Islet Dysfunction in Obese Women with Impaired Glucose Tolerance

Insulin sensitivity and islet function were examined in 22 obese women: 11 with normal glucose tolerance (mean +/- SD body mass index [BMI], 32.2 +/- 2.8 kg/m2) and 11 with impaired glucose tolerance (BMI, 30.1 +/- 2.2 kg/m2). Thirteen non-obese women with normal glucose tolerance (BMI, 20.9 +/- 1.3 kg/m2) served as controls. All women were 58 to 59 years of age. Insulin sensitivity was measured with the euglycemic, hyperinsulinemic clamp. Insulin secretion was studied after intravenous arginine (5 g) at fasting, and at blood glucose levels of 14 and greater than 25 mmol/L. Insulin sensitivity was higher in non-obese (99.8 +/- 11.5 nmol/kg/min/pmol insulin/L) than in obese subject (P < or = .002), but did not differ between obese subjects with normal versus impaired glucose tolerance (47.2 +/- 8.8 v 45.5 +/- 5.2 nmol/kg/min/pmol insulin/L, difference not significant [NS]). Obese subjects with normal glucose tolerance had a higher insulin response to both glucose (P < or = .004) and arginine (P < or = .02) than nonobese women, and higher glucose potentiation of insulin secretion, slopeAIR (P = .05). Compared with obese subjects with normal glucose tolerance, the obese subjects with impaired glucose tolerance had a lower insulin response to glucose (P = .03) and to arginine at blood glucose levels of 14 mmol/L (P = .03), as well as a lower slopeAIR levels ( P = .03). Fasting glucagon was higher in obese subjects with normal glucose tolerance than in non-obese subjects with normal glucose tolerance (P = .006). In obese subjects with impaired glucose tolerance, the glucose inhibition of glucagon secretion, slope AGR, was lower than in obese subjects with normal glucose tolerance (P = .04). Thus, obese subjects with impaired glucose tolerance have altered glucose modulation of islet function, mainly manifested as reduced slope AIR and slope AGR, yet insulin sensitivity is not different than in equally obese subjects with normal glucose tolerance. We therefore conclude that islet dysfunction, and not a further reduction of insulin sensitivity, determines the development of impaired glucose tolerance in obesity.