Nothing except dieting affords permanent relief in diabetes. Opium is said to reduce the sugar output in cases bordering on the severe type.3 The cause of this action is unknown. Experiments inaugurated upon an individual having the 3.65 :1 ratio might indicate whether its effect was really to increase the combustion of sugar or only to reduce the general metabolism. The ingestion of extracts of different organs does not apparently influence the sugar excretion. Laboratory investigations of the glycolytic power of pancreas extracts have been very numerous, but have failed to give striking results. It is possible that the supposed enzyme or activating substance is extremely sensitive to a change in normal conditions. Mandel and Lusk gave large quantities of yeast to a diabetic man without changing the D : N : : 3.65 : 1, which shows that the enzymes of yeast are not able to penetrate the intestinal wall so that they may replace the natural ferment of the organism.

Raulston and Woodyatt4 made an intravenous transfusion of blood from a normal man into a diabetic individual, with aggravation of all the symptoms in the latter.

Minkowski5 discovered that fructose largely reduced protein metabolism in the case of depancreatized dogs. This led to the wide-spread use of fructose in diabetes. Mandel and Lusk, however, found that the increase of sugar in the urine of their diabetic man, after giving 100 grams of fructose, was 80 per cent, of the sugar ingested. The fructose had no effect whatever on protein metabolism.

1 Murlin and B. Kramer: "Journal of Biological Chemistry " 1916, xxvii, 517. 2 Murlin: Ibid., 1916-17, xxviii, 289.

3 von Noorden: "Diabetes," 1905, p. 158.

4 Raulston and Woodyatt: "Journal of the Amer. Med. Assoc.," 1914, Ixii, 096.

5 Minkowski: Loc. cit., p. 131.

Von Noorden1 confirms this observation. He believes that fructose is normally produced in metabolism and is normally burned. In very rare cases, called levulosuria, fructose alone appears in the urine. One case of complete intolerance for fructose has been reported.2

The negative results as regards the value of fructose were especially interesting in the case of Mandel and Lusk. This diabetic medical student was confident of the efficacy of fructose on account of opinions expressed by the writer in his lectures. On the days of fructose ingestion the patient's spirits revived, his strength, measured on the ergograph, decidedly improved, and his companions remarked upon the benefit received, all of which shows that subjective sensations are not to be used as scientific criteria. Staubli3 states that administration of fructose reduces the diabetic's tolerance for glucose.

In this connection it may be mentioned that d-glucuronic acid and pentoses have a bearing on carbohydrate metabolism. A large variety of substances (camphor, chloral, turpentine) form syntheses with glucuronic acid in the organism, and corresponding glucuronates are then eliminated in the urine. At first glance glucuronic acid appears to be the preliminary oxidation product of glucose, as is suggested by the following equation:

OCH(CHOH)4CH20H + O2 = OHC(CHOH)4COOH + H20

Glucose. Glucuronic acid.

However, Mandel and Jackson4 administered camphor to fasting dogs for several days and noted the excretion of glucuronic acid. On giving large quantities of glucose the protein metabolism fell and with it the glucuronic acid elimination; and on giving the animal chopped meat the quantity of campho-glucuronic acid in the urine was correspondingly increased. It may be safely inferred that glucuronic acid is produced solely in the intermediary metabolism of protein. For the large literature on this subject, and also on the pentoses, the reader is referred to other sources.1

1 von Noorden: Loc. cit., p. 50.

2 Neubauer: "Munchener med. Wochenschrift," 1905, lii, 1525. 3 Staubli: "Deutsches Archiv fur klin. Med.," 1908, xciii, 125. 4 Mandel and Jackson: "American Journal of Physiology," 1902, viii. Proceedings of the American Physiological Society, p. xiii.

Pentoses, which are sugars containing 5 atoms of carbon, have been detected in animal and vegetable tissue. Hammar-sten found a pentose in the nucleoprotein of the pancreas. Neuberg showed that this pentose and the one obtained from nucleoprotein in the liver is /-xylose.2 Grund3 has found pentoses in all organs of the body, particularly in those rich in nuclear material.

Salkowski and Neuberg have shown that /-xylose may be derived through ferment action on d-glucuronic acid. Salkowski was the first to detect a pentose in the urine, and this Neuberg has shown to be i-arabinose. The elimination of pentoses in the urine may accompany diabetes, but in extremely rare cases a simple pentosuria occurs in which pentose is the only sugar appearing in the urine.

Luzzatto4 reports such a case in which the elimination of arabinose was independent of diet or mental or muscular effort. Luzzatto believes the pentose in this case to have been l-arabinose. Neuberg finds that in the normal rabbit l-arabinose is more readily burned than d-arabinose. Luzzatto's case could be explained by supposing that the body had lost its normal power to burn /-arabinose as normally produced in metabolism.

Levene and La Forge6 suggest the probable presence of d-ribose in the urine of one individual with pentosuria.

Pentosuria is occasionally discovered in the routine of life insurance examinations. So far as is known it does not indicate danger to general health.

1 Neuberg: "Ergebnisse der Physiologie," 1904, iii, 1 Abtheilung, p. 373.

2 See also Zerner and Waltuch: "Biochemische Zeitschrift," 1913, lviii, 410; Levene and La Forge, "Journal of Biological Chemistry," 1914, xviii, 319.

3 Grund: "Zeitschrift fur physiologische Chemie," 1902, xxxv, III. 4 Luzzatto: "Hofmeister's Beitrage," 1905, vi, 87.

5 Levene and La Forge: "Journal of Biological Chemistry," 1913, xv, 483.