ELEVATED PLASMA-GLUCOSE 2-H POSTCHALLENGE PREDICTS DEFECTS IN BETA-CELL FUNCTION

Studies were performed in subjects with no known family history of dia betes, normoglycemic subjects who have first-degree relatives with non -insulin-dependent diabetes mellitus (NIDDM), and subjects with nondia gnostic oral glucose tolerance tests (NDX) or impaired glucose toleran ce (IGT). Insulin sensitivity index (S-I) was similar in all four grou ps. However, a number of defects in insulin secretion were seen in the NDX and IGT groups, including reduced first-phase insulin secretory r esponses to intravenous glucose in relation to the degree of insulin r esistance, and reduced normalized spectral power of insulin secretion during oscillatory glucose infusion. The latter finding demonstrates a decreased ability of the beta-cell to detect and respond to the succe ssive increases and decreases in glucose and therefore to be entrained by the exogenous glucose infusion. The ability of a low-dose glucose infusion to prime the insulin secretory response to a subsequent gluco se stimulus was normal in subjects with IGT but reduced or absent in s ubjects with overt NIDDM. These studies demonstrate that a number of a lterations in beta-cell function are detectable in nondiabetic first-d egree relatives of subjects with NIDDM with mild elevations in the 2-h postchallenge glucose level, and these abnormalities antedate the ons et of overt hyperglycemia and clinical diabetes.