January 1, 1886
"As late as 1886, Naunyn stood as the champion of strict carbohydrate-free diet in a German medical congress where most of the speakers opposed it. As one of the few early German followers of the Cantani system, he maintained its feasibility and ultimate benefit, and locked patients in their rooms for five months when necessary for sugar-freedom."
Total Dietary Regulation of Diabetes
Bernhard Naunyn (born 1839) was the pupil of Lieberkiihn, Reichert, and von Frerichs. Though the author of a number of researches, they include no important discovery. His position as the foremost diabetic authority of the time rests upon his influence for the advancement of both clinical and experimental knowledge; upon his judgment, his teaching, and his pupils; upon the fact that from his great Strassburg school have come the soundest theories, the most fruitful investigations, and the most effective treatment.
In birth, it is to be noted that Naunyn preceded Kiilz, and was only two years younger than Cantani. He came into this field in the pioneer period when the principle of dietetic management was generally recognized, but the average practice, especially in regard to severe cases, was still a mass of ignorance and inefficiency. As late as 1886, Naunyn stood as the champion of strict carbohydrate-free diet in a German medical congress where most of the speakers opposed it. As one of the few early German followers of the Cantani system, he maintained its feasibility and ultimate benefit, and locked patients in their rooms for five months when necessary for sugar-freedom.
With experience, he gradually introduced modifications, until the rigid and inhuman method, which a majority of physicians and patients would never adopt, became a rational individualized treatment, with a diet reckoned according to the tolerance and caloric requirements of each patient. The work of various pupils requires mention in this connection. Important investigations of metabolism established the basis for this treatment, the most notable being that of Weintraud, who proved that, instead of having an increased food requirement, diabetics could maintain equilibrium of weight and nitrogen on a diet as low as or a little lower than the normal. Minkowski discovered with von Mering the diabetes following total pancreatectomy in dogs, and established the doctrine of the internal secretion of the pancreas, as well as the first clear conception of a dextrose-nitrogen ratio. After the early acetone investigations and Gerhardt's discovery of the ferric chloride reaction had failed to reveal the cause of coma, the Naunyn school accomplished almost the entire development of the subject of clinical acidosis in the following sequence. Hallervorden (1880) discovered the high ammonia excretion, confirming an earlier discredited observation of Boussingault. Stadelmann (1883) established the presence in the urine of considerable quantities of a non-volatile acid supposed to be acrotonic, correlated the condition with Walter's previous acid intoxication experiments, and theoretically suggested the treatment with intravenous alkali infusions. Minkowski proved the excreted acid to be /8-oxybutyric, and demonstrated the presence of this acid in the blood and a diminished carbon dioxide content of the blood. He, also Naunyn and Magnus-Levy, applied the alkali therapy in practice, and the latter carried out chemical and metabolism studies which made him the recognized authority in this field. Naunyn introduced the word acidosis, saying in definition ( (4), p. 15): "With this name I designate the formation of /8-oxybutyric acid in metabolism." The Naunyn school have consistently maintained that this acidosis is an acid intoxication in the sense of Walter's experiments. They demonstrated striking temporary benefits from the alkali therapy, particularly in diminishing the danger of the change from mixed to carbohydrate-free diet; but the practical results were never equal to the theoretical expectations. With Naunyn, also, acidosis became the principal criterion of severity for the clinical classification of cases. As regards other theories, the Naunyn school have upheld the deficient utilization as opposed to the simple overproduction of sugar in diabetes. They have clearly recognized the necessary distinction between diabetes and non-diabetic glycosurias." Naunyn was next after Klemperer to recognize clinical renal glycosuria. Though observing that "the course of the disease is as variable as can be conceived," he nevertheless upholds the essential unity of diabetes, finding in heredity a link which often connects cases of the most varied types. In regard to the etiology, he considers that "it is certain that disease of the nervous system and of the pancreas can produce diabetes;" other causes seem more doubtful. The nervous disorder supposedly acts indirectly by setting up a functional disturbance in the pancreas or other organs directly concerned. Underlying everything in most cases is, in his opinion, the diabetic "Anlage" or inherited; constitutional predisposition. Naunyn has particularly supported; the conception of diabetes as a functional deficiency, to be treated by sparing the weakened function. He wisely emphasized the importance of doing this at as early a stage as possible, before the tolerance has been damaged and the glycosuria has become "ha- bitual." His plan of treatment is to withdraw carbohydrate gradually, giving large doses of sodium bicarbonate in cases with acidosis as ii, further precaution against coma. A brief increase of the ferric chloride ; reaction is not allowed to interfere with the program. When the glycosuria is successfully cleared up, the aim is if possible to place the patient on a Rubner diet, representing 35 to 40 calories; per kilogram of body weight and about 125 gm. protein, carbohydrate being gradually added and then kept at a figure safely below the tested tolerance. The views concerning exercise agree with those of previous authors; brisk walking, etc., is found beneficial; but overexertion is harmful, especially in severe cases; and some patients seem to do best on a rest cure. When sugar-freedom is not attained on simple withdrawal of carbohydrate, protein may be reduced as low as 40 to 50 gm. daily and the calories also diminished, since diabetics may remain in equilibrium on as little as 25 to 30 calories per kilogram. When necessary as a final resort, temporary under- nutrition may be employed; but prolonged under-nutrition or the loss of more than 2 kilos weight should be avoided. Loss of weight continuing over the third week of treatment requires adding carbohydrate and abandoning the attempt to stop glycosuria. Occasional fast-days are advised if necessary, but only when previous treatment has reduced the glycosuria below 1 per cent; otherwise their effect is indecisive. It is stated that such fast-days are practicable for even the severest cases, and heavy acidosis is not a contraindication; the ferric chloride reaction may diminish on a fast-day. Naunyn has not stated what limitations apply to the use of such occasional fast-days, but Magnus-Levy stipulates that they must never be more frequent than one in eight or ten days, and in very thin patients must be avoided altogether.
Fasting is nowhere recommended as a treatment for coma by Naunyn. On the contrary, when restriction of diet produces really threatening symptoms, his plan is to add carbohydrate and give up the attempt to abolish glycosuria. Even the persistence of a very heavy ferric chloride reaction longer than two or three days is a signal for adding carbohydrate. The treatment for impending coma consists in maximal doses of bicarbonate and the free use of carbohydrates, especially milk. Naunyn had some conception of limiting the total metabolism, but meant by it only a bare maintenance diet, or the slight and temporary undernutrition mentioned above. Naunyn states that fat does not appreciably increase glycosuria; elsewhere that in very severe cases it may slightly increase glycosuria; Magnus-Levy that it never gives rise to glycosuria. Like others, Naunyn considers that fat is the chief food for the diabetic; that the introduction of fat is the most important art in diabetic cookery . He uses it to complete the full number of calories when other foods are restricted; this applies even to the severest cases on carbohydrate-free diet with strict limitation of protein, where accordingly much fat is given; his principal care is that the patient shall take enough of it; the only reason for limiting the quantity is the danger of indigestion , except when coma impends, in which case fats are replaced by carbohydrates, and butter is especially shunned because of its content of lower fatty acids. Even when sugar-freedom is attainable, certain cases are believed to show an inherent progressive downward tendency. Concerning patients emaciated down to 50 kilograms, with heavy ferric chloride reaction and the usual accompaniments, it is said: "In the face of these great difficulties and dangers, which accompany the energetic management of these very severe cases, the prospects of being successful in permanently removing glycosuria are in general not very great, and usually one will be content with a limitation of it which suffices to bring the patient into nutritive equilibrium, that is, down to 60 to 80 gm. sugar in 24 hours."
" This is commonly supposed to have been an intentional following up of the observations of Cawley, Bouchardat, and others. But according to Dr. A. E. Taylor (personal commumication) the epoch-making discovery was accidental. Dogs depancreatized for another purpose were in a courtyard with other dogs. Naunyn, perhaps mindful of the part played by insects in the history of diabetes, asked,
"Have you tested the urine for sugar?"
"Do it. For where these dogs pass urine, the flies settle."