Citrate metabolism in diabetes: I. Plasma citrate in alloxan-diabetic rats and in clinical diabetes

Abstract

A “bimodal” increase in plasma citrate levels was observed in alloxan-diabetic rats. Three days following alloxan injection, the plasma citrate levels in cardiac puncture blood was 9.40 mg. 100 ml. as compared to 4.95 for the control. At 14 days the value approximated that in the normal rats, whereas at 28 days (and subsequent time periods), the citrate levels were markedly elevated. In a second series of experiments in which the animals were killed by decapitation, a similar “bimodal” change in plasma citrate values was noted; however, the plasma citrate levels in both diabetic and control rats were generally higher than was the case when blood was drawn by cardiac puncture. No relationship could be established between the blood sugar level and plasma citrate values. In treated human diabetics, plasma citrate values were not significantly different from the normal, i.e., 2.70 as compared to 2.41 mg. 100 ml. However, in 2 cases of untreated human diabetes exhibiting severe ketoacidosis, the plasma citrate values were markedly elevated. In one, the initial value was 44.4 mg. 100 ml. serum; the level rapidly returned toward normal; at 4 weeks it was 1.56 mg. 100 ml. The increased serum citrate levels were not the result of citrate mobilization from bone, since there was no concomitant increase in the serum calcium levels. These results suggest the possibility that there may be an alteration in the tricarboxylic acid cycle in diabetes (both experimental and clinical), and that this alteration results in the accumulation of plasma citrate.