EXPERIMENTAL STUDIES ON DIABETES : SERIES I. PRODUCTION AND CONTROL OF DIABETES IN THE DOG. 5. VARIOUS FAILURES OF DIETETIC TREATMENT, AND THEIR CAUSES.

1. Practically every detail of clinical diabetes can be reproduced in partially depancreatized animals. The resemblance is made still more exact by the susceptibility of such dogs to acidosis and coma, as will be shown in later papers, and also by the similarity of the anatomic changes in the islands of Langerhans. These animals are therefore useful test objects for a therapeutic investigation. 2. These animals at first show considerable tendency to regain assimilation, comparable to that in the early stages of most human cases of diabetes; and in some instances they recover so as to be able to endure any degree or duration of carbohydrate feeding and can be made diabetic only by removal of additional pancreatic tissue. Similar recovery in some human cases, especially after acute pancreatitis, is a probability. This recuperative tendency can be negatived by overfeeding, even without glycosuria. With duration of the diabetes the power of recuperation diminishes and practically disappears in dogs as in human patients. 3. In the absence of progressive pancreatitis or other extraneous causes, these dogs show no inherent downward tendency in their assimilation. This conclusion rests upon observations as long as 6 years from the first pancreas operation and 3 years of known diabetes. This absence of inherent progressiveness is what should naturally be expected in animals with simple resection of part of an organ, and serves further to fit them for accurate feeding experiments. 4. Every detail of the downward progress of human patients on various diets is reproduced in such animals. They lose assimilation and die most rapidly on diets rich in carbohydrate, and less rapidly on excess of other foods. The differences between sugar and starch, and between starch and protein, seem to be only those of degree and time rather than anything absolute. The important point is that, granting the absence of spontaneous downward tendencies as stated, all the different kinds and degrees of downward progress in the records of animals in this and the preceding paper are purely the results of overstrain of the internal pancreatic function by excess of food. 5. Varying degrees of success and failure in the dietetic control of diabetes are also illustrated. The benefit of the classical treatment by exclusion of preformed carbohydrate and limitation of protein is confirmed, in the prolongation of life and well-being to some extent in nearly all cases and perhaps indefinitely in some of the mildest cases. In the great majority of cases such a therapeutic result is not permanent, and downward progress is finally observed if the observations are continued long enough. In most of these cases life, strength, and assimilation can be preserved for a much longer time by a degree of undernutrition suited to the severity of the diabetes, and accomplished by limitation of fat in the diet. The permanence of such control is supported by the unimpaired or rising assimilation in experiments of 1 to 1(3/4) years duration, but still longer observations would be desirable. Diabetes of great severity is controllable only by correspondingly radical undernutrition. In still more severe cases glycosuria can be abolished only by a degree of undernutrition which entails final death from inanition. In the most severe cases glycosuria cannot be stopped, evidently because the assimilative power is too low to dispose of even the minimum supply of food materials; namely, that derived from the body stores in fasting. 6. A claim of saving every patient, no matter how near death, would be a preposterous one for any remedy in any disease, and the animal experiments do not support such a claim for diabetes. Also it is unreasonable to expect the actual cure of an organic deficiency by diet, and the diet treatment in animals just as in patients generally represents the sparing rather than the restoration of the weakened function. The basis of the belief in the inherently progressive tendency of severe cases of clinical diabetes is shaken by the exact reproduction of such case histories by diet in animals which are free from spontaneous downward tendencies; but there is still lack of a sufficient number of patients treated on the principle of relief of the total metabolic burden to demonstrate the absence of such inherent progressiveness in human diabetes. As described elsewhere, the principle mentioned has given encouraging results in proportion as it has received actual application in practice. The clinical problem requires the same prolonged careful control of all discoverable symptoms as in animals, and cases too severe for such control, or complicated with infections, violations of diet, etc., are on the same plane as animals in which a similar condition has been produced. Some proportion of cases, especially in young persons, will be found suitable for accurate determination of the question of whether all or most cases of severe diabetes are inevitably progressive and hopeless, and the writer looks forward to publishing such a series. Irrespective of the outcome, the raising of this question is justified by its importance. On the theoretical side, it involves both the general prognosis and the nature of the process underlying diabetes. On the practical side, it is already established that diet is at least the chief cause of downward progress, and it is important to eliminate this cause by avoiding the dietary injuries illustrated in the animal experiments.