Alterations in the kinetics of C-peptide and insulin secretion in hyperthyroidism

Previous studies investigating the mechanisms underlying the hyperinsulinemia observed in hyperthyroid subjects have demonstrated increased, normal, or reduced insulin secretory rates when peripheral concentrations of C-peptide were used as a marker of beta-cell function. In this study, using individually derived C-peptide kinetic parameters, insulin secretion rates were calculated directly from plasma C-peptide concentrations in 13 hyperthyroid and 13 euthyroid control subjects matched for age, weight, and sex. Eight subjects in each group were studied during a 24-h period in which they ate three mixed meals, whereas the remaining five were studied during a 3-h hyperglycemic clamp. Although insulin secretory rates under basal conditions in both groups were similar, the hyperthyroid group had an enhanced insulin secretory response to meals and, accordingly, the total amount of insulin secreted over 24 h was significantly greater (P < 0.02) in this group. Insulin secretory rates were also 50% higher in the hyperthyroid subjects during the hyperglycemic clamp at a time when glucose levels in both groups were comparable. Despite these differences in secretion, the C-peptide concentrations were not significantly different. Analysis of C-peptide clearance kinetics using multivariate analysis demonstrated that the mean clearance rate of C-peptide was significantly increased (P < 0.02) in the hyperthyroid group. Thus, stimulated insulin secretion rates are significantly increased in thyrotoxicosis possibly reflecting an increased sensitivity of the beta-cell to glucose in subjects who are hyperthyroid. However, due to the rapid clearance of C-peptide from the circulation in the setting of hyperthyroidism, differences in beta-cell secretory responses between hyperthyroid and euthyroid subjects may not be evident by measurement of C-peptide levels alone.