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This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness, and hepatic extraction of insulin are altered in subjects with impaired glucose tolerance (IGT). The frequently sampled intravenous glucose tolerance test was performed in postmenopausal women (age 63 yr, body mass index range 21.6-28.9 kg/m2) with IGT (n = 10) or normal glucose tolerance (NGT; n = 10). Insulin sensitivity (S(I)) was significantly lower in IGT than in NGT (P = 0.030). In contrast, insulin secretion was not significantly different between the two groups as determined by area under the curve for insulin and C-peptide, acute insulin response to glucose (AIR(G)), and glucose sensitivity of first-phase (phi1) or of second-phase (phi2) insulin secretion. In NGT (r = -0.68, P = 0.029) but not in IGT (r = -0.05, not significant), S(I) correlated negatively with phi1. The B-cell "adaptation index" (S(I) x phi1) was lower in IGT than in NGT [83 +/- 25 vs. 171 +/- 29 min(-2)/(mmol/l), P = 0.042]. Also, the B-cell "disposition index" (S(I) times AIR(G)) was lower in IGT (83 +/- 25 10(-4) min(-1)) than in NGT (196 +/- 30 10(-4) min(-1), p = 0.011). In contrast, glucose effectiveness or hepatic extraction of insulin was not different between IGT and NGT. We conclude that postmenopausal women with IGT fail to adequately adapt to lowered S(I) by increasing first-phase insulin secretion.

Impaired adaptation of first-phase insulin secretion in postmenopausal women with glucose intolerance