Influence of Hyperinsulinemia and Insulin Resistance on In Vivo b-Cell Function

OBJECTIVE—Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the b-cell could cause b-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate b-cell function in subjects with normal glucose tolerance (NGT) and whether they contribute to dysglycemia in impaired glucose regulation (IGR). RESEARCH DESIGN AND METHODS—Insulin sensitivity (by euglycemic clamp), insulin-induced secretory response at iso-glycemia (IISR) (as C-peptide percent change from basal during the clamp), glucose-induced secretory response (GISR) to an intravenous glucose bolus, and b-cell glucose sensitivity (b-GS) (by oral glucose tolerance test [OGTT] modeling) were measured in 1,151 NGT and 163 IGR subjects from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study