Analysis of pathogenic factors of type 2 diabetes mellitus by stable-labeled minimal model approach

在频繁采样的静脉葡萄糖耐量试验（FSIGT）的单室最小模型分析中，葡萄糖质量作用可能被高估，而胰岛素敏感性可能被低估。另外使用稳定标记的葡萄糖使我们能够精确地估计由胰岛素（Si^2*>）和葡萄糖（Sg^2*>）刺激的葡萄糖摄取的指数，并说明在二室模型中内源性葡萄糖产生（EGP）的时程变化（Diabetes 48：1054-1060，1999）。为探讨糖耐量异常的致病因素，应用稳定标记的胰岛素修饰的FSIGT检测了20例非肥胖2型糖尿病患者（BMI 20.6±0.6kg/m^2，HbA_1c8.0±0.4%）、8例糖耐量减低（IGT）患者和20例糖耐量正常（NGT）患者。Kg值NGT组为1.93±0.11%/min，IGT组为1.38± 0.18%/min，糖尿病组为1.06± 0.08%/min（P<0.0001）。急性胰岛素对葡萄糖推注（AIR）的反应也按此顺序恶化（P<0.0001）。有W ...更多信息 三组间Si^<2*>、Sg^<2*>无差异。基础EGP NGT组为1.53±0.06mg/kg·min，IGT组为1.69±0.16，糖尿病组为1.84±0.08（P=0.0246）。基础EGP与空腹血糖呈直线相关（r=0.486，P=0.0005）。EGP的初始抑制（0- 20分钟）在NGT和IGT之间几乎相同，但在糖尿病中减弱。因此，在IGT受试者中，由于AIR的下降，外周组织中的净葡萄糖摄取减少，对于葡萄糖耐受不良将是重要的，因为EGP的调节并没有如此受损。在糖尿病受试者中，沿着AIR的进一步下降，EGP调节严重恶化。总之，在本研究的非肥胖葡萄糖不耐受受试者中，刺激葡萄糖摄取的胰岛素作用和葡萄糖质量作用没有降低。随着从IGT发展到完全糖尿病，EGP失调与AIR的进一步下降一致。少

Glucose mass action may be overestimated and insulin sensitivity underestimated in the single compartment minimal model analysis of frequently sampled intravenous glucose tolerance test (FSIGT). Additional use of stable-labeled glucose allows us to precisely estimate indexes for glucose uptake stimulated by insulin (Si^<2*>) and by glucose (Sg^<2*>), and to illustrate time course changes in endogenous glucose production (EGP) in the two compartment model (Diabetes 48 : 1054-1060, 1999). To clarify pathogenic factors responsible for glucose intolerance using this stable-labeled insulin-modified FSIGT, 20 non-obese subjects with type 2 diabetes mellitus (BMI 20.6±0.6kg/m^2 and HbA_1c8.0±0.4%), 8 with impaired glucose tolerance (IGT), and 20 with normal glucose tolerance (NGT) were evaluated. Kg values were 1.93±0.11%/min in NGT, 1.38±0.18 in IGT, and 1.06±0.08 in diabetes (P<0.0001). Acute insulin response to the glucose bolus (AIR) was also deteriorated in this order (P<0.0001). There w … More ere no differences in Si^<2*> and Sg^<2*> among these three groups. Basal EGP was 1.53±0.06mg/kg.min in NGT, 1.69±0.16 in IGT and 1.84±0.08 in diabetes (P=0.0246). There was a linear relationship between basal EGP and fasting plasma glucose (r=0.486, P=0.0005). The initial suppression (0-20min) of EGP was virtually identical between NGT and IGT, but was blunted in diabetes. Thus, in IGT subjects, the decreased net glucose uptake in peripheral tissue, due to the decline in AIR, would be important for the glucose intolerance, since the regulation of EGP was not so impaired. In diabetic subjects, along with the further decline in AIR, the EGP regulation was severely deteriorated. In conclusion, there was no decrease in insulin action and glucose mass action to stimulate glucose uptake in the non-obese glucose intolerant subjects of this study. Together with the progression from IGT to full blown diabetes, the EGP dysregulation came to be evident in concordance with the further decline in AIR. Less