Klauser R, Prager R, Schernthaner G, Olefsky J M
Department of Medicine II, University of Vienna, Austria.
J Clin Endocrinol Metab. 1991 Oct;73(4):758-64. doi: 10.1210/jcem-73-4-758.
We recently found that postprandial hyperinsulinemia does not compensate for the insulin resistance of obese subjects and proposed that postprandial hyperglycemia might be more important in promoting glucose disposal via the mass action effect of glucose. To test this idea we perform oral glucose tolerance tests (OGTT) in six lean and eight obese subjects, measuring glucose and insulin levels. Afterward two insulin infusion studies were performed. During infusion study I, insulin was infused in a dynamic square wave fashion to mimic the individual post-OGTT insulin levels at content euglycemic glucose levels. During study II, glucose and insulin infusions were varied to mimic post-OGTT levels in each subject. Overall glucose turnover was measured isotopically by infusion of [3-3H] glucose. During the OGTT the obese subjects exhibited significantly higher insulin (P less than 0.005) and glucose levels (P less than 0.002). Insulin-stimulated glucose disposal rates and total incremental glucose disposal (IGD) over 4 h during study I at euglycemia were significantly lower in obese compared to lean subjects (area under the curve, 824 +/- 166 vs. 1222 +/- 161 mmol/L.m2; P less than 0.01) despite higher post-OGTT insulin levels in obese subjects. When insulin plus glucose levels were matched to the individual OGTT levels, IGD was not significantly different between obese and control subjects (1712 +/- 253 vs. 1617 +/- 444 mmol/L.m2; P = NS). A significant inverse correlation (r = -0.73; P less than 0.05) existed between the degree of glucose intolerance (OGTT) and the decrease in IGD during the phasic hyperinsulinemic euglycemic study (infusion study I). These data suggest that with increasing insulin resistance, hyperinsulinemia is less effective in compensating for this decrease in insulin action, and hyperglycemia becomes more important in augmenting overall glucose disposal values.
我们最近发现，餐后高胰岛素血症并不能补偿肥胖受试者的胰岛素抵抗，并提出餐后高血糖可能在通过葡萄糖的质量作用效应促进葡萄糖处置方面更为重要。为了验证这一观点，我们对6名瘦人和8名肥胖受试者进行了口服葡萄糖耐量试验（OGTT），测量血糖和胰岛素水平。之后进行了两项胰岛素输注研究。在输注研究I中，以动态方波方式输注胰岛素，以模拟每个受试者在血糖正常时的OGTT后胰岛素水平。在研究II中，改变葡萄糖和胰岛素的输注量以模拟每个受试者的OGTT后水平。通过输注[3-3H]葡萄糖以同位素方法测量总体葡萄糖周转率。在OGTT期间，肥胖受试者的胰岛素水平（P<0.005）和血糖水平（P<0.002）显著更高。尽管肥胖受试者OGTT后的胰岛素水平较高，但在研究I中，肥胖受试者在血糖正常时胰岛素刺激的葡萄糖处置率和4小时内的总增量葡萄糖处置（IGD）显著低于瘦人受试者（曲线下面积，824±166 vs. 1222±161 mmol/L·m2；P<0.01）。当胰岛素加葡萄糖水平与个体OGTT水平匹配时，肥胖受试者和对照受试者之间的IGD无显著差异（1712±253 vs. 1617±444 mmol/L·m2；P=无显著性差异）。在阶段性高胰岛素血症血糖正常研究（输注研究I）期间，葡萄糖不耐受程度（OGTT）与IGD降低之间存在显著负相关（r=-0.73；P<0.05）。这些数据表明，随着胰岛素抵抗增加，高胰岛素血症在补偿胰岛素作用降低方面的效果较差，高血糖在增加总体葡萄糖处置值方面变得更为重要。
