The facts of diabetic acetonuria and diaceturia can be brought into agreement with this conclusion, for we have seen that the diabetic is often in the condition of consuming his own proteids. In fact I have myself seen a high degree of acetonuria and diaceturia in diabetics only when the output of nitrogen was greater than the income. Furthermore, whenever cases are reported in the literature, as they frequently are, in which acetone is excreted in the urine to the amount of several decigrams or grams (even as much as 10 grains) a day, we are always able to see, from the facts given in relation to the diet and to the glycosuria, that there must have been quite a considerable waste of the albumin of the body.
Beta-oxybutypic acid is perhaps, as many believe, the first stage in the formation of aceto-acetic acid. Clinically, however, it presents a certain independence, and I regard it as more probable that oxy butyric acid on the one hand and aceto-acetic acid on the other arise from qualitatively different decomposition processes.
Similar relations to those existing between the decomposition of albumin and the formation of acetone are not observed in regard to oxybutyric acid. The latter is regularly absent in diabetics who are in good physical condition, and not infrequently also in those who are suffering from a marked loss of body albumin. While oxybuty ric acid is permanently absent in a certain number of cases of diabetes, and is not necessarily present even in those who are greatly reduced by pulmonary tuberculosis and other complicating diseases, other diabetics begin after a certain time, and without any cause that we can detect, to excrete it. Sometimes the daily amount excreted is only a few grams, at other times it reaches 50, 100, or 150 grams. After the excretion has once begun, it is never interrupted for more than a few days at a time; it is permanent and shows a constant ten dency to increase. According to all our experience up to the present time, the symptom is of the gravest prognostic significance; in most cases, at the end of a few days or weeks, diabetic coma ensues and the case passes on to a fatal termination.
b. Relation of these Substances to Diabetic Coma.—Upon the ground of the just-mentioned temporal coincidence, many authors. look upon diabetic coma as an "acid intoxication" (Stadelmann, Minkowski, von Jaksch) ; others regard it as the result of a specific poisonous action of oxybutyric acid or the substances allied to it; while others again would attribute to acetone and aceto-acetic acid as well an important role in the etiology of diabetic coma. The
named opinion is hardly tenable. I have often, as have also other observers, seen marked acetonuria and diaceturia continue in diabe tics for weeks or months at a time and then disappear again. Dur ing this period the patients grew weaker and lost in weight in conse queuce of the profuse acetonuria, but they presented no symptoms of coma. These observations prove more than do those in which stress is laid upon the consecutive relation of acetonuria and coma. Acetonuria and cliaceturia are found so frequently and indeed so regularly in weakened diabetics with well-marked paralysis of the sugar-consuming functions and in those in whom there is an increas ing difficulty ill obtaining sufficient nourishment, that we need not wonder at their presence among the conditions preceding coma. But it is not permissible to predicate an etiological from a merely temporal relation.
Much more difficult is the question of oxybutyric acid, the appear ance of which in diabetes is always followed in time by coma, unless death is occasioned by some intercurrent disease. The views held concerning this substance are flatly contradictory. I incline to the opinion of Klemperer, according to which, in some stages of diabetes, for reasons unknown to us, certain toxic substances are formed. These poisons act (1), after a certain accumulation has taken place, as paralyzants of the brain, inducing coma, and (2) as destroyers of protoplasm. When large quantities of oxybutyric acid are present in these cases we must attribute to the active poison in diabetes the special property of conducting the decomposition of albumin along the special lines leading to the production of this acid, for in other forms of destruction of protoplasm (starvation or fever) there may be occasionally an excretion of oxybutyric acid in the urine, but it is always in the most minute quantities. Coma on the one hand, and the formation of oxybutyric acid and reduction of the alkalinity of the blood on the other, would be, according to this, not subordinate but co-ordinate phenomena.