The Nature of Diabetic Acidosis

Abstract

Since the discovery that ketone acids are produced in the body and accumulate in the blood to excess in severe diabetes, general opinion has held that the accumulation of these chemical compounds is responsible for the syndrome known as diabetic coma. The general application of the term acidosis to the condition is in itself sufficient evidence of the importance which is attached to this disorder of metabolism. Difference of opinion seems to have been restricted chiefly to the question of the relative parts played by the ketone bodies as such and by the reduction of blood alkali and diminution of pH which they caused. With the appearance and application of accurate and practical methods for the determination of blood bicarbonate and pH it has become increasingly apparent that alkali deficits of the magnitude found in diabetic acidosis, when they are produced experimentally or occur in the course of other diseases, are not necessarliy attended by a syndrome resembling that of diabetic acidosis. This has, perhaps, given more weight to the arguments of those who would hold that acetone and diacetic acid, by their anesthetic and poisonous effects, are responsible for the symptoms and fatalities. On the other hand there is but the scantiest positive quantitative evidence to support such a theory. The anesthetic actions of acetone and diacetic acid are notoriously slight, but hard to ascertain with certainty because of the ease with which normal animals excrete or oxidize these compounds. Ketosis unassociated with the other metabolic disorders of diabetes never attains so great an intensity. The most convenient experimental animals when rendered diabetic by pancreatectomy or phlorizin do not develop ketosis comparable in severity to that seen in humans with diabetic coma. Chemical analyses have demonstrated no exact correlation between the concentration of ketones in the blood and the profundity of coma in diabetic patients (20).

Studies in Diabetic Acidosis and Coma, With Particular Emphasis on the Retention of Administered Potassium

“…There is no means of deciding how much of the deficit in any particular patient should be assigned to losses of body fluid alone, and how much is to be considered secondary to a disappearance of circulating plasma proteins of the type observed during depletion of body water and solutes (22,23 (24). In view of the dehydration described above, it is immediately apparent that these patients had lost, in keeping with the findings in other series, considerable amounts of the chief extracellular electrolytes, concomitant with, and in most instances, in excess of, the losses of body water (25,26). Had water alone been lost, the levels of sodium and chloride would have been increased above normal.…”

“…The losses of body water, of extracellular electrolytes, of cell nitrogen, and of carbohydrate have been recognized and defined (25,26). The striking retention of potassium administered to this series of patients points to the existence of concomitant deficits of this cation in the body cells.…”

Studies on Ketone Metabolism in Man. I. A Method for the Quantitative Estimation of Splanchnic Ketone Production 12

“…However, other investigators have noted the factor of sex in ketosis, and hence further study is indicated. Peters (29) noted that female humans are more susceptible to ketosis, and Deuel and Hallman (30) observed a greater ketonemia following a high fat diet in fasted female rats than in pair-fed males. Friedemann (31) on the other hand noted that male monkeys fed a high fat diet excreted more ketones than females.…”

Chloride Excretion During Glycosuria in Patients With Diabetes

“…These findings indicate that the salt depletion which is so characteristic a feature of severe diabetic acidosis and coma (1) which had developed after voluntary omission of her usual insulin dosage, during a period in which her dietary intake had been markedly reduced. The difference in behavior may have been due to an inhibition of ketosis by the liberal carbohydrate administration during the 4-day experimental period as well as during the earlier study period.…”

“…(Received for publication November 29, 1945) Diabetic patients with acidosis and coma commonly are markedly depleted of extracellular salt (1). This is often due, in part at least, to the persistent vomiting which frequently accompanies diabetic acidosis.…”