Matsumoto K, Sakamaki H, Izumino K, Yano M, Ueki Y, Miyake S, Tominaga Y
Department of Internal Medicine, Sasebo Chuo Hospital, Nagasaki, Japan.
Metabolism. 2000 Sep;49(9):1219-23. doi: 10.1053/meta.2000.8623.
To investigate the early defects of glucose metabolism in insulin-sensitive type 2 diabetes, we performed oral and frequently sampled intravenous glucose tolerance tests (OGTT and FSIGT) with minimal model analysis in 15 offspring of Japanese type 2 diabetics with normal insulin sensitivity (insulin resistance index of homeostasis model assessment [HOMA-R] < 2.0) and in 20 healthy control subjects without a family history of type 2 diabetes. The frequency of impaired glucose tolerance (IGT) was 40% (6 of 15) in the offspring and 0% (0 of 20) in the controls. Fasting plasma glucose (4.8 +/- 0.1 v4.6 +/- 0.1 mmol/L, P = .18) and immunoreactive insulin ([IRI] 29.9 +/- 2.5 v 28.3 +/- 2.5 pmol/L, P = .64) were comparable between the offspring and the controls. The rate of glucose disappearance (KG) was significantly lower in the offspring versus the control group (2.00 +/- 0.22 v 2.60 +/- 0.17 min(-1), P= .03). The insulin sensitivity index (Si) was significantly greater in the offspring versus the controls (2.68 +/- 0.41 v 1.71 +/- 0.17 x 10(-4) min(-1) x pmol/L , P = .02). First-phase insulin secretion (FPI) to intravenous glucose was significantly lower in the offspring versus the control group (886 +/- 110 v 2,296 +/- 267 min x pmol/L, P< .01). Glucose effectiveness (SG) was comparable between the offspring and control groups. The disposition index (Si x FPI) was significantly lower in the offspring versus the controls (2,106 +/- 256 v 3,652 +/- 490 x 10(-4), P = .02). When the offspring were subdivided into 2 groups by glucose tolerance status, both normal glucose tolerance (NGT) offspring and IGT offspring showed a significant decrease in FPI and increase in Si. Thus, although the offspring of insulin-sensitive type 2 diabetics had increased insulin sensitivity, the impairment in insulin secretion was more dominant. Our results suggest that the early metabolic abnormality in insulin-sensitive type 2 diabetes is an insulin secretory dysfunction despite increased insulin sensitivity.
为了研究胰岛素敏感型2型糖尿病患者早期的葡萄糖代谢缺陷，我们对15名胰岛素敏感性正常（稳态模型评估胰岛素抵抗指数[HOMA-R]<2.0）的日本2型糖尿病患者的后代以及20名无2型糖尿病家族史的健康对照者进行了口服及频繁取样静脉葡萄糖耐量试验（OGTT和FSIGT），并采用最小模型分析法。后代中糖耐量受损（IGT）的发生率为40%（15例中的6例），而对照组为0%（20例中的0例）。后代与对照组的空腹血糖（4.8±0.1对4.6±0.1 mmol/L，P = 0.18）和免疫反应性胰岛素（[IRI] 29.9±2.5对28.3±2.5 pmol/L，P = 0.64）相当。与对照组相比，后代的葡萄糖消失率（KG）显著降低（2.00±0.22对2.60±0.17 min⁻¹，P = 0.03）。后代的胰岛素敏感性指数（Si）显著高于对照组（2.68±0.41对1.71±0.17×10⁻⁴ min⁻¹×pmol/L，P = 0.02）。与对照组相比，后代对静脉注射葡萄糖的第一相胰岛素分泌（FPI）显著降低（886±110对2296±267 min×pmol/L，P<0.01）。后代与对照组之间的葡萄糖效能（SG）相当。后代的处置指数（Si×FPI）显著低于对照组（2106±256对3652±490×10⁻⁴，P = 0.02）。当根据糖耐量状态将后代分为两组时，糖耐量正常（NGT）的后代和IGT后代的FPI均显著降低，Si均升高。因此，尽管胰岛素敏感型2型糖尿病患者的后代胰岛素敏感性增加，但胰岛素分泌受损更为明显。我们的结果表明，胰岛素敏感型2型糖尿病早期的代谢异常是胰岛素分泌功能障碍，尽管胰岛素敏感性增加。
