner of mixed food. 
 
 In cases of diabetes the ingestion of large amounts of carbohy- 
 drate, continued for any considerable length of time, always causes 
 glycosuria ; and the more pronounced the glycosuria, the more ad- 
 vanced the glycosuric dystrophy. Generally, no other saccharid is 
 then found in the urine than glucose. This is always the case after 
 ever so large doses of the polysaccharid starch. But after very 
 large amounts of disaccharids, or of other monosaccharids than glu- 
 cose, there will appear, even in cases of severe diabetes, together 
 with a large quantity of glucose, a slight quantity of the ingested 
 monosaccharid or disaccharid unchanged. This is also the case in 
 dogs diabetic after extirpation of the pancreas. Minkowski found, 
 after administration of 100 grams of levulose, 98.3 grams of glucose 
 and 2.2 grams of levulose in the urine of such a dog. Administration 
 of 200 grams of levulose yielded 105.6 grams of glucose and 15.6 
 grams of levulose in the urine. 
 
 The addition of proteids to a certain portion of carbohydrate 
 increases the glycosuria in all stages of the glycosuric dystrophy. 
 Many persons who are able to take large amounts of saccharids 
 without the development of glycosuria, often excrete small quanti- 
 ties of glucose after rich meals of mixed character ; and in cases of 
 both light and severe diabetes, a portion of meat given with a cer- 
 tain amount of carbohydrate increases the resultant glycosuria. 
 
 There is only a gradual difference between the different stages of 
 diabetes as to the power of assimilating carbohydrates. All dia- 
 14 
 
202 DIABETES MELLITUS AND GLYCOSURIA. 
 
 betics have this in common, that they lose a part of the ingested 
 and digested carbohydrates during a prolonged, abundant supply 
 thereof; on this single symptom is built the whole dystrophic group 
 of diabetes mellitus. All cases and stages of diabetes also have this 
 in common : that they utilize a part of the ingested and digested 
 carbohydrates. For the slight deficiency in the power of assimila- 
 tion that causes a simple glycosuria, only an insignificant part of the 
 ingested carbohydrates again appears in the urine as glucose ; the 
 individual may eat 300 grams of starch and excrete one gram of glu- 
 cose in the twenty-four hours. In a case of mild diabetes the 
 patient sometimes may receive sixty grams of starch without ex- 
 hibiting glycosuria, and after long abstinence from carbohydrates he 
 may even take large amounts of cane-sugar without manifesting 
 any appreciable degree of glycosuria. Even in the worst cases, 
 however, the physician, if he has the courage, in spite of the danger 
 of coma, to put his patient on an exclusively animal diet until the 
 glycosuria reaches a certain fixed degree for the twenty -four hours, 
 will find that the patient, when again allowed a certain quantity of 
 starch, will excrete a smaller excess above the former quantity of 
 glucose than corresponds to the digested part of the ingested por- 
 tion of starch. It seems that only after extirpation of the pancreas 
 in dogs the power of assimilating carbohydrates may sometimes be 
 for a short while completely destroyed (Minkowski) ; but even in 
 these cases a certain amount of starch is usually assimilated.* 
 
 Almost all of the glucose eliminated from the blood in cases of 
 diabetes passes into the urine. The saliva, the tears, and the sweat 
 are generally free from glucose, though it has sometimes been 
 found in these in fractions of one per cent.f It is sometimes found 
 
 * A dog, after extirpation of its pancreas, received 151 grams of starch, of which 64.8 
 grams were found in the feces and — not including small quantities possibly lost in the 
 intestines by fermentation — 86.2 grams were digested. The urine contained 99.2 
 grams of glucose and 12.22 grams of nitrogen. The sugar formed from proteids, com- 
 pared to the nitrogen derived from them, bears a ratio as of 2.8 : I, so that 34.21 grams 
 of glucose must have been derived from proteids and 64.99 grams from the ingested 
 starch. A considerable part of the starch — of which 54 grams correspond to 60 grams 
 of glucose — had manifestly been utilized. 
 
 fToralbi mentions a case of "salivary diabetes" in a hysteric woman, without 
 glucose, but with a large amount of oxalates in the urine and one per cent of glucose in the 
 saliva. 
 
METABOLISM AND NUTRITIVE NEEDS. 203 
 
 in serous fluids; from 0.14 to 0.27 per cent, in ascites (Letulle, 
 Naunyn), 0.5 per cent, in a pleuritic exudate (Foster), etc. Busse- 
 nius found 0.25 per cent, in the sputa. 
 
 The greatest amount of glucose to the kilogram of bodily weight 
 that can be taken without the development of glycosuria represents 
 what Hofmeister calls the limit of assimilation. This limit varies in 
 different patients, and also varies in the same patient at different times. 
 All of those influences that are known to cause diabetes or glyco- 
 suria, of course, lower the limit of assimilation. Excesses and emo- 
 tions cause glycosuria in normal individuals and increase it in diabet- 
 ics. Starvation or underfeeding has a bad influence in this direction ; 
 this was discovered by Claude Bernard and has been elaborately 
 studied by Hofmeister (see Glycosurias). Muscular activity within 
 certain limits heightens the limit of assimilation (Bouchardat, Zim- 
 mer, Kiilz, v. Mering) ; massage has the same effect (Finkler and 
 Brockhaus). Fatigue, however, has a contrary effect, and after long 
 marches or after journeys in railway cars the diabetic patient often 
 exhibits for several days a lower power of assimilation than under 
 ordinary circumstances. Kiilz made an observation which can be 
 easily verified — viz., the limit of assimilation is often higher early 
 than late in the day. A most important fact (see below) is this : 
 that the Hmit of assimilation is higher after the observance for 
 some time of a strict diet and absence of hyperglycemia and gly- 
 cosuria. Opium, syzygium jambulanum, arsenic, etc., often increase 
 the limit of assimilation ; in other cases these drugs have no effect 
 whatever. In the course of careful experiments with phenacetin, 
 which a physician recommended for increasing the power of assimi- 
 lation, I was able repeatedly to demonstrate an increased glyco- 
 suria. Lepine and his disciples have lately given an explanation 
 of the fact that the same agent may have quite contrary effects in 
 different cases ; it increases both the production and the consump- 
 tion of glucose, so that its effect on the limit of assimilation de- 
 pends on the relative state of production and consumption in the 
 case. The best remedies, of course, are those that decrease pro- 
 duction and increase consumption. Alcohol in small doses increases, 
 in large doses diminishes, the power of assimilation. Fever decid- 
 edly increases this power. Finally, the limit of assimilation often 
 
204 DIABETES MELLITUS AND GLYCOSURIA. 
 
 slowly sinks, from unknown causes, in consequence of the progres- 
 sive nature of the glycosuric dystrophy. 
 
 The limit of assimilation varies also in the same individual from 
 unknown causes. Worm-Miiller gives a striking instance of this : 
 V. C, previously mentioned, received 50 grams of glucose before 
 breakfast, and excreted 0.47 gram in the urine during the next 
 three hours. At another time, under the same circumstances, the 
 subject received 100 grams without the development of any glyco- 
 suria whatever. On a third occasion glycosuria appeared six hours 
 after the ingestion of 100 grams of glucose (rare !), and continued for 
 three and one-half hours, during which time 1.85 grams of glucose 
 were excreted. 
 
 Shortly before death and in advanced marantic states, the gly- 
 cosuria, ceteris paribus, diminishes — not by reason of an increased 
 power of assimilation, but on account of impaired digestion and the 
 retardation of all the metabolic processes. The reason why glyco- 
 suria diminishes in cases of cirrhosis of the kidneys remains to be 
 explained. 
 
 Glycosuria following the ingestion of carbohydrates in cases of 
 diabetes (and after large amounts of glucose in any person) begins, in 
 the enormous majority of cases at least, within the first hour, and 
 generally a distinct reaction can be found after half an hour. Bread 
 and well-cooked rice seem to cause glycosuria almost as quickly as 
 pure glucose. The larger part of the glucose in the urine has often 
 been excreted at the end of the first hour ; the curve afterward 
 sinks, and after from three to six hours the urine in mild cases is 
 again free from glucose. In cases of simple glycosuria the whole 
 excretion may not continue for more than an hour, beginning about 
 half an hour and often ending an hour and a half after the meal. 
 Even with a free diet the mild cases of true diabetes often exhibit, 
 some hours after a meal, no glycosuria, and the majority of such 
 patients present no glycosuria in the morning before the first meal. 
 This is, therefore, the worst time for testing whether or not an in- 
 dividual is free from diabetes. 
 
 My patient, T., suffered from simple glycosuria, and with a perfectly free 
 diet, including an abundant supply of carbohydrates, excreted about 2 grams 
 of glucose in twenty-four hours. Between 9.30 and 10 A. M. he was free from 
 
At II " 
 
 95 
 
 At 11.30 " 
 
 145 
 
 At 12 M. 
 
 36 
 
 METABOLISM AND NUTRITIVE NEEDS. 205 
 
 glycosuria, and drank 300 grams of cane-sugar in 1000 cu. cm. of water, 
 excreting afterward as follows : 
 
 At 10.30 A. M. 130 cu. cm. of urine of 1.030 specific gravity and containing 0.2 per 
 
 cent, of sugar. 
 " 1.006 " containing o. I per cent. 
 
 of sugar. 
 " 1.004 " containing about 0.07 per 
 
 cent, of sugar. 
 " 1. 018 " containing 0.15 per cent. 
 
 of sugar. 
 At 12.30 P. M. 24 " " X " containing somewhat 
 
 more than o. i per cent, of 
 
 sugar. 
 At I " 21 " " X " containing less than o. I 
 
 per cent, of sugar. 
 At 1.30 " 26 " " X " containing traces. 
 
 At 2 " X " " X " containing faint trace. 
 
 At 2.30 " the urine did not contain as much as o.oi per cent, of glucose. 
 
 The figures here given as representing sugar were obtained by polarization, 
 and thus refer to the mixture of glucose and cane-sugar in the urine. The 
 figures are, besides, all somewhat too low, the levogyration of glycuronic acids 
 not being taken into account. 
 
 A medical student, X., rang me up on the telephone, and in a trembling voice 
 asked if he might pay me a visit at once ; and I, having had several times 
 before a similar experience, at once suspected that he had passed glucose in his 
 urine. The ingestion of 250 grams of cane-sugar caused him to vomit after 
 half an hour. The urine, however, passed a few minutes later contained cane- 
 sugar but no glucose, and reduced after, but not before, boiling with some 
 sulphuric acid. On the next day X. had better luck, and was able to retain 200 
 grams of cane-sugar. About two and a quarter hours afterward he passed 100 
 cu. cm. of urine, with a specific gravity of 1.022, and which, before boiling with 
 some sulphuric acid, reduced as a solution of glucose of 0.33 per cent. ; but 
 after "inversion " (of the excreted cane-sugar) it reduced as a solution of glu- 
 cose of 0.55 per cent. In the next sample of urine, passed three and a half 
 hours after the cane-sugar had been taken, there was no appreciable amount 
 either of glucose or of cane-sugar. 
 
 I consider X. more nearly a case of true diabetes than he would be if he had 
 passed only cane-sugar and no glucose ; but he is better off than he would be 
 with greater glycosuria and less saccharosuria. 
 
 Kiilz made it a rule to give the patient the allowed daily quantity 
 of starch at one meal, believing that it induced a greater degree of 
 glycosuria if given in several portions at different times. The re- 
 sult, however, depends on circumstances. If the patient's limit (or 
 power) of assimilation is small as compared with the allowed 
 
206 DIABETES MELLITUS AND GLYCOSURIA. 
 
 quantity of carbohydrates, this quantity given in several doses may 
 occasion the presence of more glucose in the urine than when given 
 at one time ; but if the amount allowed is small as compared with 
 the power of assimilation, it may induce less glycosuria by being 
 given in divided portions than w^hen given at once. This is mani- 
 fest both from Kialz's figures and from mere reasoning as soon as 
 the patient can take any quantity of carbohydrates without the de- 
 velopment of glycosuria. 
 
 Kiilz, in addition to many other services, also rendered that of 
 teaching us that different kinds of carbohydrate are assimilated in 
 different degree by diabetics. 
 
 Starch induces greater glycosuria than any other article of 
 food — greater even than pure glucose. The formula of starch is 
 CqH-^^qO-; that of glucose, CgH^206- By taking up water, starch 
 will form glucose : CgHj^O- -f H2O = CqH^^O^. The atomic 
 weights being for C = 12, H := i, and for O = 16, the foregoing 
 equation yields 12. 6+1. 10+ 16. 5 + 1.2+ 16= 12 . 6+ i . 12 + 
 16 . 6, or 162 + 18 = 180. In other words, 162 grams of starch, 
 by taking up 18 grams of water, will form 180 grams of glucose ; or 
 9 grams of starch + i gram of w^ater will form 10 grams of glucose. 
 
 Cane-sugar is a disaccharid of glucose and levulose. Glucose 
 causes marked glycosuria in cases of diabetes ; levulose, much less. 
 Thus, cane-sugar causes less marked glycosuria than starch or 
 glucose. 
 
 Lactose is easily partly changed by fermentation in the bowel 
 into lactic acid, w^hich does not give rise to glycosuria, but often 
 causes diarrhea, in consequence of which more than usual of the 
 ingested saccharid passes off in the feces. In so far, however, as 
 neither the one nor the other occurs, lactose seems to give rise to 
 about as marked a degree of glycosuria as does glucose itself. 
 Kiilz's patient, F. S., after the ingestion of 100 grams of glucose, 
 excreted 8.9 grams of glucose ; and after 100 grams of lactose, ex- 
 creted 9 grams of glucose.* Fr. Voit, in a severe case, saw lOO 
 grams of lactose increase the glycosuria by 49 grams. 
 
 * After five weeks of abstinence from carbohydrates the power of assimilation had 
 increased, and loo grams of lactose gave rise to the excretion of only 4. i grams of glu- 
 cose. The glycosuria lasted about three and one-half hours, and the larger part of the 
 glucose was excreted within the first hour. 
 
METABOLISM AND NUTRITIVE NEEDS. 20/ 
 
 Galactose also gives rise to quite a considerable degree of glyco- 
 suria. Fr. Voit saw the glycosuria increased by JO grams in a 
 severe case, after the ingestion of lOO grams of galactose. 
 
 Kiilz has published a report stating that the polysaccharid inulin 
 and the monosaccharid levulose, which are related chemically in 
 the same way as starch and glucose, are completely assimilated by 
 diabetics. As soon as the price of levulose made this substance of 
 practical value for such a purpose I began to use it in cases of dia- 
 betes ; in severe cases with pronounced autophagia and loss of 
 weight to lessen the daily nutritive deficit, and in mild cases as a 
 substitute for cane-sugar. I found levulose of great value in check- 
 ing the loss of weight in severe cases, and I believe it has a power- 
 ful effect in warding off the coma for a time. I constantly found 
 that levulose increases the glycosuria in severe cases, and that large 
 amounts in mild cases also cause glycosuria,* though more of levu- 
 lose than of other saccharids is assimilated. 
 
 Inulin, a polysaccharid, is found in unusually large quantities in 
 the tubers of Helianthus tuberosns, which is sometimes used for 
 food in Europe and America, and is known under the name of 
 Jerusalem artichokes (topinambour). Boiled with diluted acid it 
 yields levulose. It is better assimilated by diabetics than starch, 
 though, like levulose, it decidedly increases the glycosuria. 
 
 Inosite does not give rise to glycosuria, even when given in large 
 amounts, as in young string-beans (Kiilz). Inosite is, however, not 
 a saccharid, and it is not considered as belonging to the carbohy- 
 drates. Maquenne believes it to be hexahydroxyl-benzol. 
 
 [As is well known, inosite is found in many parts of the human 
 organism, and is often present in the urine in conjunction with poly- 
 uria, with diabetes mellitus or insipidus, and with cirrhosis of the 
 kidney. Sometimes glycosuria is succeeded by inosituria. In a 
 case of diabetes, Vahl saw the glucose disappear and polyuria 
 continue, and observed an excretion of from eighteen to twenty 
 grams of inosite in twenty-four hours.] 
 
 Mannite, which is a hexatomic alcohol, causes, according to 
 
 * Gruber, Hale White, Haycroft, Heyse, Klemperer, Minkowski, Palma, and others 
 have had a similar experience. In the severe stage Palma found that loo grams of levu- 
 lose increased the glycosuria by 60.49 grams. 
 
208 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Kiilz, no glycosuria in any stage of diabetes, and normally appears 
 in the urine in only small quantities. It may be used by diabetics 
 as a mild aperient. 
 
 Other saccharids than glucose are also found in the urine, both 
 in normal and in abnormal states. Lactose, as has already been 
 mentioned, normally occurs in the urine of mothers during lactation 
 and in that of sucking children. Levulose has several times been 
 found in cases that have presented otherwise more or less the 
 clinical image of diabetes mellitus, and the same may perhaps be 
 true of maltose. Laios, found by Leo with glucose in a case of 
 severe diabetes, may possibly be a saccharid, but it is as yet very 
 little known. 
 
 Gorup-Besanez mentions levulosuria. Zimmer and Czapek have described 
 a case of diabetes with as much as 2.2 per cent, of levulose, excreted with 
 some glucose. Rohmann and Wolf saw a case with urine that turned the ray 
 of polarized light to the right as much as a 1.6 per cent, solution of glucose, 
 but reduced as a 4.3 per cent, solution of glucose. It contained in addition 
 to glucose a reducing-substance that turned the ray of polarized light to the 
 left, was decomposed by fermentation, and was thus in all probability levulose. 
 Seegen, in 1884, treated in Carlsbad a case of pure levulosuria. In the follow- 
 ing year Seegen had left the place and the patient came under my treatment, 
 as she did also in 1893 and in 1896. Both Seegen and Kiilz have published 
 the case, which clinically is more similar to one of simple glycosuria than to 
 one of true diabetes. As it presents a peculiar interest, I briefly describe it 
 herewith : 
 
 Mrs. F., a Jewess, born in 1837, knew of nothing else of anamnestic inter- 
 est than that her mother had suffered from obesity and probably from diabetes, 
 the thirst being remarkable during the latter part of life. The patient herself 
 was always rheumatic, and since childhood had from time to time been troubled 
 by furuncles. She sometimes suffered from dryness of the mouth and from 
 increased thirst. At no time, however, had there been distinct polyuria, 
 although there was marked pollakiuria. 
 
 The patient was a pronounced neurasthenic with a number of the usual 
 symptoms. She suffered from right-sided sciatica. The knee-jerks were some- 
 what weakened. A sample of the mixed urine for twenty-four hours slightly 
 reduced Fehling's solution. After an abundant dinner, with much carbohy- 
 drate, there was a deviation to the left of the ray of polarized hght of 0.3° (with 
 Hoppe-Seyler's instrument), which disappeared for the greater part after fer- 
 mentation, 'when the reduction was almost entirely gone. 
 
 In 1893, nine years afterward, the excretion did not amount to more than 0.3 
 per cent, at the utmost, and it was not possible to decide with certainty whether 
 or not sonfe glucose was mixed with the levulose. 
 
 In the summer of 1896 the patient again visited Carlsbad, being otherwise 
 
METABOLISM AND NUTRITIVE NEEDS. 2O9 
 
 in about the same state as eleven years before, i. e., in fairly good health, suf- 
 fering only from some neurasthenic symptoms and from sciatica on one side. 
 The excretion of sugar, however, was larger, and in some samples reached 
 almost two per cent. The urine contained no albumin. After removing the sac- 
 charid by fermentation I found only a slight and uncertain reducing effect on 
 the part of the urine, but a deviation of the ray of polarized light about 0.15° 
 to the left. This undoubtedly arose from combined glycuronic acids, and 
 it disappeared after precipitation with ammonia and lead acetate. This devia- 
 tion taken into consideration, quantitative determinations of the saccharid, very 
 carefully performed by methods of polarization and reduction, perfectly agreed 
 in results, and I concluded that the urine contained no other saccharid than 
 levulose. The quantity of levulose was large enough to enable me to observe 
 distinctly the decrease in the deviation of the ray of polarized light at higher 
 temperature peculiar^to solutions of this substance. 
 
 Seegen, who had the patient under his care in 1884, then found 3.2 per cent. 
 of levulose. Mauthner, who analyzed another specimen of the urine, found 
 1.59 per cent, of levulose. The results of polarization and reduction agreed, 
 and the urine contained no other^ saccharid than levulose in appreciable 
 quantity, 
 
 Kiilz, in 1886, wrote to the patient asking for five liters of her urine, and 
 found that the urine fermented slowly but completely on addition of yeast, form- 
 ing alcohol and carbonic acid ; that it had a sweet taste on concentration ; and 
 that with phenylhydrazin chlorate and sodium acetate it yielded an osazone 
 that melted at 205° C. (401° F.), and had the formula CgHigOg. It yielded 
 also Selivanoff's reaction and turned the ray of polarized light to the left. 
 This would have assured an ordinary person of the identity of the saccharid 
 with levulose. Kiilz found also that levulose in " absolutely pure, hard crys- 
 tals " dissolved in water was again precipitated by lead acetate, and that the sac- 
 charid in the urine of Mrs. F. was precipitated by this salt only on addition of 
 ammonia — a difference that, as he himself, with all his doubts, remarked, 
 might well depend on the different solvent mediums. 
 
 Le Nobel mentions a case of tnaltosuria in a diabetic patient of sixty-one 
 years, whose digestion of fat was much impaired. Von Ackeren found maltosuria 
 in a case of carcinoma of the pancreas, and Wedenski possibly also saw such 
 a case. Further investigations seem necessary, especially in view of the fact 
 that extirpation of the pancreas causes in dogs only glycosuria. 
 
 Laios, found by Leo in association with glucose in three severe cases of dia- 
 betes, reduced (less than glucose), turned the ray of polarized light to the left, 
 yielded an osazone with Fischer's test, but did not ferment and had no sweet 
 taste. 
 
 If there has been much to say with regard to the fate of carbo- 
 hydrates in normal and diabetic organisms, we may state in com- 
 paratively few words what is necessary with regard to the fats, 
 however important an item they constitute in the dietary of a dia- 
 betic patient. We know of no direct changes in the metabolism of 
 fat in cases of diabetes. 
 
2IO 
 
 DIABETES MELLITUS AND GLYCOSURIA. 
 
 We have seen that fat does not increase the glycogen in the liver 
 or elsewhere. We also know that it does not increase the glyco- 
 suria in any cases of diabetes. 
 
 The absorption of fat, as has already been mentioned, is, in most 
 cases of diabetes, normal. Fat is decomposed, as usual, by the bile 
 and the pancreatic juice into triglycerid, free fatty acids, and soaps. 
 In the chyle it is again found almost exclusively as neutral fat, and 
 is stored in the liver and in the muscles. We have seen that its fate 
 afterward is unknown, and that there are various opinions, differing 
 from the one expressed by Nasse, who believes that it is utilized 
 and oxidized exclusively in the liver, to which the fat would have to 
 return when once stored anywhere else. 
 
 Two qualities of fat — its high caloric value and that of not in- 
 creasing the hyperglycemia — make it an excellent food for diabetics. 
 Unfortunately, it is impossible to utilize practically to the full ex- 
 tent what might theoretically be expected from this kind of food. 
 Fat can be tolerated only in quantities that are far below the caloric 
 needs of the organism. Then fat does not protect the proteids of 
 the organism as powerfully as carbohydrates do. 
 
 The circumstance that the same number of calories given in the 
 form of carbohydrates diminish the consumption of proteids much 
 more than an equal number of calories in the form of fat has been 
 demonstrated by Voit, who was able to reduce the excreted nitrogen 
 with 1 5 per cent, by the administration of carbohydrates, but only 
 with 9 per cent, by the administration of fat. 
 
 I insert the following table, compiled from Kaiser's researches : 
 
 
 Daily Food in Grams. 
 
 Calories. 
 
 Nitrogen in 
 
 Urine 
 AND Feces. 
 
 Gain 
 
 Time. 
 
 Nitrogen. 
 
 Fat. 
 
 Carbo- 
 hydrate. 
 
 or 
 Loss. 
 
 I. Four days, . . 
 II. Three days, 
 III. Three days, . 
 
 21. l8 
 
 21.53 
 
 21. lO 
 
 71-65 
 217.9 
 
 70.37 
 
 338.2 
 
 0. 
 338.2 
 
 2593 
 
 2577 
 2581 
 
 20.15 
 
 24.51 
 20.17 
 
 + 1.03 
 —3.05 
 +0.93 
 
 The most curious fact, that the nitrogen in the urine is sometimes increased 
 by the ingestion of fat, has several times been observed, in contradistinction to 
 the power of conserving proteid, which certainly belongs to some extent to fat. 
 Voit believes that this happens only with a small supply of proteids and a large 
 
METABOLISM AND NUTRITIVE NEEDS. 211 
 
 supply of fat, but Weintraud's tables do not seem to corroborate this view. 
 Voit attributes to the fat two qualities with opposite results : It has the well- 
 known effect of conserving proteids ; but, on the other hand, it has a tendency 
 to increase the circulating proteids. Weintraud refers to an analogous 
 phenomenon in one of Nasse's experiments ; A dog receives a certain quan- 
 tity of phenol, excretes part of it unchanged and oxidizes the remainder to 
 hydrochinon ; with a larger supply of fat the unchanged phenol decreases and 
 the hydrochinon increases. Nasse considers that the oxidation of fat pro- 
 duces free atoms of oxygen. Still, we do not know how this is done, and we 
 stand before a most curious enigma. I should find it interesting to know how 
 the diaceturia and the glycosuria resulting from proteids in a severe case of 
 diabetes are influenced by a larger supply of fat, when fat increases the nitro- 
 gen of the urine. 
 
 An ordinary civilized person can not eat more than a certain 
 limited quantity of fat,* and — worse luck for the diabetic patients ! — 
 it is not meat, but bread and potatoes (i. e., carbohydrates), that 
 help him to eat more. A comparatively limited allowance of bread 
 — viz., from 8o to lOO grams a day — markedly increases the capa- 
 bility of eating a good deal of fat ; but even then patients generally 
 can not take more than 200 or 250 grams of this in the twenty-four 
 hours t without nausea and digestive disturbances. 
 
 The formation of fat within the organism in cases of diabetes is 
 impaired by the passing off in the urine of a part of the carbohy- 
 drates of the food which otherwise might form fat. In the severe 
 stage a deficit arises in a like manner in the formation of fat from 
 proteids, which may occur in different ways, but which certainly 
 takes place in consequence of the intermediate formation of glyco- 
 gen. It is, by the way, possible that a better knowledge of the 
 details of the formation of fat from carbohydrates and from pro- 
 
 * The Arctic nationalities are capable of devouring large quantities of fat. In l868 
 I traveled through Lapland with no other company than a Lap for a servant. I was on 
 one occasion about to throw away quite a quantity of butter which began to be rancid. 
 The Lap protested against this waste, and, on permission, devoured the whole amount at 
 once without the addition of bread or of anything else. 
 
 f The ordinary articles of food containing the largest percentage of fat are as follows : 
 
 Butter, with about 84.4 per cent, of fat and from o.i to 0.5 per cent, of carbohydrate. 
 Olive-oil, " 99 " " " o.x " " 
 
 Lard, " 76 " " " o. " " 
 
 Rich cheese, " 30.5 " " " 1.5 " " 
 
 " Lipanin " is olive-oil with about six per cent, of free fatty acid, and is said to taste 
 better and be easier of digestion than neutral olive oil. 
 
212 DIABETES MELLITUS AND GLYCOSURIA. 
 
 teids in the normal organism would contribute to a solution of some 
 of the many mysteries of diabetes. A consideration of the forma- 
 tion of fat within the diabetic organism leads me to discuss the close 
 connection that, notwithstanding the restriction of this formation, 
 undoubtedly exists between adiposity and diabetes, and also the 
 connection of both of these dystrophies with the gouty dystrophy. 
 It would be pleasant and convenient to be able to indicate the 
 nature of this connection by saying that the deficient power of 
 oxidizing fat goes hand in hand with a deficient power of oxidizing 
 carbohydrates, and that both these deficiencies are closely related 
 to the deficient power of oxidizing proteids. But, with all the 
 weakness of our present position, with our exceedingly imperfect 
 knowledge of the pathogenesis of each of the three dystrophies, we 
 now know enough to understand how premature it would be to 
 indicate in such a manner the deep mystery of the relation referred 
 to. The worst diabetic can oxidize fat and other substances in 
 enormous quantities. The theories lately emanating from Germany 
 in this connection belong, in all their ingenuity, in the domain of 
 pure speculation. 
 
 Since the end of the i8th century physicians now and then have 
 observed that the blood exhibits a grayish color in cases of severe 
 diabetes, and this color has been found to be due to the presence 
 of an increased quantity of fat in minute particles. Diabetic lipemia 
 has reached as high as 1 1.7 per cent, in man (Lecanu) and 12.3 per 
 cent, in the dog (D. Gerhardt). It is known that the customary 
 0.2 or 0.3 per cent, of fat in the blood may normally increase enor- 
 mously after digestion. Still, there seems to be no doubt that some 
 diabetes, like tuberculosis and alcoholism, sometimes causes the ap- 
 pearance of a still larger quantity of fat in the blood, a true hyper- 
 lipemia, and, sometimes, though only in rare cases, a consequent 
 lipuria. This may be a phenomenon connected with the toxic, 
 "protoplasmatic" disintegration of proteids ; but at present our 
 knowledge of the matter is restricted to what I have already 
 mentioned. 
 
 Alcohol must not be left out of consideration in a discussion of 
 human food. It has high caloric value ; a gram yields seven calories 
 gross. When large amounts are taken, about ninety per cent, of 
 
METABOLISM AND NUTRITIVE NEEDS. 21 3 
 
 these calories are utilized (Strassman) ; when the amounts are small, 
 probably more is utilized (Hirschfeld). These calories are, how- 
 ever, not of high quality ; Miura has shown that alcohol protects 
 the proteids much less than the same caloric amount of carbohy- 
 drates, and less even, it seems, than the same caloric amount of fat. 
 In large amounts it acts as a protoplasmic poison, with a well-known 
 deleterious influence in various respects, and in such amounts 
 lessens the power of assimilation both in cases of diabetes and under 
 other conditions. In most cases i^ of a gram of pure alcohol per 
 kilogram of bodily weight is a fair allowance a day ; double this 
 amount is never to be exceeded for habitual use. Even in these 
 amounts alcohol ought always to be taken miicJi diluted, to avoid 
 irritation of the mucous membranes and of other structures. In this 
 condition and in the doses stated it will do no harm and some good, 
 especially to diabetics. It economizes fat, and if any one, after taking 
 from twenty to thirty grams of alcohol a day, suddenly observes 
 absolute abstinence, he will always, ceteris paribus, lose in bodily 
 weight. In such amounts alcohol does not lessen, but rather in- 
 creases, the power of assimilating carbohydrates (Kiilz). If recent 
 investigations (of Hirschfeld) have not corroborated the claims for 
 alcohol that it facilitates the absorption of fat, there can be no doubt 
 about its value in small amounts in facilitating the ingestion of larger 
 quantities of fat and in increasing the appetite in general. The 
 many and terrible sins that mankind has committed with alcohol 
 ought not to make us blind to its real and most important advan- 
 tages. There are at present in this country (Sweden), as there have 
 always been, a great many drunkards, who ruin themselves with 
 alcohol, and a great many cranks with an unwise and blind passion 
 for total abstinence. 
 
 As a faulty metabolism of carbohydrates distinguishes the mild 
 stage of diabetes from a normal condition, so a faulty metabolism of 
 proteids distinguishes the severe stage from both the mild stage and 
 the normal condition. Unfortunately, a host of questions, that can 
 not at present be answered, present themselves with regard to the 
 fate of proteids both in the normal and in the diabetic organism. 
 We do not know much more than that proteids may form proteids, 
 
214 DIABETES MELLITUS AND GLYCOSURIA. 
 
 fat, and carbohydrates.* The differences with regard to processes 
 both of disintegration and of synthesis between different kinds of 
 proteids, especially between the simpler proteids and those of a 
 more complicated molecular constitution, the proteids sensii stric- 
 tiori (nucleins, mucins), the metabolic differences between the 
 various tissues, the successive molecular steps on the way to com- 
 plete oxidation, etc., are, for the greater part, unknown. 
 
 Our next most important task will be to become better acquainted 
 with the conditions of production and consumption of the three 
 substances, acetone, diacetic acid, and /S-oxybutyric acid, in cases of 
 diabetes. We have good general and special reasons for consider- 
 ing them to be momentarily present even in healthy organisms, 
 though the ;9-oxybutyric acid, the mother-substance of the others, 
 is normally quickly converted into diacetic acid, this acid into 
 acetone, and acetone into carbonic acid and water. I shall return 
 to this subject later. 
 
 The difference in the metabolism of the proteids between the mild 
 and the severe stage of diabetes begins in the liver. I have stated 
 that if in the mild stage the carbohydrates are restricted below the 
 patient's limit of assimilation, the formation of glycogen in the 
 liver in great probability takes place just as it does in a normal indi- 
 vidual upon the same diet. In cases of severe diabetes, however, 
 the formation of glycogen is restricted under all dietetic conditions, 
 and even a part of the products of proteids passes off in the urine 
 as glucose. 
 
 The details of the formation of carbohydrates from proteids are 
 not known. We do not know if all the glucose derived from pro- 
 teids must first become glycogen, but we have good reason for 
 believing that there is no such necessity and that proteids can 
 
 * The formation of proteids from peptones and albuminoids need not detain us, and we 
 have already spoken of the formation of carbohydrates from proteids. There is still some 
 slight doubt whether proteids can or can not form fat directly and without first forming 
 glycogen, notwithstanding the cellular manifestations in regressive metamorphosis or after 
 certain poisons, the formation of the acid of palmitin (Salkowski) and other productions 
 after death (Salkowski, Lehmann), the supposed formation of fat from proteids in larvse 
 (Hofmann), the abundant formation of milk even with an exclusive diet of meat in 
 bitches (Subbotin, Voit, Kemmerich), and the disappearance in the organism of carbon 
 with a similar diet (Pettenkofer and Voit, E. Voit). 
 
METABOLISM AND NUTRITIVE NEEDS. 21 5 
 
 directly form other carbohydrates than glycogen. Hammarsten 
 isolated (from the pancreas, the liver, and the mammary gland) a 
 nucleo-proteid which, when boiled with a diluted mineral, yielded 
 a reducing substance that was proved to be a pentose. Hammar- 
 sten admits the separation of a molecule of carbohydrate from the 
 proteids of a more complicated structure (nucleins, mucins). Pavy 
 considers the proteids glucosids that, boiled with diluted acids, 
 yield saccharids and proteids of less complicated structure, and has 
 produced carbohydrates from the albumen of eggs and from fibrin. 
 Kravkow's researches have led to similar conclusions with regard to 
 some kinds of proteids. Kassel produced formic acid and levulinic 
 acid by the action of sulphuric acid on nuclein. Levulinic acid has 
 always shown itself as a derivative of carbohydrates. 
 
 It is the presence of derivatives of proteids in the urine that dis- 
 tinguishes severe from mild diabetes. The glucose in severe cases 
 is partly derived from proteids ; the acetone, the diacetic acid, and 
 the /?-oxybutyric acid in such cases are believed to be derived 
 exclusively from proteids. 
 
 If in a case in the mild stage the carbohydrates of the food are 
 restricted below the patient's limit of assimilation his urine, as is 
 well known, remains free from glucose and does not, so far as we 
 know at present, differ from the urine of a normal person livittg on 
 the same diet. 
 
 For practical reasons I here deviate from the straight line of ex- 
 position to show the truth of this last assertion. 
 
 Among certain derivatives of proteids in the urine in the mild 
 stage we are chiefly interested in urea, uric acid, and acetone (the 
 diacetic and /5-oxybutyric acids belong exclusively to the severe 
 stage). 
 
 Acetone was first discovered in a case of severe diabetes. It is 
 undoubtedly increased in such cases. Engel found 2.8 grams, 
 which is a rare figure. In normal individuals the daily excretion is 
 only about 0.0 1 gram (v. Jaksch) ; but it is often increased in 
 children, whose breath, by the way, sometimes under apparently 
 normal conditions smells of acetone. It is increased also with 
 lactosuria during lactation, being probably derived from casein 
 (Guckelberg, V. Jaksch), and after the ingestion of certain poisons, 
 during starvation, in febrile states, in eclampsia and epilepsy, lyssa. 
 
2l6 DIABETES MELLITUS AND GLYCOSURIA. 
 
 cachexia, disturbances of digestion, and mental diseases. It is 
 normally increased when carbohydrates are excluded from the diet 
 and with a purely animal diet. Von Jaksch states that in some mild 
 cases of diabetes it does not occur in larger quantities than in nor- 
 mal individuals using the same food, and Hirschberg's researches 
 point to a similar result. At present it is not proved that there is 
 any increase of acetone at all in the mild stage of diabetes, and, 
 even in that event, it is not known under what circumstances or in 
 what class of cases (see below). 
 
 As to urea, it is now known that in the large majority of cases 
 of diabetes it is not present in the urine in larger quantities than in 
 normal individuals under the same dietetic conditions. Only in the 
 very severe cases with the toxic or protoplasmic disintegration of 
 tissues is the patient supposed to excrete more urea than a normal 
 person upon the same food. 
 
 The quantity of uric acid, about which only the newest analytic 
 methods give reliable information, varies greatly in normal indi- 
 viduals. Naunyn and Riess, by a method of their own, found from 
 0.16 to 1.05 grams ; Kiilz, by the same method, from 0.06 to 0.76 
 gram ; Bouchardat, more than three grams ; Hartz, in six cases of 
 diabetes, found at the utmost between 1.5 and 2 grams of uric acid 
 in the urine in twenty-four hours. Neither from these, nor from 
 Bischofswerder's, nor any other researches can it be concluded that 
 a greater or lessei" excretion of uric acid takes place in diabetics than 
 in normal individuals. To gain some notion of the difference between 
 normal individuals and diabetics in this respect, it would be necessary 
 to compare a large number from each of the two classes under the 
 same dietetic conditions, and especially with the same quantity of in- 
 gested nucleins. On account of the absence or presence of sediment, 
 and on no better basis than " uroscopy," it has been said that uric 
 acid is diminished in the severe stage and increased in the mild stage 
 of diabetes. Some writers have also (since 1855) spoken of a ''dia- 
 betes alternans,'' with alternation in the excretion of large quantities 
 of uric acid and of glucose (Claude Bernard, Bouchardat, Brogniart, 
 Budde, Coignard, Charcot, Ebstein). I am far from certain that 
 such an alternation takes place, and I am pretty certain that its 
 existence has never been proved. As is well known, the sediment 
 is by no means an adequate expression of the quantity of uric acid 
 
METABOLISM AND NUTRITIVE NEEDS. 21/ 
 
 present. A urine containing a greater amount of uric acid may- 
 keep the whole amount in solution, while another urine containing 
 less uric acid may present a part of it in the form of a sediment. 
 In mild gouty cases of diabetes the urine often contains consider- 
 able sediment. All that can at present be safely asserted is that a 
 marked sediment of uric acid indicates a mild case of diabetes, and 
 that such a sediment is absent from the pale greenish-yellow urine 
 of severe cases. 
 
 Kreatin was found by Winogradofif in small quantities and by Sena- 
 tor in large quantities in diabetic urine (up to two grams a day). 
 From their researches, and from those of Bunge and St. Johnson, 
 we infer that kreatin and kreatinin are in most cases of diabetes 
 (and apart from toxic disintegration of tissue), under the same diet- 
 etic conditions, to be found in the urine in the same quantity as in 
 normal urine. 
 
 In mild cases the amount of ammonia does not exceed that which 
 may be found normally with an abundant supply of proteids. Only 
 in severe cases with " acidosis " does it attain large proportions, 
 and it may equal as much as twelve grams in twenty-four hours — 
 solely because the acids have a greater affinity for it than they have 
 for urea. 
 
 Boedeker found in diabetic urine a substance that he called 
 alkapton, but which is found also in the urine of normal children 
 and of other nondiabetic persons. In some instances the sub- 
 stance found may possibly have been pyrocatechin. It is also 
 represented by uroleucin and glycosuric acid, and is otherwise 
 known as homogentisinic acid. It can not be said to bear any 
 special relation to diabetes ; according to Baumann and Walkow, it 
 is formed in the bowel under the influence of certain micro- 
 organisms. 
 
 Hippuric acid has been found in diabetic urine (from o. i to i 
 gram) by Lehmann ; it is found also in normal urine, and is in- 
 creased in febrile states, in diseases of the liver, and in neuroses. It 
 arises in the course of the putrefaction of proteids, and may be found 
 equally apart from as with diabetes, whenever putrefactive processes 
 are taking place. 
 
 The low fatty acids (formic, acetic, butyric, propionic) are but 
 rarely found in diabetic urine recently passed (v. Jaksch) ; they are 
 15 
 
2l8 DIABETES MELLITUS AND GLYCOSURIA. 
 
 sometimes found in normal urine and, according to Rumpf, they are 
 present in normal quantities in mild, but in increased quantities (up 
 to ten grams) in severe cases. Purely diabetic lipaciduria is a 
 feature exclusively of such cases. 
 
 Lipuria is sometimes found in normal persons after the ingestion 
 of large amounts of fat, and is found in association with the most 
 widely different pathologic conditions, chiefly after the taking of 
 certain poisons and in cachectic or marantic states. Purely dia- 
 betic lipuria, like purely diabetic lipaciduria, is a feature of severe 
 cases. 
 
 Lactic acid in its two slightly different modifications may occur in 
 the urine in cases of diabetes. Minkowski in a severe case found the 
 levogyrate acid in the blood ; Rumpf in a similar case found it in 
 the urine. We have already seen that lactaciduria is a common 
 phenomenon in conjunction with glycosuria after some poisons; it 
 has also been found in cases of acute yellow atrophy of the liver. 
 Colasanti and Moscatelli found lactic acid in small quantities in the 
 urine of soldiers after forced marches. We are at present too little 
 acquainted with the conditions for the appearance of lactic acid in 
 the urine to decide its relation to diabetes. Still, it seems certain 
 that it may appear under other conditions. 
 
 We undoubtedly find in cases of diabetes — especially, as it seems 
 to me, in mild cases — an increased amount of oxalic acid in the 
 urine. I have sometimes seen quite an enormous number of the 
 small crystals of calcium oxalate in cases of simple glycosuria, when 
 an abundant supply of carbohydrates has given rise to only a trace 
 of glucose in the mixed urine. I am much more inclined to accept 
 (with Prout) an alternation between oxaluria and glycosuria in cer- 
 tain cases than an alternating excretion of glucose and uric acid. 
 Fiirbringer saw oxaluria and oxaloptysis in a diabetic patient. 
 There are many records of oxaluria in cases of diabetes, and it may 
 exist without being discovered by the microscope, the calcium 
 oxalate being kept in solution by the acid phosphates, which are 
 often present in large quantities in the urine of diabetic patients eating 
 much meat. Apart from alimentary and normal oxaluria and the 
 "symptomatic" oxaluria associated with some other diseases and 
 pathologic states, and apart from diabetic oxaluria, there is a form 
 known as (Cantani's) idiopathic oxaluria with its neurasthenic and 
 
METABOLISM AND NUTRITIVE NEEDS. 2ig 
 
 slight dystrophic symptoms. This idiopathic glycosuria is probably 
 identical with the oxaluria found in neurasthenic individuals with or 
 without glycosuria. On the other hand, and so far as is known at 
 present, there are many cases of glycosuria or diabetes without 
 oxaluria. 
 
 The abundant ingestion of proteids in cases of diabetes, often 
 associated with habitual constipation and protracted retention of the 
 feces in the bowels, causes an increase in the products of putrefac- 
 tion. We thus find sulphuric acid combined with aromatic alco- 
 hols (phenol, indoxyl, etc.) and the combined glycuronic acids in- 
 creased. The sulphuric acid in the sulphates is also increased by 
 the customary abundant amount of animal food ; but we have no 
 reason to believe that in mild cases of diabetes, and apart from toxic 
 disintegration, the whole amount is more greatly increased than it 
 would be under similar circumstances in nondiabetic individuals. 
 The total acidity, too, is often increased in cases of diabetes, as 
 Derignac and others have noted, but^ in mild cases only from the 
 causes just mentioned. In severe cases the diacetic and /3-oxybu- 
 tyric and other acids contribute to the increase of the total acidity. 
 
 Phosphaturia will be considered later. 
 
 Inosite is found in cases of diabetes, but also in all states 
 attended with polyuria. Reichardt's dextrin was found in the urine 
 in a case of mild diabetes, but it is not known whether or not it has 
 any connection with diabetes. The same is true with regard to 
 Leube's glycogen, which may perhaps be identical with Reichardt's 
 dextrin. Lemaire's isomaltose is not well known, and Wedenski 
 found in normal urine something that may be maltose. Gum or 
 achrooglycogen is also found in normal urine (Landwehr, Weden- 
 ski, Amann). 
 
 Kiilz and T. Vogel found pentoses (from 0.25 to 0.43 gram a 
 day) in cases of severe diabetes. The test for phenylhydrazin in 
 normal urine also yields some crystals of osazone, which melt at 
 165° C. (329° F.), and which probably are pentoses (E. Holmgren). 
 
 Leon Kalm found urobilin absent in two severe cases of diabetes. 
 Vogel and Neubauer mention this absence in normal urine. 
 
 M. Ch. Ulrich has come to the conclusion that leucin and tyrosin 
 are present in normal urine, but absent in cases of severe diabetes. 
 (The crystals seen by Roque, Devie, and Hugonenq in the Hver, 
 
220 DIABETES MELLITUS AND GLYCOSURIA. 
 
 then, could not have been leucin and ty rosin.) Whether the two 
 substances are present in or absent from the urine in mild cases of 
 diabetes is not known. 
 
 In severe cases of diabetes the diastatic and the peptic ferment 
 have been found to be increased in the urine (Hoffmann, Stadel- 
 mann, Leo, and others). Lepine found no increase of the diastatic 
 ferment, and nothing is known of such an increase in mild cases. 
 
 Albic found diabetic urine strongly toxic (from ptomains, di- 
 amins, etc.). Neubauer and Vogel mention that diabetic urine apart 
 from cachexia is not more toxic than other urine, which indicates 
 that the increase of toxic substances is a feature of severe cases ex- 
 clusively. 
 
 From the foregoing brief exposition it may be concluded that we 
 do not at present know of any pathologic substance that is invariably 
 present in the urine in mild cases of diabetes.* 
 
 Traube's definition of severe diabetes is the best even to-day : A 
 state that is attended with excretion of glucose in the urine, even when 
 carbohydrates are excluded from the food, and when a pure diet of 
 proteids (and of fat) is observed. It will be understood that this 
 does not mean that severe diabetes is, while light diabetes is not, 
 attended with the production of carbohydrates from proteids ; it 
 having been proved long ago that proteids give rise to glycogen 
 and thus indirectly (and perhaps also directly) to glucose, in all 
 organisms, diabetic in any stage,, or nondiabetic. In the mild 
 stage, however, the patient, while losing (some of) the glucose 
 derived from carbohydrates, has the power of assimilating at least 
 all of the glucose derived from proteids. In the severe stage, 
 though the patient always retains the capability of utilizing a part 
 of the glucose derived from carbohydrates, he has lost the power 
 of utilizing all of the glucose derived from proteids. 
 
 On this point, again, we find that mild and severe diabetes are 
 only stages of the same dystrophy, and that there are intermediate 
 states representing the gradual transition from the one to the other. 
 There are patients who, when carbohydrates are excluded from the 
 food, present no glycosuria with a certain daily supply of proteids, 
 
 '* The substances whose connection with mild diabetes it seems most interesting to 
 investigate are acetone, oxalic, glycuronic, and lactic acids. 
 
METABOLISM AND NUTRITIVE NEEDS. 221 
 
 but who again excrete glucose if the amount of proteids is in- 
 creased, though carbohydrates are still excluded (Naunyn, Licht- 
 heim, Troye, Weintraud). 
 
 I wish, however, to insist most forcibly that the hyperglycemia 
 and the glycosuria resulting from proteids do not constitute the 
 most important metabolic difference between the mild and the 
 severe stage of diabetes. The main and all-important difference 
 between mild and severe diabetes is the production in the latter 
 of certain acid toxins in the blood and in the urine. 
 
 This brings us again to a consideration of that most interesting 
 trio already touched upon : acetone, diacetic acid, and /3-oxybutyric 
 acid.* The latter two substances, and especially the last, are im- 
 portant factors in the acid diathesis, the "acidosis," existing in 
 cases of severe, but not of mild, diabetes. 
 
 All three substances, free from nitrogen as they are, originate in 
 proteids, and seem to appear as soon as the organism, from some 
 cause or other, attacks its own proteid tissues ; they all three appear 
 during starvation, and in the course of different states producing 
 inanition. 
 
 Though there is little doubt as to the intimate connection of the 
 three substances as representing different stations on the way to 
 complete oxidation of molecules derived from proteids, the reason 
 why the course of oxidation is interrupted in cases of severe diabetes 
 and in some other states will probably continue for a long while to 
 be a puzzle to every student of diabetes. There are good reasons 
 for believing that the same disintegrated proteids as alone give rise 
 to glucose in the urine in cases of severe diabetes also give rise 
 to /3-oxybutyric acid and its derivatives, diacetic acid and acetone. 
 The curves representing the glucose derived from proteids and 
 the ^-oxybutyric acid show unmistakable parallelism (Naunyn). 
 Any one that follows a case of diabetes in its development through 
 the mild into the severe stage will gain the positive impression of a 
 
 * Acetone [CgHgO] is a watery, strong-smelling, neutral liquid, boiling at 56.5° C. 
 (133-7° F.). 
 
 Diacetic acid [C^HgOg] is a thick, colorless, hygroscopic liquid, which is decomposed 
 into carbonic acid and water at a temperature below 100° C. (212° F.). 
 
 /?-oxybutyric acid is a colorless liquid of the consistency of syrup, which by oxidation 
 easily yields acetone. Boiled with acid water, it yields a-crotonic acid and water. 
 
22 2 DIABETES MELLITUS AND GLYCOSURIA. 
 
 parallelism between the glycosuria due to proteids on the one hand, 
 and the three substances named on the other. The patient in the 
 distinctly mild stage can usually take some carbohydrate without 
 the development of glycosuria. During this state there is no 
 /9-oxybut}^ric acid and no diacetic acid in the urine so long as the 
 patient utilizes a sufficient amount of calories in his food, and there 
 is under these conditions no more acetone than in the urine of a 
 normal person using the same kind of food (see below). As the 
 dystrophy advances, the amount of acetone in the urine probably 
 increases before either of the acids has made its appearance. 
 There is at present some uncertainty as to the exact place in the 
 development of the glycosuric dystrophy where this happens (see 
 below). So long as the patient, with exclusion of carbohydrates 
 from the food, becomes free from glycosuria, he presents no diacet- 
 uria with a sufficient supply of calories. After some time, how- 
 ever, in slowly developing cases, — generally some years after the 
 beginning of the diabetes, — the patient, even during a period of ex- 
 clusion from the food of carbohydrates, exhibits a distinct, though 
 slight, glycosuria. At this stage the physician finds for the first time 
 Gerhardt's reaction in the urine with ferric chlorid, though he has 
 taken care to provide his patient with an adequate supply of calo- 
 ries. There is now also an increased amount of acetone in the urine, 
 and there is a faint odor of this substance on the patient's breath. 
 The urine contains no y5-oxybutyric acid. The patient is likely to 
 lose flesh, but he is only in the first part of the severe stage, and 
 he is often able to maintain his weight. There is a possibility that 
 this can be effected only by some increase in the amount of fat 
 covering a loss of proteid. As the dystrophy advances the glyco- 
 suria due to proteids increases, and pari passii Gerhardt's reaction 
 deepens in intensity until it gives rise to a dark bluish-red color, 
 the breath smells more and more strongly of acetone, and autoph- 
 agy becomes more and more manifest. Long before these last 
 symptoms become extreme, but, in slowly developing cases, often a 
 considerable time after the transition from the mild to the severe 
 stage, the physician, after having removed the glucose from the 
 urine by fermentation, and after having removed other levogyrate 
 substances than /S-oxybutyric acid (combined glycuronic acids) by 
 precipitation with ammonia and lead acetate, still finds a distinct 
 
METABOLISM AND NUTRITIVE NEEDS. 223 
 
 levogyration in the polarimeter. He can afterward observe how 
 the /5-oxybutyric acid increases in quantity as the case advances 
 in the severe stage. 
 
 It has generally been accepted that when /3-oxybutyric acid, the 
 mother-substance of diacetic acid and acetone,* appears in the urine, 
 these latter substances are certain also to be present. It has also 
 been quite generally accepted that /S-oxybutyric acid is present 
 only in urine that yields a marked Gerhardt's reaction, or, in other 
 words, in urine that contains a considerable amount of diacetic acid. 
 In general, the rule holds good that when one finds the /3-oxybu- 
 tyric acid, — which undoubtedly denotes a more advanced period in 
 the severe stage and a greater autophagy than either of the two other 
 substances, — these are also to be found. It also seems certain that 
 when diacetic acid is found, which is not rarely the case when no 
 /3-oxybutyric acid is present, acetone is usually found in an abnor- 
 mally increased quantity. The appearance of the latter substance 
 is a less grave phenomenon than that of diacetic acid, and this, again, 
 is less grave than that of /3-oxybutyric acid. It seems certain, 
 however, that the quantitative relations of the three substances are 
 not fixed, and that one can not, from the quantity of one, reach a 
 conclusion as to the quantity of either of the others. It is 
 especially worth remembering that the common idea with regard to 
 a necessarily pronounced Gerhardt's reaction in all urine containing 
 /3-oxybutyric acid is a false one. I have several times found an 
 unmistakable amount of /3-oxybutyric acid in urine that has not 
 yielded with the solution of ferric chlorid the dark bluish-red 
 color of considerable quantities of diacetic acid, but only a light, 
 transparent red. Naunyn and Albertoni have made analogous 
 observations. I find in Neubauer and Vogel's last edition a note 
 (after Stadelmann ?) that /3-oxybutyric acid may be present without 
 any diacetic acid at all. This certainly is not a common occurrence. 
 
 Gerhardt's reaction, if pronounced, indicates constant danger 
 of coma. If the reaction is absent or only faint, this seems to 
 indicate the absence of any considerable quantity of /3-oxybutyric 
 
 * Minkowski demonstrated the relation of /?-oxybutyric acid as the mother-substance of 
 diacetic acid and acetone. By administering /3-oxybutyric acid to diabetic dogs he caused 
 the appearance or the increase of both of the other substances in the urine. 
 
224 DIABETES MELLITUS AND GLYCOSURIA. 
 
 acid, and, unless the general state is extremely bad, there is then 
 no immediate danger of coma. What the actual conditions are in 
 those extremely rare cases in which a strong acidosis has been 
 found as a result of the presence of some other acid than /?-oxy- 
 butj'-ric (and diacetic) acid, I do not know. 
 
 The /3-oxybutyric acid in the urine of the three substances under 
 consideration alone reaches large amounts. One hundred grams in 
 twenty-four hours is not very rare ; seventy grams is not uncom- 
 mon. Kiilz found 226 grams in one case. The relation between 
 the quantity of /3-oxybutyric acid in the blood and the quantity in 
 the urine is not clearly knoAvn. Hugonenq found 0.427 per cent, 
 in the blood and 0.448 per cent, in the urine. In the enormous 
 majority of cases the acid diathesis — the " acidosis," as Naunyn calls 
 it — are determined chiefly by the amount of /3-oxybutyric acid. 
 This danger is also, and to a great extent, determined by the 
 general state. The same amount of acid which one patient is able 
 to endure for months may kill another in a few hours. As soon as 
 the urine for twenty-four hours contains as much as twenty grams 
 of /3-oxybutyric acid there may be danger of coma.* 
 
 Diacetic acid is found throughout the whole of the severe stage 
 and, as a mere diabetic phenomenon, not in the mild stage at all. If 
 a healthy person be given an exclusive diet of proteids or of proteids 
 and fat, no diaceturia arises so long as a sufficiently large number 
 of calories for the nutritive balance is ingested ; but the inges- 
 tion of a sufficient supply of calories without carbohydrate in the 
 food is a difficult task. A deficit readily arises, of which from 83 
 to 93 per cent, is covered by the consumption of the patient's own 
 fat, while the remainder is furnished by that of his own proteids 
 (Lusk, Miura, v. Noorden). With this kind of disintegration of the 
 latter diaceturia begins and Gerhardt's reaction with the urine will 
 appear. In this manner diaceturia will arise in cases of mild dia- 
 betes, just as it does in cases of ulcer of the stomach or of appen- 
 dicitis or of seasickness in the progress of more or less pronounced 
 starvation. Unless the starvation is very severe, however, the solu- 
 
 * This danger can also be estimated by the amount of ammonia excreted. As soon 
 as the quantity reaches 1.5 grams in twenty-four hours the acidosis is sufficient, in con- 
 junction with a greatly enfeebled general state, to produce coma. 
 
METABOLISM AND NUTRITIVE NEEDS. 225 
 
 tion of ferric chlorid will not cause the typical purple or bluish-red 
 color to appear in the urine. When the ferric chlorid falls drop by 
 drop into the urine, it becomes surrounded by a red zone ; when the 
 phosphates of iron afterward sink, the liquid above has a brownish- 
 red, sherry color. 
 
 Even in the worst cases the diacetic acid in the urine hardly ever 
 reaches twenty grams in the twenty -four hours, and, though it must 
 be considered as contributing to the acidosis and to the coma, it is 
 far less efficient in this respect than the /3-oxybutyric acid. 
 
 It is an important circumstance that, so far as I have been able 
 to ascertain, the whole severe stage of diabetes, per se and apart 
 from other causes, is attended with diaceturia. Whenever I see 
 a frank Gerhardt's reaction with the urine of a patient receiving 
 an abundant supply of calories with his food, — which generally 
 presupposes a certain amount of carbohydrate, — I know at once 
 that an exclusive diet on meat and fat will not remove the glucose 
 from his urine. On the other hand, the absence of diacetic acid 
 from the urine almost invariably indicates that the case is still in 
 the mild stage, and that a number of days * of abstinence from car- 
 bohydrates will cause the sugar to disappear from the urine. There 
 are, however, exceptions to this rule. Also with regard to diacet- 
 uria, it is known that there are individuals living on the border- 
 land between the mild and the severe stage of diabetes. I have seen 
 patients who, with an abundant supply of mixed food, presented a 
 large quantity of the glucose in the urine, but no diacetic acid, and 
 who, with an exclusive but quite adequate supply of meat and fat, 
 continued to excrete a small amount of glucose, and then also ex- 
 hibited slight diaceturia. I take it that these individuals are able 
 with an abundant supply of carbohydrates to protect their own pro- 
 teids from the disintegration that at once gives rise to both glyco- 
 suria and diaceturia ; all the glucose excreted with such a diet being 
 derived from carbohydrates. When carbohydrates are strongly 
 diminished or excluded, the glycosuria due to them ceases, but the 
 patient is no longer able to protect his own proteids, the fat being 
 
 * The length of the period of abstinence from carbohydrates for the necessary removal 
 of the glucose from the urine varies according to the patient's power of assimilation, and 
 probably, also, according to the storage of glycogen and to other causes of an unknown 
 
 nature. 
 
226 DIABETES MELLITUS AND GLYCOSURIA. 
 
 less efficient for this purpose than carbohydrates. He excretes only 
 a small quantity of glucose, but this is now derived from the dis- 
 integration of his own proteids, and the diacetic acid has the same 
 origin. 
 
 The difficulty of demonstrating the presence of acetone in the 
 urine, and the still greater difficulty of determining the quantity 
 produced in twenty-four hours,* have given rise to much uncer- 
 tainty with regard to many important points connected with this 
 substance. It is not known in what cases of diabetes acetone, as a 
 mere diabetic phenomenon, is abnormally increased. Unlike diacetic 
 and /?-oxybutyric acids, acetone is also found, though only in small 
 quantities, in normal urine. It is certain that in a great many cases 
 of fully developed but mild diabetes there is no increase of acetone 
 with an abundant supply of carbohydrate. Von Jaksch found only 
 the normal, small quantity of acetone in cases with an excretion of 
 from 250 to 300 grams of glucose. On the other hand, it seems 
 probable that an increased amount of acetone may appear in the 
 urine in mild cases. One may sometimes perceive a faint but distinct 
 odor of acetone on the breath of patients in the mild stage, even 
 when they seem to be receiving a supply of calories sufficient for the 
 maintenance of the nutritive equilibrium. When any person, dia- 
 betic or not, excludes carbohydrates from his food and lives on meat 
 and fat, the amount of acetone in the urine always increases (Hirsch- 
 berg and others). This occurs more readily in diabetics than in 
 healthy individuals (Rosenfeld), but even in healthy individuals it 
 may cause an excretion of 0.7 gram in the twenty -four hours. The 
 addition to the food of sixty grams of glucose or of starch causes 
 the acetonuria to disappear. f The excretion of acetone in the urine 
 is certainly of smaller significance than the excretion of diacetic or 
 of ,?-oxybutyric acid. If, with a sufficient supply of calories from a 
 mixed diet, including a fair amount of carbohydrates, acetonuria 
 exists at all in the mild stage, this certainly must occur in cases not 
 far from the boundary between this and the severe stage. 
 
 It is a most important fact that the whole trio of acetone, diacetic 
 
 * Acetone being constantly exhaled through the lungs, the determination of the 
 quantity excreted necessitates an analysis of the expired air. 
 
 f Mannite in considerable amounts also causes acetonuria to disappear (Hirschberg). 
 
METABOLISM AND NUTRITIVE NEEDS. 22/ 
 
 acid, and /3-oxybutyric acid seem to be more easily produced with 
 an exclusive diet of fat and proteids than when carbohydrate is 
 added. Dr. D. Gerhardt (see Naunyn) has observed that the same 
 insufficient supply of calories in the diet causes the appearance of 
 more /3-oxybutyric acid in the urine if made up of proteids and fat 
 alone than if derived from a mixed diet, consisting in part of carbo- 
 hydrates. Hirschberg has proved the analogous fact with regard to 
 acetone, and the same is probably true also of diacetic acid. It is 
 a common phenomenon that Gerhardt's reaction perceptibly in- 
 creases in diabetic urine when the patient is deprived of carbohy- 
 drates and is put on a strict animal diet. 
 
 Free fatty acids (formic, acetic, butyric, propionic, valerianic), 
 which in normal urine scarcely reach o.oi gram in the twenty-four 
 hours, may in cases of severe diabetes be present in tenfold quan- 
 tity (Rumpf ). These acids are derivatives of proteids, and the dia- 
 betic aciduria, as has been already mentioned, is a feature of the 
 severe stage. 
 
 The whole amount of acids — acetic, /S-oxybutyric, fatty acids, 
 lactic acid, oxalic acid, phosphoric acid, sulphuric acid (in the 
 sulphates and combined) — may reach a large quantity, and in the 
 course of twenty-four hours equal forty or fifty grams of concen- 
 trated sulphuric acid. 
 
 The acid diathesis, the acidosis, causes an increase of ammonia 
 in the blood and the urine in cases of severe diabetes, and the 
 quantity in the urine, which normally is about 0.7 gram for twenty- 
 four hours, may reach the enormous amount of twelve grams in 
 cases of diabetes (Stadelmann). This shows the great variation in 
 the individual ability to bear up under the acidosis and to resist its 
 comatose influence ; even 1.5 grams of ammonia constitute a warn- 
 ing of coma, and two grams are often quite a distinct forerunner of 
 it. 
 
 When in a severe case of diabetes the carbohydrates are 
 restricted or are excluded, autophagy and loss of bodily weight 
 increase ; glycosuria and generally polyuria diminish ; the urine, 
 even when diluted to its previous volume, yields a more pronounced 
 Gerhardt's reaction, from the presence of an increased amount of 
 diacetic acid ; and the polarimeter shows some increase in the excre- 
 tion of /5-oxybutyric acid. Sometimes, in cases that had previously 
 
2 28 DIABETES MELLITUS AND GLYCOSURIA. 
 
 been free from albuminuria, one also finds that with the strict diet 
 the urine begins to contain a small amount of albumin, probably 
 from the effect of the acid toxins on the kidneys. 
 
 There are in the hterature, and especially from those who defend exclusion of 
 carbohydrates, even in the severe stage, reports of a decrease of diaceturia with 
 such a dietetic change. Thus, Troye * relates the case of a patient who, with 
 mixed diet, excreted 658 grams of glucose and a moderate amount of diacetic 
 acid in more than nine liters of urine in the twenty-four hours, but who, after five 
 days of a strict diet, excreted a normal amount of urine, free from diacetic acid, 
 but containing twenty-seven grams of glucose. Such a statement is so contra- 
 dictory to all of my experience that I can only conclude that there must be 
 some mistake. 
 
 Stokvis seems to consider the occasional appearance of albumin in the urine 
 after the exclusion of the carbohydrates from the diet as resulting from the 
 decrease in the quantity of urine, so that a trace, previously undiscoverable, 
 becomes appreciable with Heller's nitric-acid test. Even after diluting the 
 urine to its previous volume one finds sometimes, with a marked restriction of 
 carbohydrates, a trace of albumin that did not appear previously. 
 
 Azotiiria f in cases of diabetes has been much spoken of. An in- 
 creased amount of nitrogen may appear constantly in the urine in 
 cases of diabetes from two entirely different causes. There may be 
 an alimentary azotiiria and a protoplasmic or toxic azotiiria. 
 
 Alimentary azotiiria of diabetes is easy to understand, and is the 
 only increased excretion of nitrogen in the mild stage. The dia- 
 betic patient either ingests much less carbohydrate with his food or 
 he again loses part of it in his urine, and he must make up for 
 this by the ingestion of a larger amount of fat and proteids. The 
 larger supply of proteids to a diabetic as to a healthy person neces- 
 sarily leads to a larger excretion of nitrogen. This excretion may 
 be temporarily increased in consequence of marked polydipsia and 
 polyuria, which per sc may for the moment increase the nitrogen 
 in the urine. During somewhat longer periods, however, with suf- 
 ficient food, the amount of nitrogen excreted in a case of diabetes in 
 the mild stage does not exceed the amount of nitrogen ingested. 
 
 The second variety of diabetic azoturia, toxic or protoplasmic azo- 
 
 * " Archiv fiir experim. Path, und Pharm.," 1890. 
 
 f Among one hundred cases Bouchard found forty-seven with an ordinarily large 
 amount of nitrogen in the urine, forty with an increased amount, and thirteen with a 
 diminished amount. Such figures are not worth much, if they do not cover a considerable 
 length of time. 
 
METABOLISM AND NUTRITIVE NEEDS. 229 
 
 turia, is a feature of the severe stage exclusively ; but it has not yet 
 been quite decided whether it occurs in all or only in advanced 
 cases of this stage. Toxic azoturia, however, was known to Ber- 
 nard, and was subsequently studied by Voit and Pettenkofer, 
 Kiilz, V. Mering and Minkowski, Chauveau and Kaufmann, Gley, 
 Thiroloix, and others. It is believed to be caused by the toxins, 
 and chiefly by the acid toxins, in the blood, and their disintegrating 
 influence on protoplasm. The most marked effect of this kind un- 
 doubtedly is caused by /3-oxybutyric acid. For my part, I am 
 inclined to believe that some toxic disintegration of protoplasm 
 takes place throughout the whole of the severe stage, and that there 
 is a slight toxic azoturia even in cases in which the /?-oxybutyric acid 
 has not yet shown itself, a purely diabetic diaceturia being already a 
 sign of toxic or protoplasmic disintegration. It will be no easy 
 matter, however, to demonstrate in such cases a constant excess of 
 nitrogen-excretion over nitrogen-ingestion. This seems to me, 
 however, to have been fully done in dogs after total extirpation 
 of the pancreas, and I consider unsustained the doubt remaining 
 in some minds as to the very existence of a diabetic toxic dis- 
 integration of tissue and the consequent azoturia. 
 
 During coma the products of metabolism in the urine generally 
 decrease. Miinzer and Strasser, however, observed the nitrogen 
 increase. 
 
 The present views on diabetic azoturia have been gradually developed by 
 the labors of Hosier, Boecker, Thierfelder, Uhle, Reich, Rosenstein, Haugh- 
 ton, and Gathgens (1853-1866), and within more recent years by the researches 
 of Kiilz, Kratschmer, Pettenkofer and Voit, Frerichs, Lusk, Fr. Voit, Minkow- 
 ski, V. Mering, v. Noorden, Weintraud, Borchert and Finkelstein, Gley, Thiro- 
 loix, and others. 
 
 The enormous amounts of animal food consumed by some diabetic patients 
 sometimes cause the appearance of large quantities of nitrogen in the urine. 
 Leube found 150 grams, Fiirbringer 163 grams of urea, and I found eighty 
 grams of nitrogen (equal to 171 grams of urea ; from 13 to 16 per cent, of the 
 nitrogen, however, belongs to other substances) in twenty-four hours. Such 
 figures are rare, but large quantities of nitrogen in the urine are common in 
 cases of diabetes. This fact favored the opinion that every diabetic patient 
 excreted more nitrogen than he ingested, an opinion which for a long time 
 prevailed, though the very analyses on which it was founded and the 
 mathematic absurdities to which it leads, considering the average duration of 
 life in mild cases of diabetes, ought to have led quickly to more rational views. 
 
 It is evident that if a diabetic and a healthy individual ingest the same 
 
230 DIABETES MELLITUS AND GLYCOSURIA. 
 
 number of calories with their food, and the diabetic again loses a certain 
 amount of them in the form of glucose in his urine, the food that is barely 
 sufficient for the healthy individual will not be sufficient for the diabetic, and 
 the latter will cover the deficit by expending a part of his own fat and a smaller 
 part of his own proteids. He will then decrease in bodily weight, and his 
 urine will contain more nitrogen than has been ingested and digested. The 
 same would happen with the healthy individual if from his food were removed 
 the number of calories represented by glucose in the diabetic's urine. If, 
 however, both individuals received the same amount of calories with a diet 
 that permits the diabetic to utilize^the whole amount, he will not, in the mild 
 stage, excrete more nitrogen than the healthy individual. 
 
 In the severe stage toxic disintegration of protoplasm is a priori not improb- 
 able, and it seems almost impossible to explain the results of recent most 
 laborious investigations without admitting its occurrence. 
 
 It is not at all certain that even all of the common toxins in cases of diabetes 
 are known at present, though those that are amply explain the comatose syn- 
 drome. Then, just as there are instances in which levulose appears in the 
 urine instead of the customary saccharid, glucose, there may be exceptional 
 products of metabolism. In fact, the more one studies diabetes, the more will 
 he be prepared for surprises. We must, therefore, not entirely close our minds 
 against the possibility of correct observation in Rupstein's (1874) and Kiilz's 
 (1875) cases of diabetes in which alcohol was excreted in the urine. It is 
 impossible to presume, in either case, the occurrence of fermentation in the 
 bladder, and there scarcely remains any other way of explaining the formation 
 of alcohol than by accepting Rupstein's theory of an oxidation of diacetic acid. 
 Kiilz, who was about as skeptical as any right-minded person is justified in 
 being, considered that the large amount of alcohol in the urine was proved in 
 the case that he pubhshed. Still, he did not observe it himself; but Dr. 
 Guckelberg, an assistant of Liebig's, performed the analytic work. The 
 patient died (in coma) in 1869, shortly after exhibiting symptoms of alcoholic 
 intoxication, but before the reactions of the substances chiefly concerned were 
 as well known as they are now ; and incipient diabetic coma may sometimes 
 resemble alcoholic intoxication. 
 
 The diabetic patient using an abundance of animal food ingests a 
 large amount of salts. Lean meat contains about 0.70 per cent, 
 of phosphoric acid, and diabetic phosphatnria may be four times as 
 marked as the normal phosphaturia. Whatever future researches 
 may have to add to our present views on the functions and influence 
 of mineral salts in the organism, the question that chiefly interests 
 us here is whether or not the component salts of the bones are found 
 in the urine in cases of severe diabetes in larger quantities than can 
 be explained by the quantity of salts ingested plus the protoplasmic 
 disintegration of the soft cellular tissues almost universally admitted 
 as taking place in such cases. Calcium and magnesium phosphate 
 
METABOLISM AND NUTRITIVE NEEDS. 23 1 
 
 and the other salts that enter into the constitution of the bones are 
 excreted in such large amounts in some cases of severe diabetes 
 that many writers in explanation suggest the existence of osteo- 
 inalacia as a result either of the acidosis or of trophoneurotic influ- 
 ences. The question has not yet been decided, and Dr. E. Ten- 
 baum's recent researches only prove what an enormous amount of 
 elaborate work will be required for its solution. 
 
 The water streaming constantly through the organism, with most 
 important functions and effects (of which there is yet much to learn), 
 is generally increased in cases of diabetes. Even normally the figures 
 are large. About sixty-three per cent, of the human body consists 
 of water. A man of ordinary size ingests about 2.5 or 3 liters 
 daily,* and excretes an equal amount. About one-third of the 
 whole excretion passes through the lungs and the skin, and the 
 greater part of the remainder is eliminated with the excreta and 
 feces, chiefly in the urine, and only a comparatively small part 
 in other excretions. In cases of diabetes the increased ingestion of 
 water causes chiefly an increase in the amount of urine. The elimi- 
 nation through lungs and the skin is usually diminished, partly on 
 account of atrophy of the latter, partly on account of the increased 
 amount of sugar in the blood, which retains the water more firmly 
 than normally. 
 
 Ever since 1580 some persons, in their amazement at the enormous quantity 
 of urine sometimes passed in cases of diabetes, have held the curious notion that 
 a diabetic patient may pass more urine than he ingests water, and even Gath- 
 gens, in 1886, beheved that he had proved this astounding fact, which could 
 scarcely be explained otherwise than upon the theory that a diabetic patient, 
 like concentrated sulphuric acid, attracts to himself the water in the air. This 
 would have to be done by the so-called " negative insensible perspiration " — one 
 of the most amusing products of speculative science. [The positive insensible 
 perspiration is obtained by weighing a person at the beginning and at the end 
 of the experiment, by adding the weight of the ingested water to the first and 
 of the excreted water to the last figure ; the difference between the two sums 
 then represents the "insensible perspiration."] Burger, Nasse, Kulz, and 
 Engelmann have put an end to all these fanciful theories by showing that 
 during somewhat extended periods no more water is excreted in cases of dia- 
 betes than is ingested. The insensible perspiration in severe cases is undoubt- 
 edly diminished. 
 
 * According to Forster, from 2200 to 3500 cu. cm. 
 
232 DIABETES MELLITUS AND GLYCOSURIA. 
 
 A diabetic needs in general the same amount of digested and 
 utilized calories as a normal individual. This was proved by Pet- 
 tenkofer and Voit,* and has been corroborated by Fr. Voit, Wein- 
 traud, Pautz, Borchert and Finkelstein, and other investigators. 
 
 According to Rubner, a normal man requires in twenty-four 
 hours per kilogram of bodily weight : 
 
 Inrepose, 32.9 calories. f With moderate work, . . . 41 calories. 
 
 With light workjj . . 34.9 " With severe work, .... 48 " 
 
 The thin individual, richer in cells, requires more calories than 
 the fat one, with more comparatively inactive adipose tissue. The 
 growing child, with a larger bodily surface compared to its weight, 
 requires more than a developed person. 
 
 One gram of carbohydrate represents gross 4.1 calories, net 3.8.^ 
 " fat " " 9.3 " " 8.4. 
 
 " " proteids " " 4.1 " " 3.2. 
 
 The figures for the gross value are Rubner's, those for the net 
 value are v. Rechenberg's, who estimated the average loss from the 
 amount of the ingested (but undigested) food in the feces. This 
 loss usually is not greater in diabetics than in normal individuals, 
 but it is probably somewhat smaller than it was in v. Rechenberg's 
 weavers, who doubtless received rather coarse food. 
 
 The alcohol represents gross seven calories, and the net value 
 may, in view of the small daily doses, be put practically at the same 
 
 * The learned Professors Pettenkofer and Voit, however splendid their life's work, 
 unfortunately were sometimes a little absent-minded. Thus, when in 1867 they made 
 their observations upon an unusually small diabetic Teuton, weighing only 54 kilograms, 
 they at first overlooked the fact that he could not be expected to eat as much and to 
 consume as much oxygen and produce as much carbonic acid as an ordinary Teuton ; 
 and from the low figures they gained the impression that the metabolism was decreased. 
 In relation to the bodily weight, however, their man consumed a perfectly normal 
 amount of calories, — 34.5 calories per kilogram of bodily weight in twenty-four hours, 
 during repose, in the apparatus used. All subsequent figures, correctly interpreted, lead 
 to the same result. (Livierato's researches can not be considered satisfactory.) 
 
 -f I always mean great calories, viz. , the amount of heat required to raise the temper- 
 ature of one kilogram of water I ° C. 
 
 j Only mechanic (and chemic) work entails expenditure of force. Nature is too 
 generous to charge us for our poor intellectual work. 
 
 § Rubner's figures are : 
 
 4. 116 calories for. starch. 3.877 calories for lactose. 
 
 3.959 " .... cane-sugar. 3.692 " glucose. 
 
METABOLISM AND NUTRITIVE NEEDS. 233 
 
 figure. The levulose, an important alimentary item in cases of dia- 
 betes, represents about 3.7 calories gross, and nearly as much net, 
 the amount taken being almost entirely absorbed. 
 
 It must be borne in mind that the isodynamic law is to be accepted 
 with some reservation, and that different kinds of food are not inter- 
 changeable with regard to the number of calories they represent. 
 The same number of calories derived from carbohydrates are more 
 efficient in protecting the proteids of the organism than the calories 
 derived from fats, and the latter rank higher in this respect than the 
 calories derived from alcohol. Then, it seems to me that diabetics, 
 especially when subjected to rigorous restriction of carbohydrates, 
 sometimes, though unfortunately only for a short while, apart 
 from the calories lost by glycosuria, consume an amazingly large 
 amount of calories. I have seen the value utilized reach nearly one 
 hundred calories per kilogram of bodily weight in twenty-four hours. 
 The toxic disintegration of protoplasm in severe cases explains this 
 phenomenon in part. In other part it may be explained by the 
 increased work necessary for the mere transformation of other 
 molecular structures into glucose. Still, I do not feel at all certain 
 that we know at present in every detail how to estimate dietic 
 values for our diabetic patients. 
 
 To estimate the caloric value of a patient's food we must weigh 
 all that he ingests and obtain the net value of the total. So' far as 
 proteids are concerned, we can take the easier way of determining 
 the nitrogen in the urine. Albumin consisting of sixteen per cent, 
 nitrogen, the ingested and digested albumin can be determined in 
 grams by multiplying the number of grams of nitrogen in the urine 
 by '^-^ (= 6.25). (We then presume that practically all of the 
 nitrogen has, as usual, been ingested in the form of proteids, and we 
 take no account of the toxic disintegration of the tissues, which is a 
 feature only of severe cases, and usually gives rise to the ap- 
 pearance of comparatively small amounts of nitrogen in the urine, 
 and which can not be determined without an immense amount of 
 analytic work.) In using this mode of calculation we must, of 
 course, value each gram of proteid at 4. i calories. From the final 
 sum of calories derived from proteids, fats, carbohydrates, and 
 alcohol we then subtract the number of calories lost in the urine in 
 the form of glucose, valued at 3.7 calories per gram. 
 16 
 
2 34 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Mr. R. has drunk 0.5 liter of milk with 17.5 grams of proteid, 18 grams of 
 fat, and 24 grams of lactose ; which represent in calories 17.5 X 3-2 + 18 X 
 8.4 + 24 X 3-8 = 298.4. He had had 650 grams of raw meat, with about 20 
 per cent, of proteids and 6.5 per cent, of fats and a net value of 416 + 354.9 
 = 770.9 calories. Four eggs may be considered as representing 280 calories. 
 Two hundred grams of butter (with 1.6 grams of proteid, 166 grams of fat, and 
 0.4 grams of carbohydrate) represent 1394.6 calories ; 100 grams of rye-bread, 
 209.84 calories; 50 grams of rich cheese yielded 13 grams of proteids + 15 
 grams of fat + 1.25 grams of carbohydrate = 172.2 calories. Sixty grams of 
 American whisky represent about 219 calories. No account was taken of some 
 tomatoes and some " sauerkraut." If I am correct in my calculations — and of 
 this I am not certain — R. received 298.4 + 770.9 + 280 + 1304.6 + 209.84 + 
 172.3 + 219 = 3345. Mr. R., again, lost 51.8 calories in 14 grams of glucose 
 in the urine, and thus really received only 3263.2 — i. e., a trifle more than 40.3 
 calories per kilogram of his bodily weight, which was 82 and was increasing. 
 
 Mr. L. had excreted 31 grams of nitrogen, and had thus utilized 62.5 X 3' 
 := 193.75 grams of proteid, or 4.1 X 193-75 = 793-3 calories. About 180 
 grams of fat had yielded, net, 1512 calories. Ninety grams of white bread had 
 yielded 179.18 calories. Twenty grams of alcohol had yielded 140 calories. 
 The man had lost 32 grams of glucose, or 1 18.4 calories. He had thus utilized 
 2624.48 — 1 18.4 = 2506.08 calories. He weighed 68 kilograms, had received 
 over 36.8 per kilogram, did not perform much work, and increased in weight. 
 
 These calculations, however, are troublesome, and will not be 
 undertaken in addition to the strain of practical work. It is easy, 
 however, to remember that soft, white bread usually yields about 
 twice as many calories as its own weight in grams ; that an egg 
 represents about 70 or 75 calories; that raw, lean meat yields a 
 somewhat larger, raw, lean fish a somewhat smaller, number of 
 calories than its own weight in grams ; that butter yields about 7 
 calories per gram, and alcohol also 7 calories per gram. All of 
 these figures represent the net value, and are all that the prac- 
 titioner need bear in mind when confronted with the important task 
 of informing his patient as to the necessary amount of food to be 
 ingested. 
 
 The oxygen consumed and the carbonic acid generated in cases 
 of diabetes equal normal quantities. Except what is represented by 
 the glucose in his urine and by diabetic toxins, the diabetic patient 
 oxidizes his food, especially the sometimes enormous quantities of 
 fat, as a normal person does, just as he oxidizes organic acids 
 (Strauss), or lactates (Weintraud), or benzol (v. Nencki and Sieber), 
 etc. The normal consumption of oxygen varies from 3 to 4.5 
 
METABOLISM AND NUTRITIVE NEEDS. 235 
 
 cu. cm., and is, on the average, 3.81 cu. cm. per kilogram of bodily 
 weight in the minute. The amount of carbonic acid excreted, esti- 
 mated on the same basis, varies from 2.5 to 3.5 cu. cm., and is, on 
 the average, 3.08 cu. cm. The figures that Leo * and others have 
 found in cases of diabetes correspond exactly with these figures. 
 
 Since Reignault's and Reiset's classic researches it has been known 
 that the relation between the oxygen consumed and the carbonic 
 acid excreted varies somewhat, for evident chemic reasons, ac- 
 cording to the nature of the food, so that the respiratory quotient, 
 or consumed'^o" ' ^^^i^^g the ingestion of food consisting essentially of 
 carbohydrates approaches the quantity i . If proteids make up the 
 greater part of the food, the figure is about 0.73. When large quan- 
 tities of fat exclusively are taken, the quotient falls somewhat, and is 
 about o./o.f It is evident that the quotient in diabetes approaches 
 in general the latter values, the patient not being able fully to 
 utilize the digested carbohydrates, J and that it is the farther from 
 the ordinary maximum value of i the less carbohydrate oxidized, 
 whether this arises from restriction of supply or from a low limit of 
 the power of assimilation. Laves' and Weintraud's researches show, 
 however, that a diabetic patient on an exclusive diet of meat and fat 
 has the same respiratory quotient as a normal person on the same 
 
 *"Zeitschr. f. klin. Med.," Berlin, 1891, Supplement. 
 
 f Laulanie found that in starvation both the respiratory quotient and the production of 
 heat are at their lowest. With an exclusive supply of meat (muscles) both the produc- 
 tion of heat and the respiratory quotient increase. Both figures in the latter become 
 higher, but the increase in the amount of carbonic acid excreted is rather greater than 
 that of the oxygen excreted. The quotient, however, still remains comparatively small. 
 With an almost exclusive supply of carbohydrates the quotient increases considerably and 
 may exceed the figure I. The thermic curve follows the curve of the absorption of 
 oxygen. A considerable part of the carbonic acid is produced without the generation of 
 heat by the transformation of carbohydrate into fat. 
 
 J Laves and Weintraud, from the results of their investigations, have reached the 
 conclusions that in cases of diabetes the ingested carbohydrates, even apart from what 
 is lost a£ glucose in the urine, do not give rise to the production of fully as much car- 
 bonic acid as in normal individuals, probably because a larger part of the carbohydrates 
 remains in cases of diabetes at a lower point of oxidation ; e.g., as oxalic acid instead of 
 forming water and carbonic acid. 
 
 Henriot, Magnus-Levy, and Bleibtreu also found that with an abundant and exclusive 
 supply of carbohydrates the amount of carbonic acid excreted may attain a higher figure 
 than the amount of oxygen consumed, so that the respiratory quotient exceeds the figure 
 I, and may even reach 1.3. 
 
236 DIABETES MELLITUS AND GLYCOSURIA, 
 
 diet, and Leo's figures of this quotient make it evident that even in 
 very severe cases of diabetes with a mixed diet a part of the carbo- 
 hydrates must have been utilized and then excreted as carbonic 
 acid. 
 
 CHAPTER VIII.— INVESTIGATION OF A CASE OF DIABETES. 
 
 It is the duty of every physician to test his patient's urine for 
 sugar. This investigation alone enables us to detect a simple, but 
 rarely insignificant, habitual glycosuria, and the presence of sugar 
 in the urine may be the one distinctive symptom of a mild but true 
 diabetes. 
 
 In making this test two most important points must be observed. 
 In testing there should be used, systematically, a sample of the 
 urine likely to contain the maximum, or nearly the maximum, per- 
 centage of sugar excreted during the twenty-four hours, and the 
 test should be so performed as to reveal the minimum distinctly 
 pathologic quantity of glucose in the urine. 
 
 There are, as we have seen, a great many individuals with a 
 lowered power of assimilating carbohydrates who secrete glucose 
 only for short periods in the day, some time after meals, and then 
 only in small quantities. Even true diabetics in the mild stage are 
 often, even apart from diet, free from glycosuria for some parts of 
 the twenty-four hours, especially in the morning before the first 
 meal. 
 
 Tlie first and most important rule is, tliercfore, never to use for 
 a test a specimen of urine passed when the patient's stomach is 
 empty, before the first meal of the day. 
 
 The best means of deciding from a single examination of the urine 
 whether a person is normal or not in this respect is furnished by a 
 sample passed an hour after the end of the dimier. In cases of sim- 
 ple glycosuria the excretion at this time is, with rare exceptions, 
 near its maximum. The bladder should be emptied just before the 
 meal, which ought to be a mixed and abundant one, including 
 
INVESTIGATION OF A CASE OF DIABETES. 237 
 
 meat, fat, bread, potatoes, rice, and sweets, but not any consider- 
 able quantity of alcoholic liquors. 
 
 The patient must be in his ordinary state ; the sample of urine 
 ought not to be taken during any illness or indisposition or after 
 violent emotion or excess of any kind. 
 
 For the purpose of revealing with certainty the presence of patho- 
 logic traces of glucose, the practitioner will do well to use con- 
 stantly two different reduction-tests, and to verify the saccharine 
 nature of the reducing-substance by the fermentation-test whenever 
 doubt exists. The best reagents known for this purpose are Ny- 
 lander's solution of bismuth and Trommer's test, used in a some- 
 what modified way with Fehling's solution of copper.* 
 
 The test with Nylander's solution is the easiest to perform and 
 to observe. A tube is filled one-fourth or one-third with urine, and 
 one-tenth or one-fifth as much of Nylander's solution is added, the 
 mixture being boiled for four or five minutes. It is important to boil 
 for the full length of time. Under these conditions urine containing 
 at least some tenths of a per cent, of glucose will be rendered more 
 or less opaque and black ; urine containing only 0.02 or 0.03 per 
 cent, will assume a somewhat brownish color, in consequence of 
 admixture of the reduced bismuth with the flakes of phosphates, 
 etc. Urine containing no sugar, or less than 0.02 per cent., will, 
 except in rare cases, maintain its transparency and its yellow color ; f 
 the latter will perhaps be somewhat deepened. 
 
 Trommer's test, as is known, has undergone many modifications, 
 and may be performed in several different ways. I have adopted 
 Worm-Miiller's modification in part, and like to combine it with the 
 decoloration of the urine by filtering it through well-pulverized and 
 
 * Both of these tests are much easier and quicker of performance than Fischer's test, 
 and are, when only hundredths of a per cent, of glucose are concerned, at least as re- 
 liable. Fischer's test, as is well known, consists in heating (over a water-bath) for about 
 half an hour about fifty parts of urine, to which have been added one part of phenyl- 
 hydrazin chlorate and two parts of sodium acetate ; the characteristic yellow crystals ol 
 glycosazone form in cooling. Even when pure phenylhydrazin is used the test — which 
 also yields similar crystals with other saccharids than glucose — yields, when 0.02 per cent, 
 or smaller quantities of glucose are present, imperfect crystals, not with certainty to be 
 distinguished from similar formations due to pentoses (E. Holmgren) or glycuronic acids 
 (except by their melting at 205° €.—401° F.) (Thierfelder, Geyer). 
 
 ")■ Apart from the white flakes of the phosphates. 
 
238 DIABETES MELLITUS AND GLYCOSURIA. 
 
 well-washed animal charcoal. In one tube I put a few cubic centi- 
 meters of the urine and in another about the same amount of Feh- 
 ling's solution. The latter is then diluted with two or three times 
 its volume of water, and the contents of both tubes are simulta- 
 neously heated to boiling. As soon as they are fairly boiling I let 
 them cool for twenty-five seconds, the temperature falling to 70° or 
 75° C. (158° or 167° F.).* I then slowly pour the urine into the 
 other tube ; reduction will take place within five or ten minutes if the 
 urine contain at least 0.0 1 or 0.02 per cent, of glucose. By following 
 Worm-Miiller's directions closely, and especially by determining 
 experimentally the best possible quantitative relations between 
 the solution and the urine, one may somewhat improve the test, 
 which, however, performed in the manner just described, is delicate 
 enough for practical purposes and consumes but a short time. 
 
 I sometimes perform the test by passing not too small a quantity 
 of urine through animal charcoal on the filter, then washing the 
 charcoal with a small quantity of water, diluting one volume of 
 Fehling's solution with two or three volumes of this water, and 
 heating to the boiling-point. 
 
 In whatever manner the reduction-test is performed, it is absolutely 
 necessary, in cases at all doubtful, to verify the saccharine quality 
 of the reducing-substances by the fermentation-test. To this end a 
 small piece of yeast is placed in a tube almost filled with urine, which 
 is permitted to stand at ordinary room-temperature or in a some- 
 what warmer place. If after fermentation the reducing-substance 
 has disappeared or diminished, it may be concluded that it was glu- 
 cose or levulose or maltose, of which saccharids glucose is very 
 common in urine and the two others are extremely rare. 
 
 By omitting the fermentation-test and by trusting only to reduction-tests, 
 one incurs great danger of increasing, in his own mind or in the literature, the 
 large number of cases of false glycosurias. 
 
 Referring for further particulars to the special manuals, I would here only 
 
 * Worm-Miiller found that though the sugar reduces more readily at a higher temper- 
 ature than 70° or 75° C. (158° or 167° F.), a reduction at this higher temperature is 
 easily brought about by other substances than glucose. At a lower temperature than 70° 
 C. (158° F.) the test is less delicate. 
 
 The decoloration of the urine, which was first practised by Claude Bernard, was 
 adopted by Seegen as a modification of Trommer's test, for the purpose of eliminating 
 the reducing uric acid and substances that prevent the cupric oxid from being precipitated. 
 
INVESTIGATION OF A CASE OF DIABETES. 239 
 
 recapitulate that glucose reduces Fehling's, Nylander's, and Barfoed's* solu- 
 tions, turns the ray of polarized light to the right, and is readily and completely 
 decomposed into alcohol, carbonic acid, etc., by the influence of common yeast 
 and of saccharomyces apiculatus. Its crystals of osazone melt at 205° C. 
 (401° F.). 
 
 Uric acid and kreatinin, which are present normally and constantly in the 
 urine, cause reduction, but do not undergo fermentation. 
 
 Many of the combined glycuronic acids, some of which are present in 
 normal urine (in combination with indoxyl, skatoxyl, phenol, etc.), also 
 cause reduction. After the ingestion of chloral there may, with or without 
 glucose, be quite a considerable reduction from the presence of urochloral 
 acid (= trichlorethyl-glycuronic acid). The combined glycuronic acids do not 
 undergo fermentation, and turn the ray of polarized light to the left.j One 
 may remove the combined glycuronic acids from the urine with ammonia and 
 lead-acetate. 
 
 Many substances besides may be responsible for the presence in the urine 
 of nonsaccharine reducing-substances, some of which probably are combined 
 glycuronic acids. Other substances, such as benzoic, salicylic, oxalic, prussic, 
 and mineral acids, turpentine, different phenols, morphium, copaiba, glycerin, 
 kairin, sulphonal, trional, arsenic, caustic alkali, etc., may cause true glyco- 
 suria. Rhubarb, senna, eucalyptus, large doses of quinin, also cause a reaction 
 with Nylander's solution similar to that caused by glucose. 
 
 Alkapton reduces Fehling's solution, but not the solution of bismuth. It 
 does not deflect the ray of polarized light, and it does not undergo fermenta- 
 tion. Urine containing alkapton presents, after some time, a brown, almost a 
 black, color. 
 
 The disaccharid maltose, which probably sometimes occurs in urine, is, 
 like glucose, attacked by common yeast ; but it reduces Fehling's solution only 
 two-thirds as much as glucose, and it turns the polarized light three times as 
 much to the right. Unlike glucose, maltose does not reduce Barfoed's solution, 
 which is, however, reduced to some extent by other substances present in all 
 urine. 
 
 Levulose causes about as much reduction as glucose, and is quite readily 
 attacked by common yeast ; but it turns the ray of polarized light to the left, and 
 its osazone melts at 190° C. (374° F.). 
 
 Lactose turns the ray of polarized light to the right and reduces Nylander's 
 and Fehling's solutions. It does not reduce Barfoed's solution, which, 
 unfortunately, with regard to urine, does not help us much, as other sub- 
 stances (than saccharids), that are constantly present in urine, cause its reduc- 
 tion ; but lactose, though it undergoes lactic-acid fermentation or alcoholic 
 fermentation with other fungi, does not ferment at all with saccharomyces 
 apiculatus, and ferments with common yeast only when it has been inverted 
 into its two monosaccharids, glucose and galactose, which both ferment. 
 
 * Barfoed's solution is a solution of from 0.5 to 4 per cent, copper-acetate with one 
 per cent, of free acetic acid. It is not reduced by lactose or maltose. 
 
 f Glycuronic acid/^r se turns the ray to the right, but it is never present in urine. 
 
240 DIABETES MELLITUS AND GLYCOSURIA. 
 
 The inversion is likely to take place spontaneously after some time. Lactosa- 
 zone melts at 200° C. (392° F.). 
 
 Galactose is not under ordinary circumstances to be expected in urine, but 
 may be present after the ingestion of large amounts of galactose, and arises 
 (with glucose) when lactose is boiled with diluted mineral acids. It reduces 
 somewhat less, but turns the ray of polarized light more strongly to the right 
 than glucose. Its osazone melts at 193° C. (379° F.). Laios (found by Leo in 
 1887) reduces, but does not ferment. 
 
 Pentoses reduce, but do not deflect the ray of polarized light and do not fer- 
 ment. They are found both in diabetic and in normal urine. 
 
 The substance found in urine after the ingestion of turpentine reduces and 
 ferments, but it does not deflect the ray of polarized light (Vetlesen). 
 
 Animal gum turns the ray of polarized light to the right, but does not fer- 
 ment. It forms a compound with the copper of Fehling's solution, which is pre- 
 cipitated in whitish-blue flakes. 
 
 If after a generous mixed meal the urine contains no glucose as 
 determined by the tests named, a distinctly pathologic deficiency in 
 the power of assimilation is excluded. 
 
 Some who have occupied themselves a good deal with similar researches 
 may feel some doubt as to the correctness of this assertion. May not, 
 they will probably urge, a simple glycosuria, or even a "periodic" or an 
 " alternating" diabetes, or a very mild common diabetes after abstinence from 
 carbohydrates continued for some time,fwithstand such a trial without the ap- 
 pearance of glucose in the urine ? To this I would answer that even in such 
 cases the urine will, an hour after a generous mixed meal, yield to the tests 
 named evidence of the presence of at least a trace of glucose. I have found 
 this to be the case even in individuals who have been capable of taking large 
 portions of rice or cane-sugar without the development of glycosuria. Escape 
 from detection in any stage of the glycosuric dystrophy under the circumstances 
 named will at all events be exceedingly rare. 
 
 If after a generous mixed meal the urine contains a considerable 
 quantity (several per cent.) of sugar, the secretion is undoubtedly 
 that of a diabetic individual. 
 
 My next step — never to be omitted — will then be to submit the 
 urine to Gerhardt's test for diacetic acid. This is done in a moment. 
 I almost fill an ordinary test-tube with urine and add six or eight 
 drops of a solution of ferric chlorid. If the urine, with the patient 
 in his customary state and with a good supply of calories in his food, 
 turns a red, or, still more, if it turns a dark bluish-red color, the 
 patient is, without doubt, in the severe stage of diabetes. It is then 
 unnecessary, and, besides, it would incur danger of coma, to exclude 
 carbohydrates from the patient's food. 
 
INVESTIGATION OF A CASE OF DIABETES. 24 1 
 
 If Gerhardt's reaction is wanting or indistinct, I may, without 
 danger, so far as possible exclude carbohydrates from the diet for 
 several days or a couple of weeks. If during this regime the urine 
 becomes free from glucose, the patient is in the mild stage ; but if 
 sugar appears, he has entered upon the severe stage of diabetes. 
 
 Having ascertained that the patient is in the mild stage of dia- 
 betes, it must be determined how much carbohydrate he is capable 
 of taking without the development of glycosuria. For practical 
 purposes this is best done by allowing the patient, in addition to 
 generous animal food, a certain amount of the kind of bread that he 
 prefers. In doing this I may either, after absolute exclusion of 
 bread, permit larger and larger amounts until glycosuria appears, 
 or diminish the amount after a more generous supply until the gly- 
 cosuria ceases ; and it is not an entirely indifferent matter which of 
 these plans I select. With exclusion of carbohydrates or restriction 
 of them below his power of assimilation the patient increases this 
 power, and thus, by progressing from small to larger amounts, I may 
 find a higher power of assimilation than by pursuing the opposite 
 course. If I am anxious in a case not to give the patient more car- 
 bohydrates than he can take continually without the development 
 of glycosuria, I proceed from amounts of carbohydrate that are 
 beyond his power of assimilation, and decrease them until glyco- 
 suria disappears. In either event I use for analytical purposes 
 samples from the whole amount of urine collected during twenty- 
 four hours. 
 
 If after a generous mixed meal I find only a small quantity of 
 glucose in the urine, I must submit the case to further investiga- 
 tion before giving the dystrophy a name or forming a concrete 
 opinion as to its nature. In this case, too, I always take for 
 analysis a sample of the urine collected and measured during 
 twenty-four hours, while the patient consumes with his daily food 
 a rather large, determined amount of carbohydrates, represented by 
 from 150 to 200 grams of bread and some potatoes, rice, macaroni, 
 peas, and cane-sugar. The patient should observe this regime for 
 a few days before collecting his urine for the test. If under such 
 circumstances, and with the patient in his habitual state, tlie mixed 
 wdne for twenty-four hours contains a determinable amount of glu- 
 cose, amounting at least to several tenths of a per cent., the case is 
 
242 DIABETES MELLITUS AND GLYCOSURIA. 
 
 one of true, though it may be very mild, diabetes, and I am then 
 generally able to find other purely diabetic symptoms besides 
 glycosuria. 
 
 If an individual excretes for a short time after every generous 
 mixed meal a determinable quantity of glucose, which in the urine 
 passed at that time may occasionally reach perhaps even one per 
 cent, or somewhat more, but which, in the whole amount of urine for 
 the twenty-four hours, during a continued, abundant supply of carbo- 
 hydrates, is present in scarcely more than traces, or, at all events, in 
 less than several tenths of a per cent., the decision as to whether 
 the case shall be called one of simple glycosuria or of light dia- 
 betes is to a certain extent a matter of opinion. 
 
 Still, continued investigation will elicit further information as to 
 the patient's state and future prospects. 
 
 The patient, therefore, may be given, one morning for breakfast, 
 exclusively, a large portion — e. g., 200 grams — of dry rice, well 
 cooked in milk or water. The urine is then collected for six or 
 eight hours. Even in cases in which, after every generous mixed 
 meal, glycosuria appears, the urine, after such an amount of rice, 
 may remain perfectly free from glucose. I am then inclined to call 
 the case one of simple glycosuria, which, especially in middle or 
 advanced age, generally is of no noteworthy clinical importance. 
 A recurring glycosuria after meals consisting exclusively of rice or 
 bread, has, on the other hand, a deeper significance than the same 
 phenomenon after generous mixed meals or after the ingestion of 
 large amounts of cane-sugar, and I consider the designation diabe- 
 tes in such a case better to represent the clinical condition and the 
 prognostic aspect than that of simple glycosuria. 
 
 If after the ingestion of large quantities of rice the patient exhibits 
 no glycosuria, I give him on another day 200 or 300 grams of cane- 
 sugar, which is most easily taken dissolved in some mineral water 
 containing free carbonic acid. An individual who, after the ingestion 
 of large amounts of boiled rice, excretes glucose with his urine will 
 also do so after the ingestion of large amounts of cane-sugar. It is 
 quite possible, however, that a person in whom, after every dinner 
 of mixed food, glycosuria appears may exhibit none after the in- 
 gestion of large amounts of cane-sugar, but only excrete some un- 
 changed saccharose, as everybody without exception does under 
 
INVESTIGATION OF A CASE OF DIABETES. 243 
 
 the circumstances. In such a case the urine will not reduce Feh- 
 ling's and Nylander's solutions before but only after being boiled 
 with several drops of sulphuric acid. I then call the case one of 
 simple glycosuria. In other cases the ingestion of a Hke amount of 
 cane-sugar will be followed by the appearance in the urine of a mix- 
 ture of cane-sugar and glucose, and I find more marked reduction 
 after boiling with sulphuric acid than before, the difference rep- 
 resenting the amount of cane-sugar that had passed through the 
 organism unchanged.* Such a case always represents a weakened 
 power of assimilation, and is either one of simple glycosuria or of 
 diabetes. Referring to chapter 11 of this book, I am the more in- 
 clined to the milder name and the more favorable prognosis, the 
 more unchanged cane-sugar and the less glucose the patient ex- 
 cretes. 
 
 It is also possible to test the power of assimilation by the administration of 
 a large amount of glucose ; only as all persons excrete glucose after the inges- 
 tion of very large amounts of this saccharid, the necessary quantity of which 
 varies greatly even in the same individual under apparently similar conditions, 
 and as under ordinary conditions such amounts of glucose are never taken, I 
 prefer the other tests. From my own researches I will say that the develop- 
 ment of glycosuria after the ingestion of 100 grams of glucose often denotes a 
 weakened power of assimilation. In using ordinary "technical" glucose, 
 mixed with dextrin, one ought to put the test-amount at least at 150 grams. 
 Achard and Weil (1898) inject 10 cu. cm. of pure glucose subcutaneous ly, and 
 consider the appearance of glycosuria after this pathologic. In a normal 
 person, whose bodily weight unfortunately is not mentioned, Fritz Voit found 
 (1896), after the subcutaneous injection of sixty grams of glucose, a trace of 
 sugar in the urine ; 100 grams given in the same manner caused a glycosuria of 
 2.6 grams. (Biedl, R. Kraus, and Pavy have made similar researches. If made 
 in large numbers under different dietetic conditions, and with a determination of 
 the bodily weight, experiments with subcutaneous injections may provide the 
 means of finding some exact expression for the normal power of assimilation.) 
 To decide immediately and after a single investigation the nature and the 
 prognosis of a slight excretion of sugar, is, as may be understood from the 
 foregoing, quite impossible. Neither does there at present exist any universal 
 rule for the refusal or acceptance of an application for life-insurance in these 
 
 * By boiling with diluted sulphuric acid the cane-sugar is " inverted " into a mixture of 
 glucose and levulose. The former turning the ray of polarized light to the right, the 
 latter to the left, polarization yields no information. Both saccharids, however, cause 
 practically equal reduction (levulose /^%% as much as glucose), and titration before and 
 after boiling yields information as to the amount of glucose and the amount of cane- 
 sugar excreted. 
 
244 DIABETES MELLITUS AND GLYCOSURIA. 
 
 cases, and the physicians of insurance companies often decide the fate of such 
 applications in a most summary way. Some examiners perform the analysis 
 in tlie morning, when the patient's stomach contains no food, or without any 
 information as to his diet. In this way many a diabetic in the mild stage 
 secures life-insurance. On other occasions applications are refused on account 
 of a slight and accidental excretion of sugar. The most rational manner of 
 reaching a decision from a single investigation is, perhaps, to have the appli- 
 cant partake of a large amount of rice with cane-sugar, and two hours afterward 
 pass his urine for analysis. If such a specimen yields no distinct reaction for 
 sugar, there is no reason, on a diabetic basis, for refusing the insurance ; if the 
 urine contains a slight amount of glucose, the insurance ought to be refused 
 until more careful investigation shall settle the question as between simple 
 glycosuria or mild diabetes, when insurance should be refused in the latter and 
 accorded on higher premiums in the former case. Even with this test many 
 persons who habitually excrete sugar after mixed meals would be accepted as 
 first-class risks, and the same might happen in rare instances of true diabetes 
 after prolonged abstinence from carbohydrates. It is perhaps possible to 
 decide diagnostic questions quickly by Bremer's new tests, which are described 
 immediately below, but which I have not yet had time to study. 
 
 Dr. Lud wig Bremer,* of St. Louis, has made the interesting and 
 important discovery that diabetic blood (to the naked eye) and its 
 red blood-corpuscles (microscopically) are colored differently from 
 normal blood by certain dyes, whether there is or is not for the 
 moment sufficient hyperglycemia to induce glycosuria. It is as yet 
 not known at what stage in the development of glycosuric dystro- 
 phy this peculiarity of the blood first appears, but some of Bremer's 
 cases were instances of glycosuria (according to his views f), and it 
 seems that we have in this method a means also of detecting the 
 glycosuric dystrophy in its incipiency. 
 
 Equal parts of saturated watery solutions of methylene-blue and 
 eosin are mixed, and the precipitate that forms, and which is insoluble 
 
 *" New York Med. Jour.," 1896. 
 
 f Dr. Bremer's views on other subjects differ widely from my own and from those 
 held by most students of diabetes. When Dr. Bremer says : " It is a well-known fact 
 that by means of dieting, and by the administratiott of certain drugs (antipyrin, calo- 
 mel, and ammonium carbonate), the sugar can be made to temporarily greatly diminish 
 or entirely disappear from the urine, even in cases of well-established and undoubted 
 diabetes," or that " fasting is a tolerably certain means of freeing the urine from 
 sugar," I can scarcely approve of his expressions, nor do I share his opinions. I do 
 admit, however, tliat Dr. Bremer deserves great credit for his important discovery, which 
 in some cases probably will constitute a valuable diagnostic means, and which may lead 
 to a better knowledge of the diabetic changes in the red blood-corpuscles. 
 
INVESTIGATION OF A CASE OF DIABETES. 245 
 
 in water, but soluble in alcohol, is washed and dried on a filter. To 
 this powder some methylene-blue (usually about one-sixth by weight) 
 and some eosin (about one twenty-fourth by weight) are added. 
 The whole forms a powder of reddish-brown color. Every time the 
 test is to be made a fresh test-solution is to be prepared by dissolv- 
 ing from 0.025 to 0.05 gram of this powder in about 10 grams of 
 dilute alcohol (1:3). A drop of blood from the finger of the 
 patient is spread between two cover-glasses, which are then boiled 
 over a water-bath for four minutes in equal parts of alcohol and 
 ether, to fix the hemoglobin in the red blood-corpuscles, and trans- 
 ferred to the staining solution described for about the same length 
 of time. After washing the cover-glasses in water, normal blood 
 appears reddish-violet, while glycosuric or diabetic blood presents 
 a sap-green or sometimes a bluish-green color. 
 
 In a later notice * Dr. Bremer has adopted a simpler method, 
 spreading a drop of blood between the cover-glasses and exposing 
 these for from six to ten minutes at a temperature of 135° C. 
 (275° F.) — not below 129° C. (264.2° F.) nor above 140° C. (284° 
 F.). The cover-slips are then placed for several minutes in a 
 one per cent, solution of Congo-red or of methylene-blue, or 
 Biebrich's or Ehrlich-Biondi's stain. The Congo-red colors dia- 
 betic blood but faintly or not at all, while it gives normal blood 
 a bright red hue. Methylene-blue, which gives normal blood a 
 violet color, gives diabetic blood a faint greenish or yellowish- 
 green color. Biebrich's stain does not color normal blood, but 
 makes diabetic blood a purple-red. Ehrlich-Biondi's stain makes 
 diabetic blood orange and normal blood violet. 
 
 Dr. Williamson, of Manchester, with a capillary tube mixes 
 twenty volumes of blood with forty volumes of water, forty vol- 
 umes of a six per cent, solution of potassium hydrate, and one vol- 
 ume of a solution of methylene-blue (i : 6000), and keeps the whole 
 in boiling water for five minutes. In the presence of normal blood 
 the mixture remains blue and afterward becomes greenish, while 
 with diabetic blood the mixture turns a pale yellow. 
 
 Loewy and others found Bremer's and Williamson's tests valuable 
 even when the diabetic patient's urine did not contain glucose. 
 
 *" New York Med. Jour.," 1897. 
 
246 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Patients, however, submit much more readily to examination of 
 their urine than to examination of their blood, and these tests are 
 little Hkely ever to come into general practice. It is, therefore, of 
 great importance that Dr. Bremer (1897) has published a method of 
 performing a color-test zvith the tirine. A small quantity of a powder 
 consisting of three parts of gentian-violet and two parts of eosin is 
 introduced into a tube almost filled with urine. Even at ordinary 
 temperature, but more quickly on application of heat, diabetic 
 urine assumes a deep violet, almost blue color ; normal urine, a 
 brownish-red color. This reaction, which appears whether the 
 diabetic urine contains glucose or not, is explained by the solution 
 of gentian-violet in diabetic but not in normal urine. In persons 
 with simple glycosuria, but living on the boundary-line of diabetes, 
 the urine presents a combination of the two colors. 
 
 I believe that these most interesting tests will, in combination 
 with those hitherto employed, prove most valuable in cases of 
 life-insurance and in cases of simulated diabetes (see below), and 
 I intend, as soon as time permits, to devote a good deal of attention 
 to Bremer's tests. 
 
 A medical practitioner's knowledge of a diabetic patient's urine 
 must comprehend : 
 
 1. The quantity 
 
 2. The specific gravity 
 
 3. The quantity of glucose ) of the urine collected during twenty-four hours, 
 upon a determined sup- 
 ply of carbohydrates 
 
 4. The absence or presence of Gerhardt's reaction and, if possible, of /8-oxybutyric 
 acid. 
 
 5. The absence or presence of albumin and of — 
 
 6. Structural elements from the kidneys. 
 
 To obtain information with regard to the excretion of urine for the twenty- 
 four hours, it is necessary expressly and most distinctly to instruct the patient 
 that he must collect every drop of urine in one vessel from, e. g., 8 o'clock one 
 morning until 8 o'clock the next morning. Any one but a physician would 
 believe this task, or at least the full understanding of it, to be the easiest possi- 
 ble. In this, however, as in everything else, we often find painful illustrations 
 of the correctness of Billroth's appropriate remark : In matters pertaining to 
 the natural sciences the average man is quite stupid (" ganz dumm "). 
 
 To take the specific gravity one must have at least two urometers, one 
 graduated from i.ooo to 1.020, and another from 1.020 to 1.040. A specific 
 gravity above 1.040 is rare. The fourth decimal must generally be taken 
 
INVESTIGATION OF A CASE OF DIABETES. 24/ 
 
 without any corresponding gradation on the urometer, which rarely is graduated 
 to more than three decimals. 
 
 A practitioner who does not observe many diabetic patients generally pos- 
 sesses no polarimeter, and finds reduction by Fehling's solution (or like 
 methods) too tedious a mode of determining the degree of glycosuria. For 
 him Roberts' method, based upon the difference in the specific gravity of the 
 urine before and after complete fermentation, is the easiest and best for deter- 
 mining the percentage of glucose present. A glass cylinder is almost filled 
 with urine, the specific gravity taken to four decimals, about two grams of 
 common yeast added, the yeast-cells somewhat evenly distributed through the 
 liquid by stirring, and the cylinder, covered with a piece of glass, placed for 
 fermentation if possible in a room with a temperature somewhat above the 
 ordinary.* After two or three days it is ascertained with Nylander's or Feh- 
 ling's solution that no determinable amount of glucose remains, and the 
 specific gravity is again taken to four decimals. The latter figure is subtracted 
 from that first obtained, and the difference is multiplied by a coefficient, which 
 has been differently estimated and varies somewhat with the percentage of 
 sugar, but which for practical purposes may, according to Lohnstein, be put at 
 the constant 234. The results thus obtained scarcely differ from the correct 
 ones by as much as o.oi per cent., and they are sufficiently accurate for the 
 purposes of the general practitioner. Thus : 
 
 Specific gravity before fermentation was 1.0345, and the 
 
 " " after " " 1.0165 ; the 
 
 Percentage of sugar is 0.0180 X 234 = 4.86. 
 
 Finally, I must again emphasize the necessity of performing Gerhardt's test, 
 the easiest, the most important, and the most neglected of all. Into an ordinary 
 test-tube nearly filled with urine, six, eight, or ten drops of a solution of ferric 
 chlorid are poured ; a red or a dark bluish-red color denotes the presence 
 of diacetic acid. There is no method of quickly ascertaining the quantity. 
 Oppler, of Breslau, adds the solution of ferric chlorid until the maximum in- 
 tensity of color is reached ; he then adds diluted hydrochloric acid until the 
 color again disappears. From the quantity of hydrochloric acid necessary for 
 this purpose an idea is gained as to the quantity of diacetic acid. 
 
 The practitioner who does not use a polarizing instrument can not determine 
 the presence or the quantity of /3-oxybutyric acid, which permits him to form a 
 distinct opinion with regard to the danger of coma. There are some points 
 apart from this best mode of estimating such a danger that it is important to 
 observe. If the reaction with six or eight or ten drops of a solution of ferric 
 chlorid in a test-tube almost filled with the patient's urine does not yield a true 
 red, but only a brownish color, there is no considerable amount of /3-oxybutyric 
 acid present either in the urine or in the blood. If a distinct, but not pro- 
 nounced, Gerhardt's reaction with a light red color appears, the amount of 
 
 * The specific gravity of urine sinks about o.ool with every increase of temperature of 
 3° C. (5.4° F.). To obviate the necessity of corrections and to avoid possible errors, it 
 is best to determine the specific gravity in both instances at the same temperature. 
 
248 DIABETES MELLITUS AND GLYCOSURIA. 
 
 j3-oxybutyric acid present is not large, and, unless the patient's general state is 
 very miserable, there will scarcely be any danger of coma. If the solution of 
 ferric chlorid yields a deep, dark bluish-red, there is good reason to suspect the 
 presence of a larger quantity of ,'3-oxybutyric acid. The degree of danger of 
 coma in such cases depends in large part upon the patient's general state. As 
 has been already mentioned, one patient may go on for months excreting in 
 the twenty-four hours many times as much /3-oxybutyric acid as is excreted by 
 another patient for only a short time before the fatal degree of poisoning is 
 reached. 
 
 By the use of a polarimeter the task is much facilitated. After precipitating 
 with ammonia and lead-acetate a sample of the mixed urine collected during 
 twenty-four hours, and waiting for some time until the urine passes perfectly 
 clear through the filter, the number of grams of the acid excreted in the twenty- 
 four hours is easily determined by introducing the degree of levogyration into 
 the formula, with the necessary correction for the dilution of the urine. As 
 soon as this number reaches more than twenty in an adult, the "acidosis," 
 operating in combination with a low state of general health, may threaten 
 coma. 
 
 To demonstrate the presence of albumin there is no easier test than pouring 
 nitric acid into a test-tube with a pipet beneath the urine. Even when only a 
 trace of albumin is present, it then quickly shows as a thin, reddish-white layer 
 immediately above the line of contact of the two liquids, below the less sharply 
 defined, more grayish layer of urates, which often forms above it ; care being 
 taken when only one of the two layers is present not to mistake it for the other. 
 
 The quantity of albumin, which generally is small and often below one- 
 half in a thousand, is most practically and enough accurately determined by 
 means of Esbach's albuminimeter. 
 
 With the aid of a centrifuge the task of finding casts of the renal tubules is 
 much facilitated, care being taken not to permit hyaline casts to escape detection, 
 and in cases of severe diabetes to keep a sharp lookout for the numerous small 
 casts described by Kiilz. 
 
 It is often worth the trouble to ascertain the patient's capabihty of ingesting 
 and digesting proteids by determining — usually by Kjeldahl's method or by 
 one of the many azotometers — the quantity of nitrogen excreted with the urine 
 in twenty-four hours. By multiplying the number of grams of nitrogen by 6.25 
 the number of digested grams of proteids is learned, not taking into considera- 
 tion the nitrogen possibly ingested with other substances than proteids and the 
 nitrogen derived from toxic, protoplasmic disintegration, both of which, in most 
 cases, only form " une quantite neglige able,'' and can not possibly be deter- 
 mined by the physician. 
 
 The general practitioner usually finding among his patients but a 
 limited number of diabetics, as a rule does not, by analytic work, 
 ascertain the changes in their nutritive state. On the other hand, 
 he ought not to omit to follow these changes, even though in a 
 somewhat crude but simple and practical manner. For this pur- 
 
INVESTIGATION OF A CASE OF DIABETES. 249 
 
 pose he may use the scales, the patient being weighed once a month, 
 or, if necessary, once a week. In doing this the patient must 
 necessarily take his weight at the same time of day and in the 
 same dress, or, if convenient, without any clothes at all. It is 
 evident that even if this is done the varying contents of the bowels 
 and the bladder may give rise to error. Further, a less important 
 gain of fat may cover and conceal a more important loss of pro- 
 teids. However crude this method of following the patient's nutri- 
 tive changes, it is of great practical importance, and, especially in 
 two classes of cases, is not to be neglected by the conscientious 
 physician. In severe cases it enables us to discover, and at once by 
 all the means in our power to combat, any increase of the autoph- 
 agy and rapid loss of weight, which often indicate the beginning 
 of the end and the overwhelming danger of coma. In mild cases 
 the scales enable us, during periods of marked restriction or exclu- 
 sion of carbohydrates from the food, to control the loss of weight 
 that usually occurs under such conditions, and which ought not to 
 be too marked. A fat diabetic patient (in the mild stage) may — 
 ceteris paribus — be permitted to lose more than a less fat patient, 
 but no diabetic should be permitted to lose in a month more than a 
 small percentage of his whole bodily weight. In the severe stage 
 the physician should always do his best to prevent any loss of 
 weight. 
 
 The remaining part of the investigation in a case of diabetes occu- 
 pies comparatively little time. I will cursorily mention the points 
 that strike me as most important. 
 
 In examining the patient as to his heredity one has especially to 
 bear in mind diabetes mellitus and insipidus, gout, adiposity, and 
 all neuroses (various forms of mental disease, neurasthenia, epi- 
 lepsy, etc.), and exophthalmic goiter. In making inquiry as to 
 mental diseases one must sometimes press the question in order 
 to gain the necessary information ; an unintelligent, and sometimes 
 even an intelligent, patient may, however, be irritated if the pres- 
 sure be made too great. A satisfactory result is often more easily 
 reached by asking as to symptoms rather than about names of 
 diseases. 
 
 With regard to the patient's own life inquiry is made as to past 
 diseases, especially gout, influenza, malaria, syphilis ; trauma, es- 
 17 
 
250 DIABETES MELLITUS AND GLYCOSURIA, 
 
 pecially of the head ; excessive intellectual work ; powerful and 
 permanent painful emotions ; sexual excesses, natural or unnatural ; 
 deprivations ; exposure ; indulgence in alcohol, tobacco, or other in- 
 toxicants (morphin, cocain, chloral) ; gormandism ; overindulgence 
 in sweets ; sedentary habits, etc. 
 
 If the diabetes has been discovered and treated before my own 
 investigation, I never omit to ask whether the discovery was made 
 from the sudden appearance of diabetic symptoms (thirst, polyuria, 
 etc.) or whether the disease has developed slowly and has been dis- 
 covered accidentally (life-insurance, etc.) or in consequence of -some 
 chronic diabetic comphcation affecting the skin, the eyes, the teeth, 
 etc. The prognosis, as has already been mentioned, is far better 
 when the development is slow than when the onset is sudden. 
 
 I likewise endeavor to secure information as to any loss of bodily 
 weight, and attach much greater significance to this if it has begun 
 before the diabetes was discovered and without any change of die- 
 tetic regimen, than if it began after a restriction of carbohydrates, 
 which, if carried to anything like an extreme, is likely to cause loss 
 of flesh in any person, diabetic or not. 
 
 I observe the patient's general appearance, complexion, manner 
 of movdng and of talking. I never omit to examine the cavity of 
 the mouth, which, from the existence of alveolar pyorrhea and 
 decay or loss of teeth, may afford evidence of diabetes of long 
 standing, or from the typical, diabetic "crocodile" tongue, and a 
 strong smell of acetone on the breath may show that the disease 
 has entered upon the severe stage. 
 
 I first try to form an opinion as to the patient's mental state by 
 my own observation, and afterward, prudently — i. e., as kindly, in- 
 terestedly, and delicately as possible — put direct questions about 
 central nervous symptoms, especially depression and irritability. I 
 pay particular attention in my examination to neurasthenic symp- 
 toms, whether revealed more directly through the nervous system 
 or the organs of perception, circulation, digestion, and reproduc- 
 tion : Depression ; irritability ; sleeplessness ; loss of memory or of 
 capacity for intellectual work ; vertigo, spontaneous or from a great 
 depth ; agoraphobia (rare) ; headache ; hj'peresthetic, dysesthetic, 
 or paresthetic sensations {casque nciirastlicniqiie, plaqtie sacree, and 
 other rachialgic manifestations, formication, sense of heat or of cold. 
 
INVESTIGATION OF A CASE OF DIABETES. 25 1 
 
 shooting, " rheumatoid " pains, neuralgia, migraine) ; neuromuscular 
 asthenia ; cramps in the calves ; neurasthenic asthenopia ; hyper- 
 esthetic, ocular, or auditory manifestations ; changes in taste and 
 smell, etc. ; pseudoangina pectoris — increased frequency of pulse ; 
 gastrointestinal disorders, with a capricious appetite ; nervous nausea 
 or vomiting ; eructations, pains, flatulence (exceedingly common), 
 sudden diarrheas, etc. ; sexual weakness and impotency. 
 
 In cases of long standing or in cases complicated by gout I do 
 not fail to look for symptoms of neuritis, and with a needle or a 
 tube filled with hot water or the esthesimeter to test the sensibility, 
 especially on the lower parts of the legs, where neuritic symptoms 
 are more frequent and more intense. 
 
 I test the knee-jerks (the prepatellar reflexes) a la Jendrassik. 
 The patient reclines upon a chair with his eyes closed, his legs bent 
 at the knee-joint at an angle of about i lo degrees, the feet some- 
 what separated, and the whole sole on the floor. His hands are 
 joined over his stomach, and he is told to relax the whole muscular 
 system, especially the muscles of the legs, as much as possible. I 
 place one hand near the knee, over the quadriceps femoris muscle, 
 to feel the jerk, while with a small book in the other I try to elicit 
 the reflex by striking a blow over the ligamentum patellae. I am 
 thus able to perceive by touch better than by sight the slightest 
 contraction of the quadriceps femoris. 
 
 By physical investigation in the usual way I ascertain the size 
 and the functional and valvular state of the heart, and I do not 
 omit in forming an opinion as to this state to weigh the patient's 
 statement with regard to his capacity for climbing, or any other 
 energetic muscular activity which increases the demands on the 
 heart. Palpation of the radial artery discloses the frequency, 
 rhythm, and strength of the pulse ; I try to detect any possible 
 atheromatous rigidity of the radial, femoral, and temporal arteries. 
 
 In examining the lungs I direct attention especially to ascertain- 
 ing the absence or presence of any incipient or advanced changes in 
 the upper lobes. 
 
 I ask the patient about his appetite, the regularity of his bowels, 
 etc. If there is any reason for presuming pancreatic disease, I 
 request him to observe if the character of the stools indicates the 
 presence of greater quantities of indigested fat than normal, and if 
 
252 DIABETES MELLITUS AND GLYCOSURIA. 
 
 this is the case, I give my own special attention to the subject. I 
 determine the size, the consistency, and the sensitiveness of the 
 Hver. In deciding as to the existence of incipient cirrhosis of the 
 liver I attach great importance to any enlargement of the spleen, 
 and sacrifice' some time in carefully ascertaining the size of this 
 organ. I seek information with regard to the presence of any 
 symptoms of gall-stones, which are not rare in cases of diabetes. 
 
 I also inquire whether the patient has been troubled by pruritus 
 or any local changes in the genitals. 
 
 I direct special attention to the eyes and look chiefly for cataract, 
 myopia, premature presbyopia, retinitis, and inflammation of the 
 optic nerve. 
 
 Simulation of diabetes is not rare in some European countries, and is 
 generally attempted by persons who wish to secure exemption from military 
 duty. 
 
 To contrive the fraud, the simulator either (i) eats a large quantity of glucose, 
 usually in honey, or (2) introduces some saccharid in his urine within or with- 
 out the bladder, or (3) takes a dose of phloridzin or of phloretin. 
 
 The ingestion of a large quantity of glucose is the shrewdest method. The 
 consequent glycosuria, however, lasts only for a few hours, and then ceases 
 when the supply is cut off. It is usually on the increase only for about an hour, 
 and after this time the fraud can be discovered by giving a large portion of 
 bread, and by observing that an hour later the glycosuria is on the wane instead 
 of increasing. 
 
 Fraud has sometimes been attempted by injecting a solution of some 
 saccharid into the bladder or by adding some saccharid to the urine outside 
 the bladder. (See the case of Abeles and Hoffmann.*) In the latter case the 
 fraud is detected by letting the simulator pass his urine under observation, or 
 by withdrawing it directly from the bladder. In both cases detection is gener- 
 ally made easy by the simulator's ignorance of the different kinds of saccharids. 
 Women scarcely ever know of any other sugar than the cane-sugar used in 
 their household. Urine containing cane-sugar will not reduce Fehling's or 
 Nylander's solutions before boiling with a dilute mineral acid, but will do so 
 after this, and will turn the ray of polarized light to the right. The cane-sugar is 
 generally added to the urine in amounts large enough to give it an exceedingly 
 high specific gravity, which will immediately turn the physician's mind in the 
 right direction. If the simulator has some knowledge of saccharids, the situa- 
 tion may be rendered more complicated. He may then contrive to get some 
 really diabetic urine and inject it into his bladder ; such a mode of simulation 
 can only be detected by keeping the simulator under observation, or by sub- 
 jecting his blood to Bremer's test. He is more likely, however, to use the glu- 
 
 * *' Wiener med. Presse," 1876. 
 
TREATMENT. 253 
 
 cose sold for technical purposes. This contains a good deal of dextrin which 
 is strongly dextrogyrate, but does not reduce solutions of copper nor bismuth, 
 and the fraud is detected by the polarimeter indicating a much higher percent- 
 age of glucose than do reduction-methods of estimation. 
 
 If simulation by means of phloridzin or phloretin is suspected, the urine 
 should be tested with ferric chlorid for the brownish-violet color yielded by 
 those substances — it being always borne in mind that a somewhat similar, but 
 more reddish, color is caused (i) by diacetic acid in cases of severe diabetes, or 
 when starvation is taking place, and (2) in any state of health by antipyrin, 
 salicylic acid and its salts, kairin, thallin, chinanisol, and other substances. 
 By cutting off the supply of phloridzin or phloretin for fully three days the 
 glycosuria due to these poisons can be stopped. 
 
 If one is provided with the proper stains he will probably find in Bremer's 
 method of diagnosticating diabetes (see above) an excellent means of detect- 
 ing at once any simulation of diabetes in whatever manner it is attempted. 
 
 CHAPTER IX.— TREATMENT. 
 
 Some prophylactic measures may be taken against diabetes ; this 
 apphes especially to members of families with a neuropathic, a 
 gouty, or directly diabetic hereditary predisposition. 
 
 These measures are, in large part, exactly those that are 
 rational in cases of nervous disposition. Children that begin life 
 thus handicapped ought, still more than others, to be protected 
 against fright and other emotions, overwork, and strains of all 
 kind, fatiguing and enervating pleasures ; and they should have all 
 of the advantages to be derived from fresh air, bodily exercise, baths, 
 early hours, and a systematic hygienic life. It is of paramount 
 importance, after puberty, to guard such children against an 
 abnormal or too early development of sexual activity. It is also an 
 exceedingly important and fully rational, though often neglected, 
 measure in the choice of a profession to direct such young persons 
 to occupations in life that are less likely than others to develop 
 neurotic tendencies. In this respect our descendants will certainly 
 provide much more carefully than we do or even than we now 
 would approve of doing. 
 
 It seems to me that something might also be done in the matter 
 
2 54 DIABETES MELLITUS AND GLYCOSURIA. 
 
 of diet to diminish an inherited danger of future diabetes, though 
 for my part I consider this item of diabetic prophylaxis to be much 
 less efficient and important than antineurotic measures. It would 
 certainly be most unwise to diminish a child's supply of bread, 
 potatoes, and other more or less necessary articles of chiefly carbo- 
 hydrate nature below fair daily portions ; but nothing is lost, and 
 perhaps something is gained, by a rigorous restriction of sweets 
 and sugar in the food of such children. The custom prevalent in 
 some countries of including beer and other liquors in the dietary 
 of persons even below fifteen years of age might also well be 
 avoided. 
 
 It not rarely happens that a diabetic patient asks his physician 
 with regard to the advisability of marriage, often, I acknowledge, 
 with a firm, though unconscious, resolution in this respect not to 
 take advice that is opposed to his own inclinations. If a case 
 of true diabetes sets in before the thirty-fifth or fortieth year, life will 
 generally be short. Impotence and sterility threaten darkly, and 
 pregnancy and maternal duties in woman, like sexual activity in 
 man, often favor the development of the dystrophy. The mortality 
 among children of diabetic parents, as has been mentioned, is 
 enormously high, the constitutional inheritance a great handicap 
 in life. It would be unwise for a physician to put all these facts 
 distinctly before a patient who thinks of marrying, and who rarely 
 is to be dissuaded from doing so, but these arguments must have a 
 profound influence on the advice the physician will give. In severe 
 cases of diabetes there are left but few of the customary reasons for 
 marrying. 
 
 The great dangers for mother and child also ought to be taken 
 into consideration in connection with pregnancy in diabetic women, 
 and they may, under certain circumstances, justify artificial inter- 
 ruption of the pregnancy. Such a course in a case of simple glyco- 
 suria, or even in one of true but mild diabetes in otherwise fairly 
 good condition, might justly be considered as malpractice, and the 
 mere name of diabetes ought never to be made a safeguard for an 
 operation of this kind. I should not hesitate, however, to give my 
 vote in favor of interrupting the pregnancy in any case of diabetes 
 
TREATMENT. 255 
 
 in the severe stage, or in any case in which the prospects of mother 
 or child were gloomy. 
 
 There is but little to say outside of general rules with regard to 
 the hygiene of diabetic patients. 
 
 The physician and his diabetic patient must never forget the 
 small power of the latter to resist deleterious influences of all 
 kinds. Diabetics are more likely than others to be affected by 
 emotions of a depressing nature and to suffer more in consequence. 
 Every physician who has seen much of these patients has learned 
 how especially careful one must be not to irritate or in any way to 
 frighten them, and he will adopt the rule of according to them, still 
 more than to others, the patience and forbearance under all cir- 
 cumstances — which is not the lightest nor the least important of 
 the many high duties of the medical profession. The necessity of 
 avoiding all kinds of strains on his nervous system must be earn- 
 estly impressed upon the patient. He must, as far as possible, 
 limit his intellectual activity not only below the level of overwork 
 for a normal person but below the level of overwork for his own, 
 usually limited, powers. He must be most moderate in sexual 
 activity. He must forswear overuse of tobacco and alcohol, 
 and it is still more important for him than for others not to fall 
 into bad habits with morphin, cocain, somniferous drugs, etc. He 
 ought to take as much exercise as he can take without fatigue. 
 He must observe regular hours, with a large allowance of time 
 for mental and bodily rest. His great sensitiveness to exposure, 
 and the especially dangerous consequences of cold make it of par- 
 amount importance for him to be warmly dressed, and to wear, 
 constantly, woolen underclothes. His whole mode of life must be 
 thoroughly hygienic. If he lives in a rigorous climate, it is of 
 great advantage to him to pass the coldest part of the year in some 
 warmer place, observing there the same scrupulously hygienic 
 regimen as at home. 
 
 The special duty of taking into earnest consideration the diabetic 
 patient's mental sensitiveness begins at the moment the physician 
 discovers the existence of any stage of the glycosuric dystrophy, 
 and concerns the statements to be made to the patient on this 
 subject. 
 
256 DIABETES MELLITUS AND GLYCOSURIA. 
 
 If only a slight glycosuria, but no true diabetes, is found, it is 
 in many cases wise to mention nothing about the matter to the 
 patient. Individuals of great sensitiveness, especially if not highly 
 intelligent, are often greatly affected by learning of the excretion 
 of sugar in their urine, however slight and however accentuated by 
 the physician its clinical insignificance. If the urine for twenty-four 
 hours does not contain more than a trace of glucose (up to 0.05 
 per cent.) with an ordinary free diet, and the patient furnishes any 
 ground for doubting his courage or judgment, other reasons than 
 the existence of glycosuria can always be found for advising avoid- 
 ance of the most objectionable kinds of food (sweets, dry fruits, rice, 
 macaroni, peas, champagne, etc.). 
 
 If the case is one of true diabetes, it is generally necessary to in- 
 form the patient of this fact. In mild cases the physician then has 
 the pleasant task of making the patient acquainted with many actual 
 reasons for comfort and hope. In severe cases the physician, who 
 alone can determine the nature and prognosis of the special case, 
 will understand that, if prudence often is the better part of valor, 
 discretion is often the better part of truthfulness. It is quite a 
 satisfaction to know that downright lying is generally not necessary. 
 The patient usually knows little else of diabetes than that a person 
 may live with it for decades in fairly good health, and the physician 
 will rather, by repeating this and other general facts, let the patient 
 deceive himself than injure and torture him by stating the whole 
 implacable truth. 
 
 On the whole, it is of great importance to arrange everything for 
 the patient with a view of reminding him as little as possible of his 
 own exceptional position. 
 
 For this reason I consider the " sanatoriums for diabetics," where the 
 patient meets only brothers in misfortune, in many cases to be of doubtful ad- 
 vantage. The one indication that may arise for a sojourn of some weeks in 
 such an institution is the period of absolute or of very rigid diet in the mild 
 stage ; it depends on circumstances whether[the dietetic discipline is not even 
 then acquired at too high a price. 
 
 The poor diabetic patient certainly derives some advantage from the hos- 
 pital, where he may for some time enjoy a rational diet at moderate cost. 
 
 One of the diabetic's most frequent and most common nervous 
 symptoms is sleeplessness. This is a trouble that often follows the 
 
TREATMENT. 257 
 
 patient throughout his whole life, and it is of the utmost importance 
 not to employ remedies that easily lead the patient into bad habits 
 and may cause a much greater misfortune even than sleeplessness. 
 We therefore, as far as possible, take refuge in simple and harmless 
 remedies. We prescribe mental and physical rest during the last 
 hours of the day. We recommend the system — already mentioned 
 for its merits in other respects — of making the last meal of the day 
 a light one, also for its better influence on the night's rest. A 
 moderately warm bath at 35° or 36° C. (95° or 98.6° F.) before 
 going to bed has a good effect in some cases. A hot foot-bath at 
 this time and a wet, warm fomentation around the abdomen during 
 the night are highly praised by some patients. In other cases I 
 have found covering the head warmly at night — with a fur cap, for 
 instance — a most efficient remedy for promoting sleep. The vibra- 
 tions on the head, recommended by Charcot and others, have 
 already been mentioned. I found Charcot's (or Gilles de la Tou- 
 rette's) " casque vibrmtt " too weak, and have seen much better results 
 from one of Zander's machines. One must sometimes try several 
 of these simple remedies, and will often find one of them efficient 
 when others have failed. 
 
 In the presence of severe exacerbations of insomnia and during 
 mental disturbances we are sometimes forced to take refuge in 
 narcotic, somniferous drugs. I prefer great economy in this, and I 
 rarely give such remedies two nights in succession ; neither do I 
 us^ them for any length of time, if this can possibly be avoided. 
 A large dose of the comparatively harmless bromids will diminish 
 the necessary dose of other remedies. (I prefer sodium bromid to 
 potassium bromid.) Among directly hypnotic remedies, I have, 
 after many disappointments, returned to chloral hydrate or chloral- 
 amid as the best and least objectionable. With all their draw- 
 backs, these are decidedly better than the much-praised sulphonal 
 and trional, both of which cause drowsiness on the next day, if 
 taken in such doses as will cause sleep during the night, and 
 both of which cut off the systolic apices on the pulse-curve. 
 Among narcotic vegetable derivatives opium and extract of can- 
 nabis indica rank foremost. Neither morphin nor codein is 
 ever to be used for this purpose. One may, for instance, 
 give at one dose : sodium bromid, 2 gm. ; chloral hydrate, 
 
258 DIABETES MELLITUS AND GLYCOSURIA. 
 
 1.20 gm. ; extract of cannabis indica, 0.05 gm. ; or some similar 
 formula. 
 
 In cases of severe diabetes, with a miserable general state and a 
 distinct excretion of /3-oxybutyric acid, our chief task must be as 
 long as possible to prevent coma. The patient must with the 
 greatest care be protected from injurious influences of all kinds. 
 No mental or intellectual exertion, no exposure, no fatigue, no 
 long journeys, no deviation from daily customs should be per- 
 mitted. I add with the deepest conviction that the diet should not 
 be made too rigid. The patient may have as much bread, green 
 vegetables, and potatoes as he likes ; several teaspoonfuls of levu - 
 lose daily will help to keep him alive. It is of paramount im- 
 portance to promote the excretion of toxins by favoring free diu- 
 resis. The patient is allowed to drink as much water as he chooses, 
 and we especially recommend a generous daily supply of the cus- 
 tomary alkaline table-waters, charged with free carbonic-acid gas. 
 Strong acids ought not to be given ; nor are large amounts of 
 alkalies to be recommended for long periods ; if large enough to 
 decrease the acidosis considerably, they cause digestive troubles 
 and have a weakening effect. It is also most important to keep 
 the bowels open by means of massage, aperient drugs,* or by in- 
 jections. The latter are advantageously performed with large quan- 
 tities of tepid water and enough potassium permanganate to pro- 
 duce a faint violet color in the water. 
 
 Whenever there is a danger of coma, great care must be observed 
 in the use of narcotic and somniferous remedies. 
 
 When the prodromes appear, or if headache and great lassitude 
 raise suspicion of coma, rapid measures may still afford some 
 respite. The patient is at once put to bed, receives a glass of 
 brandy or of whisky, or a subcutaneous injection of ether, and is 
 given enormous amounts of sodium bicarbonate in some water rich 
 
 * I often give : 
 
 Pulveris aloes, "1 
 
 Pulveris rhei, J 4 s- 
 
 Extract, colocynth. comp., 3 gm. 
 
 Extract, hyoscyamus, 1. 50 gm. M. 
 
 Ft. pil. No. Ix. 
 
 SiG. — One, two, or three pills at night. 
 The aperient effect of these pills usually follows in the morning. 
 
TREATMENT. 259 
 
 in free carbonic acid. A moderate dose of digitalis or strophanthus 
 may also be administered. The patient may also take a bath at a 
 temperature of 38° or 39° C. (100.4° o^ 101.2° F.). 
 
 If matters have progressed still further, — if the respiration is 
 dyspneic, the pulse inordinately frequent, — the same steps must be 
 taken ; except in exceedingly rare cases neither they nor any other 
 means will effect more than a transitory and fallacious improve- 
 ment. Under such circumstances the alkali?ie solution may be in- 
 jected into a vein,'* but this can not be considered necessary, as it 
 presents few advantages over administration of large amounts of 
 alkali by the mouth, and its effects are almost always of short 
 duration. The intravenous injection of an alkaline solution requires, 
 besides, elaborate contrivances, and is but rarely undertaken in 
 private practice. Stadelmann used a concentrated solution of sodium 
 bicarbonate and citric acid, and injected 150 cu. cm. three or four 
 times a day. Others use solutions of a mixture of sodium chlorid, 
 bicarbonate, phosphate, and sulphate. Lepine dissolves 7 grams 
 of sodium chlorid and 10 grams of sodium bicarbonate in a liter of 
 water ; injects slowly, but within a short while, 2 liters ( ! ! ) of this 
 solution at a temperature of 38° C. (100.4° F.) into a vein of the 
 arm. 
 
 Whether the intravenous injection be performed or not, a concen- 
 trated solution of sodium bicarbonate in large doses should always 
 be given by the mouth, and a subcutaneous injection of ether or 
 caffein citrate may also be given. 
 
 The immediate effect of the alkaline venous injections, or of 
 large doses of sodium bicarbonate by the mouth, is sometimes 
 apparently favorable, and likely to inspire the inexperienced with 
 the hope that the patient will return to his previous state before the 
 onset of the symptoms of coma. In the large majority of cases 
 this improvement will last only for a few hours or for a couple of 
 days, and the physician will do well to prepare those interested for 
 the patient's approaching death, however strongly the comatose 
 symptoms have receded for the moment. 
 
 In treating a case of diabetes our first duty — apart from the 
 
 * The subcutaneous injection of large amounts of alkaline solution presents far 
 greater inconveniences and dangers than advantages, and ought never be practised. 
 
26o DIABETES MELLITUS AND GLYCOSURIA. 
 
 almost always hopeless task of removing the cause of the dystrophy 
 — is to protect the patient from the inanition that threatens from the 
 loss of glucose. Next in importance is the task of providing 
 a sufficient number of calories in such food as to cause the least 
 possible hyperglycemia and blood toxins, and counteract, as much 
 as possible, the development of the diabetes. Dietetic prescriptions 
 will thus always constitute an important part of the treatment, though 
 they ought not, as is often the case, to make up the whole treatment. 
 The facts that ought to form the basis for our views on the dietary 
 for a diabetic are as follows : 
 
 1. An individual performing some mechanical work needs from 
 thirty-five to forty calories per kilogram of bodily weight in twenty- 
 four hours to maintain his nutritive balance. 
 
 2. Proteids yield 3.2, fats 8.4, and carbohydrates 3.8 net calories 
 per gram in healthy persons, and usually as much in diabetics — 
 minus the loss from glucose in the urine following the ingestion of 
 carbohydrates in the mild stage, and present with any diet during 
 the severe stage, of the diabetic dystrophy. 
 
 3. Carbohydrates ingested in ordinary amounts cause in all cases 
 of diabetes the distinctly, though only slightly, injurious hypergly- 
 cemia, which finds its expression in the, pei' se, almost indifferent 
 glycosuria. 
 
 4. All diabetic patients, however, utilize some portion of ingested 
 carbohydrates, and the calories thus gained contribute better than 
 calories derived from fat to the protection of the organism's own 
 proteids. Levulose is better utilized than any other yet known 
 and fully acknowledged carbohydrate. 
 
 5. Restriction of carbohydrates in the food causes a decrease or 
 a cessation of hyperglycemia and glycosuria, and, apart from other 
 advantages, counteracts the development of the glycosuric dys- 
 trophy. 
 
 6. Fat, ingested in any quantity, does not cause hyperglycemia 
 or glycosuria in any stage of diabetes. 
 
 7. Fat, however, in spite of its high caloric value, can not be 
 ingested in any quantity that even remotely covers the expenses of 
 the organism. 
 
 8. Still, fat can be ingested in much larger quantity with than 
 without the ingestion of carbohydrates. 
 
TREATMENT. 26 1 
 
 9. In cases of severe diabetes toxins arise in the blood that are 
 far more injurious that the hyperglycemia. 
 
 10. These toxins are increased by exclusion or too rigid a 
 restriction of carbohydrates from the food. 
 
 11. Normal human food — apart from water and salts — consists 
 of proteid, fat, and carbohydrate, and permanent exclusion of car- 
 bohydrate from the diet can not be effected, because it prevents the 
 supply of a sufficient quantity of calories and causes severe dis- 
 turbances of the digestive functions. 
 
 12. Among articles of food rich in carbohydrate bread is most 
 difficult to exclude. 
 
 A rational diet for a diabetic must be founded on all these facts ; 
 if too much importance be attached to dangers or to advantages 
 of any special kind, the treatment necessarily will be defective. 
 
 An absolute diet — by which I mean a diet of meat and fat with 
 the strictest possible exclusion of carbohydrates — can never be 
 followed for periods of more than weeks, or, at the longest, of 
 months. I consider the correctness of this opinion to be so univer- 
 sally acknowledged at the present time that it is unnecessary to 
 spend more words on it. 
 
 It remains, then, to decide in which cases of diabetes it may be 
 advantageous periodically to exclude carbohydrates* from the food. 
 
 This may advantageously be done in most cases within the mild 
 diabetic stage. Even with robust individuals in that stage, how- 
 ever, I do not find it rational to prescribe, nor could I prevail upon 
 the patient to submit to, longer periods of absolute diet than a 
 month. 
 
 The advantages of the absolute diet in mild cases consist in the 
 cessation of the hyperglycemia and its effects, the cessation in itself 
 counteracting the progressive tendency of the diabetes and often 
 increasing the power of assimilating carbohydrates. 
 
 The disadvantages of the absolute diet, even in mild cases, are. 
 
 * Unfortunately for diabetics, bread is the kind of food that most people find it most 
 difficult to spare. If any one should for a time live on only two of the three kinds of 
 food, — meat, butter, and bread, — he would want first of all the bread and resign the butter. 
 It is also known that large, fairly civilized populations chiefly (and up to more than 90 
 per cent, of the whole solid food) live on rice, but meat and fat nowhere constitute so 
 large apart of the food, except among the few and low-ranking tribes in the Arctics. 
 
262 DIABETES MELLITUS AND GLYCOSURIA. 
 
 unfortunately, very great. The patients with this diet often suffer 
 from constipation, which is likely to give way only to diarrhea. They 
 lose their appetite and are not able to ingest much fat or enough 
 of any permitted food to maintain their nutritive balance ; they almost 
 invariably lose flesh. The neurasthenic symptoms, rarely absent 
 in cases of diabetes, are especially prone to be aggravated by the 
 inanition. The mere absence of normal pleasure and satisfaction at 
 meals also has, in many cases, an unfortunate effect on the patient's 
 mental state. 
 
 It will generally be found that the patient will bear better the 
 absolute diet, and derive greater advantages from it, the fatter and 
 the less nervous he is. The state of the digestive organs and their 
 power to support the absolute diet is also a most important and 
 a most varying factor. It must also be remembered that there are 
 in apparently quite similar cases great individual differences in the 
 capability of supporting and in the general effects of the absolute 
 diet. I have sometimes, even in mild cases of diabetes, found it 
 wiser, after a signal failure, never to prescribe the absolute diet, 
 from which some patients suffer exceedingly in their general state 
 and well-being. 
 
 In the severe stage the advantages to be derived from the abso- 
 lute diet are always much diminished. We can no longer free the 
 patient from the hyperglycemia and its effects, and we can no 
 longer materially increase his power of assimilating carbohydrates. 
 The disadvantages arising from a rigid exclusion of carbohydrates 
 are much greater than in the mild stage, and the increase of acetone, 
 diacetic acid, and ^J-oxybutyric acid, inseparable from such a diet, 
 also directly increases the danger of coma, which, besides, becomes 
 greater by reason of the inanition itself, scarcely to be avoided 
 upon exclusion of carbohydrates. 
 
 TJie rational application of these facts forbids the exclusion of car- 
 boJiydrates in the distinctly severe stage of diabetes. 
 
 In determining the daily allowance of carbohydrates for a patient 
 in the severe stage I must, however, distinguish between two classes 
 of patients. 
 
 The first class consists of cases presenting diacetic acid but 
 no ;5-oxybutyric acid in the urine. There is in these cases no 
 danger of coma ; but the patients generally have lost in bodily 
 
TREATMENT. 263 
 
 weight, and are in a poor state of general health. An exclusion of 
 carbohydrate seems to me, even in these cases, to do more harm 
 than good, by decreasing their bodily weight and by exerting a bad 
 influence on the general somatic and mental state. I customarily 
 allow such patients from eighty to one hundred grams of carbohy- 
 drate in twenty-four hours ; usually, at least half of this portion is 
 taken in bread and the rest in vegetables of different kinds (see 
 below). 
 
 The second class of severe cases consists of those in whose urine, 
 in addition to diacetic acid, also /3-oxybutyric acid is present: i. e., 
 cases in constant danger, more or less pronounced, of coma. 
 Whenever I encounter a diabetic patient in the distinctly severe 
 stage, I allow him a moderate daily amount of carbohydrates 
 (eighty grams) until I have acquired definite information on this 
 point. If after the removal of all sugar from the urine by fermen- 
 tation, and of combined (levogyrate) glycuronic acids by precipitation 
 with lead acetate and ammonia, I still find distinct levogyration, 
 denoting the presence of /J-oxybutyric acid and at the same time 
 an advanced " acidosis " (in the blood), I am averse to any.great re- 
 striction of carbohydrates. However absolutely I condemn an ex- 
 clusion, if ever so short, of carbohydrates in these cases, I am 
 willing to admit that the rational daily amount of carbohydrate is 
 a matter open to discussion. Considerable experience, however, 
 both of the effect of my own dietetic system and of that of other 
 physicians, has forced me to the conclusion that I promote best the 
 interests of such patients by allowing them a generous, if not an 
 unlimited, amount of bread * and potatoes. I exclude from their 
 dietary only such articles as contain much carbohydrate and at the 
 same time can easily be spared (rice, macaroni, peas, dried or sweet 
 fruits, sugar and sweets, champagne, beer, sweet wines and liquors, 
 etc.). In these cases, if circumstances permit, I also use levulose, 
 recommending it strongly as a substitute for cane-sugar. It in- 
 variably increases the glycosuria, but as invariably diminishes the 
 autophagy and loss of weight, and I believe that it has in many of 
 my own cases postponed the final issue. 
 
 * In cases with advanced acidosis I allow at least one hundred grams of ordinary 
 white bread a day. 
 
264 DIABETES MELLITUS AND GLYCOSURIA. 
 
 If a patient in the advanced severe stage is, after some allowance 
 of carbohydrate in his food, put on an exclusive animal regime, or 
 only allowed a small daily amount of carbohydrate, he frequently 
 is attacked and killed by coma within a few days. 
 
 " But," some one will say, " the absolute diet has also a diagnostic 
 purpose ; and how shall I ascertain the state of the patient's dystro- 
 phy without putting him on an exclusive animal diet, with a 
 minimum of carbohydrate ? " I have already answered this objection. 
 If a diabetic patient on a mixed diet passes urine that does not 
 yield a distinct Gerhardt's reaction (a wine-red color on addition of 
 a solution of ferric chlorid), I may, without danger of coma, with- 
 draw the carbohydrate. If the urine presents a distinct Gerhardt's 
 reaction, the case is a severe one, and it would be a grave error to 
 put him on an absolute diet. / 
 
 In my opinion we must adopt the rule in all cases of diabetes, 
 mild or severe, never, as a permanent dietetic rule, to put any 
 maximum limit, any restriction, on the supply of meat or fat. There 
 are cases on the borderland between mild and severe diabetes that 
 with exclusion of carbohydrates and some restriction of meat pre- 
 sent no glycosuria, and that with exclusion of carbohydrates, but 
 with a larger supply of meat, excrete small quantities of glucose. 
 A restriction of meat also in many other cases diminishes the 
 glycosuria. The slight corresponding hyperglycemia, however, is 
 an insignificant matter as compared with too much prescribing and, 
 above all, with underfeeding. When one of Germany's greatest 
 clinicians and best authorities on diabetes (Naunyn) recommends a 
 maximum limit in the supply of meat,* even with an exclusion of 
 carbohydrates, — which he also prescribes in cases in the severe stage, 
 — with all my admiration for him personally and for his work, I can 
 not follow him here. How could a patient who has to live exclu- 
 sively on meat and fat avoid underfeeding if he is not permitted, 
 even with regard to this poor food, to satisfy his appetite, which on 
 this point affords more trustworthy indications than are sometimes 
 given by learned and otherwise clever physicians ? 
 
 The danger from underfeeding with exclusion or strong restric- 
 
 * So far as I know, Rollo was the first to urge a restriction even of proteids in cases 
 of- diabetes. I have no doubt that this dietetic principle is at present on its last legs. 
 
TREATMENT. 
 
 265 
 
 tion of carbohydrates is always imminent, and rather than restrict 
 proteids and fat, we ought as much as possible to insure the patient 
 against receiving too small amounts of both for the maintenance of 
 his nutritive equilibrium. Even when we do our best, we shall find 
 that a marked restriction of carbohydrates often necessarily results 
 in some degree of starvation. 
 
 Let us consider the dietetic needs of a man of seventy-five kilo- 
 grams of bodily weight who receives forty calories per kilogram in 
 twenty-four hours, and how to meet those needs with different pro- 
 portions of the three great classes of food. I shall, as far as possi- 
 ble, confine myself to round figures in making the whole amount of 
 the daily supply reach about 3000 calories : 
 
 Case. 
 
 Proteid. 
 
 Net Value, 
 3.2 Cal. 
 
 Fat. 
 
 Net Value, 
 8.4 Cal. 
 
 Carbohy- 
 drate. 
 Net Value, 
 i^.8 Cal. 
 
 Sums of Calories. 
 
 No. I 
 
 135 gra. 
 
 80 gm. 
 
 500 gm. 
 
 = 432 -f 672 + 1900 = 3004 
 
 " 2 
 
 420 " 
 
 200 " 
 
 " 
 
 = 1344 -f 1680 -f = 3024 
 
 " 3 
 
 120 " 
 
 285 " 
 
 60 " 
 
 = 384 -f 2394 + 228 = 3006 
 
 " 4 
 
 700 " 
 
 65 " 
 
 60 " 
 
 = 2240 -|- 546 -)- 228 = 3014 
 
 " 5 
 
 185 " 
 
 260 " 
 
 60 " 
 
 = 592 -|- 2184 -f 228 = 3004 
 
 " 6 
 
 225 " 
 
 245 " 
 
 60 " 
 
 = 720 + 2058 -|- 228 = 3006 
 
 " 7 
 
 250 " 
 
 235 " 
 
 60 " 
 
 = 800 -|- 1974 -|- 228 = 3002 
 
 " 8 
 
 345 " 
 
 200 " 
 
 60 " 
 
 = 1 104 + 1680 -f 228 = 3012 
 
 " 9 
 
 300 " 
 
 200 " 
 
 100 " 
 
 = 960 -j- 1680 -|- 380 = 3020 
 
 " 10 
 
 190 " 
 
 240 " 
 
 100 " 
 
 = 608 + 2016 -f- 380 = 3004 
 
 The first line in the table shows an arrangement that gives 
 fifteen grams more of proteid and twenty-five grams more of fat 
 with the same amount of carbohydrate than Voit's classic table. 
 I have made the additions necessary to reach the 3000 calories to 
 the proteids and to fat, because the patient, of his own choice, fol- 
 lowing only the dictates of taste, is much more likely to do this 
 than to increase the amount of carbohydrate above 500 grams. 
 Among Anglo-Saxon and Teutonic nations the free choice of pro- 
 portions for 3000 calories would often increase the proteids to at 
 least 150 grams, and the fat to an equally large or even larger 
 amount. 
 
266 DIABETES MELLITUS AND GLYCOSURIA. 
 
 The second line in the table shows at a glance how very difficult 
 it is to obtain the 3000 calories without carbohydrate. If we put the 
 fat at 200 grams, — which for many individuals represent the maxi- 
 mum possible of ingestion, and which are contained in about 240 
 grams of butter, — we must take 420 grams of proteid or nearly 1250 
 grams of cooked meat (free from fat). If we trust to the ability of 
 the patient to take daily ten eggs, each of which shall contain fifty 
 grams of food, we may decrease the meat by about 200 grams, and 
 the butter by about fifty-four grams ; but how many individuals are 
 able to eat fully a kilogram of meat, nearly ■§- of a kilogram of butter, 
 and ten eggs a day, even if the most expert chefs put their heads 
 together to make the whole as palatable as possible ? 
 
 The third and the fourth lines in the table only show that, 
 even if I allow sixty grams, or the minimum of carbohydrate that is 
 necessary in the long run, by increasing only the proteids or only 
 the fat, I obtain perfectly impossible quantities of the one or the 
 other. 
 
 The fifth, sixth, seventh, and eighth lines represent the possi- 
 bilities of ingesting enough of proteids and fat in addition to the 
 necessary minimum of carbohydrate ; but we find that however the 
 proportions of proteids and fat are arranged, the patient is likely to 
 have before him a difficult task. 
 
 The ninth and tenth lines show how the patient's task is facili- 
 tated by allowing him a somewhat larger amount of carbohy- 
 drate. There are a great many persons of 75 kilograms of bodily 
 weight who are able to keep themselves in a fair state of health by 
 ingesting in the twenty -four hours 190 grams of proteids, 240 
 grams of fat, and 100 grams of carbohydrate, or about 2.5 grams 
 of proteid and 3.2 grams of fat per kilogram bodily weight. The 
 quantity of fat is rather large ; in many cases it will be necessary to 
 diminish this and to increase the amount of proteids to something 
 more like the quantities given in the ninth column. But the more 
 fat a diabetic can ingest, the better off he is, and a patient of 75 
 kilograms ought, if possible, not ingest less than 200 grams of it. 
 The ninth and tenth lines show proportions that, especially in 
 mild cases, will often be found in the long run to be the most 
 advantageous. In very severe cases 100 grams of carbohydrate are, 
 for a person of this weight, never too much, but often too little. 
 
TREATMENT. 26/ 
 
 In this table I have not taken into consideration the loss of calo- 
 ries represented by the glucose in the urine. On the other hand, I 
 have not taken into consideration the calories that may be gained 
 by the use of a moderate amount of alcohol. If we put the 
 caloric value of glucose at 3.7 per gram, we find that a patient that 
 passes 50 grams of glucose in the twenty-four hours — a large 
 amount in the mild stage with a daily supply of 100 grams of car- 
 bohydrate — loses 185 calories of what he has ingested and digested. 
 This loss is not larger than the allowance of alcohol — equivalent to 
 7 calories per gram — that can be accorded to a person of 75 kilo- 
 grams. 
 
 Rollo was the first, in the beginning of this century, to recommend an exclu- 
 sive diet of meat and fat in cases of diabetes. He committed the error, after- 
 terward repeated by others, of prescribing a restriction even of meat. In 
 those days the laws of nutrition and the organism's imperative demands for 
 a certain number of calories were not known, and importance was attached 
 almost exclusively to a removal of the glycosuria. Rollo, however, in his 
 practice did not carry out his theories with regard to an exclusively animal diet, 
 which, according to his prescription, was adopted throughout Great Britain and 
 its colonies, and soon spread to France and Germany. Wherever this system 
 was introduced it proved unsatisfactory, from the consequent disturbances of 
 digestion, its manifest insufficiency, and from the patient's invariable aversion. 
 Opinions on this subject have since been much divided, and are so to some 
 extent at the present time. Bouchardat (from 1842) contributed largely to the 
 establishment of a better system with a mixed diet of ingestable quantities of 
 meat and fat, and a restricted supply of starch, chiefly taken in the form of green 
 vegetables and bread ; he also allowed moderate quantities of alcohol. Mean- 
 while, Prout introduced gluten-bread and inaugurated the long series of breads 
 made especially for diabetics. 
 
 The late distinguished Neapolitan physician, Cantani, was one of the most 
 energetic advocates in our time of an absolute (animal) diet for cases of dia- 
 betes. He allowed only meat and fat, and as representatives of the latter he 
 recommended olive oil and cod-liver oil. Butter was forbidden because it con- 
 tains a trace of milk-sugar. Cantani later became somewhat more reasonable, 
 and allowed butter and "fruttt di mare,''' a dish composed of different small 
 salt-water animals, some of which contain a considerable percentage of gly- 
 cogen. It was his plan to enforce this diet for at least three months, and then 
 gradually to make concessions toward a more mixed food. One gains quite a 
 curious impression from reading Cantani's opinions with regard to the possi- 
 bilities and the effects of the severe regime he prescribed. I suspect that some 
 of his patients have, without his knowledge, smuggled not inconsiderable 
 quantities of macaroni into their food. Cantani spent his life in Naples, with 
 its heavenly nature and vile population, by whom a true word, to quote Swin- 
 burne, in " Peter Simple," seems to be spoken only by mistake. 
 
268 DIABETES MELLITUS AND GLYCOSURIA. 
 
 An absolute diet in the severe stage of diabetes is now insisted upon strictly 
 by Naunyn and his school. Even his justly honored name is not sufficient to 
 sustain this position. The cases published by him and his disciples demon- 
 strate what this regime is capable of effecting in the severe stage ; the patients 
 immediately after its inception being often delivered from their sufferings by 
 death in coma. 
 
 It is a pleasure to know that the absolute diet has certainly never been 
 observed, except for a very short time, by any one not kept under lock and 
 key. A considerable experience with cases of diabetes in representatives of 
 the best nations and of the best (z. e., most educated, most intelligent, and 
 therefore most reliable and obedient) classes, has taught me that the physician, 
 even if he knows how to acquire the confidence of his patients, can only rarely 
 enforce abstinence from carbohydrates (bread) for as long time as a month, and 
 that any one by unreasonable demands in this respect only incurs the danger 
 of not being obeyed even in feasible matters. 
 
 Experience no less than late advances in physiology and experimental 
 pathology should prevent us from permitting our fears of hyperglycemia with 
 its glycosuria to overshadow other and greater dangers. 
 
 There died in Sweden some years ago a man whose case is an illustration 
 of the comparatively insignificant danger of hyperglycemia. The patient was 
 Professor Forsell, well known from his paper on his own case, published in 
 1883. Forsell was no physician, and his paper bears the stamp of the layman. 
 Some of his conclusions are entirely false. The facts with regard to his diet, 
 his polyuria, and his glycosuria, however, are certainly in the main correct, 
 and correspond with the data of his physician, who died a few years ago. 
 Forsell's diabetes began quite suddenly in 1866; the same year the percentage 
 of sugar reached 7.4, the polyuria 6.5 liters, the specific gravity 1.040, the daily 
 loss of glucose often 425 grams, and on one occasion 850 grams. Professor 
 Forsell never was my patient, and I am not familiar with the details of his 
 case ; but although its course proves it to have remained at least for a consider- 
 able length of time in the mild stage, there is no doubt that it was, in 1866, 
 already quite an intense diabetes. His physician at first put him on a strict 
 diet; unfortunately, there is no record of its effect on the glycosuria. Forsell, 
 however, soon found that the strict diet, besides being exceedingly unpleasant, 
 always made him feel ill and weak. Having ascertained the evil consequences 
 of this system, he adopted the opposite extreme, consuming a considerable 
 amount of bread and of vegetables, and every day drinking from 6 to 8 pints 
 of Bavarian beer. " By avoiding diet, watering-places, and medicine, I have 
 kept in very fair health since 1873," Forsell writes in 1883. When Forsell died, 
 he had suffered from most pronounced diabetes for about twenty years. Such 
 a prolongation of life in cases of this kind is extremely rare — much rarer than 
 it is for a gouty person with mild diabetes to live for forty years. Is there 
 any reason for believing that Forsell's life would have been longer or happier 
 if he had lived on meat and fat, without carbohydrate or with a scanty supply ? 
 
 I am particularly anxious not to be accused of approving of Forsell's 
 regime. I am perfectly certain that he might, with advantage, have made some 
 restrictions in carbohydrate — and no one will approve of his enormous consump- 
 
TREATMENT. ,269 
 
 tion of Bavarian beer. The mere fact, however, that a diabetic of this kind can 
 live in fairly good health and do fairly good work for more than twenty years 
 is worthy of consideration, and may afford a foundation for conclusions that, 
 however prudently formulated, are of great practical portent. Professor For- 
 sell's was far from being a good regime, but I feel convinced that if I had to 
 choose for my patients — as a rule, for years — between his regime and an exclu- 
 sion or a severe restriction of carbohydrates, I should act wisely in choosing 
 the former. 
 
 In the mild stage we always have to put a maximum limit upon 
 the daily amounts of carbohydrate. Except in dealing with a cer- 
 tain kind of hypochondriacal patients, we need not trouble our- 
 selves with regard to a minimum limit. In the enormous majority of 
 cases we may feel certain that if the patient does not consume more 
 carbohydrate than we prescribe, he will hardly ever consume less. 
 
 In a large number of cases the rational daily allowance of carbo- 
 hydrate is represented by the maximum that the patient can take 
 without the development of glycosuria. We should never restrict 
 the patient's allowance of carbohydrate below the amount that 
 leaves him free from sugar in his urine, and thus free from any dis- 
 tinct hyperglycemia. Whenever a patient can take the necessary 
 amount of carbohydrates for the maintenance of good digestive 
 action and nutritive equilibrium, without the development of glyco- 
 suria, he is permitted to take that amount. According to my 
 experience, the minimum amount sufficient in the long run for a 
 full-grown person is hardly ever less than 60 grams of carbohy- 
 drate, and is usually somewhat more. On the other hand, it is 
 rarely necessary to give a diabetic patient in the mild stage more 
 than 100 grams of carbohydrate ; neither is he capable of taking 
 more for any great length of time without the development of 
 glycosuria. The rational daily allowance of carbohydrate for pro- 
 tracted periods for a patient in the mild stage thus varies usually 
 from 60 to 100 grams. For reasons mentioned in the preceding 
 chapter, it is well to determine the amount in each case by giving 
 the patient the larger quantity (100 grams) and diminishing it until 
 the glycosuria ceases,* or until the necessary minimum (of about 60 
 grams) for constant use has been determined. 
 
 *We consider the glycosuria practically to have ceased when Nylander's and Feh- 
 ling's solutions react only faintly with a sample of the urine collected during twenty- 
 four hours. 
 
2/0 DIABETES MELLITUS AND GLYCOSURIA. 
 
 If the patient (in the mild stage) continues to exhibit glycosuria 
 when his daily allowance of carbohydrate is restricted to the mini- 
 mum necessary for maintaining good digestive activity and nutritive 
 equilibrium, it is preferable to risk the moderate disadvantages of 
 the slight corresponding hyperglycemia rather than the more serious 
 dangers of digestive disturbances and inanition. The rational daily 
 allowance of carbohydrate varies not only among individuals, but 
 also from time to time in the same individual. Sometimes loss of 
 appetite or of flesh, exacerbation of neurasthenic symptoms, mental 
 inability to submit to some restrictions, force us to make some con- 
 cessions. In cases complicated by gout, the hope, always faint, of 
 bringing about recovery from the diabetes by removing the hyper- 
 glycemia is lost. The chances that the diabetes will remain mild 
 are almost certain, and we are not inclined to be severe, especially 
 as we have no wish to increase too greatly the proteids, and 
 thus to put a strain on the kidneys, and as we need bread to 
 facilitate the ingestion of the necessary amount of fat. The further 
 advanced in age the patient, the less danger there is of his ever 
 reaching the severe stage of diabetes, and we can afford to be 
 more liberal ; in senile cases we never urge severe restrictive 
 measures. 
 
 If, on the other hand, there is reason to believe a case of diabetes 
 to be of quite recent origin, we should always estimate at its full 
 value the increased chance, however small, of perfect recovery by 
 removal of the hyperglycemia, and for a long while we restrict the 
 carbohydrate as much as possible. During healing processes of all 
 kinds, or before an operation, it is also desirable to remove as much 
 as possible the hyperglycemia. Finally, a sudden decline in a 
 diabetic patient's power of assimilating carbohydrate makes a rigid 
 restriction necessary. 
 
 In those cases in the mild stage in which the patient's power of 
 assimilating carbohydrate is too low to permit of the usual diminu- 
 tion of his daily allowance below his limit of assimilation and of 
 the removal of his hyperglycemia there remain several ways of 
 mitigating the hyperglycemia and its effects. 
 
 For this purpose the patient may be advised to take his whole 
 daily allowance of carbohydrate during his first one or two meals 
 of the day ; the physician should not forget to insist that he shall 
 
TREATMENT. 2/1 
 
 at the same time take as much butter as possible with his bread. 
 By entirely excluding or markedly restricting the carbohydrates of 
 the last meal the hyperglycemia also is excluded or restricted 
 during the larger part of the twenty-four hours. The last meal, 
 thus consisting exclusively of animal food, will then necessarily 
 tend to be a light one. The 'German system, with an early dinner, 
 is better for this purpose than the custom prevailing in France, 
 England, and the United States, of taking the heaviest meal in the 
 evening. 
 
 There is still another way of mitigating the hyperglycemia and 
 its effects in those cases in the mild stage in which even the 
 minimum daily allowance of bread and vegetables necessary for the 
 maintenance of digestive activity and nutritive equilibrium cause 
 glycosuria and hyperglycemia. For this purpose periods of exclu- 
 sion or of such severe restriction of carbohydrates are prescribed 
 that the glycosuria, beyond faint traces in the mixed urine, dis- 
 appears. Such periods may be prescribed several times a year ; 
 they ought to last for at least two weeks, but can scarcely ever be 
 enforced for more than four weeks. If loss of weight, neurasthenic 
 symptoms, and digestive disturbances become too marked, we have 
 to shorten these periods, which rarely pass entirely without some 
 of the troubles mentioned. If one prescribes periods of this kind 
 of as long a duration as four weeks, he may with advantage select 
 the summer for one and the winter for another. In the spring and 
 in the autumn the tendency to mental depression, common among 
 diabetics, is more marked, at least in northern climates. 
 
 TJie absolute or severe diet includes all animal food except milk 
 (and its derivative, cheese), with its nearly five per cent, of lactose, 
 and liver, with its variable, but usually small, amount of glycogen. 
 It thus allows all otherwise wholesome parts of niamnials, birds, 
 amphibia (turtles, frogs, etc.), fishes, lobsters, crabs, crazvfish, oysters, 
 etc. It would be unwise and pedantic to exclude from this 
 frugal dietary eggs and butter, on account of the insignificant pro- 
 portion of carbohydrates they contain. Eggs are easily taken, 
 easily digested, and, apart from idiosyncrasies, constitute an impor- 
 tant item in the severe diet. The butter with its eighty-four per cent, 
 of pure fat usually represents among Teutons and Anglo-Saxons 
 the greater part of the fat in the food, and more than is taken in 
 
2/2 DIABETES MELLITUS AND GLYCOSURIA. 
 
 bacon, meat of any kind, lard, olive-oil, milk, cheese, eggs, etc., 
 put together. The butter tastes better, is more easily ingested and 
 digested than most other fats, and has, besides, the great merit of 
 not reminding the diabetic, by any rarity of appearance, of his con- 
 dition. It is therefore somewhat incomprehensible why so many 
 diabetics, except for special indications, are tortured with that un- 
 palatable fat, cod-liver oil. Neither can I understand the superiority 
 of either olive-oil or " lipanin " to butter, which certainly contrib- 
 utes better than anything else to the possibility of ingesting the 
 desirable amount of fat. Unfortunately, few persons are able to take 
 large amounts even of butter without bread. 
 
 It is a most important rule to give the patient with the severe diet 
 the advantage of as great a variety of food as possible, and to 
 include different kinds of meat, birds, fish, and eggs in his dietary. 
 When his digestive power is weak, he often derives considerable 
 benefit from the modern condensed forms of proteid food. I have 
 especially often seen good effects from the use of " somatose, " 
 which is rich in albumoses. 
 
 But whatever is done, the patient will have a trying time during 
 periods when an exclusively animal diet is demanded and it is often 
 possible, even during periods of rigid restriction, considerably to 
 mitigate his dietetic difficulties by introducing into his food small 
 quantities of those vegetables that contain comparatively slight 
 amounts of carbohydrates. The German ^' sauerkraut, ^^ the French 
 " choicer oute," when well fermented, does not contain more than a 
 few tenths of a per cent, of carbohydrate. String-beans, picked 
 quite young and before the development of their seeds,* contain 
 much inosite, but only traces of carbohydrate. Lettuce, cucumbers, 
 and in many cases the leaves of spinacli may also often be taken in 
 small quantities by patients in an advanced mild stage, without 
 causing the appearance of more than faint traces of glucose in their 
 urine. The mitigation that such an addition to the dietary affords 
 during periods of severe restriction is often underrated by the 
 physician, but never by the patient. 
 
 *When the seeds are developed, string-beans contain several per cent, of starch and 
 sugar, and they no longer constitute an appropriate article of food during periods of rigid 
 dietetic restriction. 
 
TREATMENT, 2/3 
 
 During periods of anything like rigid restriction of carbohy- 
 drates, the diabetic patient has to choose between two substitutes 
 for bread. The one is the genuine, tasteless, expensive, and almost 
 worthless "gluten-bread," of which I have entirely abandoned the 
 use. The other substitute for bread is the "bread " made accord- 
 ing to Pavy's and Seegen's prescriptions, of eggs, butter, and 
 almonds deprived of their sugar. The almond bread which, as 
 bought in shops, usually contains starch, ought to be baked at 
 home, according to the original prescription,* and can even then, 
 during periods of severe restriction, be allowed only in small 
 amounts. 
 
 The most important question of bread, which must be treated at 
 some length, leads me to the subject of the more liberal diabetic diet, 
 in which at least half, often more, of the allowance of carbohydrate 
 is given in the form of bread. All proper bread certainly contains a 
 large percentage of starch, but the human digestive apparatus is too 
 accustomed to this kind of food to be able to get along entirely with- 
 out it. The bread, besides its other nutritive value, also facilitates the 
 ingestion of fat, which, from its high caloric value and its properties 
 of not increasing either the hyperglycemia or the work of the kid- 
 neys is so advantageous to diabetics. In discussing the question 
 of bread with a diabetic patient the physician should never fail to 
 point out its merit as an excellent vehicle for fat, and impose upon 
 him the necessity of always taking butter, or butter and cheese, 
 with his bread. 
 
 The impossibility of living without bread and the fear of its 
 starch for diabetics have led to many attempts to produce for 
 these patients something that might possess the advantages of 
 ordinary bread without supplying the much-dreaded starch. I be- 
 lieve this problem to be as impossible of solution as the squaring 
 of the circle or as the problem of perpetual motion. It is the 
 
 * The powder of one-quarter pound dried and finely pulverized almonds is put in a 
 linen bag and cooked a quarter of an hour in water with some drops of vinegar, then 
 well kneaded with three and a half ounces of butter and two whole eggs. Then the 
 yolks of three other eggs and some salt are added to the mass. The whites of the three 
 eggs are well beaten and also added, whereupon the whole is put in a buttered fonn and 
 baked. When prepared in this legitimate way, without meal or rice, the bread unfortu- 
 nately often lacks the proper consistency. 
 
2/4 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Starch in the bread that chiefly gives it its good taste and other 
 dietetic merits, and that diabetics, as well as others, need. Every- 
 one of the many ^' breads for diabetics'' suffers from either of two 
 faults : it contains much starch or it does not taste like real bread, 
 and is a substitute for it in almost nothing but name. Further, dis- 
 honest speculation has furnished the market with a great number 
 of preparations whose real qualities are concealed beneath false or 
 ambiguous assertions. At this moment there is before me a cir- 
 cular from a baker, accompanied by a sample of his aleuronat-bread, 
 — the former couched in such terms as to make the reader believe 
 that the ready-made bread contains only the comparatively few per 
 cent, of starch of the original aleuronat, while in reality it contains, 
 at the very least, four times that amount. Patients easily persuade 
 themselves that they may consume any amount of any bread that 
 is said to be especially prepared for diabetics. This is the case 
 even with the ordinary Graham bread, which contains about forty 
 per cent., by weight, of pure starch, or nearly eighty per cent, of 
 what is contained in the same quantity of white bread. The prep- 
 arations with a small amount of starch or with none at all are 
 tasteless, indigestible, and expensive. Upon the whole I am of the 
 opinion that the "breads for diabetics" have profited the bakers, 
 but injured the diabetics. 
 
 I would advise physicians to allow their diabetic patients, except 
 during periods of rigid restriction of diet, daily a fixed amount of 
 the kind of ordinary bread that they prefer. It is only important 
 to limit the daily allowance either by weighing it every morning or 
 by buying it in some customary form containing practically a fixed 
 and definite quantity. If the measurement of the quantity is left to 
 the patient's eye, it will not be long before the urine will show that 
 he has taken far too much of it. 
 
 Graham bread tastes well, but contains about forty per cent, of starch. 
 Bran-bread, a la Prout or Camplin, tastes badly, otherwise it contains too 
 little bran and too much starch. Bread may be baked from inulin, a substance 
 found in the roots of certain Compositae (inula, taraxacum, dahlia, etc.). 
 This bread, producing levulose and not glucose, causes much less glycosuria 
 than starch, but it has a poor taste. Soya-bread, from the Japanese Soya his- 
 pida, demands twenty per cent, of starch to render its taste at all pleasant. 
 Dika-bread, made from owala-seeds or the fruits of the African Peiitaclethra 
 macrophylla (30.5 per cent, proteids and 45.18 per cent, of fat), is still unknown 
 
TREATMENT. 2/5 
 
 to me, but does not seem to have made much progress as a food for diabetics. 
 The meat-bread oi Baron Liihdorf contains much starch. In describing its taste 
 as pleasant, the Baron does so without frenzied protests, only by virtue of the 
 proverb " de gustibus non est disputandum." Genuine gluten-bread is per- 
 fectly tasteless ; what is called gluten-bread generally contains three-fourths 
 as much starch as an equal weight of ordinary white bread. As to " florador," 
 " semolina," and other preparations of like kind, they differ from ordinary 
 bread chiefly in their price. 
 
 So far as I know, there are, among the enormous number of " breads for 
 diabetics" at present, only two of those mentioned that really deserve the 
 attention of physicians — viz., Pavy-Seegen's almond-bread, and Hundhausen's 
 aleuronat bread. I sometimes, as already mentioned, during periods of rigid 
 diet make use of almond-bread, which, prepared in the proper manner, contains 
 only insignificant quantities of carbohydrates. On boiling with the addition of 
 a few drops of acetic acid to the water, the greater part of the nine per cent, of 
 sugar and dextrin is removed, and twenty-four per cent, of emulsin and fifty- 
 four per cent, of fat are left. For the market, however, the bread is often baked 
 with the addition of some flour to give better consistency. It is not easy to 
 digest ; it is expensive ; and it has a dry, unsatisfactory taste ; but it is capable 
 of serving the purpose already mentioned. Aleuronat consists chiefly of vege- 
 table proteids. Hundhausen's preparation contains about eighty per cent, of 
 that substance, 8.7 per cent, of water, and eight per cent, of carbohydrate. By 
 mixing it with wheat-flour one may produce a bread that contains less starch 
 than ordinary bread, and that tastes the better the more wheat-flour it contains. 
 If Hundhausen's aleuronat flour is mixed with an equal weight of wheat-flour 
 (the minimum amount of the latter necessary to make a fairly pleasant tasting 
 bread), the whole mixed dry meal contains 45.1 per cent, of proteids, 41.35 per 
 cent, of carbohydrate, and 11.05 P^r cent, of water. The bread will thus con- 
 tain nearly as much carbohydrate as it does proteid ; it tastes much less well 
 and is much more expensive than ordinary bread. Its merit is that it contains 
 less carbohydrate than ordinary bread — not that it contains vegetable proteid, 
 which tastes less well, and is much less digestible than animal proteid, as it 
 leaves as much as twenty-five per cent, undigested in the feces. Ebstein 
 recommends the unmixed aleuronat flour for sauces and for the grilling of 
 meat ; about twice as much of it is taken for these purposes as of wheat-flour. 
 
 It is not to be denied that a diabetic patient may derive some advantage 
 from using bread made of as much of aleuronat and as little of wheat-flour as 
 will do for him in the long run, thus obtaining a larger amount of bread, as 
 compared to its quantity of starch, as a vehicle for cheese and butter. Even 
 aleuronat bread, in some respects the best of all " breads for diabetics," has the 
 one merit common to them all — i. e., it is not absolutely necessary. If the 
 physician wishes to prescribe this special bread, he had better have his patient 
 buy Hundhausen's original aleuronat, and bake the bread at home. This is the 
 only easy way of ascertaining its percentage of carbohydrate. 
 
 Diabetics, like other persons, know better what they want in the 
 way of food than with regard to anything else. They almost all 
 
2/6 DIABETES MELLITUS AND GLYCOSURIA. 
 
 want not only bread, but also potatoes. Now, there are many things 
 that contain more starch than potatoes ; but the cooked potatoes 
 containing at the least fifteen per cent, of starch and little besides 
 but water, we ought to persuade our diabetic patients to do without 
 it, as our ancestors had to do a couple of hundred years ago. When 
 the power of assimilation is active, or when a certain amount of 
 hyperglycemia may be tolerated, we may allow a small quantity of 
 potatoes, always insisting upon the amount being weighed, and upon 
 their being used as a vehicle for butter, in which capacity they fulfil 
 a most useful purpose. 
 
 Attempts to find a substitute for potatoes have not been much 
 more successful than those to find a substitute for bread. The 
 tubers of Heliantlms t7iberosus L., the Jerusalem artichokes, by 
 reason of the fact that they contain, when fully developed,* very 
 Httle starch or glucose, but chiefly inulin and levulose, give rise in 
 diabetes to a comparatively slight glycosuria, and the plants are not 
 rare in kitchen-gardens even as far north as Stockholm, and over 
 the greater part of Europe. Jerusalem artichokes are, to my taste, 
 far inferior to potatoes, but they are certainly of some value to dia- 
 betics, and, like potatoes, they constitute a good vehicle for butter. 
 The tzibers of Stachys affinis are chemically similar to Jerusalem arti- 
 chokes ; but, at least in my country, they are quite small, and offer 
 no advantages over the latter vegetables. 
 
 With a more liberal diet one may give those vegetables that contain 
 only a small amount of starch, but which contribute largely to 
 the necessary variety and to the maintenance of the appetite. From 
 the list at the end of this book it will be found that we have chiefly 
 to keep to lettuce, sphiach, cucumbers, young string-beans, celery, 
 asparagus, radishes, mushrooms. Tomatoes, the different kinds of 
 cabbage, almonds, and nuts,^ and some fruits {cranberries, straivber- 
 ries) may often be allowed in small quantities. " Sauerkraut'' has 
 already been mentioned as almost always admissable when well 
 fermented — unfortunately, many patients, after a short period of 
 warm appreciation, acquire a loathing for it. We almost constantly 
 
 * When younger, the tubers contain a considerable amount of starch and glucose, 
 f Hazelnuts, walnuts, peanuts, Brazilian nuts, cocoanuts, are permitted, but not 
 chestnuts. 
 
TREATMENT. 2// 
 
 exclude everything containing more than eight per cent, of carbo- 
 hydrate, except bread and potatoes, which must be weighed. Some- 
 times, however, we allow a large baked apple at breakfast for the 
 sake of its aperient quality. 
 
 Of liquids, tea and coffee with saccharin or crystallose (see below) 
 or levulose, or without any corrective at all, are permitted during the 
 earlier part of the day except during periods of severe diet. A cup 
 of tea of ordinary size contains about one gram, a cup of coffee about 
 two grams, of carbohydrate. I constantly interdict the use of both 
 of these in the evening on account of their disturbing influence on 
 sleep, which is, at best, not very sound in diabetic patients. A 
 glass of milk, or some alkahne water, or even a weak grog is a better 
 ingredient of the patient's supper or late dinner. 
 
 Moderate quantities of red wines, European or American, may 
 be allowed ; of white wines those from the Rhine are the best. 
 
 Among alcoholic Hquors, however, none is better for the dia- 
 betic patient than cognac, brandy, whisky, gin, and similar drinks. 
 These must be taken diluted, best with some carbonated mineral 
 water, and the amount of alcohol they contain must not in the 
 twenty-four hours exceed one-fourth, at the very utmost one-half, 
 of a gram per kilo of bodily weight. 
 
 All sweet wines, — champagne, port, Madeira, sherry, marsala, 
 etc., — " liqueurs," and punches are forbidden under all circum- 
 stances in cases of diabetes. 
 
 It is also well to interdict absolutely porter, beer, and ales of all 
 kinds. These contain a good deal of carbohydrates, are generally 
 drunk in considerable quantities, if drunk at all, and are easily 
 dispensed with. 
 
 The usefulness of milk * for the diabetic patient is more difficult 
 to decide, and to some extent is a matter of individuality. Milk 
 
 * Some physicians forbid milk in all cases of diabetes — a position that may possibly 
 be defended. Dr. Donkin has been unfortunate enough to recommend it skimmed as an 
 exclusive food in cases of diabetes. This prescription can not possibly be defended, even 
 if it did not include the skimming, which deprives the diabetic of a large part of the fat 
 and leaves the carbohydrate. I have myself never prescribed the " Donkin cure," but I 
 have several times seen it prescribed by others, with its necessarily signally bad results. 
 An adult person requires about six liters of skimmed milk in order to secure the necessary 
 amount of calories. This gives him nearly three hundred grams of lactose, and does 
 not, in other respects, constitute the best kind of diet. 
 
2"]% DIABETES MELLITUS AND GLYCOSURIA. 
 
 contains nearly five per cent, of lactose, and can not be allowed at 
 all during periods of rigid restriction of the diet ; it ought never to 
 be allowed in large or unlimited quantities in any case of diabetes. 
 In all severe cases, however, and in many mild cases one may allow 
 200 or 300 cu. cm. of unskimmed milk to be taken at supper. 
 The sour milk, much in use during the summer in the north of 
 Europe, in which the lactose is in large part changed into lactic acid, 
 forms a most pleasant, wholesome, and popular article of food for 
 the diabetic patient. At present there are other methods of remov- 
 ing the greater part of the lactose from the milk ; when this can 
 be done, the greatest objection to the use of milk in cases of diabe- 
 tes (not belonging to the class of persons in whom dyspeptic symp- 
 toms arise in consequence) is removed. 
 
 Diabetic patients often are very thirsty and consume considerable 
 quantities of drinking water. This is partly a result of the increased 
 amount of sugar and of toxins in the blood, of nature's attempt to 
 eliminate these toxins as far as possible, and of the difficulty in 
 providing the tissues with the necessary supply of water from the 
 strongly sacchariferous blood. There is nothing so absurd that it 
 can not be prescribed, and there are physicians who advise their 
 diabetic patients to restrict themselves in the drinking of water. If 
 this is done at all extravagantly, it tortures the patient, increases the 
 diabetic and other deleterious substances in the blood, changes the 
 working conditions of the heart, increases the dangers from too con- 
 centrated secretions (gall-stones, urinary concretions, etc.), acts 
 unfavorably on the nervous system, and in severe cases multiplies 
 the danger of coma. The drawbacks of polydipsia are the disten- 
 tion of the stomach and the increase in the work of the heart. 
 Both of these effects are greatly diminished by the avoidance on the 
 part of the patient of drinking large quantities at once. Diabetic 
 patients should be advised to drink as much water as they like 
 during the twenty-four hours, but to take the whole quantity in 
 frequent small portions. Instead of ordinary water they may with 
 advantage sometimes drink carbonated alkaline mineral waters. If 
 the polydipsia is very marked, the patient may be spared a couple 
 of hundred calories by heating the drinking water. 
 
 Different substances on account of their sweet taste have lately 
 been used as substitutes for suear in cases of diabetes. The most 
 
TREATMENT. 2/9 
 
 common of these is (Fahlberg's) saccharin (=anhydro-ortho-sulph- 
 amin-benzoic acid). This substance, taken in amounts of a few 
 centigrams every day, in the form of the small tablets to be had of 
 druggists, sweetens tea and coffee or anything else with which it is 
 used. I am not certain that I have ever observed the dyspeptic 
 effects dwelt upon by Bernstein, v. Jaksch, and others. Small 
 amounts seem harmless in this respect. The use of saccharin, 
 however, causes the appearance of a reducing substance in the 
 urine, and from this fact alone some influence on the kidneys might 
 be suspected. The taste of saccharin is not pleasant, neither is the 
 use of a sweetening substance very important to the patient ; most 
 persons become indifferent in this respect. The antizymotic quality 
 of saccharin is too weak to give it any distinct advantage in ordi- 
 nary small amounts. I usually tell patients of saccharin and 
 advise them to take as few tablets as possible daily ; they then gen- 
 erally use it for a time, and then without regret abandon it. Sticrol 
 or diilciii (=paraphenetol-carbamin) is in large doses a poison 
 (Kossel, Aldehoff). I have not used it, though several writers 
 affirm that they have seen no bad effects from small amounts. I do 
 not know of crystallose more than its appearance and its taste, which 
 latter is more pleasant than that of saccharin. Mannite causes 
 diarrhea. 
 
 Levidose has distinct nutritive value, increases the glycosuria 
 but moderately, and has no other bad effects. It is, however, still 
 too expensive for poor patients, and some persons take a dislike to 
 it. 
 
 An enormous and a significant number of "specific " and other 
 remedies have been used in the treatment of diabetes. Upon the 
 whole, too much importance has been attached to any diminution 
 in the hyperglycemia and glycosuria, however transitory, and 
 too little consideration has been given to the first duty of every 
 physician — viz., not to do harm. It seems almost incredible that 
 there are physicians who recommend, e. g., uranium nitrate for the 
 purpose of decreasing the glycosuria, and it seems certain that even 
 minimum quantities of this poison with its violently irritating 
 effects on the alimentary canal and on the kidneys must in the 
 course of an hour do more harm than considerable hyperglycemia 
 
2 So DIABETES MELLITUS AND GLYCOSURIA. 
 
 will in the course of a week. The "specific" influence of many 
 drugs may probably be only imaginary, and the diminution of 
 hyperglycemia and glycosuria a result of impaired digestion. Even 
 if this " specific " influence is real, its cost may easily be too great, 
 and I believe it to be good advice to recommend the administration 
 to diabetic patients of only such drugs as can certainly be taken for 
 some time without serious detriment. Even the best "specific" 
 remedies for diabetes are but very uncertain and weak in any 
 " specific " influence, and the longer one has the opportunity of 
 watching the effects of extolled remedies of this kind, the more 
 skeptical does he become of their great value. 
 
 Of some real, though not of great, specific value is opitan, which 
 has been used in the treatment of diabetes at least since the begin- 
 ning of the nineteenth century. In many cases — but not in all — it 
 distinctly diminishes the glycosuria and, what I consider to be much 
 more important, it improves the patient's general somatic and mental 
 state. I prescribe it when I find a rapid diminution in the power 
 of assimilation and during periods of nervous exacerbations ; under 
 the latter condition it is really of decided value. One begins with 
 small doses, increases them to quite considerable ones (from 8 to lo 
 centigrams — ly^ io ly^ grains — of pure opium per day for an 
 adult), and after some time, perhaps days or weeks, gradually 
 diminishes the dose, and finally withdraws the drug altogether. It 
 is advisable never to use opium for any great length of time. 
 
 As to codein, and still more as to niorpliin, these are in every re- 
 spect much less valuable in cases of diabetes than is opium. Con- 
 sidering the great danger to the patient of becoming addicted to 
 them from the prolonged daily use of any of these remedies, — cer- 
 tainly one of the worst of human miseries, — I think it the physician's 
 bounden duty, under all conditions, to reserve them for the mitiga- 
 tion of transitory, severe pains or of perfectly hopeless conditions. 
 
 When coma is present or there is imminent danger thereof, the 
 administration of narcotic or hypnotic remedies is avoided as much 
 as possible. 
 
 Next to opium, arsenic may, perhaps, be mentioned as having some 
 specific value in the treatment of diabetes. In some cases it does 
 somewhat, though never to any large extent, cause a diminution in 
 the glycosuria ; it may, perhaps, counteract the conversion of glyco- 
 
TREATMENT. 28 1 
 
 gen into glucose and favor its transformation into fat in the liver, 
 where, as has been mentioned, it in some way causes a diminution 
 in the glycogen. It is, besides, as is well known, a splendid tonic, 
 and in diabetic patients who are also anemic it may be given with 
 great advantage. In my opinion one had better adhere to small 
 doses, beginning with one and slowly increasing to three or four 
 drops of Fowler's solution thrice daily, after meals, or giving a 
 corresponding amount of arsenic in pills (from gr. yi^ to gr. ^). 
 After a couple of weeks the dose is slowly diminished. One may, 
 in cases of diabetes, often with advantage combine arsenic with 
 opium. 
 
 The alkaline salts, especially sodium bicarbonate, have been 
 used in the treatment of diabetes for at least since the time of 
 Willis in the seventeenth century. They are believed to diminish 
 the glycosuria, either by increasing the combustion of sugar in the 
 tissues or by facilitating the storage of glycogen and counteracting 
 the formation of glucose in the liver. The alkaline salts have dif- 
 ferent merits (see below) ; but their power of diminishing glycosuria 
 is exceedingly slight, and, unless large doses are given, conscien- 
 tious investigation often fails to discern any decrease in the amount 
 of sugar excreted in the urine. Mialhe administered twenty grams 
 of sodium bicarbonate a day, with the effect of diminishing the 
 glycosuria somewhat ; but such doses give rise to gastrointestinal 
 disorders and weaken the patient. Richardiere gives it in doses of 
 from four to ten grams a day for months ; but only periodically, 
 and never in cases of pancreatic diabetes or in any case complicated 
 by tuberculosis or by marasmus. Sodium bicarbonate is given 
 chiefly in mineral waters, and then only in doses of a few grams 
 a day, and the enormous doses are used by most physicians only 
 in the presence of coma, or when there is manifest danger of it. 
 The salts of tartaric, citric, phosphoric, lactic, benzoic, salicylic, hip- 
 puric, and boric acids are also used, though far less than sodium 
 bicarbonate. 
 
 Aminonia, especially as carbonate and citrate, is also used, and 
 has the merit of stimulating and of increasing the perspiration. 
 Bouchardat recommends potassium carbonate and sodium and potas- 
 sium tartrate for their powerful effect in eliminating uric acid. 
 Clemens' solution contains potassium carbonate, arsenic, and bromids. 
 19 
 
282 DIABETES MELLITUS AND GLYCOSURIA. 
 
 Calcmni is for the moment and in some places popular in the 
 treatment of diabetes. Grube gives his patients, four times a day, at 
 meals, large doses of a mixture of seven parts of calciiivi carbonate 
 and one part o{ calcium phosphate. These salts do not influence the 
 glycosuria, but they are said to improve the general state and to 
 facilitate the ingestion of fat. Robin uses calci?iin phosphate and 
 glycerin. Those who give their diabetic patients large quantities of 
 milk often add calcium carbonate. Magnesium hydrato-carbonate 
 and calcined magnesia are also used, especially in cases with hyper- 
 acidity of the stomach and constipation. Viau-Grand-Marais recom- 
 mends strontium bromid ; Martineau gives litlmim carbonate (with 
 arsenic). 
 
 The alkaline and alkaline-saline spas are visited by large numbers of dia- 
 betics. Carlsbad, Vichy, and Neuenahr enjoy at present the greatest repu- 
 tation for their beneficial influence on diabetes. As a student of diabetes and 
 as a practising physician in Carlsbad I have made it my purpose to acquire as 
 correct an idea as possible of what may be reasonably expected for a diabetic 
 patient from a sojourn of some weeks at one of these health-resorts. I consider 
 it as great an advantage for these resorts as for the medical profession and for 
 the patients that no false pretensions are supported and consequently no dis- 
 appointments incurred, and that, on the other hand, the knowledge of the good 
 results that undeniably are in many cases to be obtained is spread as far as 
 possible. 
 
 As for the glycosuria, Carlsbad and Vichy water, and doubtless, also, Neuen- 
 ahr water in the moderate and rational amounts recommended at present, 
 which scarcely ever go beyond a liter a day, have no appreciable influence, or 
 one that is extremely slight and uncertain.* 
 
 Does this mean that a course of treatment at Carlsbad, Vichy, or Neuenahr 
 has no value at all for diabetic patients ? By no means. I feel safe in saying 
 that most diabetic patients, especially in the mild stage, whom I or others 
 have had occasion to observe in Carlsbad, have derived as considerable a 
 
 * I protest, a priori, against any denial of this fact not founded on pure experimentation. 
 I pass entirely over the naive reports on the influence of mineral waters on the glycosuria 
 resulting from a simultaneous restriction of carbohydrates — they are not worth discussing. 
 Neither will it do first to determine the supply of carbohydrate, and the amount of glucose 
 excreted with the patient at home and occupied with his daily work, with its strains and 
 emotions, and then to make the same determinations at the spa with the patient at leisure 
 and subjected to the effect of other therapeutic agents than the mineral water. The 
 experiment requires exact determinations of carbohydrate and glycosuria during two not 
 too short periods, the one with and the other without mineral water, but both otherwise 
 under as nearly similar circumstances as possible. Any one that undertakes the consider- 
 able amount of work required in such an experiment will find that the glycosuria, 
 
TREATMENT. 283 
 
 benefit from their sojourn there as might be expected by any reasonable person. 
 [We know that most laymen, and even some physicians, are not reasonable.] 
 I do not consider the mineral water at Carlsbad, excellent as it is, to be the 
 only or even the first therapeutic resource of the place. Still, the water has a 
 good influence on dyspeptic symptoms, which are common in diabetic patients, 
 as they are in others ; it also has a good influence on the constipation, which is 
 equally common. It increases some of the secretions, — diabetic patients are, 
 during its use, often less troubled by dryness of the mouth, — and I believe that this 
 influence on the bile is of benefit in many cases. I am also willing to acknowl- 
 edge the probability of some beneficial influence on the liver in other respects, 
 and that an enlarged and tender liver becomes sometimes, under the use of 
 the mineral water, smaller and less sensitive to pressure. Finally, I will not 
 deny a favorable influence on gouty symptoms, which are very common in 
 diabetics of the florid type in the mild stage of the dystrophy. The alkaline 
 water must also have some slight neutralizing effect on the acidosis in the 
 severe stage, though, according to my opinion, only a comparatively small 
 number of patients in this stage do well in undertaking a journey of any length. 
 It is, fortunately, not necessary to enter here into details with regard to the 
 influence of the mineral water on the metabolic processes ; but if it accom- 
 plishes only what I have already acknowledged, it is well worth the drinking. 
 
 The patient's absence from home and its cares, his rest from intellectual 
 work and mental worry, the hygienic and dietetic discipline, so much more 
 easily enforced in a health-resort than anywhere else, and the other therapeu- 
 tic resources available in such a place, are, in my opinion, together of much 
 greater value than any mineral water, and it is these considerations that make 
 up the enormous difference between a " cure " at home and the " cure " at a 
 watering-place. The water, as it bubbles from the springs, or is contained in 
 well-corked and well-preserved bottles, is, as every sensible person can under- 
 stand, exactly the same. 
 
 As I attach less importance to local mineral water than to other therapeutic 
 agents, it is evident that in my choice between different health-resorts I shall 
 be influenced less by the mineral water itself than by other circumstances, some 
 of an individual and some of a local nature. 
 
 There is, unfortunately, a single feature common to almost all advice in this 
 respect recorded in the literature — viz., one always finds that the adviser 
 
 cceteris paribus, with or without the use of mineral water, remains the same, or that the 
 variations are no greater than they are without any appreciable external change whatever. 
 Even in cases of simple glycosuria one finds with the use daily of a liter of mineral water 
 that a faint trace of sugar, just large enough to cause a distinct reaction, remains as it 
 showed itself before the use of the mineral water. In the different stages of diabetes one 
 will arrive at the same results, though there may often remain some doubt as to the cause 
 of small variations in the excretion sometimes observed even under apparently perfectly 
 similar circumstances. This will be the case whether the mineral water is di-unk imme- 
 diately at the springs or from bottles ; if it were not, who would undertake to explain 
 reasonably any possible difference? Kiilz's and all other serious investigations on this 
 subject have led to the same results as my own. 
 
284 DIABETES MELLITUS AND GLYCOSURIA. 
 
 recommends, with rare exceptions, the sending of patients to the health-resort 
 in which he is personally interested and is engaged in practice. The late Dr. 
 Schmitz, who practised in Neuenahr, stated that, in order to avoid debilitating 
 the organism, patients had better be sent to Neuenahr rather than to Carls- 
 bad, whose waters, according to Schmitz, contain rather large amounts of 
 sodium sulphate ; or to Vichy, where waters were said to contain rather large 
 amounts of sodium bicarbonate. As it is always advantageous not to debili- 
 tate the organism, these statements seem to mean that one must never send 
 patients to Carlsbad or Vichy, but always to Neuenahr — and presumably (as 
 long as he lived) to Dr. Schmitz. The French have no great regard either for 
 Neuenahr or for Carlsbad, which latter place they, by the way, often believe to 
 belong to Germany. " II n'y a lieu d' essayer Carlsbad que dans les cas ou 
 une au deux cures a Vichy n'auraient pas donne de resultats satisfaisants." 
 The physicians of Carlsbad, on the other hand, think Vichy good only for 
 amusement, and smile at mention of the 0.77 gram of bicarbonate which is 
 the essential ingredient in a liter of the " Augustenquelle " in Neuenahr, and 
 affirm that this latter place is dangerous for visitors on account of the risk 
 of death from "the blues," and that their own place, in point of therapeutic 
 resources of all kinds, is the first health-resort that is, or was, or ever will be. 
 
 I do not intend to offer like recommendations. I find it a difficult task to 
 decide which of these superstitions is the sillier : the one that ascribes such a 
 debilitating effect to the small quantities of alkaline sulphates, carbonates, and 
 chlorids in Carlsbad,* or the one that attributes such wonderful effects to those 
 salts or to the sodium bicarbonate at Vichy or Neuenahr ; and I am willing at 
 once to acknowledge that many diabetic patients can derive benefits from a 
 " cure " at any one of the three places named. I would, however, advise 
 against sending thither patients in constant danger of coma, or suffering from 
 tuberculosis, marasmus, or advanced arteriosclerosis, organic heart disease, or 
 extreme senility. Fully developed mental disease also constitutes a contra- 
 indication. 
 
 The seeds of the Indian plant Syzyghun jambulanwn really in 
 many cases diminish glycosuria ; in other cases they seem not to 
 have the slightest influence in that direction, whether the fluid ex- 
 tract or the powdered seeds are used. Lewaschew administered 
 from fifteen to thirty grams of the powdered seeds. I generally 
 have given no more than ten grams, and have not observed any dys- 
 peptic or other detrimental results. Fichtner saw the glycosuria 
 increase after the use of the drug. Lepine and Barral believe that 
 it increases both the production and the consumption of glucose. 
 
 * The notion existing among laymen and, in some degree, also among physicians of 
 the debilitating influence of a course of treatment at Carlsbad owes its origin to the 
 absurd system prevailing several decades ago in this Bohemian watering-place of giving 
 patients enormous doses of the mineral water and of starving them half to death. 
 
TREATMENT. 285 
 
 Weil introduced the leaves of Vacciniuin myrtillus L. (blue- 
 berries) in the therapeutics of diabetes. The twigs, with the young 
 leaves, are collected early in summer, when the bushes are in 
 bloom. An infusion certainly causes diminution in the glycosuria ; 
 but at the same time it causes distinct dyspeptic disturbances. I 
 have also heard patients complain of dyspeptic derangement after 
 the use of Jasper's pilulae myrtilli, and I have of late entirely ceased 
 to use preparations of Vaccinuun myrtilliis L. 
 
 Antifebrm, antipyrin, phenacetin, and exalgin have been recom- 
 mended by French and other writers as " specifics " in cases of dia- 
 betes. I should not prescribe any of these substances for any length 
 of time. For the sake of the experiment, however, I gave one of 
 my patients with an unvarying amount of glucose in the urine 
 phenacetin at different times, and always with a distinct increase in 
 the glycosuria. Lepine and Barral believe that antipyrin dimin- 
 ishes both the production and the consumption of sugar. Even 
 though it causes diminution in the glycosuria in cases in which 
 there is increased production of glucose in the liver, I consider the 
 patients better off without antipyrin or related substances. 
 
 Quinin was used by Dobson more than a hundred years ago, and 
 it is still recommended as a "specific" by Worms and others. It 
 undoubtedly has a good influence in cases of glycosuria or diabetes 
 due to malaria, of which several reliable instances have been placed 
 on record. In other cases of simple glycosuria and diabetes I have 
 failed to observe any influence on the excretion of sugar. 
 
 The salts of broniin are excellent and comparatively innocuous 
 remedies, and of great value in the presence of some neurasthenic 
 disorders on account of their sedative action ; and they are often 
 used in the treatment of diabetes. I have found it most advan- 
 tageous to give them only once a day, in the evening, but then in 
 rather large doses — not less than two grams. I prefer sodium 
 bromid to potassium bromid. Neither the one nor the other salt 
 exhibited any influence whatever on the excretion of glucose in a 
 number of cases studied from this point of view. 
 
 Among vegetable " nervines," valerian is the most recommended 
 and is used especially often in France. It is said chiefly to diminish 
 the polyuria. Bouchard administers ten grams or more of the 
 
286 DIABETES MELLITUS AND GLYCOSURIA. 
 
 extract per day; Lecoche from 0.30 to 0.50 gram; Dreyfus- 
 Brisac from three to four grams with opium. 
 
 Cantia agra is used in America, but I know nothing of its value. 
 
 Potassium iodid is used in the treatment of diabetes, as it is also in that of 
 most other diseases. In some cases of diabetes complicated by syphilis I 
 failed to observe any effect upon the glycosuria, even after the administration 
 of large doses. 
 
 Sampson recommends potassium perinanganate by the mouth, in small 
 doses, especially for anemic or lymphatic diabetics. Some French physicians 
 believe that they have attained " de grands succes curatifs " with this remedy. 
 
 Potassium bichlorate and potassium chlorate have also been used in the 
 treatment of diabetes, and have shown their uselessness in this respect. 
 
 Cantani, earlier in his career, praised /a^/zir acid'vsx the treatment of diabetes. 
 It causes dyspeptic symptoms. 
 
 Glycerin, introduced in the fifties by Basham, was for a time much used as 
 a nutrient, chiefly on account of Schultzen's theory of diabetes. It is now 
 almost abandoned, less because Kiilz proved that it somewhat increases the 
 glycosuria than because it causes gastro-intestinal catarrh. So much has been 
 written on the subject that I feel unwilling to add more. If any one should be 
 anxious to give it or to take it, he had better do so according to the following 
 (French) prescription : Fifty grams of glycerin, one liter of water, five grams of 
 citric acid ; to be drunk in the course of the day. 
 
 Bouchardat tried and gave up inhalations of oxygen. Benzi trusted to 
 ozone. Richardson produced with oxygen hydrogen dioxid in water and gave 
 of this solution one-half ounce three times a day. 
 
 I must not omit to mention the different ferments that have been recom- 
 mended on various grounds in the treatment of diabetes. Pepsin does no 
 harm. Yeast (of beer) would appear likely to do so in some degree, but 
 according to Dr. Cassaet its action is fperfectly marvelous, and the agent 
 ought to be blessed by every diabetic patient. " Son etat general se releve, 
 son appetit renait, ses forces augment, ses donleurs s'attenuent son poids 
 enfin se modifie," which last means that the bodily weight may increase from 
 three to eight kilograms in a fortnight. I have never used yeast in this way, 
 and I feel certain that I never shall. Lepine saw the glycosuria diminish after 
 subcutaneous injections oi diastatic ferment {see below). 
 
 Robin has devised a system of giving specifics. He begins by administer- 
 ing antipyrin, one gram twice a day, for five days. Even he considers antipy- 
 rin contraindicated by anorexia, albuminuria, marasmus, and autophagy, and 
 to be useful chiefly in mild cases (" diabete gras "). Then for a fortnight 
 he gives a mixture of arsenic, codein, and lithium [R. Sodii arsenitis, gm. 
 0.002; Lithii carbonatis, gm. 0.12; Codeinge, gm. 0.02; Pulvis radicis Vale- 
 rianae, gm. 0.25; Extracti chin, sin., gm. 0.40. One such powder is to be 
 taken at breakfast and one at dinner, daily] , with an interval of several days in 
 the middle of this period. The treatment is concluded with opium, belladonna, 
 valerian, quinin, bromids, alkalies, and cod-liver oil. " Quid bonum faustum- 
 que sit populo Gallico ! " 
 
TREATMENT. 28/ 
 
 Theobroinin has been used by different clinicians. Lindner's " glyco- 
 solvol," put on the market as a specific in the treatment of diabetes, consists of 
 theobromin-trypsin oxypropionate. 
 
 Besides the substances mentioned, the greater number of the drugs of vege- 
 table or mineral origin found in the Pharmacopeia have been used in the 
 treatment of diabetes. As I consider all of these as worse than useless, I shall 
 only mention some of them by name : Phosphorus, iodoform, uranium 
 nitrate, alum, thallium sulphate, the salts of copper, the mineral acids, carbolic 
 acid, creosote, thymol, benzosol, salol, naphtalin, balsam of copaiba or of 
 Peru, tannic acid, rhatany, catechu, cubebs, piperazin, camphor, colchicum, 
 santonin, belladonna and atropin, jaborandi leaves and pilocarpin, secale cor- 
 nutum, and ergotin. The last remedy recommended, so far as I know, is 
 methylene-blue (Pierre-Marie, Le Goff ). 
 
 Dismissing this long list from mind, we may devote a brief con- 
 sideration to the proper use of mercury in cases of diabetes asso- 
 ciated with syphilis. The diabetic organism is often more sensitive 
 than others to poisons, and medical literature contains warnings 
 against the too free use of mercury for antisyphilitic purposes with 
 diabetic patients. As has already been mentioned, syphilis has in rare 
 cases evidently been the cause of the diabetes by affecting in some 
 way the nervous centers. If any reasons exist in such a case to sus- 
 pect the presence of an active intracranial syphilitic process, there can 
 be no doubt as to the physician's duty to take almost any other risk 
 than that of an undisturbed continuation of the local syphilitic process. 
 Neither the modern large doses of potassium iodid nor anything else 
 has shown itself as useful an antisyphilitic remedy as mercury, and I 
 would not hesitate to administer it quite energetically in such a case 
 in the manner that continues to be the best, the most efficient, and 
 the least objectionable: viz., the old "inunction-cure," Avith the 
 usual precautions against mercurial poisonmg. I have been gov- 
 erned by the rule to assume any reasonable risk rather than to leave 
 the organism a probable prey to syphilis in any case in which there 
 is a mere accidental complication of syphilis and diabetes, whenever 
 there is overwhelming reason to fear the presence of the first- 
 named disease. Views on the subject of antisyphilitic treatment 
 vary exceedingly even now, when the day of the antimercurial 
 craze has passed. For myself, I treated my syphilitic patients more 
 or less a la Foiirnier before I had ever read his work, and I believe 
 in varying its details in diabetic cases only according to the rules 
 that we follow in general. In my own cases of associated syphilis 
 
2 88 DIABETES MELLITUS AND GLYCOSURIA. 
 
 and diabetes the latter disease has been in the mild stage, and I 
 have not observed any marked or peculiarly bad effects from the 
 inunctions. 
 
 Since thyroidin has yielded such good results in the treatment of 
 myxedema, organotherapy (though with much less good results) has 
 been appUed to numerous other diseases, and also to diabetes.* 
 Some physicians simply administer portions of pancreas, raw or 
 sHghtly cooked. Others make an extract of the raw pancreas of 
 sheep or oxen, which is finely cut and macerated for twenty-four 
 hours in its own weight of ("physiologic") solution of sodium 
 chlorid or in glycerin ; this extract is later diluted with water. The 
 filtered extract is afterward used in subcutaneous injection (Comby, 
 Lancereaux, Gley, Thiroloix, Ausset de Cerenville, Battistini, etc.). 
 Lepine macerates a pancreas in one liter of water, with one gram of 
 sulphuric acid and five grams of malt-diastase, for two or three 
 hours, at a temperature of 38° C. (100.4° F.). According to him, 
 the di astatic ferment is thus changed into glycolytic ferment. Lepine 
 then neutralizes the solution with sodium bicarbonate, and has the 
 patient drink the whole in the course of twenty-four hours. This 
 remedy is at least harmless. Lepine reports that he has observed 
 from its use a decrease in the glycosuria and azoturia, an improve- 
 ment in the general state, and an increase in bodily weight. Lepine, 
 like all reliable observers, acknowledges that these results are 
 highly uncertain. 
 
 Spermin (Pohl) is praised by Eulenberg, Hofmeier, Hirsch, and 
 others for its beneficial effects in cases of neurasthenia. Its prop- 
 erty of increasing the alkalinity of the blood f ought to add to its 
 therapeutic value in severe cases of diabetes, in which something 
 besides possibly might be expected from it, especially as regards 
 neurasthenic symptoms. Spermin — which is said to exist to some 
 extent in all organotherapeutic remedies — has hitherto, so far as I 
 know, never been used in its pure form in cases of diabetes. 
 
 * Comby was, so far as I know, the first to employ this mode of treatment for 
 diabetes. 
 
 f As mentioned by Senator and by Loewy, but considered by Strauss not 10 be con- 
 stant. 
 
TREATMENT. 289 
 
 Blumenthal makes subcutaneous injections of an extract of the 
 liver and of the pancreas, and believes this to diminish the glyco- 
 suria as much as forty per cent. 
 
 Gilbert and Carnot administer an aqueous extract of the liver by 
 the mouth or by the rectum, — " opotherapie hepatigue," — and believe 
 thereby to diminish the glycosuria. 
 
 Thyroidi7i is sometimes prescribed in cases of diabetes by physi- 
 cians of a hopeful and of an experimental turn of mind. 
 
 Mechanotherapy , long neglected, has at last gained its proper 
 position in many countries, and has also been used in the treatment 
 of diabetes in the forms of both gymnastics and massage, partly on 
 account of their quality of diminishing glycosuria, partly on account 
 of other effects, in my opinion more important.* 
 
 During the warm season I have found it most advantageous to 
 prescribe gymnastics (/. e., systematic exercises) in the form of 
 walks in the open air. When a diabetic patient passes from a 
 sedentary life to one of moderate exercise, this, together with the 
 usual effects on the appetite, circulation, functions of the bowels, 
 and general state of health, also has some effect in diminishing the 
 glycosuria. Fatigue has a contrary effect, and must be avoided, and 
 the amount of exercise must be regulated in proportion to the 
 patient's strength, which in advanced cases often is quite small. I 
 recommend two walks a day, and think it best for the first to be 
 taken early in the morning and the last several hotirs before bed- 
 time. A brisk walk just before bedtime, contrary to what is some- 
 times asserted, has a disturbing influence on sleep. Next in value 
 
 * I have set forth these effects extensively in my " Handbook of Massage," to which 
 reference may be made. I can not enlarge upon the subject here, as this book on dia- 
 betes has already grown beyond its intended limits. 
 
 Exercise was prescribed in cases of diabetes mellitus in the" beginning of the present 
 century by Marsch, and in more recent times it has been recommended by Bouchardat, 
 Brouardel, Zimmer, Kiilz, and others. I have only recently had time to investigate the 
 effects of general massage in diminishing glycosuria, having used it from time to time 
 since Finkler and Brockhaus (1886) announced their results. While acknowledging 
 the effect of energetic, prolonged general massage in causing diminution in the amount 
 of sugar in the urine, I have not observed by far so good results as Finkler and Brock- 
 haus, and do not consider a diminution from 450 to 120 grams of glucose to be possible 
 as a result of mere massage. 
 
290 DIABETES MELLITUS AND GLYCOSURIA. 
 
 to a moderately brisk walk is horseback-riding. The bicycle, even 
 apart from its liability to accidents, is less beneficial. 
 
 In Scandinavian countries Zander's medicomechanical institutes 
 are highly popular in the larger cities during the winter, and they 
 have spread from Sweden to a large part of the civilized world. 
 Their purpose is to give gymnastics and massage (especially the 
 different forms of tapotement) by machinery. Here in the North 
 we consider them in many cases as excellent for giving " mouvement 
 cures" during our harsh winters; they are closed during the 
 summer. Most of the patients suffer from weak heart or from con- 
 stipation.* Gymnastics is now taught in all large communities, and 
 can easily be arranged in homes without apparatus. 
 
 The massage should be the " general," with effleurage (stroking) 
 frictions, petrissage (kneading), and tapotement (striking, vibrations) 
 of the greater part of the body. The different groups of muscles 
 of the limbs and of the trunk should be subjected to this treatment. 
 Frictions of the abdominal wall over the colon, with their excellent 
 influence on the functions of the bowels, should be carefully prac- 
 tised in the way described by me and now known almost every- 
 where. To exercise any influence at all on the glycosuria, and in 
 order that its well-known beneficial influence may be exerted besides 
 to any great extent, general massage must be practised for a full 
 hour daily, preferably in two seances. Under these conditions gen- 
 eral massage requires but little technical skill, and it may, after 
 some instruction, be performed by any intelligent and available 
 servant of the same sex as the patient. 
 
 Hydrotherapy is of considerable value in cases of diabetes for its 
 effect on the nervous system and on the skin. The diabetic patients, 
 however, are always sensitive and must be protected against exces- 
 sive temperatures, and, in general, the different forms of baths to be 
 used in these cases vary from 20° C. (68.7° F.) to 36° C. (96.8° F.). 
 
 *I shall entirely omit any description of the details of a "mouvement cure," as 
 carried out in Zander's institutes or elsewhere, but will mention that, since I saw a 
 similar treatment recommended by some Italian physicians and by Charcot, I have some- 
 times, in cases of neurasthenic sleeplessness, applied vibration to the head by means of 
 Zander's machines, and with surprisingly good results. The vibrations must be given 
 with some force ; they are contraindicated by arteriosclerosis. 
 
TREATMENT. 29 1 
 
 Different proceedings, constituting a mild cold-water- cure, are of 
 considerable value. 
 
 A sheet-batJi is sometimes used and generally given in the morn- 
 ing when the patient leaves his bed. A sheet wrung out of water 
 at a temperature of about 20° C. (68° F.) is for a moment wrapped 
 around the patient, who is then energetically rubbed with a dry 
 sheet. 
 
 I prefer to recommend to my diabetic patients another form of 
 bath, often and daily used by healthy persons of the upper classes 
 in many countries and by patients of different kinds. This bath is 
 best taken in an ordinary sitz-bath, partly filled with water, which 
 for sensitive persons may be kept at a temperature of about 20° C. 
 (68° F.). The patient, on arising in the morning, sits down in the 
 tub, squeezes the water out of a large sponge three or five times 
 upon his neck, and afterward, while drying the upper part of his 
 body, stands in the tub. The whole bath lasts little more than a 
 minute. At its conclusion the patient either immediately dresses for 
 a brisk walk or returns to bed for a few minutes, until the reaction 
 following the bath is fairly started. 
 
 The half-bath, with gradually lozvered temperature, is an excellent 
 measure which I often prescribe for diabetic and for neurasthenic 
 patients in Carlsbad. The patient sits in a large tub half filled 
 with tepid water (from 30° to 35° C. — from 86° to 95° F.) which, 
 for a little while, is thrown upon his chest and his back. Cold 
 water is then added, and the patient for some few minutes is sub- 
 jected to energetic rubbing of the greater part of the body. A 
 moderately cold douche or a dip in a moderately cold pond ends 
 the bath. 
 
 Douches may also be used alone. They should be begun with 
 tepid water, the temperature being gradually lowered to as low a 
 degree as the patient feels able to endure, and the whole operation 
 lasting not longer than about a minute. 
 
 Sea-bathing or lake-bathing is to be recommended only in mild 
 cases of diabetes. It should be indulged in only when the temper- 
 ature of both the air and the water is comparatively high and with 
 precautions against taking cold. Under these conditions sea- 
 bathing, in my experience, presents no dangers and exerts its usual 
 beneficial influence. 
 
292 DIABETES MELLITUS AND GLYCOSURIA. 
 
 The tepid bath at about 35° C. (95° F.) can also be used by- 
 diabetics. It should last about a quarter of an hour and ought to 
 be followed by a moderately cold douche. If taken in the evening 
 to promote sleep, the bath may be given for half an hour at a tem- 
 perature of 36° or 37° C. (96.8° or 98.6° F.), and it should not 
 be followed by any cold-water application. 
 
 The electric bath, moderately cold or tepid, and the bath in car- 
 bonated water, are both of some value on account of their stimulating 
 effect. 
 
 The warm bath (at 38° C. — 100.4° F. — or more) should be given 
 diabetic patients only in the presence of incipient coma, and it ought 
 to last about ten minutes. 
 
 The addition of different salts, extracts, etc., to the bath is often 
 pleasant to the patient and may be of some benefit to the skin. 
 
 Electrotherapy is employed in cases of diabetes in the same way as 
 it is in nervous diseases. It is generally the diabetic patient's neuras- 
 thenia or neuritis that necessitates the application of general or local 
 galvanization or faradization. Like almost all forms of treatment, 
 this has also been sometimes considered as diminishing the glyco- 
 suria ; D'Arsonval lately mentioned such a result from the use of 
 Tesla's apparatus. 
 
 Many causes combine to make the tissues of the diabetic patient 
 a poor soil for healing processes. The deleterious effects of hyper- 
 glycemia and blood-toxins, of weak heart, of arteriosclerosis, of the 
 diabetic endarteritis in the small vessels, and of defective nervous in- 
 fluences have already been mentioned. The patient's neurotic tem- 
 perament often adds alcoholism to his other drawbacks. Suppurat- 
 ing and septic processes and hemorrhages are more common among 
 diabetics than among others. The different physiologic phases of 
 the healing process, both in the soft and in the bony tissues, 
 take place with less energy than usual. The surgeon, ready for a 
 needed operation, has often replaced his knife on discovering sugar 
 in his patient's urine, fearing to operate in a case of diabetes, and 
 knowing that he would incur less responsibility by abstaining from 
 than by engaging in an unsuccessful operation. Many a surgeon 
 has thus been saved, and many a diabetic patient who might have 
 
TREATMENT. 293 
 
 been saved by surgery has been sacrificed. In the sixties, however, 
 antisepsis and asepsis, and the works of Griesinger, Marchal de 
 Calvi, and others on the surgical comphcations of diabetes began 
 to remove timidity of operating under such conditions. We owe 
 a good deal to the French in this connection, though surgical 
 nihilism in diabetes has had its advocates also in France (Landouzy, 
 Palle, and others). The superstition against operating in cases of 
 diabetes no longer prevails, and statistics prove that even such deli- 
 cate operations as those on the eyes have almost as favorable an 
 outlook in the presence of diabetes as in its absence. 
 
 Operations on diabetic patients should, if the circumstances 
 permit, be preceded by a course of preparatory treatment. In the 
 mild stage the hyperglycemia should be removed for a couple of 
 weeks previous to the operation, and the carbohydrates be w^ith- 
 drawn from the food until glycosuria disappears, if no urgent 
 reason, as set forth on a preceding page, to the contrary exists. In 
 the severe stage the acidosis is to be feared more than an increase in 
 the constant and inevitable hyperglycemia, and consequently a fair 
 supply of carbohydrates may be allowed. Alcoholic and other bad 
 habits are to be strenuously, but wisely, corrected during this time. 
 The general state is improved by all reconstructive remedies, by 
 iron and arsenic when anemia is present, by nutritious, easily 
 digested food, by general massage, etc., in all cases. 
 
 Asepsis is to be preferred to antisepsis in operating in cases of 
 diabetes as soon as the preparation of the skin is ended, on account 
 of the irritating influence on the diabetic's sensitive tissues by anti- 
 septics and of the patient's greater susceptibility to the action of 
 poisons. 
 
 Another rule among surgeons, in case of diabetes, is to prefer the 
 thermocautery to the knife, as soon as there is a choice between the 
 two, the better to avoid hemorrhage (and infection). 
 
 Diabetic gangrene, which occurs in about ten per cent, of all cases 
 of diabetes (Griesinger), necessitates operations more often than 
 any other complication, especially upon the lower limbs. In many 
 cases diabetic and senile changes combine to make the general state 
 poor. In other cases, however, diabetic gangrene may exist 
 despite an amazingly good general state of health. It is often pos- 
 sible to bring about heahng by the usual local (and general) treat- 
 
294 DIABETES MELLITUS AND GLYCOSURIA. 
 
 ment and to save the limb.* Surgeons recommend djy bandages 
 in such cases. If operation becomes necessary for diabetic gangrene 
 in the lower part of the limb, it is usually performed above the knee. 
 Operation at the knee-joint is rarely performed, surgeons demand- 
 ing a better state of health and better coverings than are generally 
 possessed by diabetics. Godbe recommends operation above the 
 knees in all cases with arteriosclerosis. f In diabetic patients with 
 gangrene in the lower part of the leg thrombosis is quite common 
 at the point of division of the popliteal artery, and operation above 
 the knee is then necessary. 
 
 * Constantin Panel has recently reported a case of diabetic gangrene in the lower 
 part of the leg in which a cure was effected by means of a permanent bath of oxygen, 
 removing the india-rubber apparatus twice a day in order to wash the gangrenous part 
 with a warm solution of chloral (4 : looo), by giving arsenic and lithium benzoate, 
 and by enforcing strict diet. 
 
 f As illustrated in one of my cases, the operation below the knee may sometimes 
 yield good results even in the presence of distinct arteriosclerosis. 
 
 ERRATA. 
 
 On page 56, seventh line from bottom of page, "other plausible explanations" should 
 
 read " other plausible explanations than the mere deficiency of oxidation." 
 On page 153, fourth line from bottom of page, "18 grams of nitrogen " should read " 38 
 
 grams of nitrogen." 
 On page 227, after the paragraph on acidosis, the following most important sentence has 
 
 been omitted: " The alkalescency of the blood may sink to -^^ol its normal value, 
 
 but is never entirely annihilated." 
 
TABLE OF THE COMMONEST KINDS OF FOOD, 
 
 SHOWING CONSTITUENT PERCENTAGES OF 
 
 PROTEID, FAT, AND CARBOHYDRATE.^^ 
 
 SIMPLE ANIMAL FOODS. 
 
 Meat, raw (of mammals) , 
 
 Meat, cooked (roast, boiled, etc.), 
 
 Meat, beef (smoked), 
 
 Bacon, raw, 
 
 Lard, 
 
 Meat-powder (dried), 
 
 Chicken, raw, 
 
 Pigeon, raw, 
 
 Duck (wild), raw, 
 
 Fish, fat (salmon, eel) , raw, 
 
 Fish, lean (cod, pike), raw, 
 
 Stock fish, dried (cod), 
 
 Oysters, 
 
 Eggs, 
 
 Eggs, white of, 
 
 Eggs, yolks of, 
 
 Caviar, 
 
 Milk, : 
 
 Milk, skimmed, 
 
 Cream, 
 
 Whey, 
 
 Butter, 
 
 Cheese, rich, 
 
 Cheese, , 
 
 Liver, f 
 
 MIXED ANIMAL AND VEGETABLE_FOODS. 
 
 Omelet of eggs, cream, and ham, 
 
 Omelet of eggs, cream, and flour (pancakes), . . . 
 Waffles I of cream, flour, and water (Swedish style) 
 
 Sausages, in general, 
 
 Blood-sausage, 
 
 Liver-sausage, 
 
 Fish-pudding, 
 
 Proteid. 
 
 Fat. 
 
 Carbo- 
 hydrate. 
 
 15-22 
 
 1-5-34 
 
 
 
 34 
 
 4-5-12 
 
 — 
 
 27 
 
 15-5 
 
 — 
 
 10 
 
 50 
 
 — 
 
 0-3 
 
 99 
 
 — 
 
 75 
 
 — 
 
 — 
 
 20 
 
 4 
 
 — 
 
 22 
 
 I 
 
 — 
 
 22.5 
 
 3 
 
 — 
 
 15-20 
 
 7.5-28 
 
 — 
 
 15-20 
 
 I 
 
 — 
 
 80 
 
 I 
 
 — 
 
 5 
 
 0-3 
 
 2.6 
 
 13 
 
 11 
 
 — 
 
 12 
 
 0-5 
 
 
 16 
 
 32 
 
 
 32 
 
 14 
 
 
 3-5 
 
 3-6 
 
 4.8 
 
 3-5 
 
 0.6 
 
 4.8 
 
 3-5 
 
 20 
 
 3-5 
 
 0.3 
 
 0.2 
 
 5 
 
 0.8 
 
 83 
 
 
 27 
 
 30 
 
 2-5 
 
 35 
 
 4 
 
 2 
 
 X 
 
 5-30 
 
 ~ 
 
 15-5 
 
 19 
 
 I 
 
 12 
 
 10 
 
 25 
 
 10 
 
 12 
 
 25 
 
 17-27 
 
 26-40 
 
 0--5 
 
 12 
 
 "•5 
 
 25 
 
 16 
 
 26.5 
 
 6.; 
 
 10 
 
 12 
 
 II 
 
 *The figures are chiefly taken from Konig's well-known work, in part from the 
 publications of Munk and Ewald, Jiirgensen, and others. The table has been prepared 
 with a view to conciseness, but it will enable, the physician to form an idea as to the 
 caloric value of almost any kind of food. 
 
 ■f Liver, as prepared for the table, contains only a small percentage of glycogen. 
 
 J Waffles, Swedish style, when made exclusively of cream, flour, and water, usually 
 contain about twenty-five per cent, of carbohydrate ; but they are extremely voluminous 
 and light and form a good substratum for butter with a comparatively very small supply 
 of carbohydrate. Except when a rigid diet is to be observed, they can sometimes be used 
 by diabetics instead of bread. 
 
 295 
 
296 
 
 DIABETES MELLITUS AND GLYCOSURIA. 
 
 SIMPLE VEGETABLES AND FRUITS (Uncooked). 
 
 Jerusalem artichokes (topinambour) , 
 
 Lettuce, 
 
 Cucumbers, 
 
 Asparagus, 
 
 Spinach,f 
 
 Radishes, 
 
 Celery (leaves), 
 
 Onions, 
 
 Mushrooms (agaricus), 
 
 Cabbage (white), 
 
 Cauliflower, 
 
 Cabbage (green), 
 
 Cabbage (Brussels sprouts), . . . 
 
 Cabbage (red), 
 
 Parsley, 
 
 Tomatoes, 
 
 String-beans, J 
 
 Peanuts (Arachis hypogsea), . . . 
 
 Almonds, 
 
 Walnuts, . 
 
 Hazelnuts, 
 
 Cranberries, 
 
 Raspberries, , . . 
 
 Currants (red and white), .... 
 
 Blueberries, 
 
 Strawberries, 
 
 Gooseberries, 
 
 Plums, 
 
 Cherries, 
 
 Apples, 
 
 Pears, 
 
 Oranges (juice), 
 
 Peaches, 
 
 Bananas, 
 
 Grapes, 
 
 Carrots, 
 
 Turnips, 
 
 Potatoes, . . 
 
 Sweet potatoes, 
 
 Beans (seeds, dried), 
 
 Peas (seeds, dried), 
 
 Apples, dried, 
 
 Pears, dried, 
 
 Prunes, 
 
 Raisins, 
 
 Figs, 
 
 Proteid. 
 
 2 
 
 1-4 
 
 I 
 
 1.8 
 
 3 
 
 1.2 
 
 4.6 
 
 2.7 
 
 3-6 
 
 1-9 
 
 2-5 
 
 4 
 
 4.8 
 
 1.8 
 
 3-7 
 
 1.2 
 
 2.7 
 
 28.2 
 
 24.2 
 
 16.4 
 
 15-6 
 
 0.1 
 
 0.4 
 
 0.5 
 0.8 
 0.9 
 
 o-S 
 0.4 
 0.7 
 0.4 
 0.4 
 0.4 
 0.65 
 
 1-9 
 0.6 
 I 
 
 2.1 
 
 1.8 
 
 1-3 
 
 24-3 
 
 22.8 
 
 1-3 
 
 2 
 
 2.2 
 
 2.4 
 
 5 
 
 Fat. 
 
 O.I 
 
 0-3 
 
 O.I 
 
 0.2 
 0.5 
 
 O.I 
 
 0.8 
 0.3 
 0.3 
 
 0.2 
 
 03 
 0.9 
 
 0-5 
 0.2 
 0.7 
 
 0-3 
 
 0.1 
 
 46.4 
 
 53-7 
 69.2 
 66.5 
 
 Carbo- 
 hydrate. 
 
 0.6 
 
 0.2 
 O.I 
 
 0.2 
 
 0-3 
 1.6 
 1.8 
 0.8 
 0-3 
 0.5 
 0.6 
 
 15-2* 
 
 2.2 
 
 2-3 
 2.6 
 
 3-5 
 3-8 
 10 
 
 6.5 
 6.8 
 4.9 
 
 4-5 
 
 11. 6 
 6.2 
 5-9 
 7.4 
 4-1 
 6.6 
 8 
 
 7.2 
 7-9 
 9 
 
 1-5 
 5-3 
 6.3 
 5-9 
 3-4-4 
 8.4 
 8.2 
 
 12 
 12 
 II. 8 
 
 5-54 
 "•5 
 23 
 16.3 
 
 9.4 
 
 11. 7 
 20.6 
 23 
 49 
 52.4 
 59-8 
 58.8 
 62.3 
 62 
 45-3 
 
 *The carbohydrate in the Jerusalem artichokes consists of inulin, levulose, and gum. 
 They are thus especially suitable for the diabetic's table. Tn many fruits the carbo- 
 hydrate consists partly of levulose in addition to starch and glucose. 
 
 t The figures refer to the green leaves of Spinacia oleracea — not to spinach prepared 
 with flour. 
 
 J The figures refer to string-beans with full-grown seeds. Before the seeds are developed 
 string-beans contain much inosite, but only an insignificant amount of true carbohydrate, 
 and they are an important item in the diabetic's bill of fare. 
 
PROTEID, FAT, AND CARBOHYDRATE IN FOOD. 
 
 297 
 
 SIMPLE VEGETABLES AND FRUITS (Uncooked). 
 (Continued.) 
 
 Chestnuts, 
 
 Coffee (burnt), 
 
 Tea (dried leaves), 
 
 Chocolate, unsweetened, 
 
 Chocolate, sweet, 
 
 CEREALS.PREADS, ETC. 
 
 Rice, dried, 
 
 Sago, dried, 
 
 Indian corn (maize), 
 
 Macaroni, dried, 
 
 Flour of the Soya-bean, 
 
 Rye-flour, 
 
 Wheat-flour, 
 
 Oatmeal, dry (coarse), 
 
 Rye-bread, 
 
 Wheat-bread, 
 
 Graham bread, 
 
 English biscuits, 
 
 Proteid. 
 
 5-5 
 12.2 
 21 
 
 5 
 12.3 
 
 9 
 
 0.8 
 11.67 
 
 9 
 
 3-4 
 12.8 
 10.5 
 
 IS 
 
 6.1 
 6.1 
 6 
 7.2 
 
 Fat. 
 
 1.4 
 12 
 
 3-6 
 
 IS-2 
 
 52.3 
 
 0.8 
 
 5-5 
 
 0.3 
 
 16.4 
 
 2.3 
 
 1-3 
 
 6 
 
 0.4 
 
 0.4 
 
 0.3 
 
 9-3 
 
 Carbo- 
 hydrate. 
 
 38.3 
 13-4 
 17.6 
 74.8 
 28.3 
 
 77.8 
 76.7 
 29.6 
 
 81.3 
 87.1 
 
 64-73 
 49.2 
 
 51 
 
 39-41 
 75-1 
 
 LIQUORS. 
 
 Percentage. 
 
 Vol. 
 
 Weight. 
 
 Sugar 
 
 AND 
 
 Extract. 
 
 Cognac, French brandy, 
 Whisky, American, . . . 
 
 " Scotch, . . . . 
 
 " Irish, 
 
 Cider, 
 
 Beers and ales, . . . . 
 
 Porters, 
 
 Rhine wines, white, . . 
 Rhine -wines, red, . . . 
 Beaune (Burgundy), . 
 St. Emilion (Bordeaux), 
 Swiss wine, white, . . . 
 Swiss wine, red, . . . . 
 Austrian wine, red, . . . 
 
 Sherry, 
 
 Madeira, ....... 
 
 Marsala, 
 
 Port wine, 
 
 Malaga, 
 
 Champagne, 
 
 Curacao, 
 
 Arrac-punch (Swedish), . 
 
 55 
 60 
 
 50-3 
 49.9 
 
 9 
 
 8.7 
 
 9.6 
 
 9-4 
 9-5 
 
 55 
 26.3 
 
 47-3 
 52.2 
 42.8 
 
 42.3 
 
 4.2 
 
 2.5-4.9 
 
 5-3 
 II. 4 
 10 
 
 17 
 15-6 
 16.4 
 16.4 
 "•5 
 9 
 
 0.6 
 
 4-7.2 
 8.9 
 2.6 
 
 3-4 
 
 2.7 
 
 3 
 
 1-9 
 1.6 
 2.7 
 
 5 
 
 8.6 
 8 
 10.2 
 
 30- 3 
 
 24.8 
 
 57 
 69.8 
 
 19 
 
PERSONAL REGISTER. 
 
 Abeles, 26, 38, 65, 177, 178, i^ 
 
 Abelmann, 105, 167 
 
 Achard, 60, 243 
 
 V. Ackeren, 129, 135, 209 
 
 Acri, 117 
 
 Aladoff, 34 
 
 Albertoni, 116, 117,133, 223 
 
 Albic, 220 
 
 Aldehoff, 165, 279 
 
 Althaus, 90, 94 
 
 Amann, 219 
 
 Ambrosiani, 10 
 
 Andral, 49, 55, 159 
 
 Anger, 98 
 
 Anselme, 138 
 
 Anstoots, 63 
 
 Araki, 13, 51, 56, 57, 58, 68 
 
 Argutinsky, 186 
 
 Armanni, no, 113, 116 
 
 Arnschink, 171 
 
 Arthaud, 33, 48, 49 
 
 Arthur, 49 
 
 Arthus, 180 
 
 Asher, 32 
 
 Auche, 94, 97 
 
 Auerbach, 94 
 
 Ausset de Cerenville, 288 
 
 Baisch, 26 
 
 Barlow, 36, 62 
 
 Barral, 181, 188, 191, 192, 284 
 
 Basham, 286 
 
 Battistini, 288 
 
 Baum, 37 
 
 Baumann, 217 
 
 Beale, 63 
 
 Becker (O.), 119, 120 
 
 Begbie, 41 
 
 Bence Jones, 11, 13, 26, 159 
 
 Benda, no 
 
 Benzi, 286 
 
 Bequerel, 35, 36 
 
 Beranger-Ferand, 15 
 
 252 
 
 Berger, 119 
 
 Bernard, Claude, 11, 13, 24, 29, 31, 33, 
 
 49. 54. 57, 66, 67, 105, 169, 173, 176, 
 
 183, 191, 203, 216, 229 
 Bernstein, 279 
 Berthier, 87 
 Bettman, 36, 102 
 Bial, 170, 180, 182 
 Bidder, 11 
 Biedl, 243 
 Biefel, 56 
 Bischoff, II, 171 
 Bischofswerder, 216 
 Blair, 18 
 Blake, 54 
 Blau, 82 
 Bleibtreu, 235 
 Bleile, 170, 181 
 Blocq, 36 
 Blot, 65 
 
 Blumenthal, 289 
 
 Boccardi, 97, 108, 113, 116, 117, 177 
 Bock, 53, 58, 181, 187 
 Boecker, 229 
 Boedeker, 217 
 Bohm, 34, 38, 68, 176, 181 
 Bollinger, 50 
 Bond, 35 
 Bonome, 113 
 Borchert, 229, 232 
 Bordier, 62, 63 
 Bose, 17 
 Bouchard, 12, 14, 53, 55, 74, 76, 91, 
 
 119, 120, 135, 228, 284 
 Bouchardat, 12, 13,203, 216, 267, 281, 
 
 286 
 Bouchut, 62 
 Bouveret, 121 
 Brault, 137, 177 
 Bremer, loi, 244 
 Breul, 26 
 Brieger, 133 
 Brietzke, 186 
 Bright, 105 
 Brockhaus, 203, 289 
 Brogniart, 216 
 
 299 
 
300 
 
 PERSONAL REGISTER. 
 
 Brouardel, 37, 193, 289 
 
 Brown-Sequard, 191 
 
 Briicke, 11, 26 
 
 Brunelle, 53, 54 
 
 Brunner, 135 
 
 Buchheim, 171 
 
 Budde, 115, 216 
 
 Budge, 34, 200 
 
 Bull, William T., 105, 135 
 
 Bunge, 170, 185, 217 
 
 Burdel, 64 
 
 Burger, 231 
 
 Burghardt, 68 
 
 Burns, 94 
 
 Bury, 90, 94 
 
 Bussenius, 203 
 
 Butte, 33, 34, 48, 49. ^82, 183, 192 
 
 Buzzard, 90, 94 
 
 Calmette, 18, 64 
 Camplin, 274 
 Cantani, 12, 14, 41, T] , 267 
 Cantlie, 18 
 Caparelli, 165 
 Carnot, 289 
 Caroe, 16 
 Carrion, 138 
 Cartier, 53, 54 
 Casal, 57 
 de Cassaet, 286 
 Cavazzani, A., 35, 183 
 Cavazzani, E., 35, 183 
 Celsus, 10 
 
 Charcot, 24, 63, 90, 94, 97, 216, 257 
 Charrin, 129 
 Chauffard, 137 
 
 Chauveau, 12, 32, 33, 49, 165, 166, 
 181, 185, 186, 189, 194-198. 229 
 
 Chittenden, 54, 182 
 
 Chvostek, 36 
 
 Coignard, 52, 216 
 
 Colasanti, 218 
 
 Colenbrander, 192 
 
 Colrat, 49 
 
 Comby, 288 
 
 Coolen, 60, 61 
 
 Coranda, 133 
 
 Cornevin, 62 
 
 Couturier, 49 
 
 Cowley, 135 
 
 Cramer, 66 
 
 Cremer, 60, 174, 175. 185 
 
 Crichton-Browne, 87 
 
 Cruikshank, 10 
 
 Cunningham, 36 
 
 Curee, 54 
 
 Cyon, 34 
 Czapek, 208 
 
 D. 
 
 Dalton, 180 
 D'Arsonval, 292 
 Dastre, 49, 56, 179, 192 
 Davis, N. S., 81 
 Davy, loi 
 Decker, 63 
 De Dominicis, 165 
 Deichmiiller, 133 
 De Jong, 35, 200 
 Delamare, 60 
 Demant, 57, 176 
 Demme, 35 
 Derignac, 219 
 Deutschmann, 119, 120 
 Devie, 113, 219 
 Dickinson, 96 
 Dieulafoy, 128 
 Dittrich, 108 
 Dobson, 10, 77, 284 
 Doch, 57, 174 
 Donkin, 277 
 Dreyfus-Brisac, 286 
 Dufour, 183 
 Dufresne, 58 
 Dujardin-Beaumetz, 127 
 Dumontpellier, 36 
 Duponc, 34 
 Duponchet,E64 
 V. Dusch, id, 131 
 
 E. 
 
 Ebstein, 12, 14, 37, 86, 116, 117, 175. 
 
 216 
 Eckhard, 32, 33, 55, 57, 58 
 Edel, 187 
 
 Edwards, Mile. Blaine, 35 
 Ehrlich, 117, I77, 178 
 Eichhorst, 63, 66, 94, 97. 98 
 Ehotson, 105 
 V. Engel, 215 
 Engelmann, 231 
 Erlenmeyer, 91 
 Ernst, 115 
 
 Eulenburg, 35, 55. 288 
 Ewald, 51, 58, 178, 181, 187,295 
 Exner, 49 
 
 Fahlberg, 279 
 Falkenberg, 38 
 Feilchenfeld, 54 
 
PERSONAL REGISTER. 
 
 301 
 
 Fere, 36, 133 
 
 Ferraro, 97, 100, 108, 113, 116 
 
 Fichtner, 116 
 
 Fick, 186 
 
 Finkelstein, 229, 232 
 
 Finkler, 37, 135, 203, 289 
 
 Finlayson, 86 
 
 Finn, 174 
 
 Fischer, 37, 62 
 
 Fitz, no 
 
 Fleiner, 134 
 
 Fleischer, 57 
 
 Fles, 105 
 
 Fleury, 98 
 
 Flint, 186 
 
 Fodor, 129 
 
 Foerster, 119 
 
 Forsell, 268 
 
 Foster, 203 
 
 Fraentzel, 175 
 
 Frank, Peter, 64, 78 
 
 Franque, 158 
 
 Frazer, 34 
 
 Frerichs, 11, 12, 34, 35, 36, 52, 54, 55, 
 56, 62, 63, 69, 93, 96, 98, 105, 108, 
 117, 131, 132, 172, 176, 177, 188 
 
 Freund, 58, 190 
 
 Fiirbringer, 77, 103, 218, 229 
 
 Futterer, 96 
 
 Gabritschewski, 178 
 
 Gaglio, 57, 165 
 
 Gallard, 137 
 
 Gans, 37, 104, 180 
 
 Gara, 63 
 
 Garofalo, 57 
 
 Garrod, 76 
 
 Gascuel, 83 
 
 Gathgens, 229, 231 
 
 Gaudard, 118 
 
 Gelmo, 62 
 
 Geppert, 52 
 
 Gerhardt, 11, 133 
 
 Gerhardt, D., 102, 212, 227 
 
 Geyer, 237 
 
 Gianturco, 113 
 
 Gib, Paul, 37 
 
 V. Gieson, 117 
 
 Gilbert, 289 
 
 Gilles de la Tourette, 257 
 
 Girard, 182 
 
 Giron, 81 
 
 Glenard, in 
 
 Gley, 60, 62, 165, 229, 288 
 
 Gmelin, 10, 54 
 
 Godlee, 294 
 
 Goerlitz, 120 
 
 Golowin, 49 
 
 Golz, 52 
 
 Goodhart, 96 
 
 Goolden, 36, 63, 158 
 
 Gorup-Besanez, 208 
 
 Graefe, 119 
 
 Graf, 54 
 
 Graham, 17, 61 
 
 Graser, 62 
 
 Griesinger, 12, 25, 36, 102, 293 
 
 Grohe, 178 
 
 Grube, 19, ^6, 114, 282 
 
 Gruber, 207 
 
 Gubler, 63 
 
 Guckelberg, 215, 230 
 
 Gueneau, 63 
 
 Gueudeville, 10 
 
 Guiard, 115 
 
 Guignard, 129 
 
 Guinon, 93, 94 
 
 Gull, 107 
 
 Gumpertz, 88 
 
 Giirtler, 57 
 
 H. 
 
 Habershon, 69 
 
 Hale White, 207 
 
 Haller, 135 
 
 Hallervorden, 133 
 
 Hammarsten, 170, 215 
 
 Hammerschlag, loi 
 
 Hanot, 113, 137, 138 
 
 Hansemann, no 
 
 Harden, 127 
 
 Harley, 49, 55 
 
 Hartge, 116 
 
 Hartsen, 105, 106 
 
 Hartz, 216 
 
 Hasse, 56 
 
 Haughton, 229 
 
 Hay craft, 207 
 
 Hedon, 32, 120, 165, 166, 193 
 
 Heidenhain, 81 
 
 Heine, 159 
 
 Heinemann, 109 
 
 Heintz, 63 
 
 Heller, 170 
 
 Henrat, 98 
 
 Henriot, 235 
 
 Hensay, 97 
 
 Hensen, 181 
 
 Hergenhahn, 49, 173, 174, 176 
 
 Hernandez, Gonsalez, 137 
 
 Heyneman, Newton, 185 
 
302 
 
 PERSONAL REGISTER. 
 
 Heyse, 207 
 
 Higgins, 32, 74 
 
 Hirsch, 288 
 
 Hirschberg, 119, 122,226 
 
 Hirschfeld, 105, 170, 213 
 
 Hodgkin, 81 
 
 Hoesslin, 14 
 
 V. Hoesslin, 94 
 
 Hoffmann, 55, 220, 252 
 
 Hoffmann, G. A., 12, 34, 38, 53, 58, 
 
 176, 181, 187, 214 
 Hofmeier, 288 
 Hofmeister, 24, 30, 65, 67, 171, 200, 
 
 203 
 Holmgren (E.) 219, 237 
 Holsti, 65 
 Honigmann, 104 
 Hoppe, 173 
 
 Hoppe-Seyler, 52, 177, igo 
 Horner, 121 
 Huber, 50 
 Hubner, 180 
 Hiibner, 15 
 Huchard, 35 
 Hugonenq, 52, 219 
 Hundhausen, 275 
 Hunt, W., 81 
 Huppert, 14, 63, 177 
 Husband, 29, 66 
 
 Ingerslev, 159 
 Irisawa, 56 
 Isenflamm, 159 
 Israel, 100 
 
 Jaccoud, 14 
 
 Jacobson, 119 
 
 Jacobson, Otto, 64 
 
 Jacoby (New York), 86 
 
 Jacoby (Strassburg), 58, 69 
 
 V. Jaksch, 53, 57, loi, 133, 215, 217, 
 
 226 
 James, A., loi, 131 
 Jasper, 285 
 Joffroy, 97 
 Johannowski, 65 
 Johnson (St.), 217 
 
 K. 
 
 Kahler, 30, 31, 35, 56 
 Kaiser, 210 
 Kalm, 219 
 
 Kalmus, 97 
 
 Kaltenbach, 65 
 
 Kaposi, 81, 127 
 
 Kassel, 215 
 
 Kassowitz, 129 
 
 Kaufmann, 12, 32, 33, 49, 165, 166, 
 167, 181, 185, 189, 194-198, 229 
 
 Kausch, 69, 165, 174, 175, 179 
 
 Kemmerich, 214 
 
 Kessler, 53 
 
 Kinnicutt, 158 
 
 Kirchner, 124 
 
 Kirmisson, 83 
 
 Kirsten, 65 
 
 Kisch, 66 
 
 Klebs, 34 
 
 Klemperer, 58, 60, 67, 69, 115, 207 
 
 Knies, 119, 120 
 
 Kbbner, 170 
 
 Konig, 121, 295 
 
 Koninck, 59 
 
 Kbrner, 124 
 
 Kossel, 279 
 
 Kowalewski, 54 
 
 Kratschmer, 24, 177, 229 
 
 Kraus, 36, 192, 243 
 
 Kraus, I., 79 
 
 Kravkow, 215 
 
 Kuhn, 124 
 
 Kiihne, 26, 31, 177 
 
 Kiilz, E., 17, 30, 33, 34, 38, 52, 53, 
 132, 133, 157, 159, 170, 175, 176, 181 
 203, 205-209, 213, 224, 229, 230 
 
 Kumagawa, 185 
 
 Kunkler, 36 
 
 Kuntzel, 53 
 
 Kupper, 172 
 
 Kussmaul, 54, 131, 133 
 
 Laache, 36 
 Laborde, 158 
 Lallier, 35, 36 
 Lamanski, 34 
 Lambert, 54, 182 
 Lancereaux, 36, 108, 135, 2i 
 Landouzy, 293 
 Landwehr, 219 
 Lang, 66, 179 
 Langendorff, 57, '165 
 Lapique, 138 
 Laseque, 107 
 Laub, 53 
 Laulanie, 235 
 Laves, 176, 235 
 Lavoisier, 11 
 
PERSONAL REGISTER, 
 
 303 
 
 Leber, 119, 122, 123 
 
 Leblanc, 15 
 
 Lecanu, 102, 212 
 
 Leconte, 54 
 
 Lecorche, 14, 94, 98, 100, 286 
 
 Le Goff, 287 
 
 Legroux, 39 
 
 Lehmann, 11, 6^] , 181, 214, 217 
 
 Leichtentritt, 97 
 
 Lemaire, 65, 219 
 
 Le Nobel, 105, 134, 135, 209 
 
 Leo, 209, 220, 235 
 
 Lepine, 12, 33, 58, 69, 95, 165, 181, 
 
 190, 191, 193, 220, 284, 288 
 Leroux, 157, 159 
 Letulle, 137, 203 
 Leube, 178, 219, 229 
 Leudet, 35 
 Leval-Piquechef, 94 
 Levene, 61 
 Lewaschew, 284 
 Lewin, 54 
 Levin, 171 
 Ley den, 90, 94, 97 
 Lichtheim, 134, 221 
 Liebig, 11, 174 
 Lindemann, 175 
 Lionville, 57 
 Livierato, 232 
 Loewy, 245, 288 
 Lohnstein, 247 
 Loye, 192 
 Lubinoff, 98 
 
 Luchsinger, 58, 172, 174 
 Ludwig, 36, 187 
 Liihdorf, 275 
 
 Lusk, 60, 61, 170, 171, 181, 224 
 Lussanna, 182 
 Lustig, 34 
 
 M. 
 
 McDonnel, 38, 173, 182 
 
 McGregor, 10 
 
 Magendie, 1 1 
 
 Magnus-Levy, 51, 115,235 
 
 Maitland, 10 
 
 Manchot, 51 
 
 Mannkopf, 35, d'j 
 
 Maquenne, 207 
 
 Marcet, 14 
 
 Marcus, 66 
 
 Marcuse, 165 
 
 Marechal de Calvi, 81, 293 
 
 Marie, 94 
 
 Marinesco, 36 
 
 Marinian, 91 
 
 Marklen, 103 
 
 Marsh, 289 
 
 Marthen, 116 
 
 Martin-Damourette, 52 
 
 Martineau, 282 
 
 Masoin, 53 
 
 Matrai, 190 
 
 Mauthner, 122, 209 
 
 May. 175 
 
 Mayer, 52 
 
 Meissner, 182 
 
 V. Mering, 12, 51, 52, 53, 55, 59, 60, 
 
 61, 105, 135, 136. 164, 170, 174, 177, 
 
 181, 185, 187, 188, 203, 229 
 Mermod, 14 
 Metroz, 192 
 
 Meyer, Jacques, 35, 36, 100 
 Mialhe, 281 
 Michael, 35, 96 
 Minkowski, 12, 38, 52, 105, 106, 133, 
 
 135, 136, 164-168, 177, 193, 202, 
 
 207, 223, 229 
 Minnich, 134 
 Minor, 97 
 
 Miura, 185, 199, 200, 213, 224 
 Montuori, 182 
 Morat, 33, 34, 183 
 Moriggia, 66 
 
 Moritz, 26, 59, 60, 185, 200 
 Morrison, 69 
 Moscatelli, 217 
 Mosler, 229 
 Mosse, 182 
 Mosso, U., 14 
 Miiller, Fr., 106, 115, 171 
 Munck, 34 
 Munk, 171, 184, 295 
 Miinzer, 50, 53, 132, 133, 229 
 Musculus, 170 
 
 N. 
 
 Nasse, loi, 210, 231 
 
 Naunyn, 14, 29, 32, 35, 36, 37, 38, 50, 
 52, 66, 69, 71, 94, 102, 103, 107, III, 
 115, 116, 118, 134, 174, 203, 216, 
 268 
 
 Nebelthau, 174, 175, 176 
 
 Neisser, 177 
 
 V. Nencki, 13, 174, 234 
 
 Nesbi, 116 
 
 Nettelbladt, 158 
 
 Neubauer, 220 
 
 Neumann, 28, 58, 98 
 
 Neumeister, 182 
 
 Neusser, 49, 102 
 
304 
 
 PERSONAL REGISTER. 
 
 Key, 65 
 
 Nicolas, 10 
 
 Niedergesass, 157 
 
 Niedieck, 33 
 
 Nommes, 191 
 
 Nonne, 91 
 
 V. Noorden, 12, 58, 185, 224 
 
 Nordenson, 121, 123, 149, 162 
 
 Nylander, 26 
 
 O. 
 
 Obici, 116 
 
 Ogden, 32, 74 
 
 Ollivier, 35, 56 
 
 van Oordt, 35 
 
 Oppenheim, 35, 93, 186 
 
 Oppler, 247 
 
 Orth, 135 
 
 Otto, 171, 172, 181, 187, 188 
 
 Palle, 293 
 Palm a, 207 
 Panas, 36 
 Panel, 294 
 Papanikolau, 119 
 Paracelsus, 10 
 Parkes, 186 
 Parmentier, 138 
 Parrot, 158 
 Paschutin, 177 
 Paton, Noel, 182 
 Pautz, 170, 232 
 
 Pavy, 12, 13, 19, 20, 32, 34, 36, 38, 52, 
 61, 69, 159, 174, 178-183, 186, 190, 
 215,275 
 
 Peiper, 34 
 Penzoldt, 57 
 
 Percy, 98 
 
 Pettenkofer, 11, 214, 229, 232 
 
 Petters, 133 
 
 Peyrot, 81 
 
 Pfliiger, 174, 186 
 
 Philipeaux, 63 
 
 Pichon, 58 
 
 Pick, 77 
 
 Pickhardt, 187 
 
 Pierre-Marie, 36, 137, 287 
 
 Pincus, 34 
 
 Pisenti, 116, 117 
 
 Pitres, 82 
 
 Poll, 62, 63 
 
 PoUak, 56. 66 
 
 PoUatschek, 52 
 
 Popper, 13 
 
 Praussnitz, 59, 60, 171, 177, 185 
 
 Prevost, 63 
 
 Price, 94, 97 
 
 Prout, 63, 75, 218, 267, 274 
 
 Purdy, 17, 19, 20 
 
 Ouinquaud, 53, 189 
 
 Rabuteau, 54 
 
 Range, 64 
 
 Raynor, 87 
 
 Reale, 38 
 
 Rebitzer, 68 
 
 V. Rechenberg, 232 
 
 V. Recklingshausen, 35 
 
 Redard, 63 
 
 Redon, 62, 157, 160 
 
 Reich, 229 
 
 Reichhardt, 219 
 
 Reignault, 11, 186, 234 
 
 Reiset, 11, 186, 234 
 
 Reynoso, 28, 53, 63 
 
 Richardiere, 35, 37, 281 
 
 Richardson, 35, 56, 120 
 
 Riegel, 107, 108 
 
 Rienzi, 38 
 
 Riess, 216 
 
 Ringer, 36 
 
 Ritter, 55, 60, 182, 185 
 
 Roberts, 159, 247 
 
 Robin, 282, 286 
 
 Roger, 59, 62 
 
 Rohmann, 170, 208 
 
 Rolf, 52 
 
 Rollo, 10, 264 
 
 Roos, 26 
 
 Roque, 113, 219 
 
 Rosenbach, 53 
 
 Rosenbaum, 176 
 
 Rosenblath, 82, loi 
 
 Rosenfeld, 61, 226 
 
 Rosenheim, 171 
 
 Rosenstein, 57,-91, 94. io4. io8, 229 
 
 Ross, 26, 90, 94 
 
 Rossa, 66 
 
 Rovere, 84 
 
 Rubner, 11, 171, 172, 200, 232 
 
 Rumpf, 133, 218, 227 
 
 Rupstein, 230 
 
 Ryndsjun, 34 
 
PERSONAL REGISTER. 
 
 305 
 
 Saikowski, 53, 57 
 
 Salkowski, 175, 214 
 
 Salomon, 172 
 
 Samoje, 63 
 
 Sampacchia, 113 
 
 Sandmeyer, 97, 105, 165, 174, 177 
 
 Sauer, 56, 57 
 
 Saundby, 17, 96, no, 113 
 
 Savage, 87 
 
 Scharlau, 36 
 
 Schenk, 186, 188 
 
 Schermetjewski, 13 
 
 Schierbeck, 14 
 
 Schiff, 13, 31. 32, 33, 36, 38, 56, 57, 182 
 
 Schilder, 26 
 
 Schindelka, 15 
 
 Schindler, ']'] 
 
 Schirmer, 119 
 
 Schmidt-Rimpler, 119, 122 
 
 Schmidt, G., 11, 181 
 
 Schmitz, 20, 25, 49, 76, 115, 284 
 
 Schultze, 14 
 
 Schultzen, 13 
 
 Schiitz, 35 
 
 Schwarz, 168 
 
 Schwiening, 180 
 
 Scolozoboff, 54 
 
 See, Germain, 60 
 
 Seegen, 11, 12, 29, 35,38, 58, 71, 118, 
 
 171-178, 183, 186, 187,188, 194,200, 
 
 208, 275 
 Segalas, 10 
 Seitz, 105, no 
 Semmola, 63 
 Senator, 39, 55, 67, 84, 115, 159, 217, 
 
 288 
 SenfF, 56, 57 
 Senn, N., 105, 135 
 Settenbom, 82 
 Seyfert, 62 
 Sieber, 13, 234 
 Siebert, 36 
 Siebold, 55 
 Silver, 105 
 Simons, 10 
 Sinety, 65 
 Smith, 35, 93 
 Sobeiran, 10 
 Socin, 174, 175 
 Soldani, 35 
 Sotniskewski, 177 
 Souques, 93 
 Spiegelberg, 65 
 Spitzer, 192 
 Spitzka, 35 
 
 Stadelmann, 52, no, 133, 220, 227 
 Startz, 216 
 
 I Steinhaus, n3 
 Stern, 63, 157 
 Stokvis, 173 
 Strasser, 132, 133, 229 
 Strassmann, 213 
 Straub, Walther, 57 
 Straus, 35, 37, 53, 58, n6, 234 
 Stray nowski, 118 
 V. Striimpell, 37, 90 
 Subbotin, 214 
 Susruta, 10, 127 
 Sydenham, 64 
 
 T. 
 
 Tangl, 49 
 
 Taylor, 96 
 
 Tcherinoff, 173, 174 
 
 Tebb, 170 
 
 Telz, 55 
 
 Tenbaum, 231 
 
 V. Terray, 63 
 
 Teschemacher, 58 
 
 Tessier, 25 
 
 Thiel, 60 
 
 Thierfelder, 229, 237 
 
 Thiermesse, 15 
 
 Thiroloix, 165, 166, 229, il 
 
 Tholozan, 18 
 
 Thomas, 90 
 
 Thompson, 11 
 
 Tiedeman, 10 
 
 Tiegl, 180 
 
 Toepfer, 58, 140 
 
 Toll, 148 
 
 Tollens, 133 
 
 Topinard, 35 
 
 Toralbi, 88, 202 
 
 Trambusti, 116 
 
 Traube, n, 220 
 
 Triboulet, 138 
 
 Troye, 221, 228 
 
 True, 120 
 
 Tscherinow, 49, 173 
 
 U. 
 
 Uhle, 229 
 Ulrich, 219 
 
 Vahl, 207 
 Vamossy, 57 
 Vas, 63 
 Vauquelin, 10 
 
3o6 
 
 PERSONAL REGISTER. 
 
 Velisch, 38, 165 
 
 Vergely, 94 
 
 Verron, 95 
 
 Vespa, 1"] 
 
 Vetlesen, 240 
 
 Viaud-Grand-Marais, 282 
 
 Vogel, 219, 220 
 
 Vogler, 36 
 
 Voisin, 57 
 
 Voit, 12, 170, 174, 210, i\\, 229, 232 
 
 Voit, E., 214 
 
 Voit, Fr., 171, 174, 206, 207, 232, 243 
 
 Voit, Hans, 34 
 
 Vulpian, 63 
 
 W. 
 
 Wagner, 63 
 
 Walkow, 217 
 
 Walter, 52, 133 
 
 Watson, 159 
 
 Wedenski, 26, 209, 219 
 
 Weichselbaum, 35 
 
 Weil, 243 
 
 Weintraud, 12, 104, 165, 179,211,221, 
 
 234 
 Weir-Mitchell, 84, 119 
 Weiss, 174, 185 
 Werther, 177 
 West, 159 
 
 Whitehouse, 54 
 
 Wickham-Legg, 177 
 
 Wiersma, 177 
 
 Wiesinger, 119 
 
 V. Wildt, 124 
 
 Williams, 66 
 
 Williamson, 97, loi, 245 
 
 Willis, 10, 281 
 
 Winogradoff, 57, 217 
 
 Wislicenus, 186 
 
 V. Wittisch, 49 
 
 Wolf, 208 
 
 Wolf berg, 174 
 
 WoUaston, 10 
 
 Wood, Horatio, 91, 127 
 
 Worm-Miiller, 26, 30, 46, 199, 200, 204 
 
 Worms, 14, 284 
 
 Woroschiloff, 173 
 
 Woroschilski, 54 
 
 Z. 
 
 Zander, 257, 290 
 
 Zenker, 103 
 
 Ziemssen, 90, 94 
 
 Zillesen, 56 
 
 Zimmer, 13, 54, 68, 69, 191, 203, 208 
 
 Zinn, 62 
 
 Zuntz, 57, 62, 184, 186 
 
INDEX 
 
 Acetone, 6i, 
 
 221 
 
 [, 133, 168, 214, 215, 
 
 Acetonuria, 168, 169 
 Achroodextrin, 170 
 Acid, acetic, 217 
 butyric, 217 
 carbonic, 56, 234 
 dextronic, 52 
 diacetic, 52, 53, 61, 133, 168, 214, 
 
 221, 228 
 formic, 215 
 glycosuric, 217 
 
 glycuronic, 51, 52, 179, 218, 239 
 hippuric, 217 
 homogentisinic, 217 
 hydrochloric, 52 
 lactic, 51, 52, 55, 57, 168, 179, 
 
 218 
 levuUnic, 215 
 mucous, 52 
 orthro-n i t r o-phenyl-propionic, 
 
 52 
 oxahc, 52, 218 
 /?-oxybutyric, 52, 61, 133, 168, 
 
 214, 221 
 phloretic, 59 
 propionic, 217 
 prussic, 52 
 salicylic, 52 
 sugar, 52 
 sulphuric, 52 
 
 coupled (etherous, 
 aromatic), 53, 59, 
 172, 219 
 in sulphates, 53, 172, 
 219 
 Acidity of gastric juice, 104, 108 
 
 of urine, 219, 227 
 Acidosis, 72, 168, 227, 263 
 Acids, fatty, 52, 217 
 Aciduria, 227 
 Acne, 127 
 
 Addison's disease, 68 
 Adiposity, 140 
 Age, 19, 158 
 Akromegaly, 36 
 
 Albuminuria, 51, 52, 59, 76, 114, 228, 
 
 248 
 Alcohol, 54, 203, 212, 232 
 Alcoholism, 137 
 Alkalies, 51-53, 259, 281 
 Alkapton, 217, 239 
 Altitude, 20 
 Amaurosis, 123 
 Amblyopia, 95, 123 
 Ammonia, 55, 61, 224, 227 
 Amyl nitrite, 51, 55 
 Analgesia, 91 
 Anatomy of blood, loi 
 
 of brain, 95, 96 
 
 of gastro-intestinal tube, 
 108 
 
 of heart, 100 
 
 of kidneys, 116 
 
 of liver, no 
 
 of lungs, 103 
 
 of muscles, 128 
 
 of nerves, 97, 98 
 
 of ovaries, 118 
 
 of pancreas, 108 
 
 of skin, 126 
 
 of spinal marrow, 96, 97 
 
 of spleen, 113 
 
 of testicles, 118 
 
 of uterus, 118 
 
 of vessels, loi 
 Anesthesia, 91 
 Aneurysms, 35 
 Angina pectoris, 99 
 Anhidrosis, 79, 91, 126 
 Annulus Vieusseni, 34 
 Anorexia, 80, 107 
 Anthrax, 63 
 
 Aromatic substances, 172 
 Arsenic, 53, 203, 280 
 Arterial blood, sugar of, 182, 188 
 Arteriosclerosis, 99 
 Artery, ligation of femoral, 38 
 
 of gastroepiploic, 49 
 of splenic, 49 
 Asphyxia, 38, 55, 158 
 Assimilation, 200, 203, 241 
 Asteatosis, 79, 126 
 
 307 
 
3o8 
 
 INDEX. 
 
 Asthenopia, 124 
 
 Atrophy, acute yellow, of the liver, 49 
 
 Autophagia, 81, 168 
 
 Azoturia, 228 
 
 Balanitis, 118 
 
 Balanoposthitis, 118, 160 
 
 Basophilia, perinuclear, 102 
 
 Bile, 49 
 
 Blood, acids in, 133, 224 
 corpuscles, loi 
 glycogen in, 177 
 hemoglobin of, 138 
 specific gravity of, loi 
 sugar of, 187 
 tests of, 244 
 
 Bones, 128 
 
 Brain, 32, 35, 36, 86, 95 
 
 Bread, 274 
 
 Breath, 84 
 
 Bulimia, 79 
 
 Butter, 271 
 
 Butyric acid. See Acid, Butyric. 
 
 Cachexia, 68 
 
 Calculi in gall-ducts, 37, 49, 79 
 
 in kidneys and urinary ducts, 
 
 in pancreas, 109 
 
 Calories, 232 
 
 Cane-sugar. See Saccharose. 
 
 Carbohydrate, 24, 57, 105, 170, 184, 
 232 
 
 Carbon dioxid. See Acid, Carbonic. 
 monoxid, 56 
 
 Carbuncle, 83 
 
 Casts, renal, 248 
 
 Cataract, 119-121, 160 
 
 Chalazion, 124 
 
 Chloral, 51, 55 
 
 Chloralamid, 51, 55 
 
 Chloroform, 55 
 
 Cholera, 63, 64 
 
 Chorea, 35 
 
 Circulation, 98 
 
 Cirrhosis of kidneys, 115 
 of liver, 50, 137 
 of pancreas, 109, 137 
 
 Classes, social, 22 
 
 Climate, 20 
 
 Cold, 20, 68 
 
 Coma, 85, 131-133, 161, 258 
 
 Constipation, 106, 258 
 
 Cramp, 89 
 
 Crises gastriques, 106 
 
 Croup, 63, 158 
 
 Crura cerebelli, 31, 32 
 
 cerebri, 32 
 Crystallose, 279 
 Curare, 57 
 
 Cysticercus racemosus, 35 
 Cystitis, 115 
 
 D. 
 
 Decubitus, 83 
 
 Deiter's nucleus, 31 
 
 Delphinin (=methyl delphinin), 57 
 
 Dextrin, 170, 219 
 
 Diabetes alternans, 44, 216 
 
 bronze-colored, 137, 138 
 
 constitutional, 136 
 
 decipiens, 78 
 
 fat, 136 
 
 gastro-intestinal, 137 
 
 gouty, 136 
 
 hepatogenic, 137 
 
 herpetic, 136 
 
 in animals, 15 
 
 infantilis, 157-164 
 
 insipidus, 28, 39, 67 
 
 mild, 10, 129, 202, 220 
 
 muscular, 137 
 
 neurogenic,! 134 
 
 pancreatic, 134, 164-169 
 
 periodic, 44 
 
 renal, 137 
 
 severe, 10, 130, 202, 220 
 Diacetic acid. See Acid, Diacetic. 
 Diamins, 220 
 Diet, 203, 227, 261 
 Digestion, 104, 170 
 Digestive organs, 104-114 
 Dilatation of stomach, 104 
 Diphtheria, 62, 158 
 Diplopia, 95 
 Disaccharids, 170 
 Distribution of diabetes, 16-18 
 Diuretin, 58 
 Dysentery, 62 
 
 E. 
 Ears, 124 
 
 Eczema, 41, 91, 124, 127 
 Electrotherapy, 292 
 Emotions, 22, 37, 38, 159, 203 
 Encephalomalacia, 36 
 Endarteritis, 97, loi, 138 
 Energy. See Vital Force. 
 Enuresis, 158 
 Epilepsy, 36, 86 
 Episcleritis, 124 
 Erysipelas, 63, 84 
 Erythema, 127 
 
 nodosum, 63 
 
INDEX. 
 
 309 
 
 Ether, 55 
 
 Etiology of diabetes mellitus, 16-25. 
 (Race — mode of life — sex — age — 
 climate — heredity — profession — ex- 
 cesses — emotions — sedentary life — 
 diet — exposure — trauma — sunstroke 
 — adiposity — gout.) 
 
 Excesses, 22, 23, 203 
 
 Exophthalmic goiter, 36, 86 
 
 Exposure, 24 
 
 Exudates, 203 
 
 Eyes, 1 18-124 
 
 F. 
 
 Fat, 60, 105, 170, 171, 184, 209, 212, 
 
 232 
 Fatigue, 68, 203 
 Feces, 58, 105, 135 
 Fermentation, 000 
 Ferments in blood, 180, 191 
 
 in liver, 179 
 
 in urine, 220 
 Fesselungsglycosurie, 38 
 Fever, 166, 203 
 Fibrin, 57 
 Food, 170, 189 
 
 Frequency of diabetes mellitus, 15-18 
 Furunculosis, 41, 83 
 
 G. 
 
 Galactose, 207, 240 
 Gall-stones, 37, 49, 79, 112 
 Ganglion, celiac, 34, 35 
 
 inferior cervical, 34 
 superior cervical, 34 
 thoracic, 34 
 Gangrene, 81, 91, 103, 293 
 Gastric juice, 108 
 Gingivitis, 85 
 Glands, gastric, 108 
 peptic, 108 
 salivary, 38 
 thyroid, 38 
 Glucose, 167, 170, 184, 206, 232, 239 
 Glycemia, 29, 188 
 Glycogen, 52, 97,1168, 170, 172, 173- 
 
 180 
 Glycolysin, 191 
 Glycolysis, 191-193 
 Glycosuria, alimentary, 29, 48, 173, 
 199 
 cachectic, 68 
 cardiac, 28, 58 
 concomitant, 28 
 experimental, 31 
 fatigue, 68 
 fetal, 66 
 from cold, 68 
 
 Glycosuria, gouty, 67 
 
 hepatogenous, 48 
 in animals, 37 
 marasmic, 68 
 nervous, functional, 37- 
 48 
 organic, 30-37 
 pancreatic, 165, 166 
 puerperal, 65 
 renal, 69 
 senile, 68 
 
 simple, 9, 42-48, 242 
 starvation, 67 
 toxic, 50-62. (From acids 
 — metals and salts of 
 alkalies, phosphorus, 
 arsenic, mercury, lead, 
 uranium — alcohol, 
 ether, chloroform, 
 chloral, chloralamid, 
 amyl nitrite, ammonia 
 — carbonic acid, car- 
 bon monoxid — curare, 
 strychnin, delphinin, 
 morphin, veratrin, er- 
 gotin, caffein — diuretics 
 thyroidin, tuberculin, 
 pancreatin, fecal ex- 
 tract — phloridzin and 
 phloretin.) 
 Glycosurias, 26, 204 
 Glycosuric acid. See Acid, Glycosuric. 
 Glycuronic acid. See Acid, Glycu- 
 
 ronic. 
 Gout, 25, 39, 67 
 Graves' disease. See Exophthalmic 
 
 Goiter. 
 Gum, animal, 219, 240 
 Gummata, 63 
 Gums, 85 
 
 H. 
 
 Hair, 127 
 
 Heart, 98, 100 
 
 Hemianopsia, 95 
 
 Hemoglobin, 138 
 
 Hemorrhage, 94, 100, 124 
 
 Hemosiderosis, loi, 138 
 
 Heredity, 21, 159 
 
 Herpes, 91, 124, 127 
 
 History, 10-15 
 
 Homogentisinic acid. See Acid, Ho- 
 
 mogentisiftic. 
 Hordeolum, 124 
 Hunger, 79 
 Hydrotherapy, 290 
 Hygiene, 255 
 Hyperesthesia, 90, 124, 125 
 
3IO 
 
 INDEX. 
 
 Hyperglycemia, 29, 48, 49, 56, 57, 71, 
 
 165, 190 
 Hyperidrosis, 91 
 Hypermetropia, 121 
 Hypochondriasis, 87 
 Hypoglycemia, 29, 33, 49, 56, 61 
 Hysteria, 88 
 
 Ichthyosis, 127 
 
 Icterus, 53 
 
 Impetigo, 127 
 
 Impotence, 117 
 
 Incontinence. See Emiresis. 
 
 Infection, 25 
 
 Infectious diseases, 62, 159 
 
 Influenza, 62, 64 
 
 Inosit, 207 
 
 Insomnia, 41, 256 
 
 Inulin, 207 
 
 Invertin, 170 
 
 Iridocyclitis, 123 
 
 Iritis, 123 
 
 Irritability, 41 
 
 Isomaltose, 219 
 
 K. 
 
 Keratitis, 123 
 Kidneys, 69, 114-117 
 Knee-jerk. See Reflexes. 
 Kreatin, 217 
 Kreatinin, 217, 239 
 
 Lactaciduria, 53, 57 
 
 Lactose, 62, 66, 167, 171, 206, 208, 
 
 232, 239 
 Lactosuria, 65, 199 
 Laios, 208 
 Lassitude, 128 
 Lead, 53 
 Leucin, 219 
 Leukemia, 68 
 Leukocytes, 177, 178 
 Leukocytosis, loi 
 
 Levulose, 167, 171, 206, 208, 239, 279 
 Levulosuria, 167, 199 
 Lichen, 127 
 Life-insurance, 243 
 Lipaciduria, 218 
 Lipemia, 102, 212 
 Lipuria, 212, 218 
 Liver, 48, 50, 57, 59, no, 137, 173, 
 
 214 
 Lobus diabeticus, 31, 32 
 
 hydruricus, 31, 32 
 
 opticus, 32 
 Lungs, 103 
 
 Luxuries, 23 
 Lymphangitis, 84 
 Lyssa, 63 
 
 M. 
 
 Malaria, 62, 64, 137 
 
 Mai perforant, 83, 91 
 
 Maltose, 167, 170, 209, 219, 239 
 
 Maltosuria, 135, 199, 209 
 
 Mannite, 207 
 
 Marasmus, 68, 102, 161, 204 
 
 Marriage, 254 
 
 Massage, 203, 290 
 
 Mastication, 104 
 
 Masturbation, 158 
 
 Measles, 62 
 
 Mechanotherapy, 289 
 
 Melancholia, 87 
 
 Meningitis, 35 
 
 Meningomyelitis, 36 
 
 Mental treatment, 255 
 
 Mercury, 53 
 
 Metabolism, 168 
 
 Metallic salts, 53 
 
 Migraine, 89 
 
 Milk, 276 
 
 Milk-sugar. See Lactose. 
 
 Monosaccharids, 170 
 
 Morbus gravesi. See Exophthalmic 
 
 Goiter. 
 Morphin, 57, 61 
 Mouth, 79. 84 
 Mucin, 214, 215 
 Muscles, 128, 203 
 Mydriasis, 121 
 Myelitis, 36 
 Myocardium, 99 
 Myopia, 121 
 
 N. 
 Nails, 91, 128 
 Nephritis, 60 
 Nephrolithiasis, 115 
 Nerve, abducent, 95 
 
 crural, 91 
 
 depressor of the pneumogas- 
 tric, 33 
 
 dorsal, 34 
 
 facial, 95 
 
 oculomotor, 95 
 
 optic, 122 
 
 pneumogastric, 31, 33 
 
 sciatic, 33 
 
 splanchnic, 34 
 
 supraorbital, 89 
 
 sympathetic, 34,98, 183 
 
 tibial, 97 
 Nervous symptoms, 86-95 
 Neuralgia, 37, 88, 158 
 
INDEX. 
 
 311 
 
 Neurasthenia, 39, 70, 88, 106 
 Neuritis, go, 97, 102 
 Neuroses, 36, 37, 87, 106 
 Neurotabes, 94 
 Nitrobenzol, 51 
 Nitrogen, 166, 170, 233 
 Nitrotoluol, 51 
 Nuclein, 214, 215 
 Nutritive needs, 168, 232, 260 
 
 O. 
 
 Obesity, 25, 39, 66 
 
 Oidium albicans, 160 
 
 Operations, 292 
 
 Ophthalmic goiter, 86 
 
 Opium, 203, 280 
 
 Orchitis, 118 
 
 Organotherapy, 288 
 
 Osteomalacia, 231 
 
 Osteoporosis, 85, 129 
 
 Otalgia, 125 
 
 Otitis, 124, 125 
 
 Ovaries, 118 
 
 Oxalic acid. See Acid, Oxalic. 
 
 Oxaluria, 41, 45, 218 
 
 /3-Oxybutyric acid. See Acid, ^-oxy- 
 
 butyric. 
 Oxygen, 234 
 
 P. 
 
 Pancreas, 108, 164-169 
 Pancreatic juice, 105, 168 
 Pancreatin, 58 
 Paralysis, 91 
 
 agitans, 35 
 
 general, progressive, 35 
 Paraplasma, 57, 172 
 Paraplegia, 91 
 Paresthesia, 88 
 Paronychia, 128 
 Pedunculi cerebelli, 32 
 
 cerebri, 32 
 Pemphigus, 127 
 Pentoses, 175, 215, 219, 240 
 Peptonuria, 53 
 Pericementitis, 85 
 Periostitis, 85 
 Perspiration, 231 
 Pertussis, 63, 158 
 Petechiae, 127 
 Phenacetin, 203 
 Phimosis, 118, 160 
 Phlegmon, 84 
 Phloretin, 59 
 Phloridzin, 59, 166 
 Phloroglucin, 59 
 
 Phlorose, 59 
 
 Phosphaturia, 230 
 
 Phosphorus, 49 
 
 Phthisis (pulmonary tuberculosis), 102 
 
 Pigment, 138 
 
 Piqure, Bernard's, 31 
 
 Pityriasis, 127 
 
 Pneumaturia, 115 
 
 Pneumonia, 63, 103, 161 
 
 Pollakiuria, 41, 78 
 
 Polydipsia, 76 
 
 Polyneuritis, 90 
 
 Polyuria, 31, 58, 76, 207 
 
 Potatoes, 276 
 
 Potency, sexual, 89 
 
 Pregnancy, 66, 118, 254 
 
 Presbyopia, 121 
 
 Professions, 21 
 
 Prognosis, 63, 138-141, 160 
 
 Prophylaxis, 253 
 
 Propionic acid. See Acid, Propionic. 
 
 Proteids, 57, 105, 170, 171, 184, 201, 
 
 212, 232 
 Pruritus, 126 
 
 Pseudo angina pectoris, 99 
 Pseudotabes, 93 
 Psoriasis, 127 
 Psychoneuroses, 21, 87 
 Ptomains, 220 
 Ptosis, 95 
 Pulse, 'JT , 98, 131 
 Pupil, Argyll Robertson, 92 
 Purpura, 127 
 Pylethrombosis, 49 
 Pyorrhea, alveolar, 85 
 Pyrocatechin, 5, 217 
 
 Quotient of respiration, 185, 235 
 
 R. 
 
 Race, 17 
 
 Raynaud's disease, 83, 91 
 Recovery, 65, 160 
 Reflexes, 92 
 Remedies, 280 
 Respiration, 131, 234 
 Respiratory organs, 102 
 Retinitis, 122 
 Rupia, 127 
 
 S. 
 
 Saccharids, 170, 174 
 Saccharin, 279 
 Saccharomyces apiculatus, 239 
 
312 
 
 INDEX. 
 
 Saccharose, 167, 170, 206, 232 
 
 Saccharosuria, 46, 47, 199, 201 
 
 Salicylic acid. See Acid, Salicylic. 
 
 Saliva, 104, 202 
 
 Sanatoriums, 256 
 
 Scai-let fever, 62, 158 
 
 Sciatica, 36, 88 
 
 Scleritis, 124 
 
 Sclerosis, multiple, 35 
 
 Secretions, 79, 104 
 
 Sedentariness, 23 
 
 Senility, 68 
 
 Sensibility, 91 
 
 Sex, 19, 159 
 
 Simulation, 252 
 
 Sleep, 32, 256 
 
 Spinal cord, 32, 36, 57, 91, 96, 97 
 
 Spleen, 113 
 
 Spondylitis, 37 
 
 Sputa, 203 
 
 Stages of diabetic dystrophy, 9, 10, 
 
 42-47, 129 
 Starch, 52, 170, 206, 232 
 Starvation, 24, 67, 159, 167, 183, 203 
 Sterility, 118 
 Stools, 105, 134 
 
 Strains, emotional and intellectual, 22 
 Strychnin, 51, 57 
 Sugar in blood, 10, 187 
 in liver, 11, 180 
 in urine, 9, 11, 73. See Galac- 
 tose, Glucose, Lactose, Levu- 
 lose. Maltose, Saccharose. 
 Sulphates, 172 
 Sulphonal, 56 
 
 Sulphuric acid. See Acid, Sulphuric. 
 Sunstroke, 25 
 Sweat, 202 
 Sweets, 24, 158 
 
 Symptoms of diabetes, 70-138 
 Syphilis, 35, 63, 287 
 Syzygium jambulanum, 62, 168, 284 
 
 T. 
 
 Tabes dorsalis, 35 
 
 Tears, 202 
 
 Teeth, 42, 85 
 
 Temperature, 85, 160 
 
 Test, Barfoed's (glucose), 239 
 
 Bernard-Seegen's (glucose), 238 
 Biebrich's (blood, color), 245 
 Bremer's (blood, color), 244 
 Ehrlich-Biondi's (blood, color), 
 
 245 
 Esbach's (albumin), 248 
 Fischer's (glucose), 237 
 
 Test, Gerhardt's(diacetic acid), 11,71, 
 240, 247 
 Heller's (albumin), 248 
 Kjeldahl's (nitrogen), 248 
 Nylander's (glucose), 237, 239 
 Robert's (glucose), 247 
 Troemmer's (glucose), 237 
 Williamson's (blood, color), 245 
 Worm-Miiller's (glucose), 237 
 
 Testicles, 118 
 
 Theories, 12-14, I79. 194-198 
 
 Thirst, 42, 76 
 
 Thyroidin, 58 
 
 Tongue, 84 
 
 Toxins, 71, 220, 221 
 
 Transmutation, 86 
 
 Trauma, 32, 140, 159 
 
 Tuberculin, 58 
 
 Tuberculosis, 68, 102, 137, 161 
 
 Tumors (new growths), 35 
 
 Typhoid, 62, 64 
 
 Tyrosin, 219 
 
 U. 
 
 Urea, 216 
 
 Uric acid, 216, 239 
 
 Urinary organs. 114-117 
 
 Urine, 73-76, 160 
 color, 75 
 density, 75 
 quantity, ']'] , 246 
 specific gravity, 75, 246 
 substances in. See under the 
 different headings : Acetone, 
 Albumin, Alkapton, Ammo- 
 nia, Butyric Acid, Casts 
 {renal'). Dextrin, Diacetic 
 Acid, Diamins, Fatty 
 Acids, Ferment, Glycogen, 
 Glucose, Glycosuric Acid, 
 Glycuronic Acid, Gtim, Hip- 
 puric Acid, Homogentisinic 
 Acid, Indoxyl, Inosite, Iso- 
 maltose. Lactic Acid, Lactose, 
 Laios, Levulose, Leucin, 
 Maltose, Oxalic Acid, ft- Oxy- 
 butyric Acid, Pentoses, Pto- 
 mains Pyrocatechin, Reduc- 
 ing Substances, Saccharose, 
 Skaioxyl, Sulphuric Acid {in 
 sulphates and coupled). Tox- 
 ins, Urea, Uric Acid, Uro- 
 bilin, Urochloralic Acid, Uro- 
 leucin. 
 toxicity, 220 
 
 Urobilin, 219 
 
 Urochloralic acid, 239 
 
INDEX. 
 
 313, 
 
 Uroleucin, 219 
 Urticaria, 91 
 Uterus, 118 
 
 Vaccinia, 63 
 
 Variola, 63 
 
 Vein, portal, 181, 189 
 
 Veins, hepatic, 181, 182, 188 
 
 in general, 181, 188 
 Ventricle, fourth, of the brain, 31, 95 
 
 (stomach), 104 
 Veratrin, 51, 58 
 Vermis, 32 
 Vessels, arterial, 181, 188 
 
 Virility, 41 
 Vital force, 184-187 
 Vulnerability, 81 
 Vulvitis, 118, 160 
 
 W. 
 
 Water, 231, 278 
 Weighing, 249 
 Weight of body, 80 
 
 Xanthoma tuberosum diabeticum, 127 
 
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MORRIS' 
 
 Text=Book of Anatomy 
 
 SECOND EDITION 
 Thoroughly Revised and Greatly Improved 
 
 790 Illustrations, of which many are in Colors 
 
 Royal Octavo. Cloth, $6.00 ; Sheep, $7.00 ; Half Russia, $8.00 
 
 Two Reviews Recently Published 
 by Two Leading Medical Journals 
 
 From 
 
 The Medical Record, New York. 
 
 " The reproach that the English lan- 
 guage can boast of no treatise on anatomy- 
 deserving to be ranked with the masterly 
 works of Henle, Luschka, Hyrtl, and 
 others, is fast losing its force. During 
 the past few years several works of great 
 merit have appeared, and among these 
 Morris's " Anatomy " seems destined to 
 take the first place in disputing the palm 
 in anatomical fields with the German 
 classics. The nomenclature, arrange- 
 ment, and entire general character re- 
 semble strongly those of the above-men- 
 tioned handbooks, while in the beauty 
 and profuseness of its illustrations it sur- 
 passes them. This edition ofters but few 
 changes ; a chapter on the skin has been 
 added, and a useful list of vestigial and 
 abnormal structures has been compiled. 
 Sections especially worthy of praise are 
 those on surgical and topographical anat- 
 omy, and the chapter on the nervous 
 system is presented with great clearness 
 and fullness. The ever-growing popu- 
 larity of the book with teachers and 
 students is an index of its value, and it 
 may safely be recommended to all inter- 
 ested." 
 
 From 
 
 The Philadelphia Medical Journal. 
 
 " Of all the text-books of moderate size 
 on human anatomy in the English lan- 
 guage, Morris is undoubtedly the most 
 up-to-date and accurate. The changes 
 from the first edition are not marked ; 
 perhaps the most noticeable feature is 
 that there are twenty less cuts than in the 
 first edition. Those which have been 
 omitted, however, will not be greatly 
 missed. The saving of space by the 
 omission of a discussion of histology is a 
 decided advantage, giving room for much 
 matter of importance in these days when 
 every student is obliged to own a special 
 treatise on histology. To enumerate the 
 numerous differences which are notice- 
 able in the descriptions given by this book 
 from those in many of the older anatomies 
 would require too much space. The 
 changes, however, almost without excep- 
 tion, tend toward an improved nomen- 
 clature and greater accuracy. This is 
 particularly noticeable in the parts de- 
 voted to descriptions of the abdominal 
 viscera and the joints. . . . For the stu- 
 dent, the surgeon, or for the general prac- 
 titioner who desires to review hisanatomy, 
 Morris is decidedly the book to buv." 
 
 \*The illustrations in number, correctness, and excellence of execution 
 are equaled by no similar treatise, about $1000 having been expended on 
 new and improved blocks for this edition alone. Handsome circular free. 
 
COLUMBIA UNIVERSITY LIBRARIES 
 
 This book is due on the date indicated below, or at the 
 expiration of a definite period after the date of borrowing:, 
 as provided by the library rules or by special arrangement 
 with the Librarian in charge. 
 
 DATE BORROWED 
 
 DATE DUE 
 
 DATE BORROWED 
 
 DATE DUE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 C23 (1264) BOM 
 
 
 
 
 
RC660 
 
 ^^^" 1900 
 
 <^ diabetes mp-n-; + , 
 suria, "^^ilitus and gi^^co- 
 
 
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