Studies in Patients with Chlorpropamide-Induced Hypoglycemia

Six patients with hypoglycemia due to chlorpropamide are reported. The common characteristics were old age and/or poor nutritional state. The serum concentration of chlorpropamide during hypoglycemia was not higher than that seen in a group of chlorpropamide-treated diabetics without hypoglycemia. In both groups, the serum level declined in a rectilinear fashion after the drug was stopped, and the rate of decline was similar in the two groups. The serum level of chlorpropamide in the control group covered a fourfold range at the same dose level, and had no correlation with the degree of diabetic control. The serum insulin concentration was in two instances somewhat high compared to the low blood sugar, but most of the time was found to be at a low (fasting) level. In three patients no evidence of insulin secretion in peripheral venous blood was found even after stimulation with glucagon, glucose, or meals. In two of them, however, the absence of insulin was transient and present only during the day of hypoglycemia. It is suggested that diabetics in negative calorie balance are predisposed to hypoglycemia ifthey continue to take chlorpropamide, and that they suffer this complication even with a serum concentration of the drug that is within therapeutic range. The pathogenesis probably does not involve increased peripheral utilization of glucose, but more probably an inhibiting effect on production of glucose by the liver.