% fyxmll ^vAvmxi^ pHatJg THE GIFT OF ...^ib,..H^-^.-dsu..'^.«^OiX-... kz^^-Uio t^ Cornell University Library arV19378 Diabetes: its causes, sy"j;P|0";f,'..,3!|]j',,,fK^ 3 1924 031 254 331 olin,anx Cornell University Library The original of tliis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31 924031 254331 No. 8 IN THE PHYSICIANS' AND STUDENTS' READY REFERENCE SERIES. DIABETES: Its Causes, Symptoms, and Treatment. CHARLES W. PURDY, M.D., queen's university. Honorary Fellow of the Royal College of Physicians and Surgeons, Kingston ; Member of the College of Physicians and Surgeons of Ontario ; Author of " Bright's Disease and Allied Affections of the Kidneys;" Member of the Association of American Physicians, of the American Medical Association, of the Chicago Academy of Sciences, of the Illinoia State Microscopical Society, etc., etc. ■UTTTIEa: CL,IITIC:.ft.I-. IL.I^-crSTI2..^3LTI02SrS. Philadelphia and London : F. A. DAVIS, PUBLISHER, 1890. /, ^S-^0 /\.£bA3b^ Eator«d aooording to Act of Congress, in tho yesr 1S90. by F. A. DAVIS, Id tho Office of tho Librarian of Congrass at Washington, D. C, U. S. A. Philadelphia: The Medical Bulletin l*rinting House, 1231 Filbert Street. Thomas Grainger Stewart, M.D., F.R.S.E., PHYSICIAN IN OEDINAET TO HEE MAJESTY THE QUEEN FOE SCOT- I.AN3>, PEESIDENT OF THE EOYAI. COLLEGE OF PHYSICIANS or EDINBtJEOH, PEOPESSOE OF PEACTICE OF PHYSIC AND OP CLINICAL MEDICINE, UNIVEESITY OF EDINBUEGH, AS A TOKEN OP HIGH PERSONAL ESTEEM AND IN EEMEMBRANCE OF NUMEROUS PKOEESSIONAL FAVORS AND PERSONAL KINDNESSES, THE FOLLOWING PAGES AEE INSCEIBED BY THE AUTHOR. PREFACE. The object of this volume is to furnish the physician and student with the present status of our knowledge on the subject of diabetes in such practical and concise form as shall best meet the daily requirements of prac- tice, as they seem to me from a careful study and re- corded observation of the disease extending over a period of twenty-one years. I have dwelt with some minuteness upon the treat- ment, more especially in matters of diet, well knowing that a disregard of these details constitutes the most frequent cause of failure in controlling the disease. In order to further elucidate this part of the subject, I have illustrated the various forms of the disease with their appropriate treatment from cases in actual prac- tice, selected from my clinical records. Finally, I have endeavored to bring out prominently the leading features of diabetes as it occurs in the United States, together with the natural resources of the country best suited to the disease, as the waters, foods, and climate, since the very extensive range of these entitles them to rank in point of efficiency for the relief of the diabetic patient as at least equal to those in any other land or clime. The Author. 163 State Stkbet, September, 1890. (V) CONTENTS. SECTION" I. Historical, Geographical, and Climatological Considerations op Diabetes Mellitus, . 1 Early history of diabetes. Geographical distribution : Europe, Asia, Australia, Central America, "West Indies, South America, Pacific Islands, United States. Climatology of diabetes mellitus : Cold, moisture, altitude, warmth, etc. Mortality : By States ; in cities and towns ; in rural dis- tricts ; increasing death-rate in United States. SECTION 11. Physiological and Pathological Considerations OF Diabetes Mellitus, 19 The liver: Physiological disorder; glycogenic function of. Formation of sugar : Its source. Carbohydrate foods : Their destination in health ; perversion of, in diabetes mel- litus. Nervous system in diabetes : Medulla ; the vagi. Artificial glycosuria ; Caused by traumatisms ; poisoning by strychnia, chloroform, and curare. Pancreatic diabetes. SECTION III Etiology of Diabetes Mellitus, .... 31 Predisposing influences : Heredity ; race influences ; sex ; age ; climate. Exciting causes: Mental emotion; brain dis- orders ; excessive eating ; malaria ; alcoholism ; sexual excesses, etc. SECTION lY. Morbid Anatomy op Diabetes Mellitus, . . 41 The liver : Enlargement ; hyperaemia, etc. Lungs ; Phthisical changes ; cheesy deposits ; cavity formation ; pneumonic changes. Pancreas : Fibrosis ; fatty degeneration ; cancer ; calculous concretions, etc. Kidneys: Enlargement; hy- peraemia ; tubular changes. Heart : Hypertrophy. Brain : Alleged changes in. The blood : Chemical changes ; physio- logical changes. (vii) viii Contents, SECTION Y. Symptomatology of Di.vbetes Mellitus, . . 47 Classiticatiou of diabetes moUitus. Classical features. Diges- tive SNiuptoms. Circulatory symptoms. jSorvous symp- toms. Cutaneous symptoms. Muscular sj-mptoms. Urinary sjnuptoms : Dittrt'sis ; sugar; urea; albuminuria. Coin- plicatious : Coma ; pulmonary affections ; ocular disorders ; phlegmon and gangrene; iUbuminuria. Course and dura- tiou. lii;ignosis. Examination of urine : Feliling's test for sugar; Haines's test for sugar; pheuylhydrazin test; the author's quantitative test for sugar ; approximate method. Prognosis: Age ; p;uicreatic eomplicatiou ; patellar reflexes, etc SECTION VI. Treatment of Diabetes Mellitus, ... 81 Prophylaxis. Geneiul dietetic considerations: Breads; farina- oca* ; green vegetables ; milk ; meats, etc. l^everages : Al- coholics ; mineral waters. List of foods permitted. List of foods prohibited. Systematic method of dieting. Medl- cimil treatment: Opiuiu ; antipyrin ; bromides; ergot ; ar- senic ; iodoform ; jaiubul ; oxygon givs ; alkiUies. Treatment of complications : Constipation ; dyspepsia ; furuncles ; coma. Hygienic treatment : Clothing ; veutilatlou ; baths ; exercise ; sleep, etc SECTION VII. Clinioai Illustrations of Diabetes Mellitus, . 115 Cases of severe type iu younj: subjects. Mild form after middle age. Case of oxceptioujil severity in aged subject. Case of maUirial origin. Cases illnstrating miUl type in Hebrew race. Civse iu cliildliood. Cases illustrating oxygen treat- ment. SECTION VIII. Diabetes Insipidus, 161 Classifloation. Etiology. Pathology. Symptoms and course. Duration. Diagnosis. Prognosis. Treatment. BiBLIOOllAPIlY, 173 DIABETES. SECTION I. Diabetes Mellitus. HISTOEICAL, GEOGRAPHICAL, AND OLIMATOLOGICAL CONSIDERATIONS. We have reasons to believe that diabetes was known in periods of remote antiquity. The earliest records of the disease come from India. In the Ayur Yeda of Susriita is to be found the following passage* : " Mellita urina laborantem quern medicus indicat, ille etiam in- curabilis dictus est." The presence of the disease in various parts of Europe and Asia during very remote periods is referred to by numerous writers, although nothing definite upon the subject is to be found in the extensive writings of Hippocrates. Celsus, who lived nineteen hundred years ago, wrote : " If the quantity of urine which is passed is larger than the quantity of liquids imbibed .... emaciation is caused, and life is endangered." Both Galen and Aretseus speak of the disease in several passages, but the latter especially has described it minutely, and was one of the first to use the name "diabetes." He wrote : "The patients urinate unceas- ingly .... they are tortured by an unquenchable thirst ; they never cease drinking and urinating . . . . the integuments of the abdomen become wrinkled, and the whole body wastes away." •Hirscli'8 Hand-book of Historical Pathology, vol. ii, p. 643. 1 A (1) 2 Diabetes Mellitus. During the middle at;es wiitois have made repented mention of a disease eharaeteiizod by excessive flow of iiriue, thirst, ami Tivasting, which must have referred to diabetes ; but none of tliem speak of the sweet jiroper- ties of the urine. This peculiarity of the urine, if linowii, seems to have escaped notice until about two hundred years ago, when Thomas "Willis lirst called attention to it.* It was not, however, until one hundred years later (lT7;i) that Dobsonf first showed that the [leculiar taste of diabetic urine depended upon sugar, which he demonstrated by evaporating the urine and producing the sugar in crystals. About twenty years later John Hollo published a systematic essay on diabetes, minutely describing a number of cases, and his thorough discns- sion of the subject laid the foundation of its subsequent literature. The geographical distribution of diabetes embraces the widest possible range, with few exceptions, including every land and clime. The records show a areater fre- quency of the disease in certain locations than in others, but precisely how mnch this depends upon climatic con- ditions has, up to the present time, been undetermined by systematic observation. The disease appears to be rare in St. Petersburg, as attested by Attenhofer and Lefcvie, tlie former not having seen a case in his practice, or heard of one in that of his colleagues, for six years. Similar accounts come from Copenhagen, wliere no records of death from diabetes occur in the mortality tables from 18:!5to 1S38. We have records of cases from Turkey and Egypt, and in Morocco the disease is not uncommon. Ts'o mention of the disease is made by the English or French phy- * Pliarmaooutii'o Rivtioiialis, sec. iv, oli;i]i. iii, p. (U. t Med. Observer luid Imiuirer, Loudon, 177U, v, 'JIKJ. Geographical and other Considerations. sicians in their practice on the Coast of Guinea. On the other hand, the disease is remarkably common in Ceylon and in some parts of India, notably in Bengal. From China, Japan, Australia, and the islands of the Pacific we have no authoritative records of the disease ; and the same may be said of Central America and the West Indies. Blair declares that in Guiana it is abso- lutely unknown. In Mexico it is met with quite often, but in Brazil it seems to be little known. The following table, the data of which is taken from "Hirsch's Hand-book," gives in an incomplete way the distribution of diabetes throughout Europe : — Table I. Location. Period. Deaths from Diabetes per 1000 Deaths. England .... Ireland , Schleswig liolstein . . Berlin Chemnitz .... Frankfort-on-the-Main Wurzburg . . . . , Brussels 1852 to 1841 1871 to 1877 to 1871 to 1865 to 1858 to 1864 to 1869 1879 1879 1874 1880 1855 1880 1.25 .74 .65 .94 1.00 1.60 1.20 .60 With regard to the climatology of diabetes, Dr. Dickinson, who has studied tlie subject closely in Great Britain, concludes that the disease is more common in the colder counties of the kingdom than in the warmer ones. It has seemed to me that our own country offers exceptional advantages for climatic study of diabetes. The United States comprises a territory of about 3000 miles in length by about 2000 miles in width. Its area is over three and a half millions of square miles — nearly equal to the whole continent of Europe — or 4 Diabetes Mellitus. twenty-nine times larger than Great Britain and Ireland. It possesses all ranges of mean temperatures for tlie year, from 35° F. in Vermont, to 75° F. on the Gulf coast; all elevations from the sea-level to an altitude of 10,000 feet and over; all ranges of rain-fall for the year from 10 to 60 inches. It will be readily perceived, therefore, that such a wide range of geographical and climatic features enable us to give an emphatic answer to many questions relating to the influence of climate over disease, which has proved to be exceedingly' bafliing in those countries possessing a more limited area and range of climate. In attempting a systematic study of the climatology of diabetes in our own country, I was first met bj' the unfortunate fact, tliat the United States, unlike all other civilized nations, has no system of registration of vital statistics. The data afforded by the census is, therefore, the chief source from which even an approximate esti- mate can be made of liability to particular forms of dis- ease in different parts of the countrj^. Fortunatelj', an effort has been made in the last census (1880) to obtain more complete and accurate returns of deaths than have before been furnished, and likewise to make the returns more accurate as regards the causes of death. With re- gard to diabetes, the deaths have been reported under the head of " glycosuria," and, therefore, cases of non- saccharine urine — diabetes insipidus — do not vitiate the records. In order to insure greater accuracy in calculations, I have excluded from my records and tables all States and Territories furnishing a total death-list of less than 5000 ; because the comparatively low mortality from diabetes — .5 to 6. per 1000 deaths — renders estimates on a lower basis necessarily very faulty. I have compiled the fol- Oeographical and other Considerations. lowing table (Xo. II) chiefly from the mortality reports of the tenth census of the United States, ending with the month of May, 1880 :— Table II. — Deatlis Jrom Didbeks per 1000 Deailw in each State in the United States in 1880. State. Total Deaths. Deaths from Diabetes. Ratep 1000. 17,929 10. ..55 14,812 11. .70 11,.5.30 23. 1.99 9,179 31. 3.37 21,.549 24. 1.11 45,017 98. 2.11 31,213 85. 3.72 19,377 47. 2.43 1.5,160 24. 1..58 33,718 41. 1.31 14,.514 15. 1.08 9,523 42. 4.41 16,919 19. 1.12 31,149 65. 1.96 19,743 53. 2.68 9,037 16. 1.99 14,583 13. .88 36,615 53. 1.42 5,930 10. 1.68 8,474 10. 1.18 88,332 195. 2.20 31, .547 25. 1.11 43,610 1.39. 3.23 63,881 116. 1.81 15,728 10. .63 25,919 44. 1.69 24,735 19. .76 5,034 33. 6.36 24,681 29. 1.13 16,011 45. 2.81 Alabama . . , Arkansas . , California . , Connecticut . . Georgia . . , Illinois . . . Indiana . . , Iowa . . . , £ansa8 . . . Kentucky . . Louisiana . , Maine . . . . Maryland . , Massachusetts , Michigan . . . Minnesota , . Mississippi . . Missouri . . . Nebraska . . New Jersey . , New York . . North Carolina Ohio . . . . Pennsylvania . South Carolina Tennessee . . Texas . . . . Vermont . . . Virginia . . . Wisconsin . . It may first he noted that the mortality reports of the United States census for 1880 give a total mortality for the country from all causes of 756,893. Of these, 1443 were returned under the head of glycosuria. This gives an average ratio of deaths from diabetes for tlie whole country of 1.90 per 1000 deaths. 6 Diabetes Mellitus. The most notable feature brought out by Table II is the comparatively enormous mortality from diabetes in the State of Vermont — 6.36 per 1000 deaths, — so far as I am aware, the highest ratio of any place in the ■world. Now, the chief features of the climate of Ver- mont are the long-continued and severe winters. The snow remains on the ground from five to six months of the year, and the mean range of temperature is only about 35° F. The State of Maine, which adjoins Ver- mont on the north and east, and the climate of which is little, if any, less severe than that of tlie latter, furnishes tlie next highest mortality from diabetes in the United States— 4.41 per 1000. While there can be little doubt that the severitj' of the climate in these two northeastern States is chiefly responsible for the high mortality from diabetes, it 3'et remains to account for the dill'eronce in the mortality between these two States l\ing side by side. It is true that Maine borders on the sea, but three-fourths of the State is as far removed from the sea as Vermont. What, then, determines tlie dilferenee in the mortality from diabetes between tliese two States? I have no doubt, as I shall hereafter endeavor to show by numerous illustrations, that it is largely, if not solely, determined bj- altitude. It is perfectlj- clear to me that diabetes is a more fatal disease in liigher alti- tudes, and this holds true in anj' latitude. Under di- minished atmospheric pressure oxidation is greatly im- peded, and under such circumstances the disease will prove more fatal. It must not be forgotten that the amount of oxj'gen in the system, and consequently- the activity of oxidation in the economy, depends not upon the quantity of oxygen in the atmosphere, but directly upon the degree of atmospheric pressure. Thus, De- marquaj'^ has shown that the blood of people who dwell Geographical and other Considerations. 7 in a locality where the atmospheric piL'bSure is 011I3' 380 millimetres contains but one-half as much ox3'gen as the blood of those who live at the sea-board, where the atmospheric pressure is 760 millimetres. Now, the efl'ect of increased oxidation in the sj-stem is undoubtedly a favorable one in diabetic conditions, whether it be brought about by increased atmospheric pressure through residence near the se., -level, or by the more direct way of inhalations of oxygen gas ; indeed, the latter has re- duced remarkablj' — one-half — the quantity of sugar in the urine of diabetics without any associated change of diet. The State of Vermont, in addition to being one of the coldest States in the Union, has for the most part an elevation above the sea of from 3000 to 5000 feet, while its neighbor, Maine, lies comparatively low. It is true that Maine is largely billy and brolien country, but only a comparatively small part of the State -in the west and north rises into mountains. It may then be safelj^ assumed that cold and altitude are the chief climatic features that determine higli mor- tality from diabetes. If we pass to the south sufficiently far to reach the highest mean annual temj)erature of the country, — say Y5° F., — and select a State at or near the sea-level, such as Alabama, we find that the mortality from diabetes sinks to the lowest ratio in the country — .55 per 1000 deaths. In order, however, to reach more accurate conclu- sions as to climatic influences over diabetes, it is better to group together certain tracts of country whose climatic features in each group are as nearly alike as possible. With this end in view I have adopted the grouping of Mr. Gannott, the geographer of the Census Office, since it seems to me altogether the best that has 81 Diabetes Melhtiis. iS Cb 1^ ^ < '^^ w c 2 e ^ ^ 5* ^ (^ ^ R 1 ^ i^»*i e, ^ ? H m e3 <^ 3 0001 -laa SlUUSQ H rt ooooooooooooo o 5 - -■ -g A o o o o o iO iO ic w o s:? O 5:; OOO O OOOOO IQ CO CO C* CO 04 P^pc^P^PHpHp^f^pHP^^P^fHft^F^PHf=t^F^ o o o o o o — ~ to U5 lO «5 T 5" ^ ^ I I f f ~i ^r ~i r f oooooooooooooo in CO I r O O oooooooooo ta ia u? lo 05Cil>Q0aa"^C0i-IQ0"«ia ^ E S §9 iz; g 00 cS Iz; « OS „ 1-5 o I" eg cj K "§> I 5 OD O II e e ° § « o fe o f ;z; do PM ;?; (i; "3 ¥ o > I r-tWCO-^lCCOt-QO O i-H (M CO 't »C Geographical and other Considerations. 9 been attempted. "With this as the Lasis I have, from various sources, -worked out Table III, which gives the death-rate from diabetes per 1000 deaths, tlie mean annual temperature, the mean elevation, and the popula- tion of each group. The topography of these groups is given below : — "NoKTH Atlantic Coast Region comprises a strip of land from 50 to 75 miles wide, along the coast of Maine, New Hampshire, Massachusetts, Khode Island, and Connecticut. The surface is mainly undulating and hilly, becoming less varied toward the south. The coast is bold and rocky in Maine, but mostly sandy and low in Massa- chusetts, Rhode Island, and Connecticut. There Is little swamp or undralned land. The elevation Is from 100 to 500 feet. " The Middle Atlantic Coast Region Includes a strip of land comprising the coast counties of New Tork, New Jersey, Delaware, Maryland, and Virginia. The surface Is low and sandy, and along the New Jersey coast we find sandy reefs, shoreward from which are lagoons succeeded by extensive areas of swamp. The country is low, nowhere rising above 100 feet above the sea^level. "The South Atlantic Coast Region includes the coast coun- ties of North Carolina, South Carolina, and Georgia, with extensive reefs, inclosing large bays and sounds. A large proportion of the area Is low and swampy. The average elevation above the sea Is less than 100 feet. " The Gulp Coast Region includes the entire State of Florida and the coast counties of Alabama, Mississippi, Louisiana, and Texas. In Florida and Louisiana a large portion is uninhabited swamp land . The elevation Is less than 100 feet. " The Noktheastekn Hills and Plateaus include all that portion of Maine, New Hampshire, Massachusetts, and Connecticut not comprised In the coast strip, with all of Vermont and the northern portion of New Tork State, Including the Adirondacks. The area is not all, strictly speaking, mountainous It Includes a large amount of hills and broken country. It was originally covered with dense forests, which have In the settled portion been cut away. The elevation is mostly above 500 feet, and in considerable parts rises to mountains from 3000 to 6000 feet above the sea. "The Centkal Appalachian Region comprises the Catskill region of southeastern New York, the central portion of Pennsylvania, and the western part of Maryland, and chiefly consists of narrow, par- allel ridges, with singularly uniform crests, broken by few gaps, and 10 Pidhrlcf McIIittis. risins; I'rom 1000 to -'UiiO foot abdvo tho uarrow viillo.vssop;i™tiiif;' tlioiii, wliioh in their turn aro from 500 to 1000 toot nbovo tlio son. " Tins NoKTiiERN Lakk Keoion eomprisos tlioso parts of New York, Oliio, Iiidinim, Illiuols, Mioliijiiiu, and \Viseonsin wliteli lumior on tlio g-reat lakes. Tliese lnrf;o liodios of frcsU wiiter exort ii oiiiisidor- able inllueueo upon tlio oliimito, iu moderating the extremes and in rendering tlie ntmosplioro liumid. Tho moan elevntioii is about ;>00 toot above the sea. " TueInteuuiu 1'i,.4te.vu eomprisos that portion of tlie plain from the base of the Appalaebians eastward, wbieb ineludes parts of I'enn- sylvania, \'ir!;inia, and North Carolina; and also on tho west sido of the Appalaehians,t lie plateau eonn try of central New York, and western I'ennsvlvaiiiu. Tlie surl'aee is broken and hilly, butnowhoro rises into mountains. It was upland eonntry originally, covered with forests, whieh have beeu largely eleared away. It eoiitains comparatively little water suriaoo or swamp land. "Tiiu SouTUEHN Centh.vi. Ai'r.\i..\riiiA>f Keoion ineludes por- tions of N'irginia, West Virginia, the Cm-oliuas, Kentueky, Tennessee, (leorgia, and A labania. This is largely a inountaiiioiis region, 5000 to (WOO loot in height on the north, gradually diiiilnishing in tho south to 1000 feet or below. This region is largi'ly covered, espeeinlly lu tho south, with heavy forests of pine and hard \\'ood. "Tub Ouio Riveu Belt ineludes those parts of Ohio, Indiana, Kcntneky, and West Virginia whieh border on tho Ohio liivor. It is broken eonntry, more and more diversilied in the njiper part of tho river. For tho most part the rivers flow in deeji, narrow valleys, bor- dered by high blntl's and broken hills. Eleval ion, 500 to 1000 feet. "The Soutuehn Intekiou I'i.ate.^u ineludes the seotieuof tho Atlantio plain whieli extends aoross South Oarolina, tieorgia, with tho region in eeiitral Alabama and Mississiiiiii lying between the Ainui- laeliiau region and the (Sull'-eoast belt. It is mostly level and heavily tinibered, prineipally with pine, a largo part of which being what is popularly known as " pino barrens." It is a warm elimate, the tem- perature rising liiglior than on the eoast. Klovation , below 1000 feet. " The NoiiTniiiiNMissnssii'i'i Ki vnu Belt extends from the mouth oftheOliio Kiverto tho head of the Mississippi Kiyor, iiieluding |)ortioiis of Missouri, Iowa, and Minnesota on the western, and of Illinois and ^Viseollsin on the eastern, bank. Elevation, ,'iOO to ItlOO feet "TuE Southwest Centual REGIo^f includes the uorthwostorn part of Liniisiana, tho southoni part of Missmirl, all of Arkansas exeept that belonging to the south Mississippi River belt and eenl,ral Texas. It is mainly upland, and, exeept iiarts of Texas, is heavily timbered. Elovatioii, 100 to 500 feet. Geographical and other Considerations. 11 " The Pkairie Region comprises most of the State of IlIinoiB, the Bouthem part of Wisconsin, nearly all of Iowa, southern Minnesota, the northern part of Missouri, the eastern half of Kansas, a consider- able portion of Nebraska, and part of Dakota. The surface Is nearly level, except where cut by streams. Forests cover but a small portion of the area. The soil is deep, extremely fertile, and generally very retentive of moisture. The elevation is from 500 to 1000 feet on the eastern portion, gradually rising to from 3000 to 3000 feet in the west. " The Nokthwe&teiix Region comprises parts of Minnesota, Wis- consin, and Jlichigan. It is heavily timbered and well watered, con- taining large numbers of small lakes and considerable areas of swamp. This large water surface, together with dense forests, tends to give this region a moist atmosphere, although the rain-fall is not great. The elevation is from 1000 to 1.500 feet. " The Pacific Coast Region comprises the coast regions of Wash- ington and Oregon Territories and California lying between the Cas- cades and Sierra Nevada and the Pacific coast. The surface consists of a complex range of mountains, known as the coast range, running parallel to the coast, east of which is a great valley extending from Puget Sound to the southern part of California. The elevation varies from the coast-line to 3000 feet," If, now, we examine Table III, we find the liigliest mortality from diabetes in the United States is reached in the Northeastern Hills and Plateaus. The mean tem- perature for this region is from 35° to 45^ F., and the mean elevation is about 1500 feet, — the coldest and one of the most elevated rej/ions in the country-. We there- fore find that, whether we take the State as a unit, or a group of States, the territory which furnishes the lowest mean temperature and the highest altitude also furnishes the highest mortality from the disease under consider- ation. The Pacific Coast Region furnishes the next highest mortality from dial)etes of the State groups in the country. The mean temperature of this region is about 55° F., and the average elevation is about 1000 feet. The temperature, as will be observed, is not suffi- ciently low to explain the very high mortalitj' of the disease in this region, although the altitude is such as 12 Diabetes Mellitus. to partly counterbalance the higher temperature. But, comparing both the temperature and altitude of this region with some others, — such, for instance, as the Southern Central Appalachian Region, — we still find the mortality from diabetes in the Pacific Coast Region un- duly high. After a careful consideration of all the con- ditions of this region, I have no doubt that the unduly high mortality from diabetes here is more apparent than real, as it is with other diseases, such as consumption. In other words, the salubrious climate of the Pacific coast attracts many invalids suffering from diabetes, who there die, and thus unduly swell the records. In the Northwestern Region we note a very high ratio of mortality from the disease. The mean temperature for this region is verj' low, — about 45° F., — and the ele- vation is high — 1500 feet. If, now, we pass to the extreme opposite conditions of temperature and altitude — such as the Gulf Coast and Southern Interior Plateau — where the mean tempera- ture range is from 60° F. to 75° F.,and the altitude for the most part is below 100 feet, we find the lowest mor- tality from diabetes in the country. The Ohio River Belt, the Northern Mississippi River Belt, and the Prairie Region all furnish compara- tively high ratios of mortality from diabetes ; their mean temperatures are comparatively low, and their altitudes are comparatively high. Thus, from whatever stand-point we view the subject, we must conclude that, in the United States, diabetes attains its highest mor- tality in the lowest range of temperature in conjunction with the higher altitudes, and vice versa. I have tlius far said nothing as to the effects of moisture over diabetes, because the evidence upon this point seems rather contradictory. As a rule, tlie more Geographical and other Considerations. 13 humid climates — if we measure the humidity by the mean rain-fall — are those in which the temperature range is the highest; and since, as already shown, the tempera- ture is the strongest determining influence over the mortality ratio, it follows, as a rule, that the lower mor- tality is attained in the more humid climates, not, how- ever, as a result of the greater humidity, but as a result of tlie accompanying high temperature. Thus it will be observed, upon examination of Table III, that in the South Atlantic Coast Region and Southern Interior Plateau the mean rain-fall is the highest in the country. These regions, as already noted, furnish the very lowest ratios of mortality from diabetes in the country — .16 and .86 per 1000 deaths. This has already been shown to be due to the high temperature, combined witli the low alti- tude, and thei'efore not to humidity of the atmosphere. But, notwithstanding all this, I am inclined to believe that a moist atmospliere, even in warm climates, has an appreciably unfavorable influence over diabetes ; and that in northern climates it has a still more unfavor- able influence. Thus, directly on the Gulf coast the mortality from diabetes is slightly higher than it is a few miles in the interior, and this holds true from Florida to Texas inclusive. In the North Atlantic Coast Region — one of the most humid in the country — although the altitude is low, yet the mortality from dia- betes is moderately high — 2.91. Again, take the North- western Region, where, although tlie mean rain-fall is not high (30 to 40 inches), yet in consequence of the numer- ous lakes scattered over the region the atmosphere is moist. The mean temperature is but moderately low, and nearly the whole tract is protected by dense forests, yet the mortality from diabetes is decidedly high — 2. 74. On the whole, it therefore seems probable that a moist 14 Diabetes Mellitus. atmosphere slightl}^ modifies tlie favorable influence of higli temperature over diabetes, and tliat it empliasizes tlie pernicious effects of cold over tlie disease. From all tliat has been said, it will be seen that the most favorable location for residence for diabetic patients, in the United States, is within the area of territory bounded on the east and including the Soutli Atlantic coast, and from thence extending westward and including the Southern Interior Plateau and the Southwest Cen- tral Region. It includes, in part or in whole, the States of North Carolina, Soutli Carolina, Georgia, Alabama, Mississippi, Louisiana, Arliansas, and Texas. In addi- tion to the climatic advantages of the territory just named, it possesses another, — and one of no mean impor- tance to diabetic patients, — viz., the almost perennial supply of those foods which, as will be later shown, are most suitable to their condition. On the whole, prob- ably no place on the inhabited globe is better suited for a residence for diabetic patients than the belt of country embracing the States above named. By no means the least interesting feature occurring to me, in the course of these investigations, was the de- velopment of tlie fact that the territories furnishing the highest mortality from diabetes in the United States coincide very closely with those furnishing the highest mortality from consumption. Tlie very frequent termi- nation of diabetes in consumption, as will be shown later on, lends significance to this fact. Tlie next question claiming attention in the clima- tology of diabetes is tiic comparati\e mortality of the dis- ease in the rural and urban population. Dickinson holds the view tliatthe mortality from diabetes is higher in rural than in urban populations ; while Sir William Roberts has arrived at directly the opposite conclusion. Here, aoain, Geographical and other Considerations. 15 our own country offers exceptional facilities for solving climatic features of the disease, •wMcli I have endeavored to bring forward. It will be remembered that while the population of Great Britain is about 268 to the square mile, that of the United States averages only about 14. The density of population in our own country is, there- fore, such as to render the contrast between urban and rural life much stronger than in Great Britain. I have in Table IV selected twelve regions of the countr}', and carefully tabulated the ratio of mortality from diabetes in the rural and urban population in each region. As near as possible I have selected examples of the typical climates of the country, the regions of which at the same time contain sufficient number of large towns and cities to make the contrast between rural and urban life as strong as possible. Table IV. — SfuniAng Uaiio of Death from IHdbetes in Bwrdl and Urban Fopidattons in the United States in 1880, by Megions. Kkgions. Deaths from Diabetes per 1000 Deaths. Rural. Urban. 1. North Atlantic Coast Kegiou 2. Middle Atlantic Coast Region 3. South Atlantic Coast Region 4. Gulf Coast Region .5. Northeastern Hills and Plateaus .... 6. Central Appalachian Region 3..55 1.27 .70 .49 3.98 2.51 3.47 1.76 .88 1.15 1.56 2.43 1.35 1.15 8. The Interior Plateau fl. The Ohio River Belt 10. Northern Mississippi River Belt .... 11. Central Regions (Plains) 12. Pacific Coast Region 2..51 3.96 2.09 3.30 2.69 1.42 .83 1.84 .64 3.53 An examination of Table IV discloses the fact that in the northern regions of the country, such as the 16 Diabetes Mellitus. North Atlantic Coast, the Northern Hills and Plateaus, and the Northern Lake Regions, the mortality from dia- betes in the rural population greatly exceeds that in the towns and cities, — in fact, it nearly trebles the latter. It is further remarkable that in the Central Region of Plains and Prairies the rural mortality from the disease is more than five times greater than that in the towns and cities. Tlie mean temperature of the latter region is about 55° P., and the elevation is about 1000 feet above the sea. The country for the most part is a level and exposed plain, the little timber which occupied it having been cleared away. The winds are, therefore, unobstructed, and for much of the year are cold and severe. No stronger argument could possibly be brought forward than the conditions in this region, to prove that exposure in northern climates greatl}"^ increases the mortality from diabetes in the rural over that in the urban populations. In further examination of Table IV, however, we meet with the curious fact that in the warmer climates the conditions as to mortality are directly reversed. In the South Atlantic and Gulf Coast Regions, the mortality from diabetes in the towns and cities greatly exceeds that in the country, — in fact, it is more than double the latter. It will, therefore, be perceived that the relative mortality of diabetes in rural and urban populations is chiefly determined by temperature, in the colder re- gions the mortality being decidedly higher in the country, while in the warmer regions it is higher in the cities. The explanation of these facts appears to me to be as follows: Cold, as already shown, greatly increases the mortality from diabetes. In cold climates, those who are best sheltered from exposure suffer least from the disease. This fact is brought out in strong contrast in the United States, because there the houses Geographical and other Considerations. 17 are constructed with a view to greater warmth and com- fort than in Europe. In the warmer climates of the Soutli the evil effects of cold no longer operate, and the atmos- pheric conditions affecting the disease are chiefly those of purity. The country people are able to live in the open air the year round without exposure to cold or chill, and oxidation attains its greatest activity. In the cities more or less confinement and impurity of atmosphere is inevitable, which tends to impede oxidation and give greater impetus to the disease. It is a remarkable fact that the mortality reports of the United States census for 1880 do not furnish a single death from diabetes in either the Indian or Chinese population of the country. With regard to the Indian population this, perhaps, does not seem so surprising, con- sidering the habits of this race as to eating, since, as a rule, they are spare eaters, and subsist almost exclu- sively upon nitrogenous foods. With regard to the Chi- nese populatiouj the explanation is by no means so easy. It may be observed, however, that the reports bear out the records from their native land, where, as already stated, we have no reports of the disease. The exemp- tion from the disease enjoyed by the Chinese is, there- fore, in all probability due to a race peculiarity. From a comparison of the mortality records of the four last United States census reports, I have been able to ascertain that the relative mortality from diabetes in this country has been very decidedly on the increase during the last forty years. Thus, the census reports for 1850 give a death-rate from diabetes in the United States of T2 per 100,000 deaths ; that for 1860 shows 98 per 100,000 deaths ; that for 1870 shows 170 per 100,000 deaths; and that for 1880 shows 191 per 100,000 deaths. It will, therefore, be seen that the death ratio from dia- A« 18 Tiiabt'tes Jtellitus. betes in the United States has increased 150 per cent. ■within the forty yeai-s ending in ISSO. Table V. — StiHo or" Ikul/i.^ fiv:n Pnit\t,s in t/ie I'ltUul gUihs f)vm 1S50 to iO>>'(), Iiu-llisilf. Ratio. 1S70 T'J i«?r 100,000 deaths. J)S " ■• " 170 " '• " 191 " " " It -will be observed, upon examination of these rec- ords, that the increase of tlie death ratio from diabetes during the fii-st period of ten years — from 1850 to 1860 — was about 30 per cent. Between 1S(!0 and ISTO the death-rate increased to the enormous proportion of nearly 100 per cent. In the last decade, from ISTO to ISSO, the rate of increase has only been about 8 per cent. I can assign but one cause for the enormous in- crease of the death-rate from diabetes during the period from 1860 to ISTO, viz., the decided cliange in the habits of the nation in living, consequent upon the civil war. Previous to 1860, the inhabitants of the United States were a frugal and economical people, eujoj-ing but mod- ei-ate luxuries in living. With the war of 1860 came inflation of the currency and hitherto unknown abnnd- anee of money. The consequence, as is well known was that the people entered upon a career of luxurious living, which has earned for them the reputation of being the most extravagant nation in the world. It seems altogether probable, therefore, that such marked and sudden changes of life, from those of frugality to luxury, which extended even to the hitherto poorer classes of the people, largely accounts for the decided impetus given to the disease during the period named. SECTION 11. PHYSIOLOGICAL AND PATHOLOGICAL CONSIDERATIONS. Diabetes mellitus may be defined as a disease charac- terized by a perverted elaboration in tlie economy of the food products whereby cliiefly, though not exclu- sively, the carbohydrates become converted into sugar ; and the efforts of the system to eliminate the latter give rise to certain symptoms and disturbances which will be described later in detail. Viewed from whatever etiological stand-point we choose, — whether we accept the nervous, the muscular, or the hepatic theory of its origin, — the essential features of the disease consist of a perversion of the elaborating mechanism of the organ- ism. Our present knowledge of physiological chemistry renders it more than probable tliat this disturbance is chiefly seated in the liver ; and for the last fifty years the most earnest efforts have been put fortii in attempts to unravel the nature of this morbid process. Bernard laid the foundation of subsequent research by demonstrating that one of tlie functions of the liver in health is the formation and storing up of glj'cogen, or animal dextrine, — a substance chemically identical with starcli. Bernard showed that wiieu an animal is recently killed and the liver is removed and placed in a warm place, it soon becomes charged with sugar by the con- version of part of this glj'cogen into glucose. If next all the sugar be washed out of the liver by means of a stream of water, and the organ be permitted again to remain in a warm place for twenty-four hours, it becomes abundantly chai'ged again with sugar. This may be (19) lH) Viahctes ^[t'Uitilf. ropoated again ami ngniu mitil finnlly all the glvoooen oontaiucd in the liver is oouvoi'IihI into sugar. Sinoo tlio sug-:\r olitaiiiod from glvoogou or animal doxt rino in tho livor is idoutic-al in all rospoots with tlio glucose found in diabotio urino, it cannot bo doubted that llio t'ouree of diabotie sugar is the liver. It has just boon stated that glycogen is chen\ically identical with starch. They are both convertible into glucose by contact ^Yith saliva, pancreatic jnice, or dias- tase. They possess one important dilference, however, viz., glvcogcu is converted into glucose by contact with artovial blood, while starch remains unchanged by the latter. The blood, therefore, contains a peculiar ferment, capable of converting animal dextrine into sugar; as yet this ferment has not been isolated. Scliitf has sho-wu that tliis fermont totally disappears from tho blood of frogs during tho secoi\d half of the winter and tho early spring months. Puring this time, although the liver is as full as nsnal of glycogen, no production of sugar occurs when the livor is isolated; and, moreover, art iticial glycosuria cannot be induced iu these animals at s\ich times. It is important in this connection to note that animal dextrine, although always present in tlie livers of all healthy animals, yet under a variety of diseased and unnatural conditions it quieUly and entirely disappears. This explains why it is rarely to be found if sought for post-mortem. Before it bo possible to connirohond tho part tliat glycogen plays in the production of diabetes, it is iirst neeossary to inquire into its source, formation, and des- tination in tho organism in health. Great divergence of opinion prevails among physiologists upon this ques- tion, most of whom, however, at present adhere to one of two theories. Bernard believed that a continual con- Physiological and Pathological Considerations. 21 version of this glj'cogen into sugar is going on in tlie liver during health, and that sugar is being constantly poured into the portal vein and distributed in the circula- tion to be consumed in the lungs and muscles. In other words, Bernard's view is that the liver in health is a sugar-forming organ, and that glycosuria only results from failure of the system to appropriate the sugar formed in the liver. On the other hand, Dr. Pavy holds that in health there is no conversion of glycogen into sugar going on in the liver, nor any stream of sugar flowing into the circulation through the hepatic vein, and that when such does take place it is the result of diseased conditions, similar to diabetes, or the result of jjost-mortem changes. To use his own words, " Instead of the liver being essentially a sugar-forming, it is a sugar-assimilating organ. Its great function in relation to sugar is to pre- vent this principle reaching the circulation to any material extent." The chief evidence in favor of Bernard's theory rests upon his assumption that in recently-killed animals the blood in the hepatic veins contains considerably more sugar than does the blood of other parts of the body. Dr. Pavy considers the results obtained by Bernard's experi- ments due to rapid changes which occurred during the experiments. He varied these experiments with the view of avoiding these changes, and obtained an alto- gether different result. By catheterizing the right heart, and introducing a tube along the jugular vein, he was able to obtain the blood of the hepatic veins in its normal condition. Thus obtained, the blood was found to contain only the normal traces of sugar which are common to all parts of the circulation. With regard to diabetic conditions, Bernard and his 22 Diabetes Mellitus. school take the ground that glj'cogen has its normal seat in some hepatic oells, while the ferment which is capable of converting it into sugar resides in other cells, the union or separation of these two substances being determined by the nervous system. In proof of his position Bernard pointed out that injuries to that part of the medulla which includes the vasomotor centre for the liver — floor of the fourth ventricle and vicinity — produce artificial glycosuria in perfectly healthy animals. Dr. Pavy admits the nervous influence so far as tlie production of hypersemia of the liver through vaso- motor paralj'sis; but he considers the diabetic condition as one of chemico-physiological derangement of the liver. In other words, he considers that the carbo- hydrates in healthy digestion are changed into maltose, dextrine being an intermediate product. When glucose is ingested it is converted in the stomach and intestines by means of the glucose ferment into maltose, and the maltose, from either source, under the influence of a good venous blood, becomes absorbed and assimilated. In the diabetic condition, in consequence of the vaso- motor paralysis, great dilatation of the vessels of tJie chylopoetic viscera occurs, and the blood, entering the liver in an imperfectly deoxj-genated state, gives rise to a glucose-forming ferment. Since the glucose thus formed is not assimilated, it passes into the circulation and appears in the urine. Without entering into a minute consideration of the numerous experiments and arguments which have been brought forward in support of either of the above doc- trines, it seems to me altogether probable that the ex- planations of Dr. Pavy, both as to the physiological function of the liver in relation to glucose, as well as Physiological and Pathological Considerations. 23 the production of diabetes, is more nearl}' the correct one. Our present knowledge strongly indicates the view that the ultimate destination of the carbohydrate foods in the economy is the formation of fats. Now, almost the first step in pronounced diabetes is that of rapid emaciation, without any increase of temperature or loss of appetite ; on the contrar3', the temi)erature becomes lower than normal, and the appetite becomes increased. It is evident that the emaciation in diabetes means that the elements which normally go to make up fat do not reach their destination in the economy, but are turned aside during some step in the metamorphosis, and con- stitute the waste. That this defect occurs in the liver there can be little doubt. If this be the correct expla- nation of the pathological processes in diabetes it would seem to harmonize best with the varied and uncertain lesions found, the multiple methods by which it may be artificially induced, and the many gradations of its intensity. If we accept the explanation of Bernard we must assume that considerable quantities of sugar circulate in the normal blood. If we attempt to trace it to its destination in this fluid, we find the theory that it is oxidized in the lungs is an untenable one ; for the blood in the right side of the heart is found to contain no more sugar tlian that in the left side. It has been assumed that in health the sugar is converted in the muscles into lactic acid by means of a ferment, and that lack of this ferment permits the sugar to remain unchanged when it accumulates, and escapes by the urine. Experiments upon animals, however, demonstrate that when they are frozen to death— a process which arrests fermentation^ no glycosuria results. In addition to this no antece- 24 Diabetes Mellilus. dent changes in the muscular sj-stem are present in diabetes that are observable — certainly no grave nutri- tional alterations, such as must necessarily follow the diversion of so large an amount of the normal pabulum. It has already been stated that the carbohydrate foods are the chief source of sugar in the economj-, but it must not be forgotten that the}' are not the exclusive source of that product. Dr. Pavy found hy experi- ments upon dogs that, when fed exclusivelj' upon animal food, the average proportion of glycogen in their livers ■was 7.19 per cent. Upon vegetable food, including potatoes, barloy-meal, and bread, the average percentage of glycogen reached IT. 23. Dr. McDonald* extended these observations to other animals, and obtained results which show that glycogen reaches its greatest amount under the ingestion of starch and sng.ar ; that it is still formed, though scantilj', upon a diet of albumin, fibrin, and glutin ; while upon a diet of animal oil or fat, vege- t.able oil, and gelatin, glycogen almost entirely disap- pears from the liver. "With regard to the formation of sugar upon a purely nitrogenous diet. Professor Hough- ton has suggestedf tli.it the nitrogenous elements nia_v be split up in the liver into glj'cogen and urea. Albumin closely corresponds chemic.allj- to a combination of these two products, — the nitrogen corresponding to the urea, the hydrogen and carbon to the glycogen. It will be observed that in diabetes the sugar and urea in the urine usually increase and diminish together, which strongly indicates their common origin. "We have next to consider the part plaj'ed by the nervous system in the production of glycosuria. Bernard * JIcDonald on Functions of tlie Liver, p. 14. t Houghton on Diabetes Mcllitus, Dublin Qmirterly Jour., November, 1861, p. 269. Physiological and Pathological Considerations. 25 demonstrated that puncture of the floor of the fourth ventricle of the brain is immediately followed by glyco- suria. It was at first supposed that the glj'cosuria thus induced was brought about through irritation of the pneumogastric nerves, but subsequent experiments showed that puncture of the medulla caused the urine to become saccharine, even when the vagi were divided. It was further proved that the glycosuric influence was not conveyed from the brain to the liver through the vagi by the following experiments : Without puncture of the medulla, the vagi having been divided, the cut end connected with the liver was subjected to galvanism without inducing gljxosuria; when, however, the cere- bral end of the nerves were galvanized, glycosuria at once resulted. The vagi, therefore, are capable of con- ducting the glycosuric irritation to the nerve-centres, but not toward the liver. It would occup}' too much space here to detail the numerous, though interesting, experiments conducted by Schiff, Pavj', Eckhard, Aladofi", and others, with the object of defining the route of the so-called glycosuric influence from the vasomotor centre in the medulla to the liver. It may, however, be stated that, starting with the suggestion of Bernard that the route probably lay along the spinal cord and splanchnic nerves to the liver, experimenters have succeeded in mapping out this course with a reasonable degree of certainty-, as follows : Begin- ning at the glycosuric tract, which, broadly speaking, comprises that part of the cerebro-spinal axis which is included between the optic thalami and the lower end of the cervical enlargement, the glycosuric influence passes into the spinal cord ; then by filaments of the sympathetic, which accompany the vertebral artery into the lower cervical ganglion ; then through the annulus Vieussens 2 B 26 Diabetes McUilus. into the first dorsal oangliou ; from thence throiis:h the prevertebral cord of the sympathetic and branches to the liver. Artificial olycosinia raaj- be brought about by numer- ous traumatisms and inlluences more or less profoundly afl'eoting this nervous mechaiiism, by cutting or punctur- ing various jiaits of the uerve-eeutres, or the nerves leading therefrom ; by drugs which act powerfully upon the nervous mechanism, either directly upon tlie vaso- motor centre, or indirectly by reflex action througli tlie sympathetic system. Thus, glycosuria has been induced by poisonous doses of strychnia and curare; by in- halations of cldoroform and ether; by wounding the liver by means of needles, or injecting acids or stimu- lants into tlie hepatic veins ; by violentl}' irritating some sensory nerve, and by injecting arterial blood into the portal vein, etc. It is probable that most, if not all, of those injuries act in a similar way, — paradoxical though this may seem, — viz.. by irritating the vasomotor centre, cither directly or indirectly, resulting in dilatation of the vessels of the liver and consequent hyperajmia of the organ and its attendant glycosuria. Artificial glycosuria, however brought about, — except through lesions of the pancreas, — passes away in a short time, rarely lasting longer than twenty-four hours, and this strongly suggests that the nature of the cause is one of irritation. On the other hand, in permanent diabetes the con- dition of the vasomotor apparatus is one of paralj'sis, and, although our knowledge has not yet reached precise data as to pathological causes, our researches in artificial glycosuria have paved the way to their very threshold. Finally, in addition to the diabetes of nervous origin, recentlj'-ascertained facts render it strongly probable, if indeed not certain, that diabetes sometimes arises in au Physiological and Pathological Considerations. 27 entirelj' different way, originating, as Lancereaux long ago maintained, from lesions of the pancreas. Von Mering has shown in the most conclusive manner that complete ablation of the pancreas in the dog is followed by more or less intense diabetes, which usually lasts until the death of the animal. Lupine has recently pub- lished the results of four such experiments, which are both interesting and instructive. In the first case no diabetes resulted from the experiment, there being peri- tonitis from perforation caused by gangrene of the duodenum.* The second dog presented no glycosuria during the whole time it lived after the removal of the pancreas ; but at the autopsy it was found that part of the panci'eas remained. The fragment remaining had no connection with the duodenum. This dog, althougli he had no glycosuria, j'et according to analysis he liad hyperglycsemia, — about 2 grammes of sugar per kilo- gramme of blood. The third dog, after the removal of the pancreas, had no glycosuria during the first three days ; then after having been fed there appeared 5 grammes of sugar to the litre of urine. Two hundred grammes of glucose were then administered, and the following day the urine contained 50 grammes of sugar to the litre, — about 25 grains to the ounce. This intense diabetes persisted until the death of the animal. The fourth dog survived twelve days, and during all this time it was diabetic, passing from 40 to 80 grammes of sugar daily. Examination of the blood of this fourth animal showed intense hyperglycsemia, the arterial blood containing 8 grammes of sugar per litre. f Ldpine has suggested two hypotheses in explanation of diabetes of pancreatic origin. The first suggests th.it * It wiU be remembered that febrile and inflammatory processes at once arrest the excretion of sugar in the urine of diabetics, t Lyon M^dicale, December 29, 1889. 28 Diabetes JlrUitiis. in the normal state a part of the iiaiicreatio fornient is re-ubsorbetl ami contributes to the destruction of glucose. This is supported by the known action of the diastatic feruiout of the pancreas. The second hj-pothesis si\o-szests that, as is now known, the contact of diastase with stareli does not result in the formation of glucose, but of maltose ; so the diastatic ferments of the saliva and of the panereatie juice in contact with glycogen furnish a sugar which is likewise identical with maltose. It thus results that the presence of the pan- creatic ferment is necessary to transform glycogen into glucose ; and if this ferment be wanting the hepatic sugar will not be normal glucose, but some other form of sugar incapable of appropriation by the system, wliich is eliminated by the kidnej-s. Thus, in health, the pan- creas and liver are both concerned in the elaboration of normal glucose. Therefore, according to L(5pine, " whichever of these hypotlieses be accepted, pancreatic diabetes will be the result of the withdrawal of the pan- creatic ferment, and diabetes will thus result from a relative reduction of the ferment in relation to the quan- tity of the cai'boliydrates to be destroj-ed." * The above exiieriments and suggestions are of undoubted value in furnishing a possible solution of the nature of that form of diabetes which, as will here- after be shown, so frequently follows upon disease of the pancreas. In concluding this subject, it m.ay be stated that, while our knowledge at present can scarce!}' be said to have attained exact data with regard to all the ph3'sio- logical .and pathological phenomena of di.abetes, the most recent advances upon the subject seem to fore- sh.adow the following conclusions : — • TUeiapoutio Gazette, M;u ih, 1890, p. Til. Physiological and Pathological Considerations. 29 (a) That the essential feature of diabetes consists of a more or less profound disturbance of the glycogenic function of the liver. (6) That the chemico-physiological changes in dia- betes result in arrest of the elaboration of certain foods in tlieir course toward their ultimate destination in the organism, — probably as fats, — and the intermediate product, passing into the general circulation, escapes from the sj-stem, chiefly by way of the kidneys, in the form of sugar. (c) That the disease is accompanied by a hyperaemic condition of the liver, and a more or less engorged state of the chylopoetic viscera. {d) That recently-ascertained facts indicate that, in addition to the liver, the pancreas also is concerned in the production of sugar in the organism, — or, to speali more accurately, in preventing the production of sugar in the organism, — and consequently diseases of the latter organ are liable to induce diabetes. (e) Tliat diabetes may be brought about by diseases which involve the central ganglia that preside over the vasomotor nerves of the liver, by diseases affecting the peripheral distribution of these nerves, and probably also by disorders involving inhibitory reflex action of the sympathetic nervous system. SECTION III. ETIOLOGY. Predisposing Influences. — Themost prominent feature of the disease to be noted in this connection is its strongly-stamped heredity ; probably 30 per cent, of the cases may be traced to this source. That the disease is much inclined to run in families must be apparent to all careful observers "vvhose experience has brought them mucli in contact witli it. Numerous and interesting are the instances recorded by various authors, showing its marked family preferences, sometimes extending through several generations. Dr. Ralfe has recorded an instance ■which came under his observation in which the disease attacked successive members of a family extending over a period of nearlj^ a century, and including four genera- tions. Sir H. Marsh also refers to a family in wliich he traced the disease through four generations. It is not uncommon to observe periods of culmination of this tendency in certain generations, in 'which the disease becomes almost a famil}' plague, so many are the mem- bers who succumb to it. Sir Wm. Roberts speaks of a family consisting of eight children,- every one of whom became diabetic. Dr. Pavy refers to a family of seven, four of whom were diabetic ; also to another, in which tliree brothers became subjects of the disease. Dia- betes sometimes maintains this strongly-marked fatality through two or more generations uninterruptedly. One of my recent cases is the seventh subject of diabetes in the same family, all of whoui became affected with the disease during two gener.ations. Sometimes tlie disease, like tuberculosis, shows a marked proclivity for certain (31) 32 Diabetes :ilelUtus. families for a certain period, and then sldps a generation, to ro-;\ppear after a period of exemption. It is altogetlier likely that, if a more careful system of interrogatiuii patients were practiced as regards fomily history, a mnch higher percentage of hereditary causation would be revealed. In the consultation-room patients are pro- verliially inclined to present the best sideof tlieir family histories. Family tradition, in sucii matters, is feebly cherished, apparently, and easily slips from the memory. In one of mj' cases direct inquiry at the tirst visit failed to elicit any family history of the disease. Subsequent circumstances disclosed the fact that both the lather and mother of the patient were diabetic. AYhatever be the determining influences of diabetes, they strongly leave their stan\p upon the olt'spring, as, indeed, do most diseases which involve the integrity of the liver or nervous system. In certain faniilies it is not uncommon to note the effects of transmitted hepatic defect, carrj-ing with it a legacy of gout which the off- spring is unable to silence by the most abstemious course of living. So, too, with regard to the nervous system ; to record its transmitted defects would entail rewriting a large portion of the literature of the subject, so widely distributed are these influences. It has furthermore seemed to me, indeed, remarkable how frequent are nervous disorders in families of diabetic parentage. In this connection it maj' be noted that diabetes is alleged to be unusually frequent in the Hebrew race. My own experience confirms this observation to a somewhat re- markable degree. I have, at the present writing, six Jewish patients under treatment for diabetes, and my records show nearly a score of cases of the disease among Hebrews within the past three years. In addi- tion to these, several cases have come within my notice Etiology. 33 in the practice of my colleagues witliin the same period. I can also attest, so far as my own experience is con- cerned, to the almost universally mild character of diabetes among this people. As a single illustration I would mention the case of a young Hebrew woman, 29 years of age, who has been under my care for the past two years. During all this period the disease has been kept under control by moderate limitations of diet, only occasional traces of sugar having been present in the urine. I have rarely, if ever, met with diabetes in so young a subject, save in the more pronounced form. I have closely interrogated a number of Hebrew patients with the hope of eliciting a cause especial to this race. The only probable explanation derived from these investigations seems to be connected with habits of overingestion of food. I have, been assured, by a highly intelligent Jewish member of the medical profes- sion, that, as a class, Hebrews " are very large eaters." In chronic Bright's disease and gout the subjects, as a rule, are large eaters, and I have assuredly traced gly- cosuria to the same source, as will be hereafter shown. When diabetes is brought about by habits of excessive eating, I have usually found the disease mild in form and easily controlled. Precisely these conditions obtain in the Hebrew race. Sex. — Exactly one-third of my recorded cases of diabetes to date have been females and two-thirds males. Of 380 deaths from diabetes reported in the State of Illinois from 1880 to 1888, 131 were females and 249 were males. In 1880 the number of deaths from diabetes in the United States, as shown by the mortality reports of the census, were 1443. Of these, 422 were females and 1021 were males. For the ten years ending in 1870 the deaths from diabetes reported in England and Wales 34 Diabetes Mellitus. numbered 6494. Of these, 2223 were females and 4271 were males. It will, therefore, be observed that in England and Wales diabetes is about twice as fatal among males as females ; while in the United States the disease is nearly two and one-half times more fatal among males than females. Age. — Diabetes is infrequent in the two extremes of life. The youngest patient whom I have treated for the disease was 3 years and 4 months old, although a case came within my personal knowledge in which the disease began in infancy and terminated with the life of the patient seven years later. At the other extreme of life I have met with but few cases, the oldest patient I have treated for diabetes being 66. Statistics on a large scale indicate that diabetes, from comparative infre- quency in childhood, gradually increases and attains its maximum at about 25 years of age; from thence until about the age of 65 years it maintains a prett}- constant uniformitj' ; and after 65 its frequency graduallj' declines until extreme old age, when it .again becomes rare. Climate. — Up to the present time some difference of opinion has prevailed as to the influence of climate over diabetes; and, indeed, the records of the disease — doubtless very imperfect — from various parts of the world render it somewhat confusing in attempting to draw accurate conclusions, owing to their apparently contradictory character. Thus, in Russia, which pos- sesses a typically cold climate, the disease is said to be rare. On the other hand, in Ceylon, which is almost under the equator, and consequently possessing a typi- cally warm climate, diabetes is said to be quite frequent. Notwithstanding all this, I have endeavored to demon- strate, by a careful consideration of the climatic condi- tions in the United States, that diabetes, at least in our Etiology. 35 country, is directly and decidedly increased by cold and higli altitudes, while it is as directly diminished by the opposite conditions. See Section II. I have had but limited opportunities for studying the influence of climate over diabetes outside of the United States ; but if my observations and deductions be cor- rect, there seems no good reason -why different results should follow similar conditions of climate in other countries, unless some outside influences prevail which to me are unknown. I strongly suspect, therefore, that, in those countries where the disease is reported as greatly at variance with the climatic conditions which determine its relative frequency in the United States, the apparent discrepancy is due — if the records be not defective — to some other influence than that of climate, such, perhaps, as the life or habits of the people. We have indeed seen, even in the United States, that the race peculiarities of people very profoundly modify the effects of climate over diabetes ; for, as was noted in Section I, among the natives of the country, — the In- dians, — diabetes is unknown where in the same latitudes in the white population it is frequent. In Ceylon, where, as has been stated, diabetes is frequent, it is cer- tain that the undue frequency is determined by some in- fluence other than climate, for in other climates closely corresponding in most respects with that of Ceylon, such as China, some parts of tiie African coast. Central America, some of the Pacific Islands, and the West Indies, the disease is rare. The United States combines the largest tract of territory in the world, with the widest range of climate in which the life-habits of the people * are practically identical, and therefore the » Excluding the relatively small populations of the native Indians and the Chinese. 36 Diabetes Mellitus. gomiine influence of oUraate over diabotos, as shown b}- our inortalitj' looords, must be (.■onsidi.'iod as conclusivo as are obtainablo. It only roiuains, then, to io[K'al that Avkich has already been shown in Scclion 1, viz., that cold clhuates and high altitudes very niarkodly increase the mortality from diabetes, and vice eerttd. Exciting Causes. — When \Yoeoiisider that almost any influence or agency which profoundly disturbs the vaso- motor mechanism of the central nervous system, or very seriously impairs the physiological action of the liver, is capable of bringing about glycosuria, it no longer ai)pears a matter of surprise that the exciting causes of diabetes comprise a wide range of agencies, — so wide, indeed, that it is altogether likely that many remain as yet undetermined. 3[ental emotion is nndoubtedl}' the most fruitful exciting cause of the disease. Willis traced the disease to " sadness and long sorrow," and since then numerous observers have recorded eases originating in grief, anger, anxiety, overmental toil, and various forms of mental strain and shock. Raycr mentions a ease that followed upon a violent fit of passion. Roberts cites a ease which "followed on distress of mind caused by unjust sus- picion of theft ; in another it followed the burning down of his place of business ; in a third it was attributed to anxiety attend.ant on a Chancery suit." Dickinson has recorded the case of a woman, who seven months after the death of her husband beeauio diabetic, apparently brought on by inordinate grief. Another, in which " a child fell from a third-floor win- dow, and was smashed upon the pavement to all appear- ances hopelessly. But the accident was more fatal to its mother than itself. The child survived. The mother never recovered from the shock. For three weeks she Etiology. 37 could neither eat nor sleep. Within two months she be- came much emaciated under diabetes, and died of tlie disease within ten months of the occurrence upon which it had succeeded." Dr. Garrod has recorded the following instance : "Two gentlemen fought a duel in Holland; after the first had fired he remained for some time in a state of suspense from his adversar3''s pistol once or twice miss- ing fire. He was uninjured, but a day or so after be- came diabetic." In the United States, where commercial competition is very keen, and the possibilities of rapid accumulation of fortune spurs men on to overmental exertion, I am satisfied that diabetes more frequently results than in some of the older communities, where business is conducted under more settled and ti'an- quil conditions, coupled with longer periods of re- laxation and rest. Here in the West, where the former conditions prevail so prominently, cases of diabetes very frequently present themselves for treatment from the ranks of the more active business pursuits, which are clearly traceable to the pressure and excitement of business life. As an example, I might mention the case of a bright young man, aged 29, whose diabetes without doubt originated in overanxiety in conduct- ing extensive transactions on the produce exchange. He accumulated a large fortune at the expense of contracting diabetes, which killed him within a j'ear of its onset. In another case, the patient was a man of somewhat large business interests which, becoming com- plicated , gave him much anxiety and worry. He became very markedly diabetic, and I sent him to the South Atlantic coast for complete rest, where he recovered. The vasomotor mechanism is, indeed, keenly sensitive to mental influences, and the diabetic condition may be 38 Diabetes McUitus. brought about through this chamiel in various ways, from too prolonged taxation to the more violent ngoncy of direct shock, or both combined. Disease and traumatisms of tlio brain are t'roquent exciting causes of diabetes, and an almost endless list of examples might be brought forward in illustration. Richardson has recorded a case of diaboti's, tlio autopsy of wliich revoaled an osseous tumor pressing upon the pons Varolii, and an abscess in the posterior cerebral lobes. Dompeling* recovtls a case of diabetes caused un- doubtedly by a tumor " as hu'ij,e as anut," wliieli ^Y!ls found after death occupying the whole right half of the medulla oblongata. Fritz has collected a whole series ol' eases of diabetes associated with various diseases of (lie brain and cord. As to traumatisms, blows and falls upon the forehead, vertex, or occiput are the most frequent causes in this class. In the case of the child I have already referred to, the cause seemed to arise from a fall upon the floor of a car, which caused a viok-nt blow upon the occiput. The child became diabetic very soon after, and died of coma within eighteen months. Fischer has recorded 21 cases of diabetes which were brought about by blows and falls upon the head, — some with and some without cranial fracture. The same ob- server has recorded over 20 additional cases of diabetes whicli were brought about by blows on the face, loins, thoriix, and abdomen, together with fracture of the ver- telira, contusions of the kidney, liver, etc. The disease brouglit about by tlu'se injuries comprises all grades of severity, from slight glycosuria to the most severe type, U'ading nu>ro or less rapidly to death. Freirichs traced Tf) of 165 cases of diabetes to some form of nervous lesion, consisting of organic diseases of the brain, mental * Aroli. Omi., Miiy, 1809, Eliulogy. 39 disorders, peripheral nervous disturbances, concussion, blows, and mental strain. In this connection, it may be noted that glycosuria is common in certain types of insanity. Various other causes are ascribed for diabetes, such as gout, malaria, alcoholism, sexual excesses; and re- cently Schnde has insisted that inherited syphilis is the most frequent of all cavises. I do not agree with the above-named author, since in my experience the effects of inherited syphilis are developed, as a rule, at an earlier period of life than is diabetes. I have no doubt, as before stated, that overeating frequently induces glycosuria, and in people predisposed to diabetes it sometimes leads to that disease. This result is more likely to follow from overingestion of starchy foods. In such cases the disease seems to be brought about by supernutrition of the portal system. SECTION IV. MORBID ANATOMY. The liver is frequently found to be enlarged in sub- jects who have died of diabetes. This change, however, is not a constant one ; in fact, some authors deny that it is anything more than an accidental occurrence. More recent and extensive post-mortem researches, however, plainly demonstrate its frequencj', if not usual associ- ation with the disease. Sometimes the enlargement is slight ; at other times it is very marked, the organ reach- ing two or three times the normal size. With the enlargement the organ is usually darker in color than normal, and somewhat harder in consistence. The essential and most constant changes found are marked dilatation of the hepatic capillaries, hyaline thickening of the walls of the latter, and slight interstitial over- growth surrounding the hepatic cells, either individually or in clusters, and extending along the walls of the interlobular plexuses. In addition to this, the vessels are distended and enlarged ; the liver-cells swollen, some- what granular, and indistinct in their outlines, with a diminished amount or absence of the normal fat contents. The lungs exhibit very constant lesions at the au- topsy of diabetic patients. These are partly phthisi- cal and partly pneumonic in character, — hepatization, caseation, and excavation being the leading features. It has been questioned by some authors if true tuber- culosis of the lungs is associated with diabetes at all ; and Dickinson even asserts that diabetic patients enjoy exceptional immunity from that formation. The B" (41) 42 Diabetes MclUlus. clieesy deposits of diabetes mellitus are claimed by this author to ditler from those of tuberculosis in the tendeuc}- of the former to more rapid excavation, and also to become located in the lower part of the upper lobes, while the tubereular disease nearly always begins at the apex. ^Notwithstanding all this, with the aid of recent and more exact methods it has been established that, for the most part, these lung-lesions in diabetes are tubercular. Leyden, Rutmeyer, Rngel, and many others have demonstrated the presence of the bacillus of Koch in the expectoration, the pus of the cavities, and the necrotic portions of the lungs in these cases. It maybe true that the bacillus tuberculosis is not always found in the sputum in these cases ; but the same may be said of tuberculosis in other than diabetic patients. The geographical distribution of diabetes in the United States, as I have already shown in Section I, closely corresponds with the consumption-belt ; and the clinical symptoms of tubercular phthisis are practically identical ■with those of diabetic phthisis, perhaps only modified in the latter case b}- more pronounced localized pneumonic symptoms. It may be concluded, therefore, that the phthisis of diabetes is identical with tuberculous phthisis, modified, of course, as it must be, by the presence of another disease scarcely less serious than itself. Besides the cavities found in the lungs in diabetics, the autopsy also reveals the presence of caseous nodules, which are impossible to distinguish by the naked eye from those of tubercular origin. Evidences of cireum- scribed areas of pneumonia may be noted, such as red and gray hepatization, tending to necrosis and cavity formation. The pancreas is so frequently found to be the subject of anatomical change iu diabetes as to suggest the Morbid Anatomy. 43 probability of causal relationship. In addition to this recent experiments upon animals, consisting of ablation of the pancreas, has been found to be followed almost invariably by diabetes, as was shown in Section II. Senator believes that disease of the pancreas is present in one-half of all cases of diabetes. Lancereaux has reported 14 cases of diabetes associated with lesions of the pancreas. Depierre has recently confirmed these observations of Lancereaux, and cited a number of similar cases. The most common lesions of the pancreas observed at the autopsy in diabetic subjects are fibrosis or hyperplasia of the connective tissue, fatty degener- ation of the gland-cells, cancer, calculous concretions in the ducts, with or without obstruction, and in the latter case atrophy or cystic dilatation. The kidneys are subject to more or less marked ana- tomical changes, depending chiefly upon the length of time the disease existed before death. The increased demand made upon the kidneys in diabetes, together with the irritating effects of the foreign matter (sugar) which is eliminated in such large quantities, give rise to congestive changes of all grades, from mere hyperaemia up to pronounced swelling and degenerative changes in the excretory structure of the gland. In well-marked cases of diabetes, which have long continued, the autopsy usually discloses considerable enlargement of the kid- neys. The surfaces of the organs are smooth, and the capsules non-adherent. The kidneys are overfilled with blood. The tubular epithelium is swollen, granular, and in some cases fatty. Interstitial changes are infrequent unless the disease be associated with Bright's disease. A peculiar " dropsical degeneration " has been described by Cantani,which is confined to the large medullarj'tubes. The cells become swollen and clear, and almost indistinct. 44 Diabetes Mellitus. The heart is the subject of anatomical changes in a considerable percentage of cases, — about 15 per cent., according to recent statistics. Jacques Maj'er, whose experience with the disease at Carlsbad has been con- siderable, has given this subject special attention. In his observations of 380 cases of diabetes, cardiac changes were found in 64 of them. The essential features of the heart-lesions in diabetes, as revealed at the autopsy, seetns to be enlargement of the organ without valvular changes. The enlargement is chiefly of the left ventricle, and may consist of thickening of the muscular wall or of dilatation. It has long since been observed that fatty changes in the heart are common in diabetic sub- jects. Mayer holds the view that the cardiac changes in these cases is due to the irritating effects of sugar and urea in the circulation. Israel has found hyper- trophy of tlie heart in 10 per cent, of the diabetics in the Charitd hospital, at Berlin. In 1885 I published tlie results of some studies* upon the circulation in diabetes, showing that in a large percentage of the cases there is increased vascular ten- sion, as indicated by the sphygmograph, similar to those in chronic Bright's disease. It would seem that, as in Bright's disease, so in diabetes, an extra demand is made upon the heart, and the regular sequence in all such cases is primarily hj'pertrophy of the left ventricle, ulti- mately tending to degenerative changes in the cardiac muscle and dilatation of the ventricle. The brain, which is believed to be the main-spring of the morbid changes in diabetes, has been most minutelj' studied by numerous observers in search of anatomical changes which would explain the cause of the disease. Thus far, however, it must be admitted that the results *Jour. of Am, Mod. Association, September 12, 1885. Morbid Anatomy. 45 have been far from uniform or satisfactory. Dickinson, who seems to have been the most industrious investi- gator in this field, claims that certain minute anatomical changes are characteristic of the disease, although he admits that " the brain of diabetics is almost invariably free from tangible disease, and to rough examination natural." Minute examination, however, he claims, will reveal a fine cribriform or porous condition of the white matter, as if studded with pin-holes, each of the punc- tures containing a small vessel. The favorite seats of these changes are the corpora striata, optic thalami, pons, medulla, and cerebellum. The fluid in and around tlie bi-ain is claimed to be slightly in excess, as has been termed a " wet brain " — not uncommon in other condi- tions. The fluid in the ventricles and beneath the arachnoid is colorless and limpid. A peculiar condition of the spinal cord described, although not claimed to be always present, is dilatation of the central canal, espe- cially in the dorsal and lumbar regions. These changes are perivascular in nature, and accom- panied by minute haemorrhages or extravasations of blood, apparently occurring rather by transudation than by rupture. These extravasations are said to be most pronounced in connection with the larger perivascular canals, notably between the base and ventricles. Numerous observers have sought for these changes in connection with diabetes, but without confirming Dr. Dickinson's observations. As Sir William Roberts truly says, " It cert£iinly seems strange, if this wide-spread destruction of nervous matter really occurs in diabetes, that mental aberration and paralytic accidents should usually be so conspicuously absent from the clinical history of idiopathic diabetes." A committee of the London Pathological Society, appointed to investigate 46 Diabetes Mellitus. this subject in 1882, reported that they failed to find in the brain " any changes which could be regarded as ex- clusively or constantly associated with diabetes." The blood in diabetes, as might be expected, is ab- normally charged with sugar, often reaching one-fourth to one-half of 1 per ceut. In addition to this, an abnor- mal amount of fat is present, in some cases sufficient to give the blood a milky appearance. Gamgee has given an analysis of diabetic blood in one case which showed 13 parts of fat in each 1000 parts (the normal being 2). The blood suffers some impoverishment in diabetes ; there is an increase in the proportion of water, and a reduction in the total solids, especially of the corpuscles ; and the alkalinity of the blood is markedly diminished. Such are the chief features of our present knowledge of the morbid anatomy of diabetes. It will be perceived that the disease has not yet given us anj-thing very tan- gible in explanation of its very remarkable phenomena through the source of pathological anatomJ^ It has, indeed, been truly said that this " is the most unsatis- factory chapter in our knowledge of the disease." Most, if not all, of the lesions actually present are only found after the disease has been in progress some time, tlie morbid anatomjf of recent diabetes being practicall}- nil. These facts strongly suggest that the changes thus far observed are secondary rather than primary, and their nature, for the most part, bears out this suggestion. SECTION Y. SYMPTOMATOLOGY. Before entering into a description of the symptoms of diabetes mellitus, it is proper to note that nearly all authors recognize two distinct forms of mellituria. First, a milder disorder in which but small quantities of sugar appear in the urine, and these intermittently, the general health of the patient suffering but slight, if any, disturb- ance ; by common consent this form has been termed glycosuria. Second, a more pronounced form of dis- order characterized by the excretion of large quantities of excessively saccharine urine, by thirst, morbid appe- tite, general wasting, and more or less profound disturb- ance of the general health. Since glycosuria is a transient condition of no grave import, capable of being brought about by a multitude of agencies, most of which are accidental or artificial, it is of more interest to the experimental physiologist than to the therapeutist. It will, therefore, be chiefly with the second form of the disorder that we shall have to do in the following pages. By some the second form, or true diabetes, is divided into a mild and severe type, and such division will serve practical purposes if it be not forgotten that these two types may pass indifferently from one to the other in the same subject at any time during the course of the disease. Thirst, polyuria, lowered temperature, emaciation, and certain nervous disturbances may be considered the classical -features of diabetes ; but a more minute con- (47) 48 Diabetes Mellitus. sideration of these will be greatlj' facilitated by a sj^s- tematic review of the effects of the disease upon each of the great divisions of the economy. The Digestive System. — The effects of diabetes are prominently noted here through more or less pronounced thirst. This, indeed, is often the first sj^mptom to attract the patient's attention ; he observes an in- creased and increasing desire for water. In, the mild form of the disease the thirst is not so prominent, and may attract little or no attention, but in the severe type the thirst sometimes becomes enormous, especially in j'oung subjects. I have known a diabetic child to call for water on an average every half-hour, and the amount consumed seemed prodigious. As a rule, diabetic patients will drink from 10 to 12 pints of water daily, but they have been known to drink 30 and even 35 pints per day. Notwithstanding this enormous ingestion of water, the thirst remains unquenched and seemingly' unquenchable, for the mouth and throat remain dry and parched. Together with this inordinate thirst, there is usually a morbidly -acute appetite. In the early but well-formed stages of the disease this symptom is specially promi- nent, the appetite becoming indeed so ravenous that the patient often finds it diflScult to satisfy his hunger. As might be expected, the result of such overingestion of food sooner or later tells seriousl3' upon the digestive organs, and, consequently', in the later stages of the dis- ease the patient becomes a prey to various gastro-intes- tinal disorders. The appetite fails ; indeed, often com- plete anorexia and loathing for all food sets in ; gastric pains are likely to follow tlie latter, becoming more es- pecially prominent upon the approach of a fatal termi- nation. Constipation of the bowels is the general rule throughout, although, in that form of the disease asso- Symptomatology. 49 dated with pancreatic lesions, an obstinate diarrhoea usually sets in, which baflles the most skillful treatment. In the more pronounced form of the disease, the mouth, tongue, and fauces present a reddish, congested appearance, not unlike that which is common to invet- erate tobacco-smokers. The tongue especially is red and glazed, although sometimes it becomes quite thickly coated with white fur. The whole mouth and throat in severe cases becomes dry, parched, and distressingly uncomfortable. The gums become more or less tender, and their margins frequently become sore and shrink from the teeth, to the extent in some cases that the latter loosen and fall out. In some cases a more or less constant sweet taste in the mouth is experienced by the patient. This symptom does not seem to bear any relation to the severity of the disea-se, for in one of my cases the patient was annoyed by it exceedingly when but 1 or 2 grains of sugar to the ounce were present in his urine, and it only disappeared when his urine became norrasaccharine. As a rule, the thirst, hunger, and indeed all the digestive disorders become aggravated hy the ingestion of starchy and saccharine foods. The Circulatory System. — In the early course of the disease, the most prominent feature in connection with the circulation seems to be that of lowered bodily tem- perature. The usual range is 97° F. to 96° F., although it has been known to sink as low as 93° F. Consequent upon this subnormal temperature, the patient is annoyed by more or less chilly feelings, and he instinctively seeks artificial heat by means of extra clothing, or by remaining more than usual indoors. Diabetic patients are proverbially susceptible to colds upon slight expos- ure, in consequence of their lowered bodily temperature. 3 c 50 Diabetes Mellitus. Aniemia is not uncommon, especially in advanced stages of the disease, altliough this is by no means invariably the case. I have elsewhere noted that increased arterial tension, as shown by the sph3'gmo- graph, is exceeedingly common in diabetic patients. In pronounced cases I have found this to be the rule, rather than the exception. This is probablj^ in close relation- ship with cardiac hj'pcrtrcph}', which is now known to be very frequent in diabetes. Extension of the area of cardiac dullness below and to the left, with accentuation of the second sound of the heart in the second right costo-sternal interspace, and increased tension of the pulse, indicate hj^pertrophy of the left ventricle, which is frequent in the middle stages of the disease. In late stages the pulse often loses its tension, and evidences of weakened circulation supervene, — such as dropsy and dyspnoea, more or less pronounced. These symptoms are usually associated with fatty changes in the cardiac muscle, with or without dilatation of the ventricle. The Nervous System. — It is rare to meet with a case of diabetes in which there is not more or less nervous disturbance. Periods of wakefulness are A'ery common, which, unless overcome by the use of narcotics, oc- casion great loss of sleep. Diabetic patients are usually "nervous" in the popular sense of the term. The more marked the disease, the more pronounced are these sj'mptoms. Neuralgic pains and cutaneous hj-periES- thesia are frequent. Sensations of abnormal bodily heat are often complained of. Sudden spells of perspiration are common, sometimes unilateral and sometimes more localized still, affecting only the hands or extremities. The intellectual faculties for the most part remain clear, although as the disease becomes advanced the patient often becomes Irritable and fretful, and loses much of Symptomatology. 51 his strength of charactei-. Not infrequently the pa- tient becomes cunning and deceitful in minor matters, especially those relating to his food, resorting to all sorts of ruses to obtain prohibited articles of diet. Finally, as Dr. Dickinson aptly says, " The mind dete- riorates morally and intellectually, and the disease, like advancing age, supplies fears to the brave and follies to the wise." The strong, well-balanced mind becomes weak, vascillating, and morose, and the normal equa- bility of temper gives way to frequent spells of irri- tation, or outbursts of passion. The sexual power deteriorates early in the disease, and later on it becomes abolished, — failure of the power of erection results in complete Impotence. Virility may, however, return if the disease passes away. Finally, the late stages of the disease often terminate in gradually-developed stupor, which is followed by profound coma and death. The nature and symptoms of diabetic coma will be fully con- sidered later, under the head of Complications of the Disease, to which it more properly belongs. The Cutaneous System. — For the most part the skin of diabetic patients is dry, harsh, and uuperspirable. The wasting of subcutaneous areolar tissue causes the skin to become wrinkled and loose, which gives the patient, in marked cases, a prematurely-aged appearance. The hands rub together with a harsh, parchment-like sound, and the surface of the skin may often be seen, upon close inspection, to be covered with scurfy-white dust (Pavy). Itching over the whole cutaneous surface is liable to arise at times, and greatly annoy the patient, especially at night. A case of this kind recently came under my care, which for a time proved very obstinate and rebel- lious to the usual methods of treatment. More frequent, 52 Diabetes Mellitus. however, are tlie local skin irritations which arise in these cases, especially those at the meatus urinarius in the male, and about the vulva in the female. These dis- tressing local irritations, which ma}' he of all grades of severity, from simple erj'thema to pronounced eczema, are doubtless caused by the local effects of sugar in the urine, for we find that, wherever the cutaneous surface be bathed with saccharine urine, local irritation ensues. In diabetic children, who are not carefully attended to bj'' the nurse, it is not uncommon to find quite exten- sive patches of eczema on the inner sides of the thighs and legs, consequent upon the frequent contact of urine with these parts. Eczema, lichen, and psoriasis are frequent localized accompaniments of diabetes. The Muscular System. — The chief feature of the dis- ease which claims attention in this connection is wasting. jNo more constant symptom of diabetes is present than general muscular falling awaj*. In marked cases this wasting is sometimes alarininglj'- rapid. I have seen patients afflicted with diabetes lose from 40 to 60 pounds in weight within a few weeks. The emaciation usually corresponds with the degree to which the urine becomes saccharine, and is most marked when polyuria and thirst are most prominent. If the excretion of sugar be reduced to the minimum the progressive ema- ciation becomes staj^ed, but in pronounced forms of diabetes it is rarely that the loss of flesh can be restored, chiefly because the necessary restrictions of diet do not favor the increase of weight. Occasionally it happens that diabetic patients do not emaciate, notwithstanding very pronounced polyuria and the excretion of large quantities of sugar. Roberts mentions the case of a diabetic who, although he passed 12 pints of highly Symptomatology. 53 saccliarine urine daily for some months, still maintained tlie very generous weight of 210 pounds. A few similar examples have been recorded, but they must be looked upon as exceptional cases. Muscular cramps are sometimes complained of by these patients, especially in the legs. They are, proba- bly, reflexes from gastric disturbances, as they often are when unassociated with diabetes, and, therefore, they do not merit special attention here. Aside from the weakness of the muscular system consequent upon the exhausting eifects of the disease, I would call especial attention to a peculiar sensation of weariness in the muscles, which I have never failed to observe when the urine is highly saccharine. In prac- tice I often teach my patients the significance of this indication, since it enables them to present themselves for examination upon any return of the urine to a sac- charine condition, after a period of exemption from the latter. The urine may be saccharine in some cases without the patient having noticeable thirst or polyuria, but the condition above noted will rarely be absent if the urine be saccharine. This peculiar feeling is one of fatigue, or weariness, rather than actual pain, and it is most prominent in the muscles of the legs and arms. From the fact that this symptom so uniformly appears and disappears with the presence or absence of sugar in the urine, it seems altogether likely that it is due to some deleterious effects of sugar upon the muscular fibres, as it circulates in the blood. Muscular movements become laborious and fatiguing in pronounced diabetes, and consequently these patients are disinclined to exercise ; especially is this the case with regard to active exertion, such as walking. The Urine. — Very remarkable changes occur in the 54 Diabetes MclUlus. lU'iiiaiT secretion in diabetes, both as regards its physi- cal and chemical characters. The physical appearance of the urine is quite characteristic to the practiced eye. It loses its normal deptli of yellowness by two or three shades, and becomes of a decidedly greenish hue. When passed in a vessel, it froths much more than does normal urine. It loses none of its normal transparency, but re- mains perfectlj' clear in uncomplicated cases. The specific gravity of the urine becomes decidedly increased, and it usuall}- fluctuates between 1030 and 1045, although it may rise to 1074 or sink to 1015. I have usually found, if the specific gravity of diabetic urine habitually' sinks much below 1020, that the disease is associated witli contracting kiduej'. The chemical reaction of the urine is usuall}- pronouncedly acid, and it remains so unusually long when exposed to the atmosphere. The quantity of urine becomes remarkably increased in diabetes, the increase usually keeping pretty' accurate pace with the quantity of sugar excreted. Diabetic patients usually void from 6 to 12 pints of urine a day ; l)ut in some cases the enormous quantitj' of 25 and 30 piats have been voided. The dail}- quantitj' of the urine varies exceedingly^ in different cases ; it also fluctuates much from time to time in the same case. The chief causes of fluctuation are the character and quantitj' of food ingested, and the amount of fluids imbibed. It is probable, also, that certain conditions of the system in- fluence the quantity of urine excreted. We know, for instance, that intercurrent febrile conditions cause a decided diminution, both in the quantity of urine and sugar ; and the}' sometimes even cause a temporary dis- appearance of the latter. With regard to the chemical changes in the urine in diabetes : The most marked and remarkable of these is Symptomatology. 55 the presence of sugar. The quantity of sugar present ranges from 1 to 8 or 10 per cent., the average in well- marked cases being about 4 or 5 per cent., — 20 to 25 grains per fluidounce. It will be perceived that with the great augmentation of the volume of urine, heavily charged as it is with sugar, a very considerable amount of the latter is eliminated from the system in marked cases. A pound and a half to 2 pounds may be consid- ered the highest daily range in the most severe cases ; and from this it may mark all grades in quantity, down to an ounce or less in the milder forms of the disease. As an example of the enormous possibilities of some cases in this direction, Dickinson has recorded the case of one of his patients, who passed 50 ounces of sugar in twenty-four hours, and, he sagely adds, " at which rate he would have made his own weight of sugar within the ecclesiastical period of forty daj'S." The quantity of sugar in the urine fluctuates con- siderably during the daily cycle of twenty-four hours, reaching its highest range from three to four hours after meals, and attaining its minimum range during the hours of longest fast — as before breakfast. The quantity sometimes greatly diminishes and, indeed, may disappear upon the approach of a fatal termination of the disease. The amount of urea in the urine is usually increasec^ in diabetes, the degree of increase corresponding with the severity of the disease. Ordinarily double or treble the normal amount is excreted, but it may reach five or six times more than the healthy standard. It has beeii claimed that the diet of diabetic patients accounts for the excess of urea in the urine, but this explanation does not accord with facts. The urea maintains even a higher range when the diet is unrestricted than when largely limited to nitrogenous elements ; indeed, when 56 Piabctrs Mellitiis. patients are put upon an almost exclusively animal diet, both the sugar and urea in the urine are dminished, not only proportionately, but absolutely. It will usually be found that the greatest excretion of urea corresponds with the degree of rapidity in which emaciation pro- gresses, and this strongly suggests its source, viz., tiie albuminoids of the system. Professor Houghton has shown, as already stated, that if albumin be split up its radicals correspond to the sugar and urea, the hydrogen and carbon corresponding to the sugar and the nitrogen to urea, and this is probably the nature of the retrogi'ade metamorpliosis going on in the diabetic process. Strong support is lent to this view by the fact alreadj"^ mentioned, that the amount of sugar and urea in the urine increases and decreases simultaneousl3\ Diabetic urine usually contains acetone, or an acetone- yielding substance — aceto-acctic acid. These, probably, do not exist in the urine in a free state, but in combina- tion with some base which is the product of tlie break- ing up of sugar in the blood. Acetone may be recog- nized by its quality of changing the color of a solution of chloride of iron to a mahogany red. A better test, however, consists of adding a solution of nitro-prusside of sodium and ammonium to the fluid suspected to con- tain acetone, and, upon sluiking well, a rose-violet color is produced, if acetone be jji-esent. The most important morbid chemical product in the urine in diabetes which remains to be considered is the occasional presence of albumin. For the most part, albuminuria is confined to the late stages of the disease, and it is doubtless associated with damage of the kidneys, brought about bj' long-continued excretion of highly-saccharine urine. The degree of albuminuria is usually slight, rarely exceeding ^ or ^ gramme to the Symptomatology. 5T litre. In cases in whicli it much exceeds this amount, in all probability some independent renal disease co- exists. Thus, I have seen associated with diabetes a high degree of albuminuria, — 4 grammes to the litre, the origin of the albumin being due to co-existing amyloid disease of the kidneys. When albuminuria arises consequent to, and in the early stages of, diabetes, it is likely to pass away, if the urine becomes perma- nently free from sugar. Complications. — One of the most frequent, and cer- tainly the most fatal, of all the complications of diabetes, is a peculiar form of coma — Kussmaul'scoma — sometimes termed acetonaemia. Among the younger subjects of the disease this complication is the most frequent cause of death. Few well-marked cases of diabetic coma have thus far been known to recover ; the patients usually succumb within two or three days, sometimes even more suddenly. Two forms of diabetic coma have been described by writers, and, as tj^pieal illustrations of each form, I will describe two cases that came under my observation. In the first case the bowels became constipated for two or three days ; the appetite for food almost ceased, and the patient became weak and listless. I was called after these prodromal symptoms, and found the patient complaining much of pain in the stomach and bowels. The respirations were quickened, shallow, and panting, and numbered about 30 per minute. The patient was rather drowsy, and frequently dozed off to sleep in the intervals between the pains. The pulse was small, thready, and increased in frequency to about 100 beats per minute. The patient was seen about eight hours later, wlien the symptoms were all more pronounced, except the intestiaal pain, which was less complained of. The 3» 58 Diabetes Mellitiis. following daj- the patient -vvas constantly drowsy, and slept most of the time without narcotics. He could be easilj' aroused, but Inpsed into sleep again in a few seconds if undisturbed. The respirations had increased in luuuber to 40 per minute, and the pulse liad risen to 120 beats per minute. In the evening he was found completel}- comatose ; his respirations were 45 per min- ute ; his pulse was 130 per minute, weak, and intermit- tent. No food had been taken during the day. During the night he sank rapidlj% becoming more profoundly- comatose, and died before morning — about forty-eight hours after the first alarming symptoms. In the second ease — that of a young woman 23 years of age — after unusual weakness and malaise for two or three days, she was attacked suddenly during the night with severe pain in her stomach, which was followed by vomiting. Succeeding these symptoms was intense gasping dyspnoea, causing the patient to sit up and lean forward, in the tj-pical asthmatic position. She was evidently in great distress, and expressed the fear that she would " choke to death." The pulse became feeble and rapid, the extremities cold ; and pronounced symp- toms of collapse succeeded, from which, to some extent, she rallied by morning ; but in the meantime she gradu- ally became drowsj^ with intervals of marked delirium. During the day she became more and more unconscious; the pulse became more feeble and rapid, reaching 150 beats per minute. The respirations were labored and shallow, but not panting or frequent (as in the former case), numbering only 18 or 20 per minute. The patient died in tlie evening, in a state of coma and collapse. Other sj'mptoms are not uncommon in diabetic coma, such as a peculiar fruity odor of the breath and urine, the presence of acetone in the urine, and in some cases Symptomatology. 59 tonic convulsions supervene. The chief features of the complication are gastro-intestinal pain, dyspnoea, and more or less rapidl^^-developed coma and collapse. Diabetic coma may be brought about by fatigue, mental emotion, or some trivial intercurrent illness which under ordinary circumstances would but little disturb the gen- eral health. In the case of the young woman just narrated, no especial cause for alarm was present until she contracted epidemic influenza {la grippe), which probablj' precipitated the diabetic coma and caused her death. A highlj'-acid state of the iirine, the presence of acetone in the latter, and constipation of the bowels are usually the preludes to the comatose complication. As to the cause of diabetic coma : The symptoms certainly indicate that the comatose state is brought about by some toxic agent in the blood, and that this agent is the result of alcholic fermentation of sugar in the blood has thus far been largely accepted as the true explanation. Dr. Ralfe, who has studied this subject closely, holds that the toxic agent is acetone, or an acetone-yielding agent ; that when the quantity formed is not excessive, and the kidneys maintain their func- tional activity, the acetone is eliminated without causing any systemic disturbance ; for experiments upon animals prove that considerable quantities of acetone can be ingested without serious consequences. When, how- ever, excessive quantities are liberated in the blood, or when the renal function fails, an excessive quantity is suddenly accumulated in the blood, and then toxic symptoms are at once set up. The frequent appearance of acetone in the urine just previous to the outbreak of diabetic coma, and the persistently diminished alkalinity of the blood in this condition, even when large quanti- ties of alkalies are administered, form the strongest CO Dinhctcs Mellilus. arguments in ftwor of the acetone tlicory of the cause of diabetic coma. I am inclined to believe, however, that the toxic agent or agents which bring about the com:i of diabetes, ■with its associated iihenomona, is nothing more nor less than ptomaines. The extensive retrograde metamor- phosis of albuminoid substances constantly going on in high grades of the disease, and the diminished alkalinity of the blood, which entails its diminished oxidizing power, certainly combine the most favorable conditions for originating these toxic agents. In addition to this, the prodromal symptoms of the coma, such as diminu- tion of the urine and constipation of the bowels, by diminishing the avenues of escape, tend to cause accumu- lation of any toxic agents that may be generated in the sj-stem; while some intercurrent disorder or overfatigue, such as usuall}^ precedes the attack, disturbs the normal resisting power of the organism to the poison, completes the chain of causative factors, and precipitates the com- plication, the symptoms of which strongly indicate the nature of the cause. Pulmonary Complications. — Tubercular phthisis is a very frequent complication of diabetes. It attacks, perhaps, the majority of patients in whom the disease has lasted beyond two or three years. In some respects tlic symptoms differ from those of ordinary phtliisis; tlie cough is often dry, the expectoration less profuse, hmmoptj'sis is uncommon, and the temperature is usually below 100° F. Sometimes pneumonia is lighted up in the progress of this complication, or, what is quite as common, the phthisical symptoms begin with bron- chitis. The sugar in the urine usually diminishes, and sometimes disappears in the course of the lung compli- cation, probably in consequence of pyrexia, for it Symptomatology. 61 increases and decreases with the rise and fall of the bodily temperature. Ocular Complications. — Amblyopia is said to occur in about 20 per cent, of the cases of diabetes. Tem- porary dimness of vision is not uncommon to the dis- ease, and is probably due to defect of adj usting power in the ciliary muscles. More pronounced and often per- manent amblyopia is common, and may be brought about by retinal haemorrhage, atrophy, fatty changes in the retina, or retinitis, and neuro-retinitis ; in short, very similar changes to those met with in chronic Bright's disease. These conditions are chiefly met with in chronic cases. The most interesting ocular complication of diabetes, however, as well as one of the most frequent, is that of cataract. Griesinger noted the appearance of cataract in a collection of 225 diabetics twenty times, or nearly one in every 10 cases. It usually affects both eyes, though not always simul- taneously, and by preference the right eye first. It may appear without previous defect of vision, or after one or more attacks of amblyopia. Occasionally, it pursues a very rapid course, causing complete loss of vision in one or two weeks. More often, however, it takes several weeks or even months before the vision is destroyed. The cataract is usually of the soft variety, but occasionally it may be firm, especially in aged sub- jects. Dr. Mitchell has shown that the administration of sugar to frogs causes their lenses to become opaque, the opacity passing away after the animals have been for a time in water. He also found that the lenses could be rendered opaque after removal from the animals by soak- ing them in syrup. It was thought that these experi- ments explained the formation of diabetic cataract ; but more recent observations have thrown considerable 62 Diabetes MeUitus. doubt upon the subject. Hepp has failed to find sugar in the lenses ofdiabetio patients sutlbriug from ciitiiract. Fischer records similar negative results. In addition to this, diabetic cataract is a permanent condition, and does not improve, even -when the urine of the patient ceases to be saccharine, and so remains. Moreover, diabetic c.ataifict nearly always arises in chronic cases, after the disease has lasted two or three jears, and this strongly suggests that it is one of the degenerative changes com- mon to the last stages of the disease. As a rule, opera- tions for diabetic cataract are not advisable, for they generally' fail owing to almost invariable suppuration of the eye. Wounds in diabetic patients are attended by unusual danger, owing to their proneness to obsti- nate suppuration, and operations for cataract form no exception to the rule. Phlegmonous and Gangrenous Processes are fre- qnentlj' the result of diabetic conditions. Perhaps the most frequent of these are multiple boils, which some- times occur in sufficient numbers to cover the whole surface of the back and shoulders, and even to extend over the extremities. They may be sm.all and confluent, or they may be large and scattered, but in .all cases they are phlegmonous and obstinate in their course, often lasting for months by successions of new crops. Prout went so far as to assert that " carbuncles, and malignant boils and abscesses allied to carbuncles," were always accompanied by sugar in the urine. In diabetic condi- tions they certainly hold some relationship to sugar in the organism, since the surest way of relief from them is to eliminate the sugar from the urine. Max Schuller, who has studied this subject, concludes that they are not due to the si)ecific action of sugar upon the tissues, but are caused by infection, as are other phlegmons. Symptomatology. 63 He thinks it is not even iDrobable that they are due to any special micro-organism peculiar to diabetes, since he has found in them only the round diplococci and streptococci found in ordinary phlegmonous suppura- tions. We may, perhaps, infer that the presence of sugar in the circulation lessens the resisting power of the tissues to the micro-organisms of plilegmonous sup- puration, probably through nutritional changes which it brings about. Gangrene is an undoubted though not very frequent complication of diabetes. From its preference for the lower extremities, beginning usually in the great toe, as well as from its slow course, it has been described as allied to gangrene of old age. Tlie character and course of the process are largely modified by the nature of the tissues attacked. Dr. Hunt, of Philadelphia, has studied this subject closely, and reviewed 64 cases. He records the locations attacked as follows : The leg below the knee, including the foot, 3T ; the thigh and biTttock, 2 ; nucha (not ordinary carbuncle), 1 ; external genitals in females, 1; lungs, 3; fingers, 3; back, 1 ; eyes, 1. As to the nature of the process, he concludes that '' when the tissues are succulent the gangrene will also be of that character; when they are composed mostly of skin, tendon, and bone, they will approach the senile gangrenes in appearance." It is also claimed that diabetic gan- grene " never presents the clear-cut line of demarcation between the dead and living parts that is characteristic of the senile variety, and, moreover, there is a lack in the diabetic form of the decided dryness and shrinking of the senile gangrene." Like most comxjlications of dia- betes, gangrene is a late accompaniment of the disease. Albuminuria must be considered a frequent complica- tion of the late stages of diabetes ; in fact, it is the 64 Diabetes Mellitus. rule, ratlicr than the exception. If the patient be under 40 years of age, the albuminuria is usually unaccom- panied hy primarj' lesions of the kidneys, and, as a rule, need not excite any special alarm. The kidneys, in such cases, are doubtless considerably congested, and in some cases enlarged, with slight tubular changes in progress. It is rare, however, for nephritis to assume a sulliciently acute form in these cases to threaten the life of the patient, or to outrun the primary disease. The amount of albumin in the urine is usuallj^ small, — |- gramme or less to tlie litre. In patients beyond middle age, however, especially those who are well nourished and have been large eaters, if albuminuria be present, it is well to bear in mind the fact that granular atrophy of the kidneys — interstitial nephritis — is frequent, under such circumstances. Such patients will usually be found to have hypertrophy of the left heart ; abnormal tension in their arteries ; while the urine will usually be found of low specific gravity, containing a small percentage of albumin ; and a few perfectly-clear hyaline casts may usu.illy be found, if the urinary sediment be carefully collected and placed under the microscope. The following illustration from my records of pi-actice will, perhaps, emphasize the practical importance of being on the alert in such cases. Three years ago a gentleman from an adjoining State came to consult nie in reference to sugar in his urine, which he said he dis- covered a year or so before. His " age was 58 years ; he had been a ' generous liver,' always had a good appetite, and he was well nourished ; in fact, robust. Analysis of his urine showed it to contain 8 grains of sugar to the ounce, and a mere trace of albumin. He was given some directions as to diet, which related more to his Symptomatology. 65 diabetic condition than to his albuminuria. Three months after I was summoned to his home, to find him in the last stage of uraemia, which terminated in death four hours after my arrival." As the sequel showed, his greater danger lurked beneath a faint degree of albuminuria, the result of contracting kidneys; while his greatest fears were aroused by a mild and — in men of his age — comparatively harmless form of diabetes. It is in such cases that a low specific gravity of urine is sometimes met with. The cirrhotic kidney is unable to excrete the normal amount of solids, and the polyuria still further lowers the proportion of the latter, so that considerable sugar may be present while the specific gravity of the urine remains low, — a seeming paradox in true diabetic conditions. Amyloid degeneration of the kidney occasionally complicates diabetes, though rather by accident than otherwise. A chronic necrosis or suppurative process may be in progress, and the system may withstand the drain for months or years until diabetes sets in, which further impairs nutrition and precipitates the amyloid disease. An illustration will be found among the clinical cases in Section VII of this volume.* When amyloid disease of the kidneys complicates diabetes, the urine becomes highly albu- minous — 2 to 6 grammes to the litre ; digestive disorders and diarrhoea foUow, and the patient becomes decidedly dropsical. Course and Duration of the Disease. — In most cases diabetes begins gradually, if, indeed, not insidiously, and it may exist in a latent form for some time. Sooner or later, however, unusual thirst or weakness, and, per- haps, increasing desire to urinate arouses the sus- picions of the patient to the fact that he is not welL » Case 102, J. W., Section VII. C 66 Diabetes Mellitus, An increased appetite, however, freqnentl3' lulls his sus- picions, and he may continue for some weeks in the belief that with good digestion he must obviously be all right. His increased appetite, however, but quickens the pace of his disease, bj^ causing an increased ingestion of sugar-forming foods. Increasing thirst, more frequent calls to urinate, and advancing weakness compel him at length to seek advice, which leads to the discovery of his true condition. Sometimes the disease begins much more abruptl3', so much so that the patient is able to fix upon the very day in which it began. His thirst and polyuria make such frequent demands upon his time and attention that it is impossible to overlook them. The disease may assume still another form of onset, in which nearly all the sj'^mptoms remain latent for a lengthy period of time. Slight traces of sugar in the urine may constitute all that is discoverable to indicate any abnormal condition ; thirst, polyuria, and wasting being absent. In elderlj' people especiall}', the disease often thus begins and continues for a j-ear or more. The course of the disease, after it has become fully developed, depends upon several circumstances, such as the age of the patient and the character of the treat- ment employed. In young subjects the disease is x(su- ally progressive toward a fatal termination ; and the younger the patient, the more certain does this hold true. In patients under 30 years of age the disease usually advances with a steady and decided marcli in its most pronounced form. The thirst and polyuria are promi- nent ; weakness and emaciation become more and more pronounced ; the appetite fails ; and the patient, in his reduced state, becomes a pre}* to various nervous dis- turbances, especially that of insomnia. Dropsy may or Symptomatology 67 may not appear near the end ; but finally one or more of the complications already described — usually coma — closes the struggle, the patient rarely succumbing to the direct prostrating effects of the disease. If judicious treatment be employed, the symptoms may be considerably modified. Thus the thirst and polyuria may be largely controlled, and even the quan- tity of sugar in the urine may be reduced to 1 or 2 per cent. But in this especial class of cases, notwithstand- ing these indications of apparent improvement, the increased emaciation points to the progressive character of the disease. However favorable the aspect of the disease at times may appear, these patients can rarely be made to increase in weight to any material degree ; and sooner or later some intercurrent disorder disturbs the balance of resistance, and the disease redoubles its force and carries the patient farther from the line of health. A chance exposure lights up an intractable bronchitis, or a localized pneumonia may be the result, to which phthisis may soon after form the sequel. A score or more of disorders apparently lie in wait for the young diabetic patient, while rarely does the avenue to recovery cross his course. The result, consequently, however long delaj'ed, is pretty surely a fatal one. Sometimes, as Dr. Pavy has pointed out, the disease advances by a succession of short bounds or leaps, the treatment seeming at times to check its progress ; but relapse after relapse at length bring the patient to a condition of extreme marasmus, ending in death. The disease sometimes pursues still another course ; beginning with the most pronounced and even violent symptoms, and after thus continuing for a few weeks, it suddenly assumes a milder form, and so remains, or even passes away. As an illustration of this form of 68 Diabetes Mellitus. the disease, a lady from St. Louis two years ago placed herself under my care, -who had for six weeks suffered from the usual symptoms of the disease in the most severe form. She had lost 40 pounds in weight within the time above named. She was put upon treatment — chiefly dietetic — and soon her urine ceased to be saccha- rine, and so far as I know it has so remained. She had regained much of her lost weight before passing from my immediate observation. The course of diabetes in patients beyond middle age is more variable ; but on the whole its progress is more tardy and its symptoms are much less violent. It is not uncommon, indeed, for elderly people to have sugar in their urine almost constantly, without suffering from any marked or disturbing symptoms whatever. Neither thirst, polyuria, nor wasting are present, and the patients are in no way incapacitated for their usual business and social duties. In other cases the disease, while naturally more pronounced, yet a few restrictions of diet hold it well under control, and the patients, by following a few rules as to eating, continue without dis- comfort from the disease for years, without any apparent progress of the latter. Exceptionally, even in those well on in years, the dis- ease assumes the moi-e severe type common to youth, as in the case of a woman at present under my care (Case 185, Section VII). The patient, although 50 years of age, suffers from diabetes in its decided and progressive form, notwithstanding the most careful observance of all details of well-directed treatment. Witli reference to the duration of the disease, it may be stated that diabetes is essentially a chronic affection, and its course is marked by a compass of years rather than by that of weeks. It is true that occasionally the Symptomatology. 69 disease quickly proves fatal. Dr. Roberts has recorded a case which succumbed in nine days ; but such instances are very exceptional. In younger subjects the usual duration of diabetes is from one to three years, the largest number of deaths recorded being those in the second j'^ear. It is not uncommon to meet with cases, in subjects beyond mid- dle age, which survive from five to ten yeai-s. Finally, it must not be overlooked that cases are on record in which the urine has been continuously saccharine for over twenty years. Owing to the somewhat irregular course of diabetes and its susceptibility to modification by treatment, it is impossible to assign a definite duration to any given case. Diagnosis, including Examination of Urine. — The diag- nosis of diabetes presents no difficulties, if attention be directed to the urine. In typical cases, it is almost im- possible for the phj^sician either to overlook the disease or to confound it with other conditions. Thirst, dryness, of the mouth, polyuria, muscular weakness, and emacia- tion are likely to lead to an examination of the urine and the discovery of sugar. It is necessary, as a matter of accuracy, to observe the case for some time, in order to ascertain if sugar be constantly or only occasionally present in the urine, — thus to distinguish between dia- betes and glycosuria. In less pronounced forms of the disease, the presence of sugar in the urine may be over- looked, owing to absence of such symptoms as are likely to lead to an examination of the latter. The more rou- tine practice of urinalysis now in vogue renders this error less common than heretofore ; especially is this the case in hospital practice. As the diagnosis of diabetes hinges so largely upon 10 Diabetes Mellitus. the examination of the urine, I will briefl}' review the most practical features of testing tlio urine for sugar which -will best serve the convenience of the general practitioner, without an attempt to include all the tests for sugar which have been brought forward from time to time, many of whicli I have found too complicated and unsatisfactory for routine work. Among the numerous qualitative tests for sugnr in the urine which have been brought forward to date, the most popular, perhaps, has been that form of tlie copper test known as Fehling's solution. The original formula for this solution is as follows : Dissolve 34.639 grammes of sulphate of copper in 200 grammes of distilled water ; 173 grammes of pure crj^stallized neutral sodic tartrate are dissolved in 500 or GOO grammes solution of caustic soda (specific gravity 1.12), and into this basic solution the copper solution is poured, a little at a time. The clear, mixed fluid is diluted to one litre. The above solution is very unstable, so much so tliat it must he freshly prepared in order to be depended upon. With the view of rendering Fehling's solution more stable, Schmiedeburg proposed substituting mannite for the sodic tartrate, wliicli I liave found to answer the purpose A'ery well. The formula for the preparation of Feliling's solution, improved as I am in the habit of using it, is as follows : 34.639 grammes of pure copper sulphate are dissolved in 200 grammes of distilled water, to which are added 15 grammes of pure mannite ; 500 or 600 grammes of solution of caustic soda are added to the first solution, little b.y little ; finallj' the wliole is brought with distilled water to the volume of 1 litre. In applying tliis test, 1 drachm should be diluted with an equal bulk of distilled water in a test-tube, and gently boiled for a few seconds. If it remain clear, add the Symptomatology. ti. suspected urine, drop by drop, and if sugar be present the first few drops will usually cause a yellow precipi- tate. If no precipitate occur, continue dropping until 1 drachm — not more — of urine be added, re-applying the heat occasionally. If no precipitate occur, sugar is — clinicall3' speaking — ^absent. As above prepared, Fehling's solution is entirely stable, and will keep indefinitelj'. One drachm of the solution responds to jV to tJtt grain of sugar. Prof. Haines's Test. — On the whole, the most satisfac- tory qualitative test for sugar in the urine, in my experi- ence, is that prepared after the formula devised by Prof. Walter S. Haines, of Chicago. Its construction is A'ery simple, as follows : Take of pure sulphate of copper, 30 grains ; pure water, ^ fluidounce ; make a perfect solu- tion, and add pure glycerin, -J ounce ; mix thoroughly, and add 5 ounces of liquor potassae. A perfectly-clear, transparent, dark-blue liquid results, which, being per- fectly stable, may be set aside indefinitely for use. In testing with this solution, take about 1 fluidrachm of the test, and gently boil, when no change should take place ; now add 6 or 8 drops — not more — of the sus- pected urine, and again boil. If sugar be present, an abundant j'ellow or yellowish-red precipitate is thrown down ; if no such precipitate appear, sugar is absent. The white, flocculent deposit thrown down, when non- saecharine urine is added, consists of the phosphates of calcium and magnesium of the urine, which the alkaline character of the test-liquid has precipitated, and it should not be mistaken for an indication of the presence of sugar. The above test has given me most satisfactory quali- tative results in dailj'' work during a continued use of six years. By comparative experimentation I find that 12 Diabetes MelMus. 1 drachm of Professor Haines's test responds to ^J^ grain of grape-sugar. It is well to bear in mind the fact that the copper tests are liable occasionally — though in reality very rarel}' — ^to lead to erroneous conclusions as to the pres- ence of sugar in the urine. Certain normal constituents of the urine — ^notably uric acid, urates, creatinin, mucus, and pj'rocatechin ; as well as certain occasional constitu- ents, as oxj'butyric acid, urochloralic acid, uroleucic acid, and uroxanthic acid ; as well as such drngs as tannin, morphine, salicylic acid, carbolic acid, cubebs, etc. — pos- sess more or less reducing power over the copper tests. The normal elements of the urine possess, for the most part, but feeble reducing powers over these tests, and therefore the errors spoken of are actually encountered but rarely. Nevertheless, since such errors are possible, it is well, in cases of doubt, to appeal to such methods as may be considered absolute. Fortunately, we have, in the phenylhydrazin test, introduced by Fischer, one that is entitled to be considered positive in its capa- bilitj' of detecting sugar. The Phenylhydrazin Test. — This is best conducted as follows : First, introduce in the bottom of an ordinary test-tube a laj-er of phenylhydrazin — say ^ to ^ incli in thickness ; upon this place another ^ to ^ inch of pulverized sodium acetate ; next, add water to one-fourth the capacity of the tube; and, lastly, add sufficient of the suspected urine to half-fill the test-tube. Gradu- aWy bring the whole to the boiling-point, and boil for about one minute, and then decant into a conical glass vessel, and set aside to cool. In from three to twelve hours take up a few drops of the sediment from the bottom of the glass vessel with a pipette, and place them under a microscope. If sugar be present in the Symptomatology. 73 urine, very peculiar, yellow, acicular crystals will be readily seen — phenylglucosazone — which are altogether characteristic. They have a marked tendency to crys- tallize in stellate or rosette form, or in bundles, like sheaves of wheat. The phenylglucosazone crystals may frequently be seen in half an hour after the boiling ; but if none are found after the test has stood twelve hours it may be confidently stated that the urine is free from sugar. So far as at present known, this test reacts only with glucose, maltose, and lactose. The above tests leave little, if anything, to be desired in the way of qualitative analysis of urine for sugar. Having once determined the presence of sugar in the urine, it becomes all-important to know, with some degree of accuracj', the quantity thereof, in order to be able to estimate the degree of severity of the disease, as well as to gain some knowledge of its course from day to day. Now, most of the quantitative tests for sugar in the urine, if, indeed, not all of them brought forward to date, are either complicated, time-consuming, unstable, or inaccurate, and therefore far from satisfactory for practical purposes. The fermentation-test of Roberts requires twenty-four hours' time to reach results which are by no means accurate when obtained. Fehling's solution, perhaps the one most generally depended upon, has been by no means satisfactory in my hands. In view of these facts, I have constructed a formula for a solution which, I trust, will prove as satisfactory in gen- eral practice as it has in my laboratory work, where it has answered all that could be desired. The Author's Quantitative Method. — The formula for this test is as follows : — i D 74 Diabetes Mellitus. R Cupric sulphate (pure), . . . 4.15 grammes- Caustic potash, " ... 20.4 " Strougammoula (sp. gr. 0.9), . . 350 c. cm. Pure glycerin, 50 " AqusB destill. ad 1 litre. The solution is prepared by dissolving the copper sulphate in part of the water and adding the glycerin. In another portion of the water dissove the caustic potash. Mix the two solutions and add the ammonia. Finally with distilled water bring the volume of the whole to 1 litre and filter. If it be desired to use the English weights and meas- ures in preparing this test, the formula is as follows: — R Pure sulphate of copper, . . . J^ drachm. Caustic potash (pure), .... 2i^ drachms. Strong ammonia, 5)4 fid. ounces. Pure glycerin, 6 fid. drachms. Distilled water, ... to 1 pint. The principle upon which the application of this test depends is the fact that a definite quantity of the solu- tion is reduced upon boiling with a definite quantity of grape-sugar, causing the complete disappearance of the beautiful blue color, and leaving a perfectly clear and colorless fluid as the result. Thus, 30 cubic centimetres of this solution are reduced, upon boiling, by ^ grain of grape-sugar. The test should be applied as follows : Into a 4- onnce glass flask pour 30 cubic centimetres (about f§j) of the test-solution, to which should be added an equal volume of distilled or soft water, and bring the whole to the boiling-point over a spirit-lamp. A pi pette, gradu- ated in minims and holding not less than ^ drachm, is now filled with the saccharine urine to be tested, and while the solution is boiling the urine is slowly dis- charged from the pipette, drop by drop, into the test- Symptomatology. 75 solution, until tbe blue color completely vanishes and leaves the solution perfectly colorless and clear. The number of minims it takes to discharge the blue color of the solution contain just \ grain of sugar. By multi- pl^'ing this number of minims until the product is 480, the multiple thereof represents the number of quarter- grains of sugar to the ounce, which, if divided by four, gives the number of grains of sugar in each ounce of the urine tested. The accuracy of this test may be readily proved as follows : Bring 30 cubic centimetres of the solution, in an equal volume of distilled water, to the boiling-point in a glass flask. Then fill the pipette with a solution of grape-sugar of known strength in water (better still, in urine), — say 8 grains to the ounce, — and, as the test- solution is boiling, discharge the sugar solution from the pipette into the boiling fluid, drop by drop, when it will be seen that exactly 15 minims of the sugar solution (or urine) completely discharges the blue color : therefore, 15 minims of the solution contained \ grain of sugar, — the exact proportion of a solution of the strength of 8 grains to the ounce. In testing, the solution should be raised to the boil- ing-point, and kept slowly boiling ; and the urine to be tested should be slowly discharged from the pipette, two or three seconds elapsing after each drop, until the blue color begins to fade ; then the drops should be added still more slowly, about ten or twelve seconds elapsing after each drop. By this means the precise quantity of urine may be determined which completely eliminates the blue color of the test-solution, and the most accurate results are obtained. It may be noted after testing, that, upon cooling, the test-solution slowly resumes its blue color, owing to TG Diabetes MellHus. alDSorption of oxyiicn from the atmosphere and reform- ing the blue protoxide of copitor from the suboxide held in solution by the ammonia. By means of the above test the quantity of sugar in a given sample of urine may be determined accurately within five minutes ; the solution is entirely' stable aud will keep indefinitely ; it is perfectly cleanly and simple in application ; no copper products cling to the utensils or obscure the chemical reactions from view.* Finally, this solution may be used in an ordinary test-tube, and remarkably accurate results obtained by attention to the following details : Measure accu- rately 1 drachm of the test-solution in an ordinary test- tube and raise it to the boiling-i)oint over a spirit- lamp. Dilute the urine to be tested with an equal volume of water. With a minim pipette, or one the point of which is sufficiently large to drop minims, dis- charge the diluted urine, drop by drop, into the boiling test-solution until the blue color is completely dis- charged. If 1 minim of the diluted airine discharges the blue color of the test, the urine contains 30 grains of sugar to the ounce, or over. If it requires 2 drops to discharge the blue color, the urine contains between 15 and 30 grains to the ounce. If it takes 3 droi)s to eliminate the blue, there are between 10 and 15 grains of sugar to the ounce. If it requires 4 drops of the diluted urine to reduce the blue color, there are between T| and 10 grains of sugar to the ounce. If 5 drops, tliere are between 6 and H grains to the ounce. If 6 drops are required, there are from 5 to 6 grains to the ounce. If 8 drops are required, there are from 4 to 5 grains to * All tho copper tests here described are prepared Tor me and kept in stock by Messrs. Gale & Blooki, 44 and 46 Monroe Street, from whom they may be procured at any time. Symptomatology. 77 the ounce. If 10 drops are required, there are from 3 to 4 grains to the ounce. If 15 drops are required, the urine contains from 2 to 3 grains to the ounce ; but if the blue color fails to yield to 15 minims, the urine con- tains less than 2 grains of sugar to the ounce. Thus, the relations may be seen at a glance by the table below : — One Drachm of Test-solution. If reduced by 1 minim of diluted urine, it contains over 30 grains to 1 ounce. If reduced by 2 minims of diluted urine, It contains between 1.5 and 30 grains to 1 ounce. If reduced by 3 minims of diluted urine, it contains between 10 and 15 grains to 1 ounce. If reduced by 4 minims of diluted urine, it contains between 7J^ and 10 grains to 1 ounce. If reduced by 5 minims of diluted urine, it contains between 6 and 7}^ grains to 1 ounce. If reduced by 6 minims of diluted urine. It contains between 5 and 6 grains to 1 ounce. If reduced by 8 minims of diluted urine, it contains between 4 and 5 grains to 1 ounce. If reduced by 10 minims of diluted urine, it contains between 3 and 4 grains to 1 ounce. If reduced by 15 minims of diluted urine, it contains between 3 and 3 grains to 1 ounce. In making the above approximate analysis, the first 5 drops of urine should be slowly added, about five seconds elapsing after each drop, during which the solu- tion should be gently boiled ; after 5 or 6 drops have been added, the solution may be kept slowly boiling and the urine added, drop by drop, continuously, hut slowly, until the blue color completely fades, or till 15 minims of the diluted urine be added. The above tests seem to me all that are required for practical purposes. Those who desire to make them- selves acquainted with the other tests for sugar in the 78 Diabetes Mellitus. urine which ba^-c been brought forward are referred to Dr. Tyson's excellent little hand-book on " Practical Examination of TJriue." If, then, upon chemical examination of the urine as described, it be found that sugar is present to the oxtont of 5 to 10 or more grains to the ounce, it is strongly probable that the case is one of diabetes ; if repoali'd examinations be made, extending over sometime, with the same result, the probabilitj' becomes a certainly, and the diagnosis of diabetes mellitus is complete. Prognosis. — The prognosis in a given case of diabetes depends upon a number of circumstances, the most im- portant of which, perhaps, is the age of the patient. Under 20 j'cars of age the disease is very fatal ; indeed, under such circumstances few reooveiies are recorded. Prom 20 to 45 3'ears of age the outlook is more hopol'iil, the disease being somewhat more amenable to treatment. At the same time, it must not be overlooked that up to 45 j-ears of age diabetes is a very fatal disease, and causes the death of the majority of those who become the subjects of it. After middle age — say, after 50 — the outlook is de- cidedly more favorable, as the disease then, for the most part, assumes a mild course, and not unt'requently termi- nates in recovery. It may be laid down as a general rule that the danger to life from diabetes is in inverse ratio to the age of tlie patient, thus forming a prominent exception to the usual rule of increasing mortality with increasing age, which is the sequence in most diseases. The cause of the disease influences the prognosis. Thus, cases traceable to mental anxiety and overmental toil are of more hopeful outlook, especially if the cause be removable. When the disease arises from trauma- Symptomatology. 19 tisms the prognosis is generally more favorable. On the other hand, as Lancereaux has pointed out, when the disease is traceable to diseases of the pancreas, the prog- nosis is especially gloomy. The length of time the dis- ease has been in progress and the urgency of the symp- toms have an important bearing on the prognosis. Cases in which the disease has become confirmed and the ema- ciation pronounced give little encouragement or hope for the future. On the other hand, if the disease be discovered early, and but little inroads have been made upon the flesh and strength, the general prognosis is always more hopeful. It is a somewhat remarkable fact, as bearing on the prognosis, that diabetes in stout people is much less serious than in spare people. The development of cata- ract is usually regarded as very unfavorable in these cases, indicating an early fatal termination. Such cases are said to usually end in death within from six to twelve months ; and, although some of them may survive longer, they may be considered as essentially incurable cases. Finally, absence of the patellar reflexes is believed to prevail only in unfavorable cases. Complications of the disease and intercurrent con- ditions always render the prognosis grave, and this ap- plies to the most trivial maladies as well as to the more serious. Thus, it is not uncommon for some slight ail- ment, such as a cold or diarrhosa, to precipitate the more serious features of the disease which before gave no occasion for immediate alarm. Such compli- cations as gangrene, pulmonary tuberculosis, and es- peciall}' diabetic coma render the prognosis at once unfavorable. Lastly, the results of treatment enable one, in a measure, to estimate the gravity of the case. Thus, if so Diabetes Melliltis. the urine become t'leo from sugar upon a restricted diet, we are justified iu forming a favorable prognosis ; while, if the disease tail to yield to strict dietarj- measures, and the urine continues heiivil^v laden with sugar, the outlook must be considered unfavorable. SECTION VI. TREATMENT. Prophylactic measures are advisable for people of diabetic parentage, or for those whose families present marlsed tendencies to the disease. In such cases it is wise to adopt a system of diet which limits the use of starchy and saccharine foods to the most moderate pro- portions. Occupations should be selected which entail the least possible mental pressure and excitement ; and, if practicable, a residence should be chosen as near the sea-level as possible, with a mean temperature range of about 70° r. The observance of the above conditions will insure the individual the best chances of avoiding the disease. The treatment of diabetes proper may be most sys- tematically considered under three divisions, — dietetic, medicinal, and hygienic. General Dietetic Considerations. — Until future in- vestigation shall have revealed some agency through which we are able to check the excessive formation of sugar in the liver, our chief resource against the disease must consist in withholding from the system that which it is capable of converting into sugar, and in supplying that which it is capable of assimilating as nourishment. The accomplishment of this object is the essential aim of the dietetic treatment of diabetes. Physiological chemistry as well as experience have shown us that the chief source of sugar-production in the system is the carbohydrate foods, more especially starches and sugar. In nearly all mild cases of diabetes, ** (81) 82 Diabetes Mellitus. and in most cases of recent origin, the avoidance of these foods arrests the excretion of sugar, as well as the more prominent symptoms of the disease. It has just been stated that the chief source of sugar in the organism is the carbohydrate foods ; but, unfor- tunately, ■while they are the chief, they are not alwa3's the only, source. Experimental investigation has shown tiiat when animals are fed upon purely nitrogenous foods — even for lengthy periods of time — a small amount of glycogen still continues to be present in their livers. In the graver forms of diabetes the " sugar-forming vice " of the organism becomes so strong that the liver is capable of splitting up a portion of the nitrogenous foods, and probably even the albuminoids of the tissues, and of transforming a part of these into sugar. In such cases, while the dietetic treatment is able to modify the excretion of sugar, as well as most of the symptoms, it is not able to entirely arrest the progress of the disease. Fortunately, such cases form a minority of those who become subjects of the disease, and are in nearly all cases very young people, or long-neglected and advanced cases. The sugar-forming powers of the organism in diabetes are feeblest in their operation upon niti'ogenous materials, and therefore animal foods are the least susceptible of conversion into sugar. Next in order rank the green parts of certain vegetables, which quite strongly resist sugar transformation. Finally, the starchy and sac- charine members of the carbohydrate group are the most easily transformed into sugar of all, and are there- fore the most dangerous for use. Practically, then, the more completely we are able to eliminate the starchy and saccharine foods from the diet, the more completely we are able to hold the disease under control. At first Treatment. 83 sight this might seem to be a very simple matter ; but when we come to furnish a diet-list that strictly con- forms to the above principle, it will be found a most difficult problem to solve, owing to the very wide diffusion of starch and sugar throughout the organic world. It has recently been claimed by Eickhorst, and otlierSjthat an exclusively nitrogenous diet is damaging to the organism in diabetes, and that the safer course is to permit a variety of foods, which includes the carbo- hydrates. Except in special cases, in which some organ is crippled by organic disease, such as the kidney, there is not a particle of evidence to support such assertion. It is well known that whole tribes of men live uninter- ruptedly upon an exclusive meat diet, and enjoy the most robust health, as well as a muscular and mental vigor that will compare favorably with those who live upon a mixed diet. Besides such examples upon a large scale, it has been demonstrated in private practice and experimental investigation, repeatedly, that a thoroughly nourishing and sustaining diet can be furnished, exclusive of the carbohydrates, upon which diabetic patients can live, not only without damage, but with uniformly bene- ficial results. In comparison with the damaging effects of sugar in the circulation, which is sure to result from the ingestion of starchy foods, the fancied damage due to the exclusive use of animal diet sinks into in- significance. We know that when the blood is charged with large quantities of sugar, it not only gravely alters the nutritive qualities of the former, but it is also liable to induce chemico-toxic changes in that fluid, which are dangerous to life. We know that the perverted elabora- tion of food (chiefly the carbohydrates), the saturation of the tissues with the resulting morbid products, and S4 Biabeles MtUilus. the necessary eftorts at tkeir elimination, lead with cer- tainty to altered nutrition, emaoiatiou, wasting of the vital forces of the economy, secondary disease of im- portant organs, and, in short, to that complex of morbid changes which in diabetes bring about exhaustion and death. First in importance ranks the question of bread in the construction of any diabetic diet-list. The with- drawal of this article from the list is usually the most serious deprivation the patient has to encounter. In consequence of this fact, an almost endless number of breads have been phiced upon the market, which are claimed to be free, or nearly free, from starch, and are hence named diabetic breads. Now, I do not hesitate to say that most breads whicli have been put upon the market with such claims are " a snare and a delusion,'' and have unquestionably shortened the lives of hundreds of diabetic patients. Most samples of so-called "diabetic flour," from which the starch is claimed to have been eliminated, "or nearly so," contain from 30 to TO per cent, of that article. Some time ago I became very skeptical of these preparations, in consequence of find- ing, upon analysis of a sample coming from a prominent firm, that it contained about 60 per cent, of starch. But Dr. Chas. Harrington, of Boston, has rendered us under perpetual obligations to him for fearlessly ex- posing the most of these deceptions, by publishing a careful anahsis of most of them in detail. It may first be noted that his analj-sis of home-made bread gives the proportion of contained starch as 44.99 per cent. The Graham wafer, made of Graham flour, contains 58.45 per cent, of starch. The gluten flour, of Farwell & Ilhines, of Watertown, N. Y., contains 61.11 per cent, of starch. The special diabetic foods of these makers Treatment. 85 contain 68.18 per cent, of stareli; and the bread made of this flour would contain 36 per cent, thereof. Tlie gluten flour of the New York Health Food Company contains 66.18 per cent, of starch. Bread made of this flour would contain 35 per cent, of starch. The gluten wafers of the same company contain 66.96 per cent, of starch. Dr. Johnson's " Educators," a biscuit said by the seller to be " absolutely free from starch," contain of the latter 71.42 per cent. The Boston Health Food Company's diabetic flour, No. 1, sold as absolutely non-starchy, contains 62.94 per cent, of starch. Bread made of this flour would contain 30 per cent, of starch. In view of the above facts, there seems but one course to pursue with reference to bread if we expect to cure our diabetic patients, and that is to limit or curtail its use in all forms. By simply reducing the ordinary allowance of common bread to one-half the daily amount, we have it in our power still to furnish bread to the pa- tient which gives him a less quantity of starch than does the use ad libitum of most diabetic foods in the market. After varied and laborious experiments with substitutes for bread, I have found the following method the most satisfactory : Permit the patient to use his own regular table-bread, but limit the allowance to one-half the usual daily use. If sugar still appear in liis urine, reduce the allowance to one-quarter the ordinary amount. If sugar still appear in his urine, curtail the use of bread completely. The advantages of this method are that we know, with some degree of certainty, the amount of starch that the patient is getting in his bread-supply. The article supplied is, at least, digestible, which is more than can be said of most of the substitutes. In my experience, if the patient cannot assimilate one-half to one-quarter the usual amount of ordinary bread — 86 Diabetes Mellilus. 2 to 3 ounces dail}- — -without excreting sugar in the urine, he cannot assimilate an3' substitute tlierefor, and, under such circumstances, the sooner all bread is stricken from his diet-list the better. When bread is permitted it should be as fresh as possible, and it is better cut in thin slices and well toasted on both sides. The daily allowance of bread will be better assimilated by diabetic patients if taken but twice a day, — at the morning and evening meals; the long intervals between its introduction into the stomach insure its more thor- ough disposal in the normal waj-. Of the other foods derivable from the vegetable king- dom, the cereals and some of the tubers are the most dangerous. Potatoes, beets, parsnips, carrots, among the latter; and, of the former, rice, sago, oatmeal, cornmeal, buckwheat, rj'e, barley, peas, and beans, should be prohibited without compromise in most, if not in all, cases. In the strict form of dieting we are obliged to avoid the whole list. In cases of moderate severity we maj^, however, draw upon one class of vegetables — greens. Green vegetables consist mostly of cellulose, and contain little, sometimes almost no, starch. They are rendered still less objectionable if boiled before being e.aten, as the hot water dissolves out much of the remaining starch and sugar. The starch and sugar contents of vegetables vary considerably, according to the degree of cultivation and the nature of the soil and climate in which thej- are grown. As a rule, a high degree of domestic cultivation favors an increase of the starch and sugar, while high temperature and sunny skies have an opposite tendencj'. Among the least objectionable vegetables m.iybe mentioned lettuce, cucumbers, olives, mushrooms, brussells-sprouts, cab- bage, spinach, and water-cresses. Treatment. 87 Soja, or Japanese bean, owing to its high nutritive properties and its low percentage of starch, is likely to enter largely into the diabetic diet of the future. It has recently been much cultivated in some parts of Europe, especially in Hungarj'. Its composition is as follows : Nitrogen, 36.6 per cent. ; fatty matter, 17 per cent. ; starchy matter, 6.4 per cent. A sauce is made from soja which bears the name of stiso and soju. A kind of cheese is made from it, and very much prized in Japan as a table-luxury.* In Europe the soja has already been utilized for food of men and animals, and recently the attempt has been made to make bread of it. This is very difficult because of the large proportion of oil which it contains. This oil is very purgative, and hence it becomes necessary to rid the meal of it in order to render it fit for domestic usages. Lecerf in Paris and Bourdin in Rheims have succeeded in rendering the bread made from this meal very well supported by the stomach. This bean, which, as the analysis shows, is more nu- tritive tlian meat, serves for nourishment to a great country like Japan, under the forms of sauce, of cheese, of farina, and even of real artificial milk.f Most nuts except chestnuts may be permitted, the list including almonds, walnuts, Brazil nuts, filberts, butternuts, and cocoanuts. Great differences prevail in practice with regard to the use of fruits in diabetic conditions, some authorities allowing them freelj', while others curtail them. Some fruits, such as apples and strawberries, really contain very little sugar, and in the case of apples the sugar is * See article of Egasse, on Economic and Therapeutic Applications of Soja, in Bulletin de Th^rapeutique, vol. cxv, p. 133. t Therapeutic Gazette, March 15, 1890, p. 150. 88 Diabetes Mellihts. in such form that it is often well assimilated by diahotics. The truth is that it is more difficult to make a rule which will apply universally with regard to the nse of fruits than with any other class of foods in these cases ; and therefore it must to some extent be a matter of experiment in each individual case. It may be stated, however, in a general way, that mild cases will bear a moderate use of such fruits as apples, tomatoes, and strawberries ; but in severe cases it is best to prohibit their use without exception. With regard to foods of animal origin, fortunately but three articles are open to question as appropriate for use, viz., honej'', liver, and milk. The first of these requires no comment further than to say that its liiglil}-- saccharine composition excludes it without exception from use in all cases. Liver contains a varying per- centage of sugar, besides large quantities of glycogen, which is readil}' convertible into sugar, and therefore it is objectionable in strict dieting. Oj'sters must be in- cluded in this restriction, owing to their proportionately' enormous livers. With regard to the proprietj' of the use of milk, authorities differ very greatly. Dr. Donkin, the most enthusiastic advocate in its favor, published a book in London, in 18Tl,upon the exclusive use of skim-milk as a cure for both diabetes and Bright's disease, and since then the " milk cure " has attracted considerable atten- tion. Dr. Donkin 's method of treating diabetes by a milk diet, however, has met with but feeble indorsement by his own countrymen, most of whom either limit or exclude it from use. On the other hand. Dr. Tyson, of Philadelphia, whose experience has been verj' large in these cases, very strongly indorses the milk cure. My own experience with the use of milk in the treatment of Treatment. 89 diabetes began nine years ago, since whieli time I liave made thorough and varied trials of it. My conclusions are that a milk diet is successful, chiefly, in milder forms of the disease. Such cases are, as a rule, controlable by moderate limitations of diet, which ofter a greater range and nutritive power than does milk. I believe that the milk treatment, therefore, fi^nds its most appropriate range of application in cases of children, and those cases which are complicated by renal lesions — albuminuria. I have searched in vain, among the published cases which Dr. Donkin has treated by skim-milk diet, for a single record of cure ; nor have I found any result that could be called at all remarkable, as compared with those treated by an animal diet. Dr. Donkin's " Case I, J. Gr., complete recovery," so called, must be considered the best result obtained. This was a ease in which, upon skim-milk diet, the urine became free from sugar, and so remained thirteen months ; but here the record ends without the patient ever having returned to a mixed diet, save the addition of meat. Now, when we consider that J. G. was " a large, robust man, 58 years of age," we would at once expect that a very moderate restriction of carbohydrate foods would eliminate the sugar from his urine. Certainly, as a rule, we can readily eliminate the sugar from the urine, in cases of that age and type, by very moderate restrictions of diet. Dr. Donkin's young dia- betic patients, according to his own records, without exception, ultimately died from some typical complication of the disease, as pneumonia, phthisis, or bronchitis, — as did his cases III, IV, and VI ; and moreover, as a rule, they continued to excrete more or less sugar with their urine, although he speaks of these cases as examples of " rapid and complete recovery," " immediate relief and arrest of the disease," etc. 90 Diabetes MeUilus. The facts appear to be, Tvith regard to milk, that it acts by reducing — not curtailing — the sugar-convertible food. Milk contains about -1- ounce to each pint of lac- tine (milk-sugar), an animal hydrocarbon, which I do not doubt, as Dr. Pavj- says, '' comports itself in the intestinal canal precisely as does grape-sugar." It has been claimed that lactine is changed in the stomach into lactic acid, and thus escapes sugar transformation ; but the fallacy of this doctrine maybe readily proved by administering lactine to patients affected with pronounced diabetes, when without exception it will be found to quickly in- crease the excretion of sugar by the kidneys. The oft- repeated statement that milk-sugar is well assimihited by diabetics, in my experience, only holds true in mild cases. In the more severe type of the disease an exclusive or even adjunct diet of milk has invariably been attended by unsatisfactory results. In the matter of beverages, I am satisfied that dia- betic patients are usually permitted greater liberties than is good for them ; indeed, I do not doubt that the excessive use of the highly-saccharine wines often has much to do in bringing on the disease. Until very recently, when I took the pains to analyze most of the beverages in domestic use, I was in the habit of permitting the usual stereot3ped list. I find, however, that many of them which are usually allowed contain very considerable amounts of sugar, and I now exclude them from use, with perceptivelj- good results to my patients. Thus, coffee is permitted in all the diabetic diet-lists I have seen, and yet the best grades of Java and Mocha contain at least 10 per cent, of sugar. Bj' taking ^ ounce of Java coffee commonly sold in the markets, and with a cup of boiling water I have ni.ade the usual cup of coffee in domestic use. Analysis Treatment. 91 of this cup of coffee demonstrated that it contained 1.5 per cent, of sugar — about 1^ grains to the fluidounce. Analysis of Mocha gave closely corresponding results. With regard to alcoholic beverages, it is doubtful if their temperate use is harmful to diabetic patients, pro- vided they be free from sugar. The importance, how- ever, of the last-named point cannot be too strongly insisted upon, and, since I have carefully analyzed most of the list, the following results are subjoined as a guide in practice : — SuoAR Contents of Leading Alcoholic Betekageb, Accokding TO THE AuTHOK'S ANALYSIS. NATIVE AMERICAN WINES. IT Tir /I ri; /-< T-y • C0KTONT8 or SnOAE H. W. Vraoo s California. m each ri,. ounce. ChaWis, 1 grain. Rielings, 1 " Sauterne, 1.3 grains. Old Grape-Brandy, 4 " Burgundy, 3-4 " Cabernet, ) Medoc, kUarets, a-3 " Beclan, ) Sherry, Old Dry, 10 " Mareala, 10 " Madeira, 24 " Port, Old, 34 " Tokay, 48 " Muscatel, 80 Malaga 40 " Angelica, 50 " Steuben County Wine Co.'s Wines. New York Catawba, 1 grain. Ohio Catawba, 1 " Ohio Delaware, 3 grains. Norton's Virginia Seedlings, .... 4-5 " Burgundy, 5-6 " Extra Family Claret, 3-4 " Walters' Sheri-y, Dry, 8 " P. J. Port, Dry 24 " Gold Cross Champagne, 30 92 DiaMrs MeUittts. IMPOKTED WINES. CONTENTS or snOAR IN KACll I'L. OUKCK. Port, Oporto, .... . . SO grains. Sherry, Viuo de Paste, 13 " Malaga, 140 " Madeira, 45 " St. Julien, 3-8 " Poutet Canet, 4-5 " Chateau Larose 4-5 " Budal Imperial* (L. Reich, N. T.), . . .None. Diatetischer Rothweiu* (Schreilier's), . . " Shins and MoseUc Wines. Deinheimer, 1 grain. Niersteiner, 1 " Geisenheimer, 1 " CardeJis, 1 " Laubenheimer, 1 " Llebfraumilch, 1 " Marcobruuer, 1 " Johannisberger, 1.5 grains. Santernes. Graves, 13 grains. Haut Sauternes, 10 " Sauternes, 30 " Barsae 17 " Burgundy Wines. Beanjolais, 4-5 grains. Chambertin, 4-5 " Pommard 5-5.5 •' Clianipaipics. Pomery Sec, ... . . . SO grains. G. H. Mum's Extra Dry, . . . SO " Veuve Clicquot SO " Ruinait, Extra Dry, 13 " Ruinart, Brfit, 10 " Mo6t & Chandon's Imperial Brftt, ... 15 " Piper Heldsieck, Sec SO " Roederer, Carte Blanche, 48 " Monopole Club, Dry, 20 " * The Budai Imperial of L. Reich, New York, and the Diatetisihor Rothwein of Ijoeb & Co., 55 Warren Street, N. Y., are the only wines I have found absolutely free from sugar in the market. Treatment. 93 Drp Monopole, Delbeck, Extra Dry, . Delbeck, Brftt, . Perier Jou6t, Special, . Jules Mum's Grand Sec, COKTENTS OF 8UCAE IK EACH TL. OUNCE. 30 grains. 8 " 10 34 40 " Jamaica Rum, St. Croix Bum, Medford Rum, Gin, Old Tom, Gin, Holland, Brandy, Hennesy, Brandy, Reno, Whisky, Scotch, Whisky, Bourbon, Whisky, Rye, Whisky, Irish, Arrack, Tequila (Mexican), 7..5 grains. None. 2.5 grains. 4 " None. 24 grains. BBEB8, ALES, AND POBTEES. Domestic Beers. Schlltz'g Pilsener, 4 Schlltz's Extra Pale, 4 Schlitz's Export, 4 Schlitz's Porter, 7.5 Blatz's Export Beer, 4 Pabst Beer, 5 Schoenhofen Beer, 4.6 XJ. S. Brewing Co.'s Beer, 5 Imported Seers. Pilsener, Light, 3 Erlauger, Dark, 6 Llebotschaner (Bohemian beer), .... 2 Capuziner, 4 Augustiner, 6 Wurzburger, 5 Culmbacher, 6 TIvoll, 5 Budweiser, 5.8 Kaiser, 2 grains. grains. 94 Diabetes Mellilus. IN ILVl'U PI. Ol XCK. Bass, 'J si':iii>s. AlUov's 0.5 ■• 1V« s ;! IXwtfr. Guinuess's stout, 6 gnuus. It will be seen, from an ox;iminatiou of tlio foroiroini!; list of alcoholics, that, of the wines, the Khiiie and Mo- selle type is tlie most suitaMe for the use of (iialietio patients on aeeouut of tlie very low pereeiitaire of siiirar which they contivin, — only 1 to 1.5 grains to the tUiid- ounoe. Special attention is called to tlie fact that a number of native American wines of this type — notably Chablis and Eislings of California, and the cat^vwbas of New York and Ohio — are nowise inferior in this respect to the very best brands of imported wines ; indeed, they are considerably superior to some of the most expensive Rhine wines, such, for instance, as Johannisberger. For the plethoric diabetic patient, therefore, the American ■wines jnst named may be considered very suitable. Ou the other hand, in the spare and auajmic class of patients a red wine is more suitable, and in this class no wines approach the Budai Imperial and Diatetischer l\oth- wein, since they are probably the only clarets in our market that are free from sugar. Of the various spirits, rum should be avoided, .ns in-obably most brands contain more or less cane-sugar, and in the case of Jamaica rum a very considerable per- centage of grape-sugar is also present. Brandy contains a varying amount of sugar, as usuallj'^ found in the markets, ordinarily from 2 to 5 grains to the ounce. It should tlierefore be used but sparingly. AVhislvies are free from sugar. W'Mi regard to beer, ale, etc., the grape-sugar added Treatment. 95 in manufacture for fermentative purposes is never tlior- onghly removed by the latter process. Bass's pale ale anrl the pale Bavarian beers contain the least amount of sugar of this class — about 2 grains to the ounce. The quantity of these beverages usually drunk quite makes up for the quality, and therefore, on the whole, they are best used but sparingly by diabetic patients, or alto- gether avoided. Champagnes, sauternes, and sweet wines — either native or imported — are altogether unsuitable for the use of diabetic patients, as will be readily seen upon ex- amination of the list. All mineral waters are permissible as beverages, and some of them are curative, especially the alkaline waters. Among the American waters, those of Waukesha, and especially the Bethesda Spring, stand at the head of the list. The best results are derived from these waters by drinking them at the springs for a few weeks, where I have invariably found them to be beneficial to diabetic patients. The Saratoga Vichy is also an excellent water ; its alkalinity renders it especially suitable in these cases. Finally, the Idaho Springs, near Denver, especially the Bath Spring, deserves mention as approaching closely in composition the Carlsbad waters in Bohemia, though of somewhat lower temperature.* With such excellent and appropriate waters at home, it seems not only foolish but hazardous that so many of our countrymen should undertake the risks, inconveniences, and expense of long pilgrimages to European springs, for it is well known that such long, fatiguing journeys are peculiarly dan- gerous to diabetic patients. Having, in a general way, reviewed the leading * Unfortunately, the liiKh altitude of the Idaho Springs renders that location unsuitable for lengthy visits by diabetic patients. 96 UiaMci' Mt'llilus. features of tlie dietetics of tlio disease, a list of appro- priate foods is here appended !\s a luoi-e minute guide, followed by a list of those wliioh should be prohibited. Foods Permitted. — Meats of all kinds except livers, — beef, nuittoii, pork, poultry, game ; either fresh, roasted, broiled, dried, smoked, cui-ed, potted, or prepared in any ■wTiy except Tvith sugar, flour, or prohibited vegetables. Soups made from me.ats without flour and excluded vege- tables. Fish of all kinds except oystei-s ai\d the inner parts (jf crabs and lobsters. Eggs, butter, cheese, and oils. Jellies made from Cox's gelatin, unsweeteuetl ex- cept with saccharin. Spinach, lettuce, olives, cucumbers, summer cabbage, mushrooms, brussells-sprouts, .and ■\vater-cress. Almonds, filberts, walnuts, cocoauuts, and Brazil nuts. Beverages. — "VTater, including all mineral waters, Rhine wine, California Eisliugs and Chablis, >'ew York and Ohio cAtawbas, Budai Imperial, Schreiber's " dietetic wine," whisky, and gin. Foods Prohibited. — Common bread, except as speci- fied below ; biscuits, crackers, .ind cakes. Farinaceous articles, such as potatoes, rice, sago, tapioca, macaroni, A'crmacelli, common flour, oatmeal, cornuieal, buckwheat- flour, barlej'-meal. The liver of all animals, oysters, and sugar. Saccharine vegetables, as turnips, carrots, p.ars- nips, peas, beans, beets, onions, and rhubarb. Blanched vegetables, as celery, seakale, endive, radishes, and all roots, fruits, and chestnuts. Bevei-ageg. — Tea, coftee, milk, whey, buttermilk, skimmed milk, chocolate, cocoa, malt liquors, cider, champagne, sauternes, sherry, port wine, Madeira, and all sweet wines and liquors. The discovery of saccharin has furnished us a sub- stitute for sugar which has a sweetening power of nearly Treatment. 9T three hundred times greater than the latter. The tablet form in which saccharin is now put up is very convenient for sweetening beverages. My patients have usually found that food and beverages flavored with saccharin, if not oversweetened, are quite as agreeable and pleasant as when flavored with sugar. Systematic Method of Dieting. — A systematic method of dieting diabetic patients is of no less importance than the quality of the diet employed. In order to determine accurately the effects of certain foods upon the disease, no specific medication should be employed until the sugar excretion is reduced as far as possible by diet alone. This method enables the pliysician to distinguish how far improvement is due to diet and how far to the medication, the practical importance of which will be readily perceived. When a case first comes under observation, it is a useful plan to permit the patient to eat and drink what- ever he chooses for the first twenty-four or forty-eight hours, in order to gauge the character of the disease. At the end of that time careful note should be taken of the quantity and specific gravity of the urine, as well as the percentage of sugar. In beginning treatment, an abrupt change to a strict diabetic diet would carry with it more or less danger, and therefore such course is not advisable, but rather a gradual change should be brought about. Step by step the more objectionable foods sliould be limited or cut off until sugar ceases to appear in the urine, or until we reach an exclusively animal diet. The first step should consist in excluding the use of potatoes, sugar, and farinaceous foods, and reducing the bread-allowance to one-half the usual amount eaten by the patient — 3^ to 4 ounces daily. With these restrictions the patient may continue without other changes for about 5 E 98 Diabetes jUellilus. two weeks. In tlie milder cases this " first step " in diet- ing will have caused a reduction of the sngar in the urine to relatively small proportions ; indeed, in many cases it will disappear. If, however, at the end of two weeks sugar still appear in the urine under close observance of the above restrictions, we may know that the disease is at least of fairly severe type, and we should proceed to the next step in dieting. This should consist in the ex- clusion of milk and all vegetables except the green ones enumerated in the permissible list. Greater care should be exercised in the use of bread ; not more than one small slice should be permitted at the morning and evening me.ils, — 2 ounces daily. Perhaps one apple a daj-, if not sweet, may be allowed ; one tomato, or, in place of the latter, a few strawberries. The urine should be examined from time to time, and if sugar does not disappear the restrictions should be increased until the patient is liviu"- upon meats, a few greens, and some nuts, and but 1 ounce of bread daily, with water and the permissible alcoholics as beverages.* After three or four weeks' adherence to the above restrictions, if sugar still appear in the urine, we may be sure that we have to deal with the disease in its most severe type, and, accordinglj-, we must bring to bear against it all our resources of diet in the strictest form. Everything containing starch or sngar that can be avoided should be strictly prohibited; in short, the patient should be reduced to an absolute animal diet. Meats, gelatin, eggs, and fish should constitute exclu- sively the food, while water and a little spirits should be the limit of beverages. It will be found that a strictly animal diet will often » It will be found that a slice of froslily-made tjible-bread ^ ineU thick and 3 Inches in diameter, if ncvrly eirculai-, will weigh about 1 ounce. Treatment. 99 remove the last traces of sugar from the urine ; and after continuing it for a few weeks or months, a reversion to some of the less objectionable articles of the vegetable order will cause no re-appearance of sugar in tlie urine. It must not be supposed that it is always an easy matter to place patients upon an absolute animal diet. Aside from the difficulties of securing the thorough accord and assistance of the patient, those especially with weak digestive powers frequently suffer from gas-^ ti-ic disturbances and diarrhoea. When such compli- cations arise the diet must be relaxed a little, and the patient should be brought more gradually under restric- tions. Time and patience will, in the majority of cases, overcome all obstacles. I once labored with a young diabetic patient for about four months in accustoming his stomach to an animal diet, upon which he now lives in perfect contentment and excellent health, with his urine free from sugar, now considerably over a year. In accustoming patients to a diabetic diet, care should be exercised not to permit the stomach to be overloaded with food, light meals being the better rule to follow. The beneficial effects of temperate eating in diabetes were prominently illustrated during the siege of Paris, as Bouchard tells us that sugar entirely dis- appeared from the urine of diabetics in whom up to that time it had persisted, even though they had been living on a carefully-regulated diet. The diminution in the quantity of food, occasioned by its great scarcity during the siege, effected that which alteration in quality had failed to accomplish. In stout, overnourished diabetics of middle age and over, the disease often yields completely to habits of moderate or spare eating. The disease in such cases is doubtless brought about by overeating, for, as a rule, 100 Diabetes Mellitus. such patients are large eaters. If in these cases the amount of food be reduced to a limit -which the system cim appropriate, vrithout even altering the qualitj- there- of, the disease will pass a^Ya3■ ; and, moreover, if habits of temperance in eating and drinldng be continued, the cure will usually be permanent. About two years ago a patient withdrew from my care because I did not give him medicine to remove the sugar from his urine. The percentage of sugar in his urine was small, and was due to intemperate habits of eating and drinlving, which he could not be induced to correct. It was no uncommon occurrence for him to eat all the luxuries and delicacies within the range of a well-appointed table, and to imbibe therewith a quart or two of champagne, and finallj' to finish the day with a plebeian potation of eight or ten glasses of lager beer. He has since made one or two trips to Carlsbad, but without essentially altering his habits, and it is needless to add that he still has his diabetes. Like too manj- wealth}' men, he evidentlv lives up to the belief that his money should procure him not only all the luxuries of life, but also exemption from the ills of " the world, the flesh, and the devil." With regard to the use of water by diabetics, I have usually placed no limit upon the quantity allowed, per- mitting the patient to follow his own inclinations in this respect, only stipulating that it should not be drunk ice cold. The increased thirst of diabetics points to deh3dration of the blood and tissues, and it is more than probable that the liberal use of water serves a useful purpose in taking up and carrj-ing sugar from the system, which might otherwise accumulate sufficiently to give rise to serious consequences. The dietetic treatment of diabetes has been dwelt Treatment. 101 upon at considerable length because, with our present knowledge, it undoubtedly holds the ke^- to the most successful management of the disease. In concluding this review of dietetics, the importance of at first sepa- rating this from the medicinal treatment cannot again be too strongly insisted upon, since, as already shown, when a system of diet and medication are employed simultane- ously from the beginning, it is impossible to estimate, with any degree of accuracj^, the beneficial effects of either the one or the other. When we have accomplished all that seems possible with the aid of diet, if sugar still remain in the urine, then, and only then, should we have recourse to drugs, unless it be to combat special symptoms. Medicinal Treatment. — It remains next to speak of the medicinal treatment of diabetes, and, of the extended list of drugs which have been from time to time extolled for their curative powers over the disease, only those will be considered which have met with sufficient indorse- ment to entitle them to notice. Opium. — Considering the decided nervous element in the causation of diabetes, it would naturally be ex- pected that nervous sedatives would have some con- trolling influence over the disease. To some extent these anticipations have been realized, since opium, as the representative of this class of drugs, tends to re- strain the excretion of sugar; indeed, of the various drugs that have been recommended, opium maintains its reputation best. To be effective, opium must be em- ployed in full doses, and therefore it is fortunate that diabetic patients, as a rule, are remarkably tolerant of the drug. The indications for the employment of opium are a continued high percentage of sugar in the urine, which 102 Diabetes Mellitus. fiiils to yield to strict dietetic measures. In such cases it may be administered in gradually increasing doses until the sugar disappears from the urine, or until no further reduction in the percentage of sngar seems to be obtainable. As to the method of administration, I be- lieve Dr. Ralfe's practice, of giving one suflicient daily dose at bed-time, to be the most useful. This is least liliel3- to disturb the digestion, or to cause the patient headache and other dislAirbauces. Of the various prep- arations of opium, codeine is probably the most useful, as it is less likel.v to induce constipation than the crude drug, and, moreover, it is much better borne by the stomach. The dose, to begin with, should be ^ to |- grain, which ma_v be graduallj' increased to from 5 to 15 grains per day. Morphine, or, better still, the bimeco- nate of morphine, maj' be emplo^-ed if codeine be not obtainable. It must not be forgotten, however, that in opium we have an agent capable of doing much harm if recklessly emplo3-ed. Its prolonged use is liable to induce the opium habit, and, although the danger of the latter is said to be diminished in diabetics, it is still a danger which no condition confers complete immnnitj- from j and this applies both to opium and its preparations. The dose required to control the excretion of sugar is usually so large that, sooner or later, in my experience, the drug has to be abandoned on account of its damag- ing etl'ects upon nutrition. The exceptions to this rule, I am satisfied, .are so few that the opium treatment should be reserved, for the most part, for failures by other methods. Antipyrin. — Somewhat allied to opium may be classed the recently introduced agents of the phenol and aromatic series, — antipyrin, phouacetiu, salol, acetauilid, exalgin, Treatment. 103 etc. Anti pyrin, the most powerful and most popular of these, has been heralded as almost a specific for diabetes. Like so many alleged specifics for diabetes in the past, it is likely to enjoy a season of popularity and then pass into merited oblivion. The first case that I treated with antipyrin was one of typical severity, in a young subject in whom careful dieting had kept the urine down to an average of 4 pints daily, and a varying percentage of sugar of from 2 to 5 grains to the ounce for many months. All restrictions of diet were thrown off, and the patient was put upon 45 grains of antipyrin a day. The quantity of urine and tlie percentage of sugar steadily increased from the beginning. At the end of ten days the sugar had reached about 15 grains to the ounce, and three days later the patient passed into typi- cal diabetic coma and rapidly succumbed. The second case was quite as typical, although in an older subject. The sugar had been reduced to 1 per cent, or under by careful dieting for two years. Die- tetic restrictions were only partly relaxed, and under 45 grains of antipyrin a daj' the quantityof sugar doubled, as did also the volume of urine, by the end of one week. The third case was one of glycosuria, in which, upon a strict diet, the urine was usually free from sugar. Upon relaxation of diet rules, sugar appeared in the urine to the extent of 2 or 3 grains to the ounce, which antipj^rin failed to eliminate at the end of a week. Antipyrin is unsuitable for lengthy periods of ad- ministration in doses of 45 grains per day, and in smaller doses it is not claimed to modify the disease. Moreover, it is liable to cause albuminuria, and therefore it cannot be considered a safe agent for use in these cases. The bromides have long been used in the treatment of diabetes. They are excellent remedies for many ner- 104 Piahctfg MeUitus. vous conditions -(vliich so often .accompany the disease ; but I have never been able to trace any reduction of sngar in the urine to their use. It is possible, liowover, that they maj' indirectly contribute toward a lessened degree of sugar excretion hy iuducing a more tranquil nervous state. The bromides of sodium and lithium are prefei-able to the potassium salt, being more acceptable to the stomach. The bromide of sodium is given in 15- to 20-gr:iin doses, and the lithium salt in S-gniin doses, well diluted, and the dose Biaj be repeated several times a day. Urgot has enjoj-ed a popularity in the treatment of diabetes second onlj' to that of opium, and probablj- not without some slight merit. Its vaso-constrictor action upon the portal circulation doubtless accounts for its beuelicial etfects in these cases. Its controlling- power over typical diabetes, however, is feeble; but in mild eases it often sensiblj' diminishes the sugar excre- tion. Ergot is, therefore, best suited to mild cases, and especially those in which the patient has good digestive powers. The drug is best administered in tlie form of €rgotiue, or the fluid extract of ergot jMcpared by Squibb. The latter may be given in ^drachm doses, gradually increased according to the tolei-ance of the stomach. Arsenic has long been used in the treatment of diabetes. Its nse was first suggested from the fact noted by Salkowslvv, that when animals were given large doses of arsenic, glycogen greatly diminished in their livers. More recently bromide of arsenic lias been strongly recommended in doses of ^ grain, which may be increased to tjV gtain, or more, if no toxic symptoms arc observeil. Tlierc are two standard solu- tions of bromide of arsenic in the market, — Giliford's, Treatment. 105 of which the dose is 10 drops to begin with, which may be increased to 20 drops, or over ; and Clemen's solu- tion, which is considerably stronger, and the dose of the latter, to begin with, should not be over 5 drops. A few 3'ears ago it was thought that bromide of arsenic promised brilliant results in diabetes, but it must be confessed that it has disappointed expectations. In one of ray cases Giliford's solution was given for a long time, in 25-drop doses three times a day, but during all this time the patient continued to excrete urine that contained 30 grains of sugar to the ounce. Upon with- drawing the bromide of arsenic, and placing the patient upon a restricted diet, I had the satisfaction of seeing the sugar speedily reduced to 2 or 3 grains to the ounce. I have given the bromide of arsenic treatment a thorough trial, in at least 10 or 12 other cases, without obtaining any result which could be called satisfactory ; certain!}', it has not materially lowered the percentage of sugar in the urine. In conjunction with lithium, as suggested by Rouget, arsenic has attained some popularity, being especially lauded by Martineau, who claims to have cured 61 out of 10 cases of diabetes by this treatment. In other hands, however, this treatment has not been attended by appreciable benefit ; at least, such is the report from Bordeaux, where opportunities for trying it on a large scale have been carried out. The chief benefits I have obtained from the use of arsenical prep- arations in diabetes have been from arsenite of iron, in cases complicated by anaemia or malaria. In such cases I often employ the latter, in pill form, beginning with t'j- grain, and gradually increasing the dose to J or ^ grain. Iodoform was recommended by Moleschott, about ten years since, as a remedy for diabetes. Since then 6* 106 Diabetes MelUtus. it has been used considerably, and with somewhat favorable results, seeming to cause a diminution of thirst, polyuria, and the excretion of sugar in the urine. Its well-known tendency to produce toxic symptoms renders great care necessary in its administration. Its use should, therefore, not be continued bej-ond two weeks at a time ; but after two weeks' interruption it maj' again be resumed for another two weeks. Iodoform ru-ay be given in doses of 1 to 3 grains, repeated throe times a da}' ; or one sutficient dose ma^- be administereil at bed-time, which is probably the least unpleasant method. Moleschott's formula, which is claimed to disguise the unpleasant odor of the drug, is as follows : Iodoform, gr. xv; ext. lactucari sat., gr. xv ; cumarin, gr. iss ; to be made into 20 pills. Jambid. — The seeds of the Syzi/gium jambolantim are highly extolled bj' the natives of India as a remedj' for diabetes. The jambul treatment was introduced into Europe about five years ago, and has met with varying success. The drug appears to be very uncertain in its action as obtained here, occasionall}' giving very good results, or apparently so, while at other times it seems to exert no favorable influence over the disease. I have certainly observed marlied benefit from it in one chronic case, as it completely eliminated the sugar from the urine, while the patient was on a non-restricted diet. I have since used it in a number of other cases, but with much less satisfactory results. The dose of tiie powdered seeds is from 3 to 5 grains. A fluid extract of jambul is prepared, the dose of which is from 6 to 8 drops. Oxygen. — Inhalations of oxygen gas have been strongly recommended for diabetes by Bouchard, Day, Demarquay, Walliau, and others. My own experience Treatment. 107 with this agent has led me to think very favorably of its use in these cases. I have already shown that diabetes is a much less fatal disease in low altitudes, and, moreover, the evidence may be considered conclusive that the increased oxidizing power of the blood consequent to low altitudes is the chief cause of this favorable influence over diabetes. By the systematic employment of oxygen inhalations we may secure the same beneficial results to our patients at home which are afforded by a residence at or near the sea-level. In my hands, tlie best results in these cases have followed upon the inha- s*- SS lation of from 3 to 5 gallons of oxygen twice daily, — morning and afternoon. The gas may be more economi- cally, as well as more effectually, administered by diluting it with about an equal volume of atmospheric air, and inhaled slowly and deeply, half a minute or so elapsing between the inhalations. Various appliances have been devised for the genera- tion and administration of oxygen, but for the use of those in general practice the apparatus furnished by the American Oxygen Association of New York, under the name of No. 1 (see cut, above), is, altogether, the best 108 Diabetes Mellihis. in the market. This appanitus has a capacity of S to 10 gallons in ton luinutos, — sutlicioiit for '2 doses, — and the ox_ygen furnished is reuiarkaW_\' puio. The instrument is as jiortable as an ordinary hand eleotrio Inittery, and may, therefore, be used iu the otlice or at the home of the patient. Another, though tur less etlioiout, means of obtaining the benefits of oxygon is by the administration of dioxide of hj-drogon, or so-oallod jioroxido of hydrogen. The dioxide of hydrogen is usually adniinistored in the form of a 3-per-cent. solution, — preferably Marehand's, — the dose of wliieh is from 1 to 2 toaspoonfuls, largely diluted ■^^"ith frater. A better artiele still is the glyoozone of the same manufacturer. Those who desire to make themselves more thoroughly acquainted with recent methods in the use of oxygon are referred to the excel- lent work of Demarquaj-, on " Medical Pneuniatologv," recentl_y translated, with valuable additions, bv Dr. Wallian. Alkalies. — Finally, the beneficial ollVcts of tlie ad- ministnition of alkalies in diabetes deserves mention here. The blood iu diabetes becomes greatly reduced in its alkalinity, and, as a consequence, its oxygen-hold- ing powers are greatly weakened. It follows, therefore, that the use of alkalies are very appropriate in these conditions, and exiicrieuce has amply demonstrated their usefulness. A number of other drugs have been more or less highly extolled for their alk^god specific infiuence over diabetes. Among these may be mentioned: Sodiitm 2^hosphate, nitrate of ^n•amum, salici/Uo acid, picric acid, catabar-hcan, potassium iodide, iodine tincttire, lactic acid, codliver-oil, belladonna, ealerian, and phosphorus. There does not appear to be sulllcieut evidence in favor Treatment. 109 of any of these to entitle them to any degree of confi- dence. Carefully discriminated from the benefits derived from dieting, these drugs are probably nearly inert, so far as their influence over diabetes is concerned. Treatment of Complications and Special Symptoms. — It remains next to consider the treatment of the special symptoms and complications of the disease. Those referable to the stomach command special attention, since disordered digestion is so frequent an accom- paniment of diabetes that it may be considered the rule, after the disease has become thoroughly established. Tlie digestive and assimilative functions should, there- fore, receive special support, through such agents as general experience has taught us prove the most efficient. Among these may be mentioned pepsin, the vegetable bitters, — especially strychnia, — and the mineral acids. Constipation of the bowels, so frequently accom- panying the disease, should be especially guarded against, as this condition reacts very markedlj', in enfeebling the digestive and assimilative powers. In addition to this, it is believed that constipation often tends to. precipitate diabetic coma. I have an especial I)reference for the natural alkaline purgative waters to meet the requirements in such conditions, since they relieve the overacid state of the intestinal canal, so common to the disease. Freidrichshall water; or the recently-introduced Spanish Rubinat Condal water, given before breakfast, are very appropriate ; or 1 or 2 teaspoonfuls of Sprudel salt may be taken in a glass of hot water, upon rising in the morning. In middle-aged people inclined to stoutness and overeating, a course of purgation by either of the above-named agents often proves highly beneficial. An occasional purgative dose of blue mass (10 grains) 110 JPiabtifg MelUlits. Las an admirable effect at times. The continued action of small doses of mercuiials is justly open to question in those c:\ses ; but -nhen an occasional decided dose is given, the liver is stinmh\ted to clear away the etl'ote bile products, and the nssiniilative powers of the in- testinal tract are improved by the relief afforded to the sluggish portal circulation. The pneumonic and inthimrnatory bronchial complica- tions are best met by such agents as ergot, combined with digitalis and muriate of ammonia. Fin-ui>clcs. — The complication of multiple boils some- times yields to quinine, when given to the extent of 10 or 12 grains dailv. Thej are sometimes very chronic and rebellious to treatment, however, in which case the only certain relief to be obt.iined is by eliminating tlie sng-nr from the urine, and every effort should be made in that dii'eetion. Diabetic Coma. — The most dangerous, and certainlj- the most rapidly fatal, of all the complications of dia- betes is that of Kussmaul's ooma — sometimes, though I think improperly, called acetonfemia. Dr. Ealfe, who has studied this subjecU closely, advises, in the early stage, a vapor bath given in bed, and the use of powerful stimulants, as ether, ammonia, musk, valerian, and camphor. He records a case in which he rescued a patient from a threatened attack by the prompt administration of a hot bath. Tempoiivry improvement has followed the intra-venous injection of sodium-caibonnte solution in these cases. Thus, J. Hesse has recently injected a 4-per-cent. solution of sodium carbonate into the veins of a comatose diabetic, ■with the result of a decided improvement for some hours. The patient relapsed into coma, however, but was again relieved by injection of S ounces more of the Treatment. Ill sodium solution. The patient, after twentj'-fonr hours, had a third attack, from which he died. Dickinson has recently recorded a very similar case. If the conclusions which I have reached as to the causation of diabetic coma be correct, viz., as elsewhere stated, that the condition is due to the toxic influence of ptomaines, then the inlialation of oxj'gen gas would seem to offer the best chances of relief in such cases. I regret that, since I began the use of oxygen in the treatment of diabetes, I have not had opportunities for observing the effects of oxygen inhalations over diabetic coma, for they seem to me altogether likely to be capable of affording substantial relief in such cases. I do not regard tlie temporary benefits derived from intra-venous injections of alkalies in diabetic coma as due to their neutralizing effects upon acetone in the blood, but rather to their increasing the oxidizing powers of that fluid, which alkalies are well known to do. In dia- betic coma, therefore, I should employ the sodium-car- bonate injections, as has been the practice heretofore, but I should also re-inforce these by the most liberal inhalations of pure oxygen gas. Since the treatment of diabetic coma has thus far proved so unsatisfactory, the physician should be con- stantly on the alert for its early indications, in order that every possible means may be employed to prevent its appearance. In advanced eases, especially if emaci- ation be marked and progressive, the patient may be considered in constant danger. Constipation, mental emotion, and fatigue should be avoided. Any unusual illness, however slight, but especially in the way of gastric disturbance, should be the signal for confine- ment in bed, and appropriate treatment to prevent the attack. 112 Diabetes Mellitus. In coTiclnsion, it seems desirable to emplinsize the immense importance of careful dieting, as greatly out- ■weigliing all our other resources against the disease combined. This foot should be strongly impressed upon the patient from the beginning. He should be taught to rely but little upon medication, and the most effectual means of accomplishing this is to teach him how much can be achieved by careful dieting alone. When he has once learned through experience that the amount of sugar in his urine alwajs bears a direct ratio to the quantity of prohibited foods indulged in, he is less likely to overstep the proper limits imposed. Diabetic patients are proverbially intelligent people, and Tvith tlieir thirst, poljuria, and other discomforts relieved, a sure sequence iu most cases of careful conformance to the diet rules, imless greatly lacking in gratitude they will cheerfullj' submit to the restrictions imposed. Hygienic Treatment. — In the hygienic management of diabetes two points should be constantly kept in view : the lowered bodily temperature, and the reduced oxidizing powers of tlie economy. In order to com- pensate for the first, these patients should be clad iu pure-wool under-garments (all wool) from head to foot, thus economizing the body-heat as far as possible. To mieet the second indication, the respiratory apparatus should have the widest possible scope, thus to facilitate as perfect oxidation by the lungs as possible. Tlie patient should live as much as practicable in the open air, and on no account should he live or sleep in small rooms or confined atmosphere. Ilis chambers should be thoroughly ventilated by night as well as b^' day, with- out, however, being permitted to become cold. Both the indications above-named are more easily attained by a residence in warm climates, near the sea-level, the par- Treatment. 113 ticular location of which will be seen by referring to Section I, where this subject has been sj^stematically considered. Warm-water baths are very beneficial to these patients, and they may be rendered more efficient by the addition of some alkali, such as sodium bicarbonate. These baths should be repeated frequently', and they may be followed by thorough rubbing of the skin by meaus of brushes or coarse towels. On no account should cold plunges or sea-baths be indulged in. A moderate degree of exercise in the open air is usually beneficial ; at the same time, care should be taken to prevent great fatigue. The dangers of overexertion are well known, and especiall}' in elderly and debilitated subjects it is unwise to permit overexercise. The cares and anxieties of business, especially if exacting, should, if practicable, be exchanged for more moderate and clieerful emploj'ments, or, better still, thrown aside, and a jjeriod of rest and relaxation indulged in. Habits of regularity in eating, drinking, and sleep- ing should be established. The question of sleep is of special importance, for, as a rule, dialjetic patients do not sleep well. At least seven or eight hours' sleep should be secured each night, as the tranquilizing influ- ence of sleep upon the ceutral nervous sj'stem secures a more stable control of nerve-force in the vasomotor tract. The noise and distractions of city life are un- suitable because of the constant tension and waste of nervous force. These should be substituted, when prac- ticable, by the quiet of country life, more especially in the summer months. SECTION VII. CLINICAL CONSIDERATIONS. In order to better illustrate the clinical features of saccharine diabetes, as well as to demonstrate the influ- ence of treatment over the disease, the following cases are subjoined from my records of private practice. Cases of Severe Type in Young Subjects. — The first 3 cases may be taken as fair average types of the dis- ease as usually found in young subjects, showing the features of severity and intractability to treatment almost universally characteristic of the disease in such patients. Case 108, J. L. — December 10, 1885. Patient's age, 29 years. He states that his general health has always been good ; that he never had any serious illness. He has been very actively employed in business since he was 18 years old. He first noticed weakness and debility in September last. He has suffered from dyspepsia, more or less, for a year. He has been rising at night to urin- ate for the past three weeks, and he has noted very pro- nounced thirst of late. Examination of his urine shows a specific gravity of 1045, reaction sharply acid ; sugar is present in quantity between 5 and 6 per cent. The ui'ine is free from albumin. He was ordered nitro- muriatic acid, dil., 10 drops, with strychnia, -^fj grain, three times daily, for his dj^spepsia ; the diet to be gradually restricted to meats, green vegetables, and a small amount of bread. (115) 116 Diabetes Mellitus. December 18th. The quantity of urine is much re- duced; its specific gravity is 1030, and tlie quantity of sugar present is about 2 per cent. He no longer rises at night to urinate, and his thirst has subsided, January 11, 1886. The patient passes, by measure, 118 to 134 ounces of urine daily. The specific-gravity range is 1035 ; sugar, about 2 per cent. February 5th. His condition seems somewhat im- proved. The quantity of his urine averages 80 ounces daily ; the specific gravity, 1033, sharply acid in reac- tion, and it contains no albumin, but sugar is present in quantitj' of 6 grains to the ounce. His diet is restricted to meats, green vegetables, fish, eggs, gelatin, and one small slice of bread a day. He was now put upon arsenite of iron, yV grain, three times a daj^, after food. He is to leave for Florida, in a day or two, for a few weeks' change. February 16th. The patient reports marked improve- ment since he arrived in Florida. His urine now averages 50 to 60 ounces daily, and he has gained 5 pounds in weight. 3[ay 2Jfth. The patient has just returned from Florida, where he spent three and a half months. Ex- amination of his urine to-day shows it to contain 2 per cent, of sugar; noalbumin present; quantity, 100 ounces. He was ordered codeia at bed-time, in -^grain doses, to be gradually increased, and to omit the arsenite of iron. June 1st. No substantial improvement is apparent in tlie condition of the patient; in fact, he seems rather to be losing ground. It was, therefore, deemed wise to send him to the country to get him beyond reach of his business, since wiiile in the city he conld not be kept from dipping into commercial transactions, which made him very nervous. He was sent to Minnetonka for a Clinical Considerations. 117 few weeks, with directions to follow closely the diet rules laid down, and to take no medicines. September 1st. The patient lias just returned to the city much improved by his two months' stay in the countrj'. He reports that his urine was free from sugar a good deal of the time he was away. Examination of his urine to-day shows the specific gravity to be 1025, reaction acid, and entirely free from sugar and albumin. September 20th. Sugar re-appeared in his urine in moderate quantity, owing largely to relaxation of his diet restrictions without orders. November 11th. More or less sugar has been present in his urine since September 20th. The quantity of urine ranges from 80 to 100 ounces daily. The patient concluded, upon his own responsibility, to go to California for the winter, where he died from diabetic coma almost immediately after his arrival. The termination of the above case, under the circum- stances, illustrates the dangers to diabetic patients of undertaking long journeys ; the fatigues incident thereto so often precipitate diabetic coma. The patient derived much benefit from his residence in the country, but con- cluded, without my knowledge, to make the trip to California, — nearly three thousand miles by rail, — when he was not in condition to bear the fatigues of travel, and the result was as reported in the records. Case 212, A. K.—June 16, 1888. Patient's age, 21 j-ears ; unmarried ; apparently a very bright young woman. No family history of diabetes or tuberculosis is obtainable. She states that she was never seriously ill, except with scarlatina two years ago, until her present illness began. She states that about two years ago she US DiaMes MeUilus. beinm to liiive unusual thirst, and to pass largo quan- titios of urine; and she sutlered much from >Yoakness and a muscular lassitude. Those symptoms -vvoro first notiood immedlatoly after graduatiou from eollogo, fol- lowing a hard year's work iu competing for a prize. She consulted Dr. S.. who found sugar iu her urine, the quantity of the urine measuring S pints. The patient passed through the hands of sevenil physicians, her condition being sometimes bettor, and at others worse, until the present date, when her symptoms were noted as follows : The quantity of urine averages :2^ to 3 quarts daily ; she complains of much weakness ; con- siderable thirst ; is easily chilled ; tiio throat and tongue are dry and red ; she is rather nervous, and her menstrual flow has appeared but once during the last year. Her urine is pale, and rather green in color; its s|iecitio gravitv marks 1038; its reaction is sharply acid, and it contains about 2^ per cent, of sugar. The urine is free from albumin. The patient was directed to gradually restrict her diet to animal foods and green vegetables. !No medi- cines ordered. June 26th, The patient states that she feels less tired ; that her thirst has sensibly diminished, ani^tlifit tlie quantity of urine averages about 5 jiints dailj'. Examination of the urine shows its specific gravity to be 1028, and to contain about 8 grains of sugar to the ounce. She was directed to draw the line very rigidly in the matter of diet — only taking meats and green vegetables, with eggs, and gelatin. Jiihj 10th. Patient reports that the qu.antity of urine has measured from 3 to 5 pints daily since last visit. She has sutlered from diarrhuja and more or less pain in her bowels during the last live days. The speoifio Clinical Considerations. 119 gravity of the urine to-day is 1030, and it contains 6 grains of sugar to the ounce. She was directed to relax the diet restrictions somewhat for a few days, taking a small slice of bread twice daily, and she was ordered deodorized tincture of opium, 10 drops, after each loose movement of the bowels. My absence abroad for three months necessitated referring the case to my colleague until my return. October SOth. The patient reports as follows : Diar- rhoea was present, more or less, for two or three weeks after last consultation. She has followed the diet rules advised faithfully up to date, and the quantity of the urine has not exceeded 4 pints daily. She now has no unusual thirst, no chills, and is very little tired, and she has gained a few pounds in weight. Her urine to-day, before breakfast, marks a specific gravity of 1035, and contains 1 grains of sugar to the ounce. After breakfast, sample shows specific gravity 1035, sugar 8 grains to the ounce. Patient's diet at present consists of meats, eggs, green vegetables, some cream. Ordered the same continued, excluding cream and adding almond-bread. November 22d. Patient comes complaining of diar- rhoja, distress in stomach, with flatulence, headache, some thirst. The urine is clear, colop light ; specific gravity, 1034 ; reaction acid ; sugar present, 6 grains to the ounce. The urine is free from albumin. As the almond-bread disagrees, she is to be permitted two or three small slices of common bread each day. To take 10 drops dilute nitromuriatic acid, with tea- spoonful doses of pepsin-essence at meal-times. February 8, 1889. The urine is clear ; specific gravity, 1028; sugar, 6 grains to the ounce. Her stomach has been weak, more or less, since last visit, and some pain and flatulence present, but no diarrhcea. The urine has 1-20 Dttth'tus ^frlliliis:. averaged 3^ to 4 pints in quantity diiily. Some days a little thirst has been present. She is to be permitted one apple a day, or one tomato, radishes, celery, green peas, and string-beans. March 14th. The urine to-day is acid in reaction, clear, specific gravity 10:J9, and contains 5 grains of sugar to the ounce. The patient feels better; appetite is good ; very little flatulence is now present. Ti'eat- ment to be continued unchanged. April 7th. The urine two hours after breakfast marks a specific gravity of 10"J9, and contains between 4 and 5 grains of sugar to the ounce. The daily volume of urine averages from 4 to 5 pints. The patient rises at night once to urinate. She was ordered to tiUce 6 grains of lithium bromide an hour before retiring, as she has been somewhat sleepless of late. Maij 17th. The urine has averaged from 3^ to 4 pints in daily volume since last consultation. The urine ex- arnined to-day, after breakfast, marked a specific gravity of 1023, and contained 3 grains of sugar to the ounce. June 1st. Patient reports not having felt so well since last visit. She complains of pain in the top of her head ; her stomach is disordered, and she suffers distress after food, with flatulence. Her bowels have been irregular, her tongue is coated, and she has disrelish for food, but she has no undue thirst. The daily volume of urine ranges from 3| to 4 pints. Urine examined two hours after breakfast: specific gravity, 1021; sugar, about 1 grain to the ounce. The patient is following a closelj' restricted diet, consisting of meats, fish, eggs, gelatin, green vegetables, and occasionallj' a small slice of bread. No medicines. July 9th. Tiie volume of urine has ranged from 3 to 3^ pints daily since last consultation. The patient sleeps Clinical Considerations. 121 much better, — in fact, better than for years ; but her stom- ach is still weak. The urine to-day is acid in reaction, specific gravity 1026, and contains 2 grains of sugar to the ounce. The patient was sent to Waukesha for a few weeks to drink the waters. September 3d. The patient returned from the springs about a week since, apparently improved. Slie states that she sleeps well ; is not so easily tired ; her appetite and digestion are much improved. The urine contains, a small amount of sugar. October 30th. Patient says she has not been so well since last visit, having had more or less trouble with her stomach. The urine to-day is clear, sharply acid in re- action, specific gravity 1028, and contains 8 grains of sugar to the ounce. Her gums are swollen and tender, and in places recede from the teeth. Very marked and typical xanthoma is present upon the lower and inner margins of both upper eyelids, — a condition claimed by some dermatologists to be associated very frequently with diabetes. The diet is maintained as strictly as possible according to the usual lines. No medicines save iron-wash for the mouth. November 25th. The patient reports improved diges- tion, but the bowels have become rather costive. The mouth and gums are much improved under the use of iron-lotion. Tlie urine marlis a specific gravity of 1031, and contains 7 grains of sugar to the ounce. December 12th. The patient states that she passes less urine of late ; that she is very nervous and weak. She looks thin, and is evidently emaciating rather rapidly of late. December 2Jfth. Patient reports great disrelish for food, and complains of long-continued restrictions of diet. The urine is clear, acid in reaction, specific gravity 6 P 122 Diabetes Mellitus. 1020, and coutaius 5 grains of sugar to the ovuioe. The restrictions as to diet were largely removed, and the patient was put upon 10-grain doses of antip3rin, re- peated tliree times dail3-. December SSth. Tlie nrine marks a speuific gravity of 1032, and contains 12 grains of sugar to tlie ounce. Xo change in diet was made, the patient to take what- ever she chose except sugar and potatoes, and the anti- pyrin was increased to 45 grains a day. Dcceinhcr Slst. The urine marlcs a specific gravity of 1031, and contains 10 grains of sugar to tlie ounce, the volume of urine being about 5 pints daily. She has some thirst. Jan liar >/ 5, 1890. The urine marks a specific gravity of 1035, its reaction is acid, and contains 10 grains of sugar to the ounce. To continue antipyrin. January 13th. The patient was suddenly seized dur- ing the night of the 11th with intense dyspna-a, vomit- ing, pain in her stomach, and collapse. Upon my visit she presented all the typical symptoms of diabetic coma, from which she died January 12th, at 10.50 p.m. The above case well illustrfites the worst type of the disease, as well as the dififlculties to be encountered in the management of such cases. The patient was naturally a delicate woman, of nervo-sanguine temperament, the neurotic features being inherited from a pronouncedly hysterical mother. The chief obstacle in the way of successful treatment was her very delicate stomach, which could not be made to long tolerate the restrictions of diet essential to completely control the disease. When we consider that such cases usually run a rapid course, we must conclude that the treatment was not without influence in the above case, as the patient survived five years under the disease. Clinical Considerations. 123 The next case belongs to the same class and type. The patient, however, possessed much better powers of digestion, and tlie result illustrates how much can occa- sionally be accomplished by treatment in the very worst type of the disease. Case 194, G. S.— February 10, 1888. The patient comes from an adjoining State for advice about sugar in his urine. He states that his age is 18 years and 3 months. He began to be thirsty over a year ago, and about the same time he began to pass large quantities of urine. He experienced muscular weakness, and he found himself easily chilled. He relates that at one time he passed from 120 to 160 ounces of urine daily, and the specific gravity rose to 1050. His appetite became voracious. At 4 years of age he had diphtheria severely, but has suffered no serious illness since until the present disease appeared. He has been strong and hearty as a boy. No family history of diabetes could be traced. He was put upon a restricted diet by his family phy- sician, at home, which modified his symptoms, al- though it did not eliminate the sugar from his urine. At present he seems well preserved, of healthy appear- ance, and the tendon reflexes are present in both legs. Examination of his urine showed it to be pale in color, clear, of acid reaction, specific gravity 1040, and to con- tain 15 grains of sugar to the ounce. The urine is free from albumin. He was ordered to gradually restrict his diet to meat, fish, eggs, gelatin, green vegetables, and a limited amount of bread, well toasted. No medicines were prescribed. February 15th. The urine to-day marks a specific gravity of 1029, and contains 10 grains of sugar to the ounce. He has some constipation of the bowels and 124 Piahetes Jfrlliliis. lieadauhe ; otherwise he is doing well. He has much less thirst, and does not rise at iiii;ht to urinate. March 1st. The urine marks a specific gravity of 1033, and contains about 7 grains of sugar to the ounce. The patient was directed to confine himself exclusively to animal food, not including milk. March 15th. The patient has had considerable difli- cult}' in accustoming his stomach to the restricted diet, as it has resulted in some pain and diarrhea, although he is better to-daj-. The volume of urine for the last twentj'-four hours was 64 ounces ; its specific gravity is 1028, and it only contained about 1 grain of sugar to the ounce. Api-il Jd. The patient has suffered from pronounced diarrhoea with gastric pains for some days past ; his bowels moved ten times yesterday. His urine marks a specific gravity of 1025, is free from sugar, and the volume for twent3^-four hours past is 45 ounces. The urine contains a trace of albumin. lie ■mis permitted to relax slightly his diet restrictions, viz., to take one small slice of bread dailj'. To take tincture of opium, 8 drops, after each loose movement of the bowels. April 5th. Patient looks pale, but he states that he feels better; his diarrhoea is much imiu'oved, — oul^- one movement of the bowels yesterday. His urine averages from 45 to 50 ounces in volume dail^- ; specific gravity, 1033 ; sugar, 3 grains to the ounce. April SSd. Urine, to-day, specific gravity 1032 ; sugar, 5 grains to the ounce. Since last report there has been more or less diarrhoea, although he has been improving in that respect during the last week, — about two stools daily, unaccompanied by pain. He has sufl'ered considerably from nausea, and he feels rather weak. Diet to consist of string-beans, cresses, some Clinical Considerations. 125 milk, meats, tea, eggs, and a little bread. Ordered im- ported Carlsbad water to be taken three or four times daily. May 8th. The urine has averaged from 44 to 46 ounces in volume daily. Patient says he feels " first- rate ;" no weakness ; stomach and bowels in good con- dition. The urine to-day is entirely free from sugar. May nth. TJrine, 43 to 47 ounces daily ; specific gravity, 1026 ; free from sugar. May 21st. TJrine to-day, 46 ounces ; specific gravity, 1026 ; free from sugar. The patient's general condition has been improving. No weakness complained of; his digestion is good, but his bowels are slightly inclined to looseness. His diet to be practically limited to animal food. June 2d. The urine averages from 40 to 52 ounces in volume daily. To-day the specific gravity of the urine is 1026, and sugar is absent. The patient continues well ; no thirst, no diuresis, no weariness. June 18th. Urine averages 43 to 45 ounces in volume; specific gravity, 1023 to 102'! ; no sugar. The urine has now been free from sugar, except occasional traces, for a month, and the patient has gained 10 pounds in weight. He is to leave for home in a few days, and is directed to continue strict diet, consisting of animal food with some selected green vegetables ; no bread to be used. January 7, 1889. The patient has returned to the city for treatment to-day. He relates that he is stronger than when he departed, in June ; his stomach has given him little or no trouble, his bowels are regular, and there has been no essential change, so far as he is able to judge, although he has not measured liis urine since June. His diet, while at home, has consisted chiefly of 126 Diabetes ATeUitus. animal food, with lettuce, string-beans, cabbage, eggs, and nuts. His xirino to-day is clear, of acid reaction, specific gravit}' 1031, and contains about 7 grains of sugar to the ounce. lie was directed to restrict his diet more closely to animal food. January 14th. Urine, to-day, specific gravity 1028; reaction, acid ; sugar, 5 grains to the ounce. Fibru?-y iJd. Urine, to-day, specilic gravity 1028; acid reaction; 3 grains of sugar to the ounce. As the quantity of sugar seems to fall no lower upon practically an animal diet, he was given codeine, ^ grain at bed'-tiuie, to be slowly increased from day to day. February 9th. The codeine causes some headache and nervousness, especially at night. Ilis stomach remsiins in good condition. Urine, to-day, specific gravity 1026 ; sugar, 3 grains to the ounce. To continue codeine at bed-time, in doses of 1 grain and over. February 16th. Patient states that his appetite has fallen off, and his bowels have become constipated ; some flatulence is present, and he does not feel as well as usnal. The quantity of urine has increased some- what ; specific gravity, 1031 ; sugar present, about 3 grains to the ounce. Codeine was omitted, and str3-chnia was ordered, in doses of ^ grain, after meals. February 83d. Urine, to-day, specific gravity 1026 ; reaction acid ; sngar present, 4 grains to the ounce. No increase in volume of urine; no thirst; digestion improved. Treatment continued unchanged. Mareh. 16th. Urine, to-day, specific gravity 1028 ; sugar, 2 grains to the ounce ; patient feels " very well." March SOth, Urine, to-day, specific gravity 1025; sugar, 2 grains to the ounce. The patient feels well, sleeps well, and has g.aincd about 4 pounds iu weight during the last two weeks. Clinical Considerations. 127 April 20tli. Urine specific gravity, 1026 ; sugar present in mere traces. May ^th. Urine to-day, after luncheon, specific gravity 1026 ; sugar present in faint traces. Patient feels exceptionally -well. Treatment unchanged. May 11th. Urine, before breakfast, specific gravity 1022; entirely free from sugar. After breakfast, sample, specific gravity 1025 ; entirely free from sugar. May 18th. Urine, to-day, specific gravity 1022 ; entirely free from sugar. Tlie patient feels very well; his digestion is excellent ; he sleeps well. The patient returns home with directions to live upon meats, fish, eggs, and gelatin. He was instructed to test his urine for sugar every week, and record the results. December 1st. The patient reports that he has been doing excellently since he left tlie city, in May last. His urine lias been free from sugar nearly all this time, until very recently, when he fell through the ice while skating, and became thoroughly chilled. Since then sugar has re-appeared in his urine in small amounts. He reports his general condition as better than for two years past, and that he is qnite contented with his diet, which agrees with him admirably. Cases of Mild Type. — The next 2 cases present pre- cisely the opposite features from the preceding ones. They belong to a class in which the disease is almost invariably mild in character. For the most part these patients are between 45 and 75 years of age, usually well nourished, and have been rather generous in their habits of living, as well as active mentally and physicall3^ If such patients can be induced to practice habits of mod- erate restriction of diet, it is usually a matter of no diffi- culty to eliminate the sugar fi'om their urine, and to 12S Diahiifs 3rcUili(S. maintain fin excellent ilogioe of general health, in which state tlioy may continue almost indefinitely, without abridgment of the usual duties or comforts of life. Case 140, G. 11. — Januan/ .C6\ i.s>V. The patient states that he is 01 j-ears of age, and has heen an active business man all his life, lie comes for advice in refer- ence to thirst and diuresis, which he first noticed about a year ago. No family history of diabetes obtainable. He says that he has had great anxiety over his business affairs during the last two years, lie rises at night to urinate very frequently; is thirsty, and very susceptible to cold. His appetite is very good ; but he complains of being very nervous, and does not sleep well. His urine examined to-day is light in color, clear, reaction sharply acid, specific gravity 1035, and contains 25 grains of sugar to the ounce. The urine contains a small percentage of albumin, and, upon microscopic examination, a few hyaline casts were observed. Diagnosis. — Diabetes, complicated by contracting kidney (interstitial nephritis). lie was directed to avoid potatoes and farinaceous foods, as well as fruits, and to take but little bread. January Slst. The patient reports that he has less thirst; rises, at night, but once to urinate. Examina- tion of his urine shows 12 grains of sugar to the ounce. I\'bruari/ Sd. The urine contains but 5 grains of sugar to the ounce. He was directed to live upon meats, green vegetables, and a small slice of bread t\Yioo dail^-, well toasted. Ft-bniary 6th. Urine specific gravity, 1024 ; free from sugar. February ISth. Urine, to-daj'^, specific gravity 1021 ; no sugar present. Clinical Considerations. 129 February 21st. The urine to-day is free from sugar, and the specific gravity is 1018. A small amount of albumin is still present in the urine. March 3d. The urine to-day is free from sugar; specific gravity, 1016 ; a trace of albumin is present, and a few hyaline casts were observed upon microscopic examination. The patient complains of weakness, and says he is very nervous. The drain upon his system, consequent to the disease for the last year, has evidently reduced him considerably. It was therefore deemed best to order rest for a time, and he was accordingly sent South, with directions to practice restrictions of diet to a moderate degree while absent. April 9th. The patient has just returned from the South, greatly improved in general health. He states that he feels stronger, sleeps well, is not so nervous, and he looks much better. His urine is free from sugar ; specific gravity, 1018; contains a trace of albumin and a few perfectly hyaline casts. He was permitted some relaxation in diet rules. In view of his interstitial nephritis, it seemed desirable to reduce his meat diet as much as possible, and to substitute therefor as much carbohydrates as possible, without causing sugar to re-appear in his urine. He was, therefore, allowed a medium amount of toasted bread, apples and tomatoes ad libitum, and nearly all vegetables, except potatoes, beets, and turnips. To substitute saccharin for sugar in sweetening his food and drinks. No medicines. 3Iay 6th. Patient states that he feels very well ; has attended to his usual business duties for the past month. His urine is free from sugar. July 11th. Patient reports that he feels very well, has no thirst, is not nervous, sleeps well, etc. Examina- 6* 130 Diabetes Melliius. tion of urine shows specific gravity 1020 ; free from sugar, but contains a small amount of albumin. He now lives upon his usual diet, except sug:\r and potatoes. August Soth. PatieHt repoi-ts that he has been very well since last visit, and has gained considerably in weight. His urine to-day is free from sugar, specific gravity 10i20, and a trace of albumin is present, lie was permitted to throw off all restrictions of diet. October Slst. Patient comes complaining of weak- ness in his limbs, tired feeling, and some nervousness. The urine contains about 4 grains of sugar to the ounce ; its specific gravity is 1026. The unrestricted diet upon which he has lived for the last two months is evidentl}' the cause of return of some of his diabetic symptoms. He was directed to avoid amylaceous and saccharine foods for the present. Noveviber !3Sth. Urine to-day contains about 2 grains of sugar to the ounce; specific gravity, 10'23. Janvary SI, 1888. The urine to-day is free from sugar, specific gi-avity 1014, and a trace of albumin is present. March ISth. Urine is free from sugar ; specific gravity, 1016. To continue moderate restrictions of diet. May 16th. Urine is free from sugar ; specific gravity, 1019. Patient states that he feels very well. July ISth. The patient has been on rather a liberal diet for a month, and his urine again contains sugar — about 4 grains to the ounce. Tlio specific gravity of his urine to-daj' is 1025, and a trace of albumin is present in his urine. He was directed to limit his diet more closely. November Sd. Examination of urine shows specific gravity 1022 ; no sugar ; a trace of albumin present, Clinical Considerations. 131 and a few hyaline casts. He has been very well since last report, except for a week in August, when he suf- fered from slight diarrhoea. December 80th. The urine contains a mere trace of sugar ; specific gravity, 1021 ; some albumin is present. January 10, 1889. The urine is free from sugar, and the patient feels well. The patient has now observed the effects of diet upon his urine so long and so closely that he can, as a rule, tell that which best agrees with him and that which will cause sugar to appear in his urine. He is able to use bread rather liberallj-, — 3 to 5 ounces daily, — to eat strawberries, apples, tomatoes, and, in fact, nearly all table-vegetables except potatoes and farinacese, without causing his urine to become saccharine. September 5th. Urine, to-day, specific gravity 1020, free from sugar ; a trace of albumin present. October 2Sd. Urine is free from sugar ; specific gravity 1017 ; patient feels very well. January 10, 1890. The urine is free from sugar, the specific gravity is 1022, and a small amount of albumin is present. The above case illustrates how much can be accom- plished by diet without medication in this class of cases. Upon moderately restricted diet no sugar is ever present in his urine. He is able to eat almost his usual amount of bread, and most vegetables except potatoes, rice, and farinacese ; also to eat liberally such fruits as apples and strawberries without sugar appearing in his nrine. He has never, except in the beginning, been strictly dieted, because, in view of his contracting kidneys, it was deemed wise to permit as free use of vegetable foods as possible, short of causing sugar to appear in his urine. It will be noted that the specific gravity of his urine 132 Diabetes Srellitiis. frequently sank below 10'20, and that on Januavy 31, ISSS, it even rejiistered as low as 1014. It lias nhvaay lieen pointed out tlintwheu granular kidney oouiplieates diabetes, not only does the speeifie gravity of the urine often range low, but sugar may be present when the specilio gravity is eonsiderably bulow normal. Case 153, L. Ij.— June 14, 1887. Tatient's age is 55 years, lie states that ho has always enjoj'ed good health, although he has lived liberall3', taking more or less wino and spirits daily. He began to rise at night to urinate about two months ago. He tinds himself weak and easily tired, is very sensitive to cold, and complains of much thirst. He states that his nrine measures from S to 10 pints in volume daily. The urine marks a siiecitic gravity of 1033, is acid in reaction, and contains 15 grains of sugar to the ounce. The urine is free from albumin. Potatoes, sugar, and farinaceous vegetables were prohibited, and bread was reduced to one-half the normal daily use. June instil. Patient reports that he feels somewhat better, though still weak. His urine contains 5 grains of sugar to the ounce ; specific gravity, 1030 ; no albumin present. July I'^th. Urine specific gravity, 1020 ; acid in reac- tion ; free from sugar and albumin. The patient was directed to live upon a moderately restricted diet, and to practice habits of temperance. His nrine was ex- amined a number of times subsequently and found to be free from sugar up to the end of the year. I meet the patient frequently, and upon questioning him find no indications that sugar is present in his urine to date. It would be easy to add numerous other cases from Clinical Considerations. 133 my records here in ■vvliicli the disease proved mild and amenable to treatment in patients between 45 and 70 years of age. Such cases are to be met with daily in f)ractice. Case of Severe Type in Middle Age. — The following case is the most marked exception to the general rule laid down that I have ever encountered, and, since it is likely to prove of interest, I herewith transcribe it from my records in detail. Case 185, Mes. M..— November 28, 1887. Patient states that she is 41 years of age, married, and has had 10 children. She has had no serious illness until the present ; no family history of diabetes obtainable. She states that her appetite and digestion have always been exceptionally good. She has had no special grief or worry or mental strain. No history of traumatism. She is not especially nervous. Her normal weight is 163 pounds ; her present weight is 136 pounds. In January last — ten months ago — she first noticed that she was lui- usually thirsty, and that she arose frequently at night to urinate. She became much annoyed by a trouble- some itching on the inner part of the thighs. These symptoms continuing, she consulted a physician, who discovered sugar in her urine, and ordered Giliford's solution of bromide of arsenic, which she took in gradu- ally increasing doses until the present. Her daily dose now is T5 drops. Some restrictions in diet were also advised by her attending physician. Her urine to-day is clear, of light-greenish color ; reaction acid, specific gravity 103Y, and contains 30 grains of sugar to the ounce. A trace of albumin is present, and the volume of urine is 10 pints in twenty- 134 Pialk-lcs :\h-Uitiis. four liours. She was directoil to avoid potaloos, forina- ciw, snocliariue foods, aud to reduce her usvial quantity of broad one-half. She -n-as also ordered 6 grains of powdered jumbal after meals. Pcct-inbcr 19th. Urine speoitie gravity, 1030 ; reac- tion acid ; sugar, 'JO grains to tlie ounce. The urine is free from albunun. Diet restrictions were dniwu more closely, and jumbal continued as before. Januan/ 9. ISSS. Tlve urine to-day marks a specific gravity of 1032, and contains 30 grains of sugar to the ounce. The patient was ordered codeine, begiuuing with ^graiu doses after meals, to be increased daily. The dietary rules were drawn somewhat more lirmly. January :2JiL ITrine, to-day, specific gravity 10.32 ; sugar present, 20 grains to the ounce ; volume of nrino for twenty-four hours, 6 pints. Codeine was increased to 2 grtiins a day. Januari/ Slst. Urine specific gravity, 1030; sugar, S graius to the ounce. Codeine increased to 3 grains a day. Fchruanj 9th. Urine specific gravity, 1029 ; sugar present, 5 grains to tlie ounce. Codeine was ordered in- creased to 4 grains daily. JFarch Sd. Urine, to-day, specific gravity 102S; sugar present, 5 graius to the ounce. Piet to be limited to animal food, and codeine to be t.aken to the extent of 5 grains a day. JIarch x'7,s'/. Urine, to-day, specific gravity 1028; sugar, 3 grains to the ounce. The urine is free from allnunin. The patient was obliged to discontinue the codeine on account of nausea, vomiting, constipation, and lieadaclie. Slie is to take no medicine for the present, but to live upon animal food. A})ril Slst. The urine, before breakfast to-day, has Clinical Considerations. 135 a specific gravity of 1025, and contains 2 grains of sugar to the ounce. Tlie patient has had some nausea during the last two weeks, otherwise she has felt better. Directions were given to relax the diet rules slightly for the present, as follows : To take some milk, oysters, lettuce, radishes, and 2 oimces of bread daily. April 26th. Urine to-day marks a specific gravity of 1031, and contains 8 grains of sugar to the ounce. Volume of urine for twenty-four hours is 5 pints. May Sd. Urine, to-daj^, specific gravity 1030 ; sugar, 6 grains to the ounce. Patient complains of weakness in her muscles ; weary feeling ; she is sensitive to cold, and has considerable thirst. She was ordered to dis- continue the use of milk and bread, and confine her diet to meats, eggs, gelatin, and a few green vegetables. May SSd. The urine marks a specific gravity of 1024, and contains 2|^ grains of sugar to tlie ounce. Patient states that she feels much stronger and better generally. June Jiih,. The urine averages 5 pints daily in volume. To-day the specific gravity is 1029, and the urine con- tains 5 grains of sugar to the ounce. The urine is free from albumin. The patient was ordered Clemens's solu- tion of bromide of arsenic, to begin with 5-drop doses after meals, which is to be slowly increased. June 28th. Tlie patient complains of some thirst, is very tired much of the time. She states that her appe- tite is good. She is now taking 6 drops of Clemens's solution after her meals. Her urine to-day is as fol- lows : Specific gravitj^ 1032 ; sugar, 7 grains to the ounce ; no albumin present. November 10th. The patient states that she has lost about 5 pounds in weight since last record. She now passes about 6 pints of urine daily ; is thirsty at times, at others not. She states that she feels tired a good 136 Diabetes Melliltis. deal of the time, but is never nervous. Urine, to-day, specific gravity 1028; reaction acid ; sugar, 6 grains to the ounce ; no albumin present. To eat fish, oysters, tomatoes, green vegetables, eggs, gelatin, cheese, and meats ; also to eat almond-broad. To take no medicine for the present. December 1st. The patient relishes the almond-bread ver}' much ; she is to continue diet as named unchanged. The urine, to-daj', specific gravit}- 1030 ; sugar, 6 grains to the ounce. December 17th. The urine has averaged 4 pints daily since last consultation. To-day examination of urine shows as follows : Specific gravity, 1026 ; sugar, 5 grains to the ounce. To continue diet as before, and to take ergotine (3 grains) after meals. December SSth. The urine is about 5 pints in volume ; specific gravity, 1029 ; sugar, 5 grains to the ounce. Ergotine to be increased to 5 grains after meals. No other change in treatment. January 23, 1SS9. Patient states that the daily vol- ume of urine is abont 3i pints. Urino, to-day, spei'ilic gravity 1027 ; sugar, 4 gi-ains to tlie ounce. To discon- tinue ergotine, and to diet very strictly upon animal foods, taking, in addition, almond-bread only. February 15th. Tlie urine averages from 3 to 4 pints in A'olume dail3\ Tlie specific gravity to-day is 1033, and the urine contains 3 grains of sugar to the ounce. The patient states that slie has had considerable nausea, headache, and constipation of late. She was ordered strychnia, ^V grain, with 10-drop doses of nitromuriatic acid, dil., after meals ; the diet continued unchanged. March Int. Volume of urine has averaged 4 to 5 pints daily. Ilor appetite is still poor, although no nausea is present. The urine to-day is as follows ; Spe- Clinical Considerations. 137 cific gravity, 1030 ; sugar, 5 grains to tlie ounce. She was ordered morpliine, ^ grain at bed-time, to be slowly increased. April 3d. The patient was obliged to discontinue the morphine on account of the nausea, headache, and con- stipation it induced. She was ordered, in place of the morphine, ^ grain of nux-vomica extract with gentian. No essential changes in diet. April 2^th. Urine, to-day, specific gravity 1028; sugar, 2^ grains to the ounce ; volume, 4 pints. The patient was ordered strychnia, -^^ grain, after meals. May 17lh. The urine has averaged from Z^ to 4 pints daily. Examination to-day as follows : Specific gravity, 1030 ; sugar, 2 grains to the ounce. Ordered strychnia increased to -^^ grain after meals. To diet strictly and to discontinue almond-bread. June 1st. The patient states that she has no unusual thirst. She rises at night to urinate once each night. Her appetite and digestion are good, and she feels very well. The urine, to-daj', specific gravity 1030 ; sugar, 3 grains to the ounce. July 17th. Urine 4 pints in volume ; specific gravity, 1028, acid reaction; sugar, 2 grains to the ounce. The patient was sent to Waukesha to drink the waters for a few weeks. She was permitted to use green vegetables while there. September 26th. Patient has just returned from the Springs apparently improved in general condition. She was ordered an exclusively animal diet. November ^th. Patient has had a cold for some days. She states that the urine has averaged from 5 to 6 pints daily. Some thirst is present. Urine specific gravitj-, 1027 ; sugar, 6 grains to the ounce. To take arsenite of iron, j\j grain, after meals. pa 138 Diahclcs Mvlliliig. Bt'cciiihcr 17th. Urine to-day is clear; acid in reac- tion ; specific gravity, 1029 ; sugar, 6 grains to the ounce ; no albumin ; volume ranges from 5 to 6 pints. She was ordered nitro-glycerin, ^Jiy pill (MeK. & R.),to be taken tliree times daily. December ',27th. Urine specific gravit}', 1029 ; sugar, 8 grains to the ounce. Treatment to be continued, 5 pills of nitro-glycerin to be taken dail}-. No changes in diet. January ^, 1890. Patient states that the volume of urine has ranged from 5 to 6 pints dally. Specific grav- ity of urine to-day is 1027 ; reaction acid ; sugar, 6 grains to the ounce. The patient has some thirst. She was ordered 15-grain doses of .intipyrin three times daily, and to take green vegetables and one or two small slices of bread each day. January 8th. Urine specific gravit}', 1027 ; acid re- action ; sugar, 4 grains to the ounce ; no albumin. Patient complains of nausea, much of the time, since beginning antipj'rin. To continue antip3'rin, 45 grains daily. January 16th. Urine specific gr.avity, 1028; sugar, 8 grains to tlie ounce. There lias been no decrease in the volume of urine. To discontinue antipyrin. January 25th. Urine specific gravity, 1026; acid reaction ; sugar, 6 grains to the ounce ; volume, 6 pints. Some thirst is present. The patient was again ordered an absolutel_y animal diet, mostly meats, fish, eggs, and gelatin. February l~th. The patient notes no special changes. She has plainly fallen away in flesh during the last six months. Her skin looks wrinkled. She rises at night twice, on an average, to urinate, and the daily volume of urine is from 5 to 6 pints, ller gums are somewhat in- Clinical Considerations. 139 flamed and tender. Urine specific gravity, 1029 ; sugar, 7j grains to the oune It will be seen, from a review of the above record, that the patient, although over 50 years of age, suffers from the disease in the most obstinate form. The very strictest form of dieting has been enforced from time to time, and nearljf every medicine resorted to of repute in such cases, without eliminating the sugar from the urine. The quantity of sugar has been greatly reduced, and maintained at a comparatively low range (about 1 per cent.), but it has never been entirely absent ; the lowest point it ever reached was 2 grains to the ounce. The patient has always had excellent digestive powers, and no nervous complication lias been present. The disease has been very decidedly checked, and dur- ing the first two j-ears' treatment it might be said to have been held fairly well under control. During the last six months, however, it is very plain that she is losing ground, and I have no doubt that a fatal termination of the case is not far distant. With reference to the drugs employed in this case, codeine seemed to diminish to a slight degree the excre- tion of sugar when given in full doses ; but ultimately codeine, as well as the other preparations of opium, had to be abandoned, because they induced nausea, headache, constipation, or other unpleasant after-effects. Ergot for a time seemingly lowered the percentage of sugar in the urine to a slight degree, but ultimately it also disturbed the digestive organs. Antipyrin proved worse than useless, and, like in most other cases in my hands, it only did harm. On the whole, it will be per- ceived, from a close study of the case, that the patient did the best upon a restricted diet, with little or uo medication. 140 Diabetes Mellilus. Mild Type in Hebrew Patients.— It is plons.ant t(i tuin from such exceptionally intractable and iinsatisiactory cases to another class in which the disease is usually mild and more amenable to troutniont. It has already been pointed ont that diabotos in the Hebrew race is nearly always mild and comparatively easily manaued. The following cases are submitted as illustrations of that fact : — Case 26G, ]\[rs. A.— 0clohe7- 15, ISSQ. Patient's age is 44 years ; inclined to stoutness j her mother and father were both diabetic. She states that in June last sugar was discovered in her urine ; she also had much thirst and polyuria. She has recently sutfered much from metrorrhagia, for which the uterus was curetted, but without relief, as she still has recurring hannorrhages. She has practiced some restrictions of diet prescribed by her family phj'siciaii. Examination of her urine to-day gives the following results : Specific gravity, 10'28 ; reaction acid ; sugar, 8 grains to the ounce. The urine is free from albumin. She has some thirst, and rises at night several times to urinate ; she states that she feels Aery weak and easilj'' chilled. She was ordered to gradnall}^ restrict her food to meats, fish, green vegetables, eggs, gelatin, and to use 110 bread. No medicines were inescribed. October ISth. Urine specific gravity, 1025 ; sharply acid ; sugar, 4 grains to the ounce. October i?od. Urine is clear ; specific gravity, 1036 ; reaction acid ; sugar, 2^ grains to the ounce ; no albumin present. She was ordered to diet strictly upon meats and green vegetables. November L' J. Urine to-day is clear; acid in reac- tion ; specific gravity, 1021 ; entirely free from sugar and Clinical Considerations 141 albumin. Some nric-acid crj-stals of large size are present as urinary sediment. November 12th. Urine to-day is clear ; acid in reac- tion ; specific gravity, 1023 ; free from sugar and albumin. Deceviber Glh. Urine to-day is clear; acid in reac- tion ; specific gravity, 1020 ; free from sugar and albumin. Tlie patient states tliat she feels stronger and better in every waj^ Tliirst has disappeared, and slie no longer rises at night to urinate. She is to talie one small slice of bread at her morning and evening meal, — 2 ounces daily, — and more liberal use of vegetables is to be per- mitted, excluding potatoes, farinaceas, and sugar. December 28th. The urine to-day is clear ; of acid reaction ; specific gravity, 1024 ; free from sugar and albumin. To continue diet as before, unchanged. January 20, 1890. The urine continues to be nor- mal, and the patient is in good general condition, upon a moderately restricted diet. Her haemorrhages have passed away, with the return of the urine to the normal condition. Case 221, Mrs. L. — February 9, 1889. Patient's age, 54 3'ears. She states that she has had sugar in her urine for over a year. At present thirst and diuresis is mod- erate in degree, as she has been dieting to some extent. Her back and shoulders are covered with small boils, whicli have been extremely painful and irritating for liearlj' three months. The urine is clear, of acid reac- tion, specific gravity 1027, and contains 10 grains of sugar to the ounce. The urine is free from albumin. She was directed to gradually restrict her diet to meats, fish, green vegetables, eggs, and gelatin, and to take one slice of bread morning and evening. She was ordered 10 grains of quinine daily in divided doses. 143 Diabetes Mellihis. Febi-uary IStlu Urine to-day clear ; reaction acid ; specific gravit}', 1020 ; free from suuar. February i?od. Urine, to-dsxy, spi'cilic gravity 1025 ; a trace of sugnr is present. The boils are rapidly dis- appearing. The patient wns directed to discontinue the use of bread : otherwise to continue diet as before. March 0th. Urine, to-day, specific gravit}' 1021 ; no sugar; no albumin. The boils have disappeared; but the patient complains of nervousness, for which bromide of lithium was ordered in 5-grain doses after meals. March 19th. Urine to-day is cle:ir ; acid in reaction ; specific gravity, 1021 ; no trace of sugar or albumin is to be found. Tlie patient states that she feels excel- lently well, and is perfectly contented with the diet allowed. To discontinue lithium bromide and to con- tinue diet as before. June Sid. Urine to-day is clear ; acid in reaction ; specific gravity, 1020 ; perfectly free from sugar. The patient lias continued perfectly well, her strength being entirely restored. No thirst, polyuria, or nervousness remain. January, 1890. Urine, to-day, specific gravit}' 1020, acid in reaction, and absolutely free from sugar. Case of Malarial Origin. — The next case is one of special interest as illustrating the occasional origin of diabetes in malaria, as the history' of the case very clearly indicates : — Case 135, C. \f.—June 5, 1SS5. Patient's age, 54 years ; a robust, strong-looking man ; says that he has always lived regularly and temperately, but that ho has had a good deal of exacting mental labor. lie states that he has been under treatment for severe bronchitis Clinical Considerations. 143 for a number of weeks past. He says that sugar was first discovered in his urine about two years ago. He was advised to practice some restrictions of diet, and to take arsenite of iron, which he thinks have done him some good. He states that he has suffered much from .malarial attacks during the last twenty years. His ma- larial complications doubtless originated in Michigan, where much of his time has been spent in the forests as lumber-merchant. Examination of to-day's urine shows the following characters : Color light ; reaction acid ; specific gravity, 1035 ; sugar, 15 grains to the ounce ; no albumin. He was directed to restrict his diet to meats, fish, green vegetables, eggs, gelatin, etc., and to take arsenite of iron, -jJ^ grain, after meals. June 18th. The urine is free from sugar, and the patient goes East for a few weeks' rest. November Sth. Urine, to-day, specific gravity 1036 ; sugar present, 10 grains to the ounce. The patient has been living upon unrestricted diet for some weeks past. He states that the use of quinine always benefits him. He says that without change of diet quinine lowers the specific gravity of his urine when it is unduly high. The patient was again instructed to regulate his diet and to take Giliford's solution of bromide of arsenic, in 10-drop doses, after his meals. March 2, 1886. The patient has spent most of the winter on the Pacific coast, but was not especially benefited thereby. Had chills and fever while there and while traveling. He thinks he has had some sugar in his urine of late. Urine, to-day, specific gravity 1030 ; sugar present, 5 grains to the ounce. He was instructed to diet more closely, and to discontinue arsenic treat- ment. May 8d. Urine specific gravity, 1025 ; no sugar. 144 Diabetes MeUiius. Tlie patient states that be rarelj- rises at night now to urinate, and that lie feels very well. June ISth. The urine is free from sugar, and the patient says he feels very well, except that he has some rheumatism. He was ordered to take sodium salicylate, 20 grains dail3^, for his rheumatism. No changes in diet. July 6th. The urine is free from sugar. Rheuma- tism not much improved. He was ordered to continue lithium salicylate and warm baths. No change in diet. July li^th. Urine specific gravitj', 1025 ; no sugar present. Patient states that he feels better ; his rheuma- tism is passing away. He is to continue the lithium salicylate, July 19th. The patient states that the specific gravity of his urine has ranged, since last visit, at about 1020. He feels better than for three months past. July 26th. The patient reports that he is free from rheumatism. His urine is free from sugar. He was directed to practice moderate restrictions of diet, and, for the present, to take no medicines. August 20th. Urine, to-day, specifiic gravity 1023; free from sugar ; contains no albumin. October 26th. Urine, to-day, specific gravity 1018 ; free from sugar and albumin. November 9th. Patient states that his urine has ranged, since last consultation, as follows: Specific gravity, 1016 to 1026; no sugar present. He states that he is feeling very well in all respects. December 6th. Urine, to-day, specific gravity' 1020 ; no sugar present. February S, 1887. Urine, to-day, specific gravity 1022; free from sugar. The patient was permitted to take a slice of white bread morning and evening, also to eat tomatoes ; otherwise diet to be restricted to Clinical Considerations. 145 meats, fisli, green vegetables, gelatin, and eggs. No medicines prescribed. March 22d. Urine, to-day, specific gravity 1024; free from sugar. April 18th. Urine, to-day, specific gravity 1022 ; a faint trace of sugar is present. Patient complains of some rheumatism, for which he was ordered lithium salicylate, 5 grains three times daily. May 5th. The specific gravity of the urine fluctuates much between 1014 and 1026. A slight trace of sugar is present in the urine to-day. Patient was ordered to continue lithium salicylate. May 18th. Urine, to-day, specific gravity 1028 ; free from albumin, but contains 2 or 3 grains of sugar to the ounce. He was ordered Giliford's solution of bromide of arsenic, in 10-drop doses, after meals. The lithium salicylate to be discontinued. July 11th. The patient states that he has been very well for the last month. Urine, to-day, specific gravity 1023 ; entirely free from sugar. September 26th. Urine to-day is clear ; acid in reac- tion ; specific gravity, 1 023 ; a trace of sugar is present. The patient has been allowed to indulge in fruits — peaches and apples — which he is now directed to dis- continue. To continue Giliford's solution, as before. November 5th. Urine to-day is clear ; acid reaction ; specific gravity, 1024 ; free from sugar. To continue treatment as before, unchanged. March 20, 1888. The patient has just returned from New York, where he states he was not feeling well of late. For the past two or three days he has had acute cystitis, with some slight elevation of temperature. Urine to-day is cloudy ; specific gravity, 1020 ; free from sugar ; contains a large deposit of pus-corpuscles. He 7 G 146 Diabetes Mellitus. ■was confined to his room, and pnt upon an infusion of triticnm repens, with 10-giain doses of ammonium ben- zoate for his cystitis. March Slst. Cystitis is not improved ; patient nrin- ates every hour, with pain and vesical tenesmus; some blood in the urine to-day. II is temperature is 99.5° F. To take 12 grains of quinine daily, as malaria was sus- pected to be the cause of the elevation of temperature ; triticnm repens and ammonium benzoate to be continued as before. March 34th. Cj'stitis continues more or less annoy- ing ; at times there is much pain in urinating. Urine to-day very cloudy ; specific gravity, 1009 ; free from sugar ; a small amount of albumin and a large amount of pus present. Treatment for cystitis continued un- changed, and quinine to be continued in the same doses as before. Diet restrictions to be somewhat relaxed. March SOth. Urine very turbid still ; specific gravity, 1011; free from sugar; considenible sediment of pus in urine still. There is much less distress from the cystitis to-day. April Sd. Urine, to-day, specific gravity 1012; free from sugar, but very cloudy, and much sediment still. The lowered specific gravity of the urine is doubtless due to the large amount of demulcent drinks the patient takes for his cystitis. April SOth. The patient has been very ill for the last three weeks. The cystitis was followed by remit- tent fever of almost malignant tv pe, which refused to yield to quinine until the dose had been inci-eased to 80 grains per day. Nothing short of SO-grain doses, repeated three or four times daily, seemed to have any modifying effect over his chills .and elevated temperature. The patient is now much better in all respects.' Clinical Considerations. 14'7 May 5th. Urine, to-day, specific gravity 1030 ; sugar present, Y grains to the ounce. The urine is increased in volume, but is now clear, and contains little or no pus. As the re-appearance of sugar in tlie urine is doubt- less due to relaxation of his diet rules, he is now directed to diet again strictly. May 10th. Urine, to-day, specific gravity 1023 ; a trace of sugar is present — less than 1 grain to the ounce. The patient's general condition is improving very markedly. He was directed to talie, once a week, 50 grains of quinine in divided doses during the day. May 19th. Patient states that he is feeling stronger, and has gained somewhat in weight. Urine, to-day, specific gravity 1021 ; a trace of sugar is present. May 21st. Urine,to-day, specific gravity 1021 ; sugar present, 2 grains to the ounce. The patient leaves for Carlsbad in a few days, to spend the season at the springs. It should be stated that during the four years the patient has been under observation, he has suffered from attacks of chills and fever (malarial) about twice each year. Most of these attacks have occurred while he was absent from home. If he undertook a railway journey he was jjretty sure to have an attack, an occurrence I have frequently observed in those who are saturated with malarial poison. His attacks have been comparatively mild, except the last one described in the records, complicated with cystitis. Case Complicated by Amyloid Kidneys. — The next case is cited as illustrating an interesting but rather uncommon class of cases, in which diabetes becomes complicated with amyloid disease of the kidneys. 148 Diabetes Mellitus Perhaps, in the majority of such cases, as in the one to be related, diabetes is the complicating disease, tlie amyloid condition probably having existed for some time previous. The case also illustrates the relation- ship of tuberculosis to diabetes and amyloid conditions, which is not uncommon. Case 102, J. y^.— February 17, J, potatoes, and saccharine foods. August 1st. Urine specific gravity, 1020; color normal ; acid reaction ; free from sugar and albumin. To continue treatment as before, unchanged. October i?d. Urine, after breakfast of bread, eggs, and steak, specific gravity, 1021 ; acid reaction; free from sugar and albumin. He states that he never rises at Clinical Consider alions. ] 53 night to urinate now, has no thirst, is not weak, stomach is in excellent condition, and he sleeps well. He was permitted to eat apples and tomatoes, with bread, in moderation ; in fact, diet to be very liberal in quality, but strictly moderate in quantity. October 9th. The patient has been eating, for a week past, nine slices of white bread daily, and everything except sweets, potatoes, and farinaceae. He has no thirst or diuresis. Urine, to-daj', specific gravity 1020 ; no sugar. To throw off all restrictions as to quality of diet except in the matter of sugar. He was especially instructed to eat moderately. January 11, 1890. The patient states that he has been very well since last visit. He has no thirst ; does not rise at night to urinate. He eats everything ex- cept sugar, " the same as before he took sick." Urine specific gravity, 1023; no sugar; no albumin. He was directed to jDractice habits of temperance in eating, and to report if thirst or diuresis returns. There can be no doubt that in the above case diabetes was brought on by overloading the stomach. The patient was an enormous eater, for, as he frankly con- fessed, he "never knew when he had eaten enough." For nearly a year before sugar appeared in his urine he vomited his breakfast almost dailj', and when he first came under observation he was suffering from the usual symptoms of food poisoning. Case 282, H. B.— December 7, 1889. Patient's age 38 years ; weight, 230 pounds ; stout, plethoric man ; comes for advice in reference to sugar in his urine, which was discovered yesterday by medical examiner for life-insurance company. His life was accepted three 7* 154 Diabetes Mellilus. years ago by another company. Preliminary examina- tion of his urine shows it to contain 13 grains of sugar to the ounce ; no albumin present. Patient states tliat he noticed thirst of late ; he also sjxj-s that he rises at night to urinate, passing large quantities of urine by night and by day. He has notiood considerable wonk- ness, especially for the last sixty days or so. He states that he is a vevj- large eater ; has taken oatmeal very liberally for breakfast for the past fifteen or eighteen years. He eats his oatmeal with m,nch sugar. lie states that he is very fond of sweets. He does not eat nnieh meat, but is A-ery fond of bread and potatoes, lie does not use spirits, but is a libeiiil tobacco-smoker, lie snfl'ers much from flatulence and eructations after meals. Xo history of diabetes is obtainable, either on liis father's or mother's side of the family. Urine, to-day, specific gravity lt12S; acid reaction; sugar present, r2 grains to the ounce. The mine contoins no .albumin. He was directed to avoid oatmeal, farinacenj, sweets, etc., and to use bread in moderation. No medicines were prescribed. December IJth. TJrine, to-day, color norm.il ; acid reaction; specific gravity, 10i5; sugar, 3 grains to the ounce ; no albumin. December 19th. Urine, to-day, color normal ; acid reaction; specific gravity, lO'Jl ; free from sugar. Patient feels greatly improved; is no longer weak; does not rise at night to urinate ; is not thirsty. lie was directed to use but little farinsiceous foods and sweets, but especially to cat tetoperately, and to report any return of thirst or diuresis, especially if he rises at night to urinate. Blarch J,, ISW. Patient continues well, and his urine is free from sugar. Clinical Considerations, 155 Case in Childhood. — The rarity of saccharine dia- betes in childhood forms a sharp contrast with diabetes insipidus, so frequent in the early years of life. The following case, the 3'oungest patient with diabetes whom I have treated, will illustrate both the severity and usu- ally rapid course of the disease in subjects of tender age. Case 223, B. G;.— December SI, 1888. Patient's age, 4 years and 3 months. His mother first noticed in August last that he was urinating very frequently, " wetting the bed " at night. About the same time he became very thirst3^ He has recently lost considerably in weight. He complains of being weak and tired much of the time. His mother states that he urinates about every half hour. Careful inquiry fails to reveal any history of diabetes in the family, but tuberculosis is prominent. The patient has had no serious illness before ; but he fell upon the floor of a car a short time before his present illness begun, and sustained a severe blow upon his head. His urine to-day is clear ; color light greenish-yellow ; acid reaction ; specific gravity, 1033; and contains 20 grains of sugar to the ounce. The urine is free from albumin. The patient was ordered a diet of milk, meats, a little cracker, and some green vegetables. No medicines were prescribed. January S, 1889. Urine, to-day, specific gravity 1025 ; sugar, 12 grains to the ounce. February ^th. Urine specific gravity, 1080 ; sugar, 10 grains to the ounce; no albumin. Diuresis and thirst greatly diminished. He gives his nurse no more trouble at night from calls to urinate. The family phy- sician now volunteered to cure the patient, and, as my prognosis was such as to afford the parents no hope of recovery, the patient passed into the hands of the more sanguine phjsicifl.n. 156 liiahelcg MrnHiis. October 1^, AsVs'P. The pnreiits of the okiUl loturnotl ami requested me to resume treatment of the ease. Examination of the pat lent diselosed extreme emaciation, great thirst, and diuresis. The patient had been jier- mitted a mixed diet, including all fruits and farinacea\ and, as a consequence, the disease had progressed at a rapid pace. Examination of the nrine resulted as fol- lows : Color light; reaction acid ; specific gravity, 1038 ; sugar present, 25 gnuns to the ounce ; urea, .013 gramme to cubic centimetre of nrine ; phosphates greatl_y in excess ; the urine is free from albumin. The patient seems tired, ■weak, restless, and has little or no appetite. He was put upon milk, with a little bread ; and quinine was ordered in 1-grain doses three times a daj'. October ISth. The appetite has somewhat improved, and the patient seems less weak. The nrine to-day is clear, acid in reaction, specific gravity 1033, and con- tains 25 grains of sugar to tlie ounce. Phosphates greatly in excess ; no albumin present. Diet to be re- stricted almost entirely to millv. To continue quinine, 3 grains daily. October Sl^ft. TJrine, 4 pints ; specific gravity, 1029 ; sugar, 18 grains to the ounce. To continue treatment as before. October SSlh. The patient seems very weak, has little or no appetite. Urine, to-day, specific gravity 1033; sugar, 16 grains to the ounce; phosphates iu excess ; no albumin present. Xovembcr 4lh. TJrine, to-day, specific gravity 10^29 ; clear; acid reaction; sugar present, 13 gmins to the ounce ; phosphates in excess. To continue milk diet, with very little bread, and some green vegetables. November l'2th. Urine specific gravity, 1024 ; acid reaction ; sugar, 10 grains to the ounce. The patient is Clinical Considerations. 157 weak, has little relish for food, and is troubled with slight cough. November £4th. The cough is better, and, on the whole, the patient seems somewhat stronger. Urine, 5 pints ; specific gravity', 1028 ; sugar, 10 grains to the ounce ; no albumin. December 6th. Urine is clear ; color light ; specific gravity, 1033 ; sugar, 10 grains to the ounce. December 18th. Patient began to complain of pains in his stomach and bowels and to grow a little drowsy to-day. His respirations were somewhat quickened. He was given a hot bath, and hot bottles were applied to his extremities, and 10-grain doses of sodium bicarbonate were ordered every hour. December 19th. Patient is more stupid to-daj'; sleeps much of the time. The respirations have in- creased in frequency to 40 per minute ; the temperature is 101° F. The abdominal pains have subsided. Toward evening the patient became more stupid, and refused all food. December 20th. Patient died to-day in a comatose state, without convulsions. Cases Treated by Oxygen Inhalations. — The 2 fol- lowing cases are herewith taken from my records of practice, more especially with the view of illustrating the oxygen treatment of the disease : — Case 296, W.—July 5, 1890. Patient's age, 54 years; tall, dark, strong-looking man. States that he has had sugar in his urine, more or less, for four or five years. Last year he visited C.irlsbad, and put himself under the care of one of the local physicians there for several weeks, with the result of considerable improve- 158 Diabetes McUiitts. ment. Since his return liome he has been dieting care- fully, according to the instructions he received at Carls- bad. The patient's face, neck, and shoulders are covered with multiple boils, which he states liave been gradnalh' growing worse for the last six weeks, to his great annoj-- ance. He rises at night to urinate, has slight thirst, some weariness of the muscular system. The urine is clear, specific gravit3^ 1027, sharply acid, and contains 15 grains of sugar to the ounce; no albumin present. Since his diet, as advised at Carlsbad, — which he is observing strictly, — seems proper, no essential changes were made in this respect, except to reduce his bread- allowance to 3 ounces daily, instead of 5 ounces, which has been his former allowance. InhaLations of pure oxygen gas were administered daily to the extent of 12 litres. July 7th. The urine is clear, specific gravity 1030, reaction acid, and contains 12 grains of sugar to the ounce. No special improvement in the boils. July 8th. Urine clear; acid in reaction; specific gravity, 1028; sugar, 8 grains to the ounce. July 10th. Urine clear ; color normal ; reaction acid ; specific gravity, 102*? ; sugar, 7 grains to the ounce. He was given 10 grains of quinine daily and oxygen Inhalations continued as usual. July 12th. Urine is clear; color normal; specific gravity, 1024; sugar, less than 2 grains to the ounce. July 14th. Urine is clear ; color normal; reaction acid ; specific gravity, 1022 ; absolutelj^ free from sugar. The boils are rapidly improving, and the patient states that he feels greatly improved. July SOth. The urine to-daj- is clear ; color normal; reaction acid; specific gravity, 1019; it is perfectly free from sugar. The boils have practically disappeared, Clinical Considerations. 159 the thirst is gone, and the patient no longer rises at night to urinate. The oxygen inhalations were discontinued, and the patient was ordered to take glycozone (Ch. Mar- cband's) in teaspooiiful doses before meals. July 29th. The urine is clear ; color normal ; reac- tion acid; specific gravity, 1019; and perfectly free from sugar. The patient is, apparently, x>erfectly well, but was directed to continue the glycozone for the present. August 16th. The urine is clear; color normal; specific gravity, 1022 ; reaction acid ; quite free from sugar. Case 298, H. B. 7.— June 15, 1890. Patient's age, 4T ; weight, 210 pounds; tall, robust-looking; rather stout. He states that sugar was first discovered in his urine about five years ago. For the last three months he has had much thirst, and passes about 5 or 6 pints of urine daily. His digestion has been poor for five years or more. Bowels inclined to constipation. No hereditary history of diabetes. He recently returned from Carlsbad, where he went for the cure, and thinks he was much better while there. His urine to-day is clear ; acid in reaction ; specific gravity, 1027 ; it contains 24 grains of sugar to the ounce. No albumin present. He was ordered inhalations of oxygen gas to the ex- tent of 12 litres daily, and he was directed to limit his bread-allowance to 3 ounces daily. June 18th. The urine is clear ; color rather greenish ; reaction acid ; specific gravity, 1024 ; and contains 10 grains of sugar to the ounce. Patient states that his thirst has disappeared, that he does not rise at night to urinate, and that he passes but little more urine than normal. Oxygen inhalations to be continued as before, daily. 160 Diabetes Mellihts. June ~lst. The urine contains but 4 grains of sugar to tlie ounce to-daj-. Treatment to be continued as be- fore. June mth. Urine to-day is clear ; color normal ; re- action acid ; specific gravity, 1022 ; and perfectly free from sugar. Oxj'gen inhalations were ordered to be reduced to 6 litres per daj-. June SOth. Urine is clear; color normal; reaction acid; specific gravity, 1020 ; absolutely free from sugar. Patient is to take 6 litres of oxygen every alternate day. July M. Urine clear ; color normal ; reaction acid ; specific gravity, 1020 ; no sugar. July 11th. Urine to-day is clear; color normal ; spe- cific gravit}', 1021 ; reaction acid; free from sugar. July 17th. Urine clear ; color normal ; reaction acid ; specific gravity, 1019 ; no sugar. Patient states that he feels perfectly well. He was ordered peroxide of hydro- gen (Ch. Marchand's) in doses of 1 teaspoonful before meals in water, and the oxj'gen inhalations were discon- tinued. The patient was directed to avoid saccharine and starchy foods, but was permitted 2^ ounces of common bread daily. July 25th. Urine to-day is clear ; color normal ; specific gravity, 1020 ; free from sugar. August 3d. Urine to-day clear; color normal; reac- tion acid ; specific gravity, 1019 ; free from sugar. The patient goes to the sea-shore for a month with directions to continue the diet as laid down above, and to discon- tinue peroxide of hj^drogen. SECTION VIII. Diabetes Insipidus CLASSIFICATION. Diabetes insipidus, polyuria, polydipsia, or hydruria, as the disease has been severally called, is a morbid con- dition of the S3'stem, the characteristic symptom of which is an excessive flow of urine of low specific gravity. As a rule, the urine contains neither albumin, sugar, or other morbid chemical products. Willis was the first to attempt a classification of the disease, and he described it under three divisions, as follow : (1) cases characterized by excessive excretion of aqueous urine, the solid matters being deficient — hydruria; (2) cases characterized by excessive flow of urine deficient in urea — anazoturia ; (3) cases in which the flow of urine is excessive, and characterized by an abnormal quantity of urea — azoturia. Parkes adopted a classification of the disease which had reference to the degree of tissue changes involved. It seems more convenient and practical, as Dr. Ralfe has suggested, to adopt a classification which has refer- ence, first, to the excessive excretion of water by the kidneys, and, second, to the increase of solids in the urine. Hydruria may be applied to cases characterized by excessive flow of aqueous urine, and polyuria to cases in which urea or other urinary solids are excreted in excess. Our knowledge of the physiology of diabetes insipi- dus — meagre as it at present is — is largely due to the G' (161) 162 Diabetes Insipidus. investigations of Bernard. He has shofrii tliat tlio vaso- motor centres for both the liver and kidnov are comprised ■within the mednlla oblongata. B^^ experiments upon animals Bernard has shown that when the floor of the fonrth ventricle of the brain in the centitil line is ■wounded the urine becomes saccharine and excessive in quantity. Wounded somewhat higher up, tlie urine becomes excessive in quantity, but contains no sugar. The higher area, therefore, comprises the vasomotor centre which presides over the kidney, while the lower area presides over the liver. Thus far, however, pliysi- ologists have failed to trace the path of the nervous influence from the vasomotor centre to the kidnej', as has been done in the case of the liver. ETIOLOGY. Diabetes insipidus, like diabetes mellitus, is over twice more frequent in males that it is in females ; but it differs from the saccharine disorder in its greater frequency in early life — most of the cases occurring under 30 3-ears of age. It is quite common in childliood, and even in infancy, but the disease is rai-e in advanced life. In a large proportion of the cases it seems impos- sible to clearly trace the disease to any definite cause. In a considerable number of cases, however, a distinct history of heredity is traceable. Lancereaux was able to trace about 15 per cent, of the cases to this cause. Diseases and traumatisms of the brain are, undoubtedly, frequent causes of diabetes insipidus. Lancereaux found about Ifi per cent, of the cases to be due to this cause, while Roberts found a still larger percentage of cases originating from this source. A considerable number of cases seem to owe their Pathological Anatomy. 163 origin to intemperance, especially to habitual alcoholic The remaining causes assigned for the disease are : Exposure to cold, or sudden chills ; drinking cold fluids when the body is overheated; hysterical and nervous conditions; mental emotion; acute inflammatory and febrile conditions. A cause which I do not remember to have seen recorded, but which I have more than once tiaced, is that of sexual excesses. The frequent mictu- rition associated with irritable bladder, so common to excessive sexual indulgence, is not to be mistaken for polyuria. Finally, it is probable that nearly 40 per cent, of the cases of diabetes insipidus cannot be traced to any determinate cause. PATHOLOGICAL ANATOMY. The most frequent lesions found at the autopsy, in cases of diabetes insipidus, are those of the brain, although they are by no means uniform. From what has already been said of the ph3'siology of polyuria, it is evident that any disease involving the higher area of the medulla oblongata is liable to give rise to this dis- ease. Besides the various injuries to the head involving the cerebellar substance, it is not uncommon to find, at the autopsy, tubercular lesions implicating the upper medullar tract. More rarely syphilitic deposits have been found, as well as some of the hyperplastic growths. It is not absolutely essential that the primary lesion of the brain, which gives rise to diabetes insipidus, should be situated in the vasomotor centre for the kidney. Morbid growths or degenerative changes, elsewhere situated, may, by involving the circulation of or ex- erting pressure upon the renal vasomotor centre, bring about the disease secondarily. Miliary tuberculosis and 164 Diabetes Instipidus. thickening have been found at the base of the brain in these cases, and in other localities not directly involv- ing the fourth ventricle. "With regard to the kidneys, the changes usually found are slight, and, for the most part, sucli as we might expect to lind as a result of ex- cessive functional activity of these organs, the most constant of these being hj-perwmia and some enlarge- ment. In those cases in which the disease has long- continued, evidences of inllanimatory action are frequent, and in some cases interstitial changes and atrophy are to be found. Dilatation of the bladder, ureters, and of the renal pelvis are common ; and certainly their almost constant distention in these cases might be expected to bring about such results. SYMPTOMS AND COURSE. The most prominent symptoms of diabetes insipidus are diuresis and thirst. These are sometimes enormous,, and they usuallj"- correspond closely in degree. Cases are commonly observed in which from 30 to 40 pints of urine are voided dail}-. Perli:n)s tlie largest quantity recorded was in a case related by Trousseau, in which the patient passed, during twenty-four hours, 56 pints of urine. Sir TVm. Roberts has recorded the case of a girl who passed more than a third of her weight of urine daily for several weeks. Tliese, however, must be considered exceptional cases, ordinarily the range being from 10 to 30 pints daily. The urine is pale in color, almost watery in appearance, and usually of very low specific gravity, ranging from 1008 to 1002, and it maj^ even descend lower. Notwithstanding this low specific gravity of the urine, and consequent disproportion of solids, the gross quantity of the latter eliminated by the kid- neys may sufl'er no reduction whatever; indeed, the Symptoms and Course. 165 quantity of urea and phosphates is often increased. The urine often contains inosite, but since this substance is often present during diuresis, however induced, it can scarcely be considered a morbid product, or at least one characteristic of this disease. In exceptional cases albumin or sugar may appear in the urine, especially in chronic and inveterate cases, but this is unusual. Thirst is quite as prominent a sj'mptom in diabetes insipidus as is diuresis ; in fact, as already indicated, they usually go hand in hand together, the volume of fluid ingested corresponding closely with that eliminated. Some observers have claimed that the volume of urine exceeds the quantity of fluids imbibed in some of these cases ; but more recent and accurate observations show that when the patient is unrestricted in the matter of drinks, the amount of fluid eliminated by the kidnej'S corresponds closely to that ingested. When the quantity of imbibed fluid is restricted, however, there seems to be some excess eliminated for a time, at the expense of dehydration of the tissues. The thirst in diabetes insipidus is even more urgent than it is in diabetes mellitus, and, moreover, the capacity for fluids seems to be greater. There is this diffierence, however : in diabetes insipidus a copious draught usually satisfles the craving for water for a time, while in saccharine diabetes the thirst seems unquenchable. In many of these cases the general health seems to be little, if any, impaired ; more especially is this the case in that form of the disease termed hydruria, in which the elimination of solids is not excessive. Numerous cases are on record in which the disease has existed from childhood to middle and even ad- vanced age, during all of which time the patients have IGR Diabetes Insipidus. enjoyed a. very fair degree of health aiul vigor, bodily and mentally. Indeed, it is recorded that some of the sub- jects of this disease have become fathers and mothers of large families, apparently suflering no discomforts or physical disadvantages except the frequent demands made bj' the system to ingest or void fluids. lu other eases hydruric patients exhibit symptoms which corre- spond in a measure to a mild type of saccharine diabetes. Thus, more or less gastric discomfort may be expe- rienced, often amounting to pain ; the appetite may be morbidly increased, or again it may be impaired or abol- ished. The patient may become nervous, fretful, or querulous ; and emaciation and general enfeeblement are sometimes the sequel in the more chronic cases. The abstraction of heat, caused bj^ large quantities of fluids passing through the bodj', renders the patient suscepti- ble to disagreeable sensations of cold, or to actual chills. The bowels are usuall3' constipated, and sometimes this state alternates with attacks of diarrha\a. In the polyiiric form the general symptoms are apt to be most pronounced. The increased elimination of urea and phosphates point to retrograde tissue metamorpho- sis in progress, which sooner or later must tell upon both the vital and muscular forces. The quantity of urine, though greatly increased in this form of the disease, never reaches the enormous range common to bydruria. The specific gravity of the urine ranges usually from 1010 to 1025, and the reaction is distinctly acid. I'essier has described certain of these cases, charac- terized by excessive quantities of phosphoric acid in the urine, under tlie name of " i^liospliatie diabetes." 'Die e-^sential features of these oases are slight, if any, in- crease in the volume of urine ; but very decided increase Diagnosis. 167 in the solids, especially of the phosphates. There is usually great debility, neuralgic pains, but moderate thirst, and the urine is of high specific gravity. Dr. Ralfe has confirmed Tessier's observations and recorded a number of similar cases. The course of diabetes insipidus is exceedingly va- riable, depending much upon its cause. Thus, when brought about by diseases and traumatisms of the brain, its course is largely influenced bj- the extent and con- sequences thereof in each individual case. As a rule, the disease is not directly fatal through its own effects. The loss of sleep consequent upon the frequent disturbance to urinate, or to quench thirst, coupled with mental worry and depression in delicate subjects, may at length bring about an enfeebled state of health, which often precipitates some secondary- dis- ease, from which the patient may succumb. In the late stages of the disease oedema of the feet is common, and this is doubtless due to anaemia. Furun- culae (multiple boils) sometimes complicate this stage, although this is not so common as in diabetes mellitus. The duration of the disease, as shown by the records, varies from a few months to fifty -nine years. The cases that recover usually do so within one or two years, although recoveries are recorded after the disease had lasted twenty years. In fatal cases death is most common within the first two years. DIAGNOSIS. Diabetes insipidus may be confounded with irritable bladder unless the symptoms are carefully distinguished. In irritable bladder the urine may be voided as fre- quently as in diabetes insipidus. Careful inquiry, how- ever, will elicit the fact that the quantity of urine voided 168 I>iahctes Iii^pidus. is only an ounce or two at a time. iNEeasurement of the tweuty-tbiir hours' luiue will :it once determine the point in question. In granular atrophy of the kidneys (interstitial ne- phritis) the j)atient often rises at night and passes con- siderable quantities of urine of low specific gravity, with or without albumin. The quantity of urine, however, in these cases, if measured for the whole twenty-four hours, will usually be found only slightly to exceed the normal standard, and, moreover, the specific gravity rarely sinks so low as in diabetes insipidus. In granular kidney the polj'uria occurs only — or chieflj' — at night. Cardiovascular changes are usually present, and thii-st is absent. The absence of sugar from the urine distinguishes the disease from diabetes mellitus. PROGNOSIS. Diabetes insipidus may be regarded in general as a less serious disease than is diabetes mellitus ; at the same time, it often resists all treatment, and runs a fatal course. In the hj-druric form the disease is less fatal, though long continued, and absolute cure is tiie excep- tion rather than the rule. Cases arising in tlie wake of inflammatory diseases, or those beginning in youth without assignable cause, may be regarded as most favorable in a prognostic point of view. In the polyuric form, ■which is attended bj'' the loss of much solids by the urine, the prognosis must be looked xipon as serious. Such cases are more apt to lay the foundation for some intercurrent disease, such as phthisis, or organic disease of the central nervous system, which precludes a favorable prognosis. Treatment. 169 TREATMENT. Experience has demonstrated that restrictions of food serve no useful purpose in tliis disease, and ttiat restriction of drinks only do harm. It was thought, at one time, that the diuresis might be brought under con- trol by limiting the amount of fluids ingested. This course not only greatly increased the suffering of tlie patient, but also, in at least one case, brought about a fatal termination through uraemia. The more advisable course is to permit the patient the use of water without restriction. In cases attended by excessive tissue meta- morphosis — and they are the most numerous — the free ingestion of fluid serves to absorb and wash out the effete products, which must otherwise accumulate in the system, without doubt to the detriment of the latter. In addition to this the free use of fluids relieves the chief discomfort of the patient — his thirst ; and we have no right to deny him this relief through measures that are, in themselves, harmless. The patient may, therefore, indulge in aqueous beverages ad libitum, and he will find lemonade, especially if made with soda- water, very grateful to the palate. Alcoholic drinks increase both the thirst and diuresis, by abstracting water from the tissues, and, therefore, they should be avoided. The patient should not take his beverages too cold (iced), — an injunction not to be overlooked, as he is sure to select iced drinks, if not otherwise instructed. The patient should be warmly clad ; pure-wool gar- ments should be worn next tlie skin at all times. With a view to relieve the tension of the visceral circulation, which favors diuresis, warm baths should be employed, as they invite the blood to the surface and prove very serviceable. The good effects of warm baths are ren- 8 H 170 Diabetes Ingipidus, dered more dunible by following thorn with thorough frictions of the skiu by means of coarse towels. Of the medicinal agents eni|ilovod for the relief of diabetes insipidus, ergot seems to have enjoyed the highest as well as the longest popuUirity in point of time. On theoretical grounds, the indications for the use of ergot are clear. Its contractile power over the small vessels should lessen the blood-tension in the renal circulation, and thus lessen the excessive diuresis. In some eases the drug undoubtedly exercises a favorable influence over the disease, as a number of unquestion- able cures have been effected by it. It is somewhat uncertain, however, in its effects, many cases failing to improve under its use. It should be employed in full doses in order to be olfective — 51 to 5ii of the fluid ex- tract (preferably Squibb 's). Valerian was long ago recommended by Trousseau for diabetes insipidus. Both he and Raver claimed the very highest merit for large doses of this drug; but these claims have scarcely been realized by its subsequent use. Opittin seems to diminish the diuresis in some cases, but in others it onl^' aggravates the symptoms, and, on the whole, the e\'idence does not favor its emplojanent iu these cases. The same may be said of belladonna. Various other drugs have been recommended for diabetes insipidus, among which are acetate of lead, ar- senic, the broviidcx, camphor, jahorandi, etc. The only one of these that I have derived good results from has been the bromide compounds, especially the bromide of sodium. In at least two cases of recent origin I believe the disease was arrested by full doses of sodium bro- mide. To be olfective the dose should be rather large. The patient should be rapidly brought luider its influ- Treatment. lYl ence \>y tUe administration of from 2 to 4 diachms dur- ing the first twentj'-four hours ; after that, 20 to 30 grains should be given ever}- four to six hours, until some muscular relaxation in the legs is noted, or slight unsteadiness in walking. After the above effects are obtained, the dose should be decreased to a point just sliort of affecting the locomotion. The constant gal- vanic current has been found beneficial in some cases. The best results are said to follow the application of the positive pole to the cervical region over the vertebra and the negative pole to the lumbar region and pit of the stomach, alternatel3\ Antipyrin has recently been brought forward as a remedy for diabetes insipidus, and several cures are re- corded from its use. The dose recommended is from 2 to 5 grammes dail}\ In the polj'uric form of the disease, where the loss of solids by the urine is excessive, an effort should be made to conserve the tissue waste by tonic medication. Among the most useful agents of this class will be found strychnia, iron, quinine, and arsenic. In cases in which the disease is traceable to traumatic lesions of the brain, intra-cranial growths, constitutional taints, etc., the treatment should include appropriate measures for the relief of the primary disease. BIBLIOGRAPHY. It has been found absolutely necessary to limit the following list to treatises on the subject. The large mass of current literature on diabetes, if included, would occupy altogether too much space in a volume of this size. Aenstools, P. Zur Etiologie und Symptomatologie des Diabetes Mel- litus. 8vo. Griefswald, 1869. Andrey. Du Diabfete et de son Traitemeut. 4to. Paris, 1869. Auch, F. G. De Diabete. 8vo. Berlin, 1835. Autfan, A. Du Diabfete Sucre ou de la Glucosurie. 4to. Strasbourg, 1859. Baudelow, B. De Diabete Mellito. 8vo. Berlin, 1838. Barnaud, A. Du Diabete Sucr^. 8vo. Berne, 1862. Barow, F. De la Glucosurie ou Diabete Sucr^. 4to. Paris, 1853. Bell, H. An Essay on Diabetes. 8vo. Transl. London, 1842. Burnett, J. B. Diabetes Mellitus. 8vo. Edinburgb, 1801. Bennighof, J. P. Ueber Meliturie. 8vo. Muniob, 1843. Bernard, C. Lefons Bur le Diabfete et la Glycogenfese Animale. 8vo. Paris, 1877. Bertail, B. fitude sur la Ptbisie Diabfetique. 4to. Paris, 1873. BiaiUe-Lalongeay, J. B. A. A. Du Diabfete Sucr^, et specialement de ses rapports avec les diSerents modes d' alimentations. 4to. Paris, 1848. Blbergell, H. On Diabetes Mellitus. 8vo. Berlin, 1835. Biggs, B. B. Diabetes Mellitus. 8vo. Edinburgb, 1803. Bos, J. J. Bijdrage tot de kennis der Glycogenese bij den Diabetes Mellitus. Svo. Amsterdam, 1867. Brandao, A. B. de S. Glycosuria. 4to. Bahla, 1871. Brlgham, C. B. Diabetes Mellitus. Svo. Boston, 1868. Brouwer, N. Akademisch procfacbrif t over den Diabetes Mellitus. 8vo. Groningen, 1862. Bndde, T. De Diabete Mellito. Svo. Gryphie, 1835. ChampUn, J. M. On Diabetes and its Successful Treatment. Svo. From second London edition. New York, 1861. Capezzuoli, S. Sul Diabete. Svo. Florence, 1861. Carter, C. De Diabete Mellito. 4to. Paris, 1811. Cazalas, I.. Du Diabfete. 4to. Montpellier, 1876. Chaloin, i. B. Du Diabfete Sucre. 4to. Paris, 1853. Cludius, O. C. De Diabete qui dicetur Mellitus quaedam. Svo. Regi- moiite, 1843. Contour, l. A, Du Diabfete Sucr^. 4to. Paris, 1844. Currie, F. On Diabetes. Svo. Edinburgli, 1798. (173) It4 Bibliography. C>T, J. Etiologie et Pronostio de hv Glycosnrio ct dvi Diabftte. 8vo. Paris, 1S79. Dautaguau, K. M. fitudie Pliysiologique sur la Glycosurio. 4to. Paiis, vm. Dedebaut, J. P. l. Du Dialu'te Snor<5. 4to. Paris, 1856. I>estOttoUes, A. A. Du Diabtte Sucri?. 4to. Paris, 1817. Ulcfclusou, AV. H. Diso:vsesof the Kidneys aud IJrmaiy nevangcinents. Part I, Diabetes. 8vo. London, 1875. Ulehl, G. Butrajie zur Pathologic und Tlicrapio des Diabetes MoUitus, 8vo. Erlangon, 1875. Doukin, A. S. The Skim-Milk Treatment of Diabetes and Bright's Disease. 12mo. London, 1871. Urlessen, J. C. De Phosphuria et Diabete Mellito. Svo. Oroningen, 1818. During, A. von, ITrsaohe und Heilung des Diabetes Mollitus, Svo. Hannover, 1808. Doiuoullu, A. Considerations snr la Pathog&uie et sur leTnvitemcnt du Diabfete. Svo. Louslo-Sauluier, 1877. Dupla, A. Du DiabSte Suci-S. Ito. Piuis, 1864. Duport, S. F. E. De la (.iluoosurie ou Diabfete Bucr^. 4to. Paris, 1853. Duquesnal, P. J. Sur le Diabftte Sucre. 4to. Paris, 1816. Uusseaux, I,. J. F. Snr le DiabDte. 4to. Paris, 1835. Dyett, K. H. Diabetes Mellitus. 8vo. Edinburgh, 1808. Dzoudi, C. H. Diabetes uatura Oouli Pathologia Illustiatur. 8vo. Halis, Saxony, 1830. Eokholt, D. De Di.ibSte. 4to. Argentorati, 1863. £Urn\anii, J. Die Honigartige Harnrubr. Svo. NVurzbnrg, 1S30. Elohelbaum, M. Pe Diabete Mellito. Svo. Berlin, 1818. EUebreoUt, A. Ueber Diabetes Jlollitus. 8vo. Bonn, 1S80. Elliott, J. On Diabetes Mellitus. 8%'0. Edinburgh, ISOU. Erhard, C. J. Ueber Diabetes Jlellitus. Svo. NVurzburg, 1862. Ersklne, P. On Diabetes. Svo. Edinburgh, 1801. Esser, P. Ueber Diabetes Mellitus. Svo. Bonn, 1869. EUenger, N. von. Diabetes Mellitus. Svo. Berlin, 1868. Evans, t. Diabetes Mellitus. Svo. Edinburgh, 1805. Ftvnnlnger, F. De Diabete JlolUto. Svo. Berlin, 1820. Feitli, B. Physiologioo-Pathologioa de Diabete Mellito Coniracntatio, 8vo. Berlin, 1861. Filkln.T. Diabetes Jlellitus and its Complications. Svo. Edinburgh, 1821. Fisclior, C. De Mellituria. Svo. Berlin, 1867. Fitzgerald, J. On Diabetes. Svo. Edinbui-gh, ISOO. Fock, F. De Diabete. Svo, Berlin, 1889. Forstuuinii, G. De Diabete. S\ o. Berlin, 1839. Franke, H. Ueber die lleilbaskcit des Diabetes Mellitus. Svo. Hallo, 1873. Friedel, 1. A. F. De Diabete. Svo. Berlin, 1839. Fronlng, F. Versuehe zuni Diabetes Mellitus boi Isohias. Svo. Got- tingen, 1870. Fnlierton, R. On Diabetes. Svo. Edinburgh, 1827. Uuelitgens, C. Uobor don Stoffweiksol einos Diabotikers vorgliohcn mlt dem oines Gesuuden. Svo. Dorpat, 1866. Bibliography. 175 GaiUard-Boarnazel, J. De la Glycosurie ou Diabfete Sucr^. 4to. Paris, 1856. Gantz, J. C. V. De Diabete. 4to. Jena, 1770. Gamier, E. De la Glucosurie ou Diabete Sucre. 4to. Paris, 1858. Gaalard, L,, De la Glucosurie. 4to. Paris, 1871. Georgeon, J. B. Du Diabete Sucrg. 4to. Paris, 1843. Gley, F. F. De Diabete Mellito ejusque Medela. 4to. Jena, 1829. Glogowski, F. De Mellituria. 8vo. Dorpat, 1854. Grant, J. Diabetes. 8vo. Edinburgh, 1821. Grohmann, J. F. B. De Diabete. 4to. Leipsic, 1808. Gross, G. Ueber die Zuckerliarnruhr. 8vo. Munich, 1862. Grosse, C. A. De Diabete. 4to. Leipsic, 1806. Giinzler, A. Ueber Diabetes Mellitus. Small 8vo. Tubingen, 1856. Haerlng, C. H. H. A, Einige Boebachtungen ueber Diabetes Mellitua. 4to. Kiel, 1869. Haenslmair, J. B. De Diabete. 8vo. Monachii, 1832. Hall, G. Diabetes. 8vo. Edinburgh, 1794. Harley.G. Diabetes: its Various Forme and Treatment. 8vo. London,1866. Harvey, J. Diabetes Mellitus. 8vo. Edinburgh, 1820. Heidenrelch, F. A. Obserrationes quaedam institutse in tribus Dia- betices. 8vo. Regimonti Pr., 1844. Heinemann, J. G. De Dyscrasia Saccharlna. 4to. Argentorati, 1843. Helfreich, F. C. Ueber die Pathologenese des Diabetes Mellitus. 8to. Wurzburg, 1866. Hobelmann, P. Ueber die Harnruhr. Svo. Wurzhurg, 1834. Hohlfeld, E. De Diabete Mellito. Svo. Berlin, 1828. Huelsmann, C. J. De Diabete. 8vo. Berlin, 1837. Hanseler, P. Ueber Diabetes Mellitus. 8vo. Bonn, 1867. Huld, F. C. L. De Diabete Mellito. Svo. Berlin, 1867. Hulme, J. On Diabetes Mellitus. Svo. Edinburgh, 1798. Hummel, M. Ueber Diabetes Mellitus. Svo. Munich, 1849. Jail, E. De Diabete. Svo. Monachii, 1S34. Jangot, C. M. De la Thgorie du Diabete Sucrd. 4to. Paris, 1851. Jansen, F. De Diabete. Svo. Gryphia, 1833. Kalinowskl. Du Diabfete Sucre. 4to. Paris, 1866. Karth, J. De Dyscrasia Saccharina. Svo. Bonn, 1840. Klawilter, B. De Diabete Mellito. Svo. Gryphia, 1863. Kocli, E. Ueber Diabetes Mellitus. Svo. Jena, 1S67. Koesen, G. E. De Diabete. 4to. 1767. Korseck, C. De Diabete. Svo. Berlin, 1840. Krause, J. G. A. Annotationes ad Diabeten. Svo. Halle, 1S53. Kraussold, H. Zur Pathulogie und Therapie des Diabetes Mellitus. Svo . Erlangen, 1S74. Knntzel, P. Experimentille Butrage zur Lehre von der Melliturie. Svo. Berlin, 1872. Knester, B. De Diabete Mellito. Svo. Berlin, 1S63. Kuse, H. De Diabete Mellito. Svo. Berlin, 1865. I/abosse, J. B. De la Glucosurie. 4to. Paris, 1853. I.ail'ont, M. Reclierclies sur la Glucosurie Considdree dans ses rapports avec le systeme nerveux. 4to. Paris, 1880. 176 Bibliography. I.alller, H. Discussion sur la. nature du DiabSte Sucre. 4to. Paris, 1S53. Lammergelle, T. W. De Diabete. 4to. Jena, 1717. Landau, T. A. Th^orie etTraitemcnt de laGlyoosurie. 4to. Paris, 1S6S. Lankers, A. De Diabete. 4to. Lugd Bat, 1720. I^atliam, J. Facts and Opinions Concerning Diabetes. 8to. London, 1811. L,ecorolie. Traits du Diabfete Sucre, Diabfete Insipidi. 8vo. Paris, 1877. Leffevore, B. A. Du Diabfete Sucre. 4to. Paris, 1822. lieow, A. De Diabete MeUito. 8vo. Berlin, 1849. LetelUer, J. A. t. T. Sur le Diabete. 4to. Strasbourg, 1823. r.evel, J. Des Symptomes des IHabfetes. 4to. Paris, 1841. L,iiuan, C. li. C. De Diabete Mellito. 8vo. Hallis, 1842. Limbers, D. De Diabete. Small 8vo. Heidelberg, 1737. landner, J". De Diabete. Monachii. 8vo. 1810. IjTicli, J. C. Diabetes Mellltus. Sto. Edinburgh, 1804. MalUard, K. P. M. Sur le DiabE'tes Sucr€. 4to. Paris, 1804. Mallocli, J. M. G. On Diabetes Mellitus. Sto. Edinburgh, 1808. Mann, A. Diabetes Mellitus. 8vo. Edinburgh, 1785. Maracet, A. On Diabetes. 8vo. Edinburgh, 1797. niarianl, T. De la Gluoosurie ovl Diab&te Sucre. 4to. Paris, 1867. Melsenberg, C. De Diabete Mellito. 8vo. Bonn, 1865. Mensert, H. M. De Diabete. Svo. Amsterdam, 1841. Merekel, A. E. E. Nonulla de Diabete Mellito. 12mo. Dorpat, 1835. Mettegang, li. De Diabete Prtesertim Mellito. 8vo, Berlin, 1838. MichaeUs, T. De Diabete MeUito. Svo. Berlin, 1838. Micliels, W. Ueber Diabetes. Svo. Berlin, 1868. Mueller, E. De Diabete. Svo. Berlin, 1845. Mueller, G. li. De Diabete Prsesertim Mellito. Svo. Gottingcn, 1822. Myers, J. H. On Diabetes. Svo. Edinburgh, 1779. Micolal, E. A. De Diabete. 4to. Jena, 1770. NoeUer, E. De DiahetJB Melliti Natura. Svo. Berlin, 1848. Nurnberger, G. T. Die Zuckerharnruhr. Svo. Berlin, 1867. Olivier, R. J. t. B. Du Diabfete SucrS. 4to. Paris, 1859. Oltendorf, M. De Diabete Mellito. Svo. Berlin, 1833. Fellasin, C. J. Du Diabfete Sucre. 4to. Paris, 1853. Pilting, T. De Diabete MeUito. Svo. Jena, 1851. Plass, H. L. Ueber die "Wahre Harnruhr. Svo. Wurzburg, 1838. Planter, E. F. De Diabete Mellito cum Lithias^ Coniparando, Svo. Leipsic, 1835. Front, W. Niiture and Treatment of Diabetes, Calculus, etc. 2d ed. London, 1825. Kaben, C. De Diabete MeUito. 12mo. Ha^^ue, 1806. Kanke, A. De Diabete MeUito. Svo. Berlin, 1854. Keenielin, R. Ueber Diabetes Mellitus. Svo. M'urzburg, 1S75. Keick, F. T. Do Diabete Mellito Questiones. Svo. Gryphie, 1859. Roicliard, J. De Diabete Mellito. Svo. Pestini, 1834. Rhode, li. Ueber Diabetes Mellitus. Svo. ^^'urzburg, 1880. Robaglla, S. Du Diabfete SucriS. 4to. Paris, 1849. Robertson, A. J. On Simple Diabetes Mellitus. Svo. Edinburgh, 1820. Ruchabruu, C. E. Du Diabete. 4to. Paris, 1849. Bibliography. Ill RoUo, J. An Account of Two Cases of Diabetes Mellitus, to which are added a general view of the nature of the disease, and its appro- priate treatment. VoL ii, 8vo. London, 1797. Kouquler, T. Sur le Diabetes. 8vo. Paris, 1803. Raickoldt, A. Eiu Beitrag zur lehre von der Zuckerhamruhr. 8vo, Jena, 1865. Byan, B. On Diabetes Mellitus. 8vo. Edinburgh, 1799. Salomon, D. De Diabete MeUito. 8vo. Gottingen, 1808. Saloy, A. C. Du Diabfete SucrS. 4to. Paris, 1861. Sarran, L. Du Diabete Sucre et de son Traitement. 4to. Paris, 1865. Sanberg, G. A. De Diabete MeUito. 8to. Berlin, 1865. ScharUm, G. W. Die Zuckerhamruhr. 8vo. Berlin, 1846. Schjaee, E. Diabetes and its Treatment. American translation. Small 8ro. Philadelphia, 1889. Schenck, F. L. De Diabete Mellito Pathologia. 8vo. Berlin, 1841. Schmidt, A. T. De Diabete Mellito. 8vo. Halis Sax, 1844. Scholtz, B. Ueber Diabetes Mellitus. 8vo. Halle, 1868. Schwerin, M. De Diabete Mellito Nonulla. 8vo. Berlin, 1839. ScUiilfort, T. P. Du Diabete. 4to. Strasbourg, 1858. Seegen, J. Der Diabetes Mellitus auf Grundlage Zahlreicher Beobach- lungen Dargestellt. 8to. Leipsic, 1870. Seelmair, B. Ueber das Wesen der Zuckerhamruhr. 8vo. Munich, 1859. Seyfried, B. De Diabete. 8vo. Berlin, 1849. Shirreff, J. H. On Diabetes Mellitus. 8to. Edinburgh, 1804. Shnter, J. Diabetes Mellitus. 8vo. Edinburgh, 1800. Siegmayer, J. C. G. De Diabete. 8vo. Berlin, 1827. Siemssen, F. C. A, De Diabete. 8to. Halae, 1828. Smith, A. H. Diabetes Mellitus and Insipidus. 12mo. Detroit, 1889. Spleker, B. De Diabete. 8vo. Berlin, 1839. Spieseke, A. B. De Diabete Mellito. 8vo. Berlin, 1865. Stevenson, G. On Diabetes. 8vo. Edinburgh, 1762. Stranss, G. D. F. Die Einf ache Zuckerlose Hai-m uhr. 8vo. Tubigen, 1870, Streppel, C. De Diabete Mellito. 8vo. Berlin, 1867. Thllloy, H. B. Du Diabfete. 4to. Paris, 1852. Tyson, J. A Treatise on Bright s Disease and Diabetes. 8to. Phila- delphia, 1S81. Ueberliorst, E. De Diabete MiUito Nonulla. 8vo. Berlin, 1841. Ullrich, F. Sur le Diabfete. 4to. Paris, 1879. Vaysslfe, P. C. Du Diabfete Sucrg. 4to. Paris, 1848. Vernon, N. On Diabetes. 8to. Edinburgh, 1796. Volkmann, J. F. T. De Diabete Mellito. 8to. Begemonto Pr., 1849. TVandner, G. Die Zuckerige Hamrahr. 8vo. Regensburg, 1859. Washington, W. An Essay on the Disease Commonly Called Diabetes. 8to. Philadelphia, 1802. ■Weber, G. De Diabete Mellito. 8vo. Berlin, 1865. ■Wunnenberg, L. Ueber Diabetes Mellitus. 8to. Bonn, 1870. Zabel, C. A. De Diabete Mellito. 8vo. HaUs, 1858. Zimmer, K. Der Diabetes Mellitus. Small 8vo. Liepsic, 1871. ZoIUng, G. A. De Diabete. 8vo. Berlm, 1822. 8* INDEX. PAGE Acetone in the urine in diabetes mellitus 56 Age as a cause of diabetes mellitus 34 in prognosis of diabetes mellitus 78 Albumin in the urine in diabetes mellitus 56 Albuminuria complicating diabetes mellitus 63 Alcoholic beverages in diabetes mellitus 91 in diabetes insipidus 169 Ales, quantity of sugar in 94 Alkalies in treatment of diabetes mellitus 108 American wines, sugar contents of 91 Amyloid disease with diabetes mellitus 65 Anaemia in diabetes mellitus 50 Antipyrin in treatment of diabetes mellitus 103 in treatment of diabetes insipidus 171 Appetite in diabetes mellitus 48 Approximate test for sugar, the author's 76 Arsenic in treatment of diabetes mellitus 104 in treatment of diabetes insipidus . . 170 Artificial glycosuria 26 Belladonna in treatment of diabetes mellitus 108 Beverages in diabetes mellitus 90 permitted in diabetes mellitus 96 prohibited in diabetes mellitus 96 Bibliography of diabetes 173 Blood, changes of, in diabetes mellitus 46 Brain-lesions as causes of diabetes mellitus 38 Brain, anatomical changes of, in diabetes mellitus .... 44 Bread, use of, in diabetes mellitus 84 Bromides in treatment of diabetes mellitus 103 in treatment of diabetes insipidus 170 Burgundy wines, analysis of, for sugar 92 Calabar bean in treatment of diabetes 108 Cases of diabetes treated by oxygen 157 of mild type of diabetes mellitus in aged subjects . . 127 of severe type of diabetes mellitus .115 showing mild type in Hebrew race 14fl (n9) 180 Iiiikx. TAOE Cases of diabetes in childliood 155 of diabetes of probable malarial origin 143 of diabetes complicated by amyloid disease 147 of diabetes caused by ovcroatiug 151 of severe type of diabetes mellitiis in aged subjects . 133 Camplior in treatment of diabetes insipidus 170 Cataract in diabetes mellitus 61 Central Appalachian region, diabetes mellitus in 9 Champagnes, quantity of sugar in 93 Chinese race, absence of dialSetes in 17 Circulatory symptoms of diabetes mellitus 49 Civil war, American, influence of, over diabetes . ... 18 Classification of diabetes mellitus -17 of diabetes insipidus 161 Climatic influences over diabetes mellitus o4 Climatology of diabetes mellitus 3 Clinical considerations of diabetes mellitus 115 Cold, influence of, over diabetes mellitus . 7 as a cause of diabetes insipidus 163 Coma, diabetic 57 treatment of 110 Complications of diabetes mellitus 57 treatment of 109 Constipation in diabetes mellitus 48 treatment of 109 Course and duration of diabetes mellitus 65 of diabetes insipidus 167 Curare as a cause of glycosuria 36 Cutaneous symptoms of diabetes mellitus 51 Diabetes mellitus 1 clinical illustrations of 115 diagnosis of 69 duration of 65 etiology of 81 morbid anatomy of 41 physiology and pathology of 19 prognosis of 78 symptomatology of 47 treatment of ... . 81 Diabetes insipidus 161 course of . . . . 167 diagnosis of 167 duration of 167 etiology of 163 pathological anatomy of .... < 163 prognosis of • 168 symptoms of 164 treatment of 169 Diabetic coma . ." : 57 Index. 181 PAGE Diabetic coma, treatment of 110 Diagnosis of diabetes mellitus 69 of diabetes insipidus 167 Dieting for diabetes mellitus ; 97 Digestive symptoms of diabetes mellitus 48 of diabetes insipidus . 166 Duration of diabetes mellitus 65 of diabetes insipidus 167 Emaciation in diabetes mellitus 52 Ergot in treatment of diabetes mellitus 104 in treatment of diabetes insipidus 170 Etiology of diabetes mellitus 31 of diabetes insipidus 163 Examination of urine for sugar ■ 69 Exercise in diabetes mellitus 113 Exciting causes of diabetes mellitus 36 Exclusive meat diet in diabetes 83 Farinaceous foods in diabetes mellitus 86 Fatality of diabetes mellitus in young people 66 Fehling's test for sugar . . 70 Foods permissible in diabetes mellitus 96 prohibited in diabetes mellitus 96 Fruits, use of, in diabetes mellitus 87 Furuncles in diabetes mellitus 110 General principles of diet for diabetes mellitus 81 Geographical distribution of diabetes mellitus 2 Glycogenic function of the liver 19 Glycosuria from puncture of medulla 23 Green vegetables, use of, in diabetes mellitus ... 86 Gulf Coast, topography of 9 low mortality from diabetes in 13 Habits of Americans as influencing diabetes 18 Haines's test for sugar in urine 71 Heart-lesions in diabetes mellitus 44 Hebrew race, frequency of diabetes in 33 mild character of diabetes in 33 Heredity as a cause of diabetes mellitus 31 History of diabetes _ • 1 Humidity of atmosphere, influence of, over diabetes mellitus 13 Hygienic treatment of diabetes mellitus 113 Hypertrophy of heart in diabetes mellitus 50 Imported wines, sugar contents of 93 Indian race, exemption from diabetes in 17 182 Inde.r. PAOB Intellectual faculties in diabetes niellitus 50 Interior Platejiu, topography of . 10 Interstitial nephritis with diabetes mellitus (!4 Iodine tincture in treatment of diabetes mellitus .... 108 Iodoform in treatment of diabetes mellitus 108 Jaborandi in treatment of diabetes insipidus 170 Jambul in treatment of diabetes mellitus 106 Liver, morbid anatomy of, in diabetes mellitus .... 41 Lung-lesions in diabetes mellitus 41 Elaine, high mortality from diabetes mellitus in . . . 6 Medicinal treatment of diabetes mellitus 101 Blental emotion as a cause of diabetes mellitus 86 as a cause of diabetes insipidus 163 ^Middle Atlantic Coast, topography of 9 ^Mineral waters for diabetes mellitus 95 Morbid anatomy of diabetes mellitus 41 JNIortAlity from diabetes, rural and urban 14 Muscular symptoms in diabetes mellitus 53 Nervous system in diabetes mellitus 24 symptoms in diabetes mellitus 60 Nitrate of uninium in treatment of diabetes mellitus . . . 108 North Atlantic Coast, topography of 9 Northeastern Hills and Plateaus, topography of 9 high mortality from diabetes in 11 Northern Mississippi River Belt, topography of 10 Northwestern Region, typography of 11 high mortality from diabetes in 13 Ocular complications of diabetes mellitus 61 Ohio River Belt, typography of 10 Opium in treatment of diabetes mellitus 101 in treatment of diabetes insipidus 170 Oxygen gas in treatment of diabetes mellitus 106 Pacific Coast, topography of 11 mortality from diabetes mellitus ia 11 Pancreas, lesions of, in diabetes mellitus 42 Pancreatic diabetes 27 Patellar reflexes, prognosis of, in diabetes 70 Pathologicjil anatomy of diabetes insipidus 168 considerations of diabetes mellitus 19 Phcnylhydrazin test for sugar in urine 73 Phlegmon in diabetes mellitus 63 PUospUatic form of diabetes insipidus 166 Index. 183 PAGE Phosphorus in treatment of diabetes mellitus 108 Physiological features of diabetes mellitus 19 Picric acid in treatment of diabetes mellitus 108 Potassium iodide in treatment of diabetes mellitus .... 108 Prairie Region, topography of . . 11 Prognosis of diabetes mellitus . . . 78 of diabetes insipidus 168 Pulmonary complications in diabetes mellitus . . . . 60 Quantitative determination of sugar in urine, the author's method 74 Quinine in treatment of diabetes insipidus 171 Rhine wines, sugar contents of 92 Rural mortality from diabetes mellitus 16 Salicylic acid in treatment of diabetes mellitus 108 Sauterne wines, sugar contents of . 92 Sex as a cause of diabetes mellitus . 33 Sexual symptoms of diabetes mellitus- 51 excesses as a cause of diabetes insipidus 163 Sodium phosphate in treatment of diabetes mellitus . . 108 Soja as a food in diabetes mellitus 87 South Atlantic Coast Region, topography of 9 Southern Central Appalachian Region, topography of . . 10 Interior Plateau, topography of 10 Southwest Central Region, topography of 10 Spinal cord, alleged changes in diabetes mellitus 45 Spirits, analysis of, for sugar . . . . .... 93 Starch, relation of, to glycogen 20 Strychnia in treatment of diabetes insipidus 171 large doses of as a cause of glycosuria 26 Sugar, source of, in the economy 24 percentage in urine in diabetes mellitus 55 in urine, tests for 70 Symptoms of diabetes mellitus 47 of diabetes insipidus 164 Sweet taste in diabetes mellitus 49 Table showing distribution of diabetes in Europe .... 3 showing mortality ratio of diabetes in United States . 5 showing mortality ratio of diabetes by State groups . 8 showing rural and urban mortalities from diabetes . 15 showing increase of diabetes in United States for forty years ... ... 18 Temperature in diabetes mellitus 49 atmospheric, influence of, over diabetes 7 Thirst in diabetes mellitus 48 1S4 Indcr. PAGE Thirst in diabetes insipidus 163 Treatment of diabetes mcllitus 81 of compli&it ion of diabetes uicUitus 101) of diabetes insipidus Ili9 Vi'bau mortality fi-om diabetes mellitus 16 Urea in urine in diabetes mellitus 55 Urine in diabetes mellitus 5;! in diabetes insipidus , . . . 164 Valerian in treatment of diabetes mcllitus lOS in treatment of diabetes insipidus 17t) Vermont, high mortality in, from diabetes 6 Warm baths in treatment of diabetes mellitus 113 in treatment of diabetes insipidus lO'J