One of the very pronounced characteristics of the diabetic is his constant emaciation. There is usually a larger excretion of nitrogen in the urine than is necessary for a healthy person. It may be recalled that carbohydrates diminish the protein metabolism, and also that a person may support life on meat and fat alone without tissue waste. But in this latter case there is a supply of carbohydrate derived from protein metabolism. This is also true in starvation. But when the protein sugar is withdrawn from the tissue cells in diabetes, there is at once a largely increased protein metabolism. This is most obvious in fasting animals treated with phlorhizin, as the glycosuria can be immediately induced. The increase in protein metabolism is most marked where the higher D : N ratio exists. In this connection the following experiments on fasting animals are suggestive:

Table Illustrating The Influence Of Diabetes On Protein Metabolism

In the goat the protein metabolism rose to 238, in the dog to 450 per cent, of that in the normal animals, as the result of the loss of the influence of the small quantity of protein sugar produced in starvation.

Falta, Grote, and Staehelin3 found increases in the protein metabolism of fasting dogs which had been depancreatized, equal to three. and fivefold the normal amount.

In the case of diabetes mellitus reported by Mandel and Lusk where the ratio D : N was 3.65 : 1, it was found that the ingestion of broths containing 7.7 grams of nitrogen was followed by an elimination of 21.7 grams of nitrogen in the urine or a loss of body nitrogen approximating 14 grams. The patient was greatly emaciated, and passed this day in bed.

1 Lusk: "Zeitschrift fur Biologie," 1901, xlii, 43.

2 Reilly, Nolan, and Lusk: "American Journal of Physiology," 1898, i, 397.

3 Falta, Grote, and Staehelin: "Hofmeister's Beitrage," 1907, x, 199.

He could not be maintained in nitrogen equilibrium with 19 grams of protein nitrogen in the food, but was in nitrogen equilibrium when given 27 grams. In all cases of intense diabetes this factor of an increased protein metabolism must be considered. In mild cases in which sugar disappears from the urine when carbohydrates are cut out of the food, and in which the patient may burn his protein sugar, the protein metabolism is not different from that of a normal person living on meat and fat.

As would be expected under conditions involving an increase in protein metabolism, amino-acids are found in increased quantities in both blood and urine of diabetic patients.1

The preeminence of fat metabolism in the diabetic as the mainstay of his organism leads to inquiry as to the origin of the fatty acid called β-oxybutyric acid, and of aceto-acetic acid and aceton which are directly derived from it.2 Whence do these aceton bodies arise? They were at first supposed to come from glucose, following a chemical process analogous to the butyric acid fermentation of carbohydrates, but it was soon discovered that in normal persons the aceton bodies were especially found in the fasting state. Many then attributed the presence of aceton to the specific breakdown of body protein, since, when protein was given in the food, the aceton bodies disappeared in the urine. However, Magnus-Levy3 has reported a case of a boy in coma who eliminated an average of 97.5 grams of β-oxybutyric acid and aceto-acetic acid daily for three days in addition to an unmeasured quantity of aceton in the breath, and during this time the protein metabolism amounted to 90 grams, of which latter at least 40 grams appeared as sugar in the urine. The 97.5 grams of aceton bodies in this case could not have been entirely derived from the 90 grams of protein, but they must have originated largely from fat.

1 Galambos and Tausz: "Zeitschrift fur klin. Med.," 1913, lxxvii, 14; 1914, lxxx, 381. Loffler: Ibid., 1913, lxxviii, 483.

2 This description is taken from Lusk: "Metabolism in Diabetes," Harvey Society Lecture, "Archives of Internal Medicine," 1909, iii, 1.

3 Magnus-Levy: "Ergebnisse d. inn. Med.," 1908, i, 374.

Stadelman1 first pointed out the relationship between the formation of β-oxybutyric acid and the occurrence of coma. Coma has been compared to the sword of Damocles which hangs suspended over every diabetic. It has been discovered that whenever the organism is thrown suddenly from a carbohydrate regimen to a combustion of fat the aceton bodies appear in the urine. This condition is greatly intensified in diabetes when even the sugar derived from protein is not burned.

Each molecule of butyric acid can yield one of β-oxybutyric acid. It has been calculated by Magnus-Levy2 that 100 grams of neutral fat made of stearin, palmitin, and olein may yield 36.2 grams of β-oxybutyric acid. It is therefore evident that the higher fatty acids are the more valuable nutriment. Butter, with its high content of butyric acid, largely increases the output of the aceton bodies in diabetes; 50 to 100 grams of butter fat when administered to a diabetic may raise his urinary aceton four- to eightfold.3 Oleomargarin is to be preferred.

Magnus-Levy4 gave 11.7 grams of /3-oxybutyric acid to a normal dog. This was completely burned. He then gave 11.5 grams to a phlorhizinized dog, with the result that there was an increased elimination of 7.6 grams of β-oxybutyric acid and aceton. Since some aceton was eliminated in the breath, it is evident that the animal had largely lost the power to burn ingested β-oxybutyric acid.

The evidence concerning the formation of the aceton bodies from fat and from some amino-acids has already been discussed (see p. 208). It suffices here to recall that Otto Neubauer5 found that the ingestion of either β-oxybutyric acid or aceto.acetic acid by a diabetic patient always caused the partial excretion of the one given in the form of the other. The reaction is reversible:

1 Stadelman: "Experimentelle-klinische Untersuchungen," Stuttgart, 1890. 2 Magnus-Levy: "Ergebnisse d. inn. Med.," 1908, i, 384.

3 Fejes: "Magyar orvosi Archivum," 1907, viii, 335.

4 Magnus-Levy: "Ergebnisse d. inn. Med.," 1908, i, 372.

5 Neubauer, O.: "Verhandlungen des deutschen Congresses fur innere Medizin," 1910, xxvii, 566.

CH3.CHOH.CH2.COOH + O → CH3.CO.CH2.COOH + H20.

In marked acidosis Neubauer found that β.oxybutyric acid amounted to between 60 and 80 per cent, of the total urinary aceton bodies.