PERIPHERAL AND HEPATIC INSULIN SENSITIVITY IN SUBJECTS WITH IMPAIRED GLUCOSE-TOLERANCE

Recent evidence suggests that the postprandial hyperglycaemia in impai red glucose tolerance is primarily due to impaired suppression of basa l hepatic glucose output. This in turn appears to be secondary to decr eased first phase insulin secretion, although decreased hepatic insuli n sensitivity, which is a feature of non-insulin-dependent diabetes me llitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose toleran ce test to assess first phase insulin secretion. Insulin sensitivity w as examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatost atin was infused from 150 min to suppress endogenous insulin secretion , and glucagon and insulin were replaced by constant infusion, Glucose with added dideuterated glucose (labelled infusion technique) was inf used to maintain euglycaemia. First phase insulin secretion (Delta 0-1 0 min insulin area divided by Delta 0-10 min glucose area) was signifi cantly decreased in the subjects with impaired glucose tolerance (medi an [range]: 1.2 [0.2-19.4] vs 9.1 [2.6-14.5] mU . mmol(-1); p < 0.01). During the clamp, circulating insulin (93 +/- 8 [mean +/- SEM] and 81 +/- 10 mU . l(-1)) and glucagon (54 +/- 4 and 44 +/- 6 ng . l(-1)) le vels were comparable, Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78 +/- 0.27 vs 4.47 +/- 0.53 mg . kg(-1). min(-1); p < 0.02), and was primarily due to decreased non-oxi dative glucose disposal. However, hepatic glucose output rates were co mparable during the clamp (0.38 +/- 0.10 and 0.30 +/- 0.18 mg . kg(-1) . min(-1)). Therefore, the main defects in subjects with impaired gluc ose tolerance are decreased first phase insulin secretion and peripher al non-oxidative glucose disposal, but hepatic glucose output shows no rmal responsiveness to insulin.