The long-term effects of chlorpropamide on insulin, C-peptide, and proinsulin secretion.

It had been suggested that long-term lowering of blood glucose by sulfonylureas in non-insulin-dependent (NIDD) diabetes is not due to a sustained increase in insulin secretion. We have re-examined this question. Thirteen nonobese NIDD patients not controlled on diet alone were studied prospectively on treatment with chlorpropamide for over 3 mo. Of these, 9 were also studied after 1 yr. Improvement in glucose tolerance was associated with an increase in fasting and postglucose serum insulin and C-peptide concentration. We conclude that at least for over 1 yr chlorpropamide increases insulin secretion. After 3 and 12 mo the fasting proinsulin percentage of immunoreactive insulin was increased.