β-Cell Response During a Meal Test

Abstract

OBJECTIVE—To assess the effects of incremental doses of repaglinide on postprandial insulin and glucose profiles after a standard 500-kcal test meal. RESEARCH DESIGN AND METHODS—Sixteen diet-treated Caucasians with type 2 diabetes (mean HbA1c 8.4%) were enrolled in this randomized, open-label, crossover trial. Subjects received 0.5, 1, 2, and 4 mg repaglinide or placebo in a random fashion, followed by a standard 500-kcal test meal on 5 separate study days, 1 week apart. RESULTS—The insulinogenic index (ΔI30/ΔG30) and insulin area under the curve (AUC) from 0 to 30 min (AUC0–30) were higher with the 4-mg drug dose compared with the two lower doses and with 2 mg compared with 0.5 mg. On subgroup analysis, the incremental insulin responses were apparent only in the fasting plasma glucose (FPG) <9-mmol/l subgroup of subjects and not in the FPG >9-mmol/l subgroup. There was a significant dose-related increase in the late postprandial insulin secretion (insulin AUC120–240), which resulted in hypoglycemia in four subjects. Proinsulin-to-insulin ratios at 30 and 60 min improved with increasing doses of repaglinide; higher drug doses (2 and 4 mg) were more effective than the 0.5- and 1-mg doses. CONCLUSIONS—Significant dose-related increases in early insulin secretion were found only in less advanced diabetic subjects. In advanced diabetic patients, only the maximum dose (4 mg) was significant compared with placebo. Better proinsulin-to-insulin processing was noted with increasing drug doses.