The clinical interpretation of these three bodies becomes very clear when we adhere to the view just enunciated, namely, that the appearance of the three acetone bodies is due to one common cause, i.e., a peculiar inhibition of the oxidative processes. By studying these acetone bodies we are able to gauge the intensity of the perversion of oxidation; for we are justified in assuming that the excretion of oxybutyric acid represents a much more advanced degree of oxidative perversion than the excretion of acetone or of diacetic acid. We know this from the results of the chemical investigations that I have described and from experiments with feeding these substances. A natural consequence of this interpretation is the following: acetonuria, instead of maintaining the dignity of an independent disease symptom, must be included under a more general category of acid autointoxication. At the same time the theories that have been formulated to explain the occurrence and the formation of acetone must be amplified to include its chemical precursors, viz.: B-oxybutyric acid and diacetic acid. The appearance of acetone in the urine has up to now been credited with too much importance, and this is due to the historical development of our knowledge of the pathological appearance of the acetone bodies in the urine. Petters who was the first to find these bodies in the urine of a diabetic subject, and Kaulisch who studied the excretion of acetone soon after the former author, arrived at the conclusion that subjects excreting acetone were in a state of autointoxication and that the poisoning of the organism was due to acetone, a body that had heretofore never been found in the urine. This theory dominated all the investigations into the nature and the significance of acetone that followed. Cantani, Betz, von Jacksch and Buhl attributed poisonous properties to acetone and formulated the assumption that it was the cause of so-called acetonemia, a disease picture that was constructed more according to symptoms produced in animals by the sub-cutaneous injection of acetone than from clinical observation. In the animal experiments performed by von Buhl von Jacksch, Albertoni, Buschhaupt, and Franz Müller, the injection of acetone into the circulation or the simple inhalation of this body was followed by grave stupor and occasionally a drop of temperature; sometimes glycosuria was also observed. The latter result, however, seems to have been due more to the reduction of the temperature than to the effect of the acetone itself (Franz Müller). On the other hand, the administration of acetone even in large quantities by mouth (Kussmaul, Frerichs,) produced absolutely no symptoms in human subjects. Frerichs consequently repudiated the idea that acetonemia was an independent disease picture and that acetone was a determining factor in the production of the symptoms included under this head.

The valuable investigations of Rosenfeld and his pupils and of Hirschfeld demonstrated the connection between the excretion of acetone and the composition of the food. This revelation, as we shall see below, threw a great deal of light upon the subject. The dicta of Hirschfeld in regard to the prognostic significance of acetonuria in diabetes were one-sided and had to be considerably modified as soon as the relationship between acetonuria and the excretion of oxybutyric acid was cleared up and the pathology of acetonuria was better understood.