DISCUSSION OF RESULTS AND GENERAL CONCLUSIONS. 135 



presence of a very much larger amount of the acid in order to produce a given 

 stimulating effect. 



In a recently concluded experiment with a fasting man in this laboratory, 

 after 31 days of fasting it was found that the amount of /3-oxybutyric acid in 

 the urine was not materially greater than that found with these two subjects 

 when they were subsisting upon a carbohydrate-free diet. There was, how- 

 ever, no measurable increase in the metabolism noted with this subject; on the 

 contrary there was a marked decline in total metabolism as the fast progressed. 

 While, therefore, it would appear possible to explain the increased metabolism 

 noted with diabetics upon the ground that the severity of the acidosis caused 

 an increased metabolism, we can at present only state the fact that coincidental 

 with the severe acidosis there was found an increased metabolism. Whether 

 the presence of /3-oxybutyric acid molecules passing through the blood stimu- 

 lates the cell activity, or whether the decrease in the alkalescence of the blood 

 produces a similar effect, we can not at present state. Whatever the effect, the 

 body probably to a certain extent may accustom itself to this stimulus and thus 

 react less as time goes on. The fact that there may be 55 grams or more of 

 /3-oxybutyric acid excreted per day with diabetics, with no greater increase in 

 the metabolism above normal than the increase found with a normal individual 

 subsisting on a carbohydrate-free diet, who had but 4 or 5 grams of /3-oxy- 

 butyric acid, would imply that as the disease progressed from day to day, the 

 body became accustomed to the specific stimulus (probably the presence of 

 acid) and responded less and less. 1 



Clinical experience with diabetic patients suggests that an acid intoxica- 

 tion of moderate severity suddenly produced by the withdrawal of carbo- 

 hydrates is more dangerous than a much more severe acidosis produced by a 

 gradual withdrawal of carbohydrates. Thus the sudden withdrawal of carbo- 

 hydrates from diabetic patients upon entrance to hospitals may result in the 

 acute onset of coma. It is often a surprise to find that in the urines of such 

 patients the quantity of acid is so small. In contrast, cases of severe diabetes 

 subjected to marked restriction of carbohydrates for a long period may present 

 an acidosis of severe degree amounting to even 50 grams of (8-oxybutyric acid 

 daily, and yet show no inconvenience therefrom. In these cases the acidosis 

 apparently greatly exceeds for weeks at a time the acidosis of the former group 

 of cases. 



1 Rolly (loc. cit.), noting that the high oxygen consumption observed when patients first 

 came to the hospital was frequently lowered by dietetic treatment, infers that this can not 

 be explained alone by the reduction in protein ingestion, but that the previous high oxygen 

 consumption must be due to improper diet, exercise, consumption of food, or other causes 

 as yet unknown. 



Leimdorfer (loc. cit.) maintains that the increased metabolism of severe diabetes is 

 caused for the greater part by an increase in the intermediary metabolic processes, such as 

 the formation of sugar and acetone bodies from protein and fat. A small part is due to the 

 increased work of respiration. 



As the page proof of this publication leaves our hands, we note that Grafe and Wolf 

 (Deutsch. Archiv f. klin. Med., 1912, 107, p. 227) probably have evidence in regard to the 

 increased metabolism in severe diabetes as a later communication is promised. 



