INTERMEDIATE METABOLISM OF THE FATS 405 



when it has once been formed. A slight change in the configuration of 

 the molecule of sugar which is absorbed and carried to the liver enables 

 the liver to perform its customary function. 



The Urine of diabetics has very frequently a pronounced fruity odor, 

 and is usually decidedly acid in reaction. These characteristics of 

 diabetic urine are due to the presence therein of extraordinary amounts 

 of Aceto-acetic Acid, CH 3 COCH 2 COOH, Acetone, CH 3 COCH 3 and 

 Hydroxybutyric Acid, CH 3 CH(OH)CH 2 COOH. These products are 

 all closely related to one another and unquestionably arise from the 

 same source. Thus aceto-acetic acid may be derived from hydroxy- 

 butyric acid by oxidation, water being split off, while aceto-acetic acid, 

 with the loss of carbon dioxide, is convertible into acetone. It is 

 probable that hydroxy butyric acid is the parent substance of all the 

 "acetone-bodies" which are found in the urine of diabetics. The 

 production of these substances rapidly and in large amounts, produces 

 the extreme Acidosis which is characteristic of the later stages of 

 untreated or improperly treated diabetes, and which culminates in the 

 Diabetic Coma or acid-intoxication which formerly was the invariable 

 and still is the very frequent termination of the disease. 



The amount of acetone in diabetic urine is comparatively small and 

 it is of minor significance. The aceto-acetic acid may be detected by 

 the deep red color which is communicated to urine containing this 

 substance if Ferric Chloride solution be added to it in excess of the 

 amount necessary to precipitate the phosphoric acid as ferric phosphate. 

 It was formerly believed that the acetone bodies in urine were derived 

 from the imperfect oxidation of Carbohydrates and that they probably 

 represented intermediate stages in the degradation of carbohydrates 

 to carbon dioxide and water. This view has now been abandoned with 

 the recognition of the fact that Fats play a predominant part in the 

 genesis of diabetic Acidosis. The very slight change in the glucose 

 molecule which suffices to render it assimilable and utilizable points, in 

 any case, to the improbability that succeeding stages in the oxidation 

 of glucose are exceptionally delayed in the tissues of the diabetic. If 

 oxybutyric acid were in truth an intermediate stage in the oxidation of 

 carbohydrates, as lactic acid, for example is known to be, then the 

 accumulation of this substance in the blood and in the tissues must 

 mean that the subsequent steps of oxidation have become exceptionally 

 difficult. But the very slightest initial oxidation of glucose renders it 

 readily utilizable, so that we must infer that all stages of oxidation 

 succeeding the formation of gluconic or glucuronic acids, for example, 

 are readily performed by the diabetic. Now oxybutyric acid, if it were 

 formed at all from glucose, must succeed the formation of gluconic or 

 glucuronic acids, so that the accumulation of this substance in the 

 tissues of a diabetic evidently cannot be due to the arrested oxidation 

 of carbohydrates. As a matter of fact, Macleod and Pearce have found 

 that the oxidation of glucose in the tissues of depancreatized or even in 

 eviscerated animals is in no way defective, and Meltzer and Kleiner 



