Henriksen J E, Alford F, Handberg A, Vaag A, Ward G M, Kalfas A, Beck-Nielsen H
Department of Endocrinology M, Odense University Hospital, Denmark.
J Clin Invest. 1994 Sep;94(3):1196-204. doi: 10.1172/JCI117436.
20 normoglycemic first degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients were compared with 20 matched subjects without any family history of diabetes using the intravenous glucose tolerance test with minimal model analysis of glucose disappearance and insulin kinetics. Intravenous glucose tolerance index (Kg) was similar in both groups (1.60 +/- 0.14 vs 1.59 +/- 0.18, x 10(-2) min-1, NS). However, insulin sensitivity (Si) was reduced (3.49 +/- 0.43 vs 4.80 +/- 0.61, x 10(-4) min-1 per mU/liter, P = 0.05), whereas glucose effectiveness (Sg) was increased (1.93 +/- 0.14 vs 1.52 +/- 0.16, x 10(-2) min-1, P < 0.05) in the relatives. Despite insulin resistance neither fasting plasma insulin concentration (7.63 +/- 0.48 vs 6.88 +/- 0.45, mU/liter, NS) nor first phase insulin responsiveness (Phi1) (3.56 +/- 0.53 vs 4.13 +/- 0.62, mU/liter min-1 per mg/dl, NS) were increased in the relatives. Phi1 was reduced for the degree of insulin resistance in the relatives so that the Phi1 x Si index was lower in the relatives (11.5 +/- 2.2 vs 16.7 +/- 2.0, x 10(-4) min-2 per mg/dl, P < 0.05). Importantly, glucose effectiveness correlated with Kg and with basal glucose oxidation but not with total glucose transporter 4 (GLUT4) content in a basal muscle biopsy. In conclusion we confirm the presence of insulin resistance in first degree relatives of NIDDM patients. However, insulin secretion was altered and reduced for the degree of insulin resistance in the relatives, whereas glucose effectiveness was increased. We hypothesize that increased glucose effectiveness maintains glucose tolerance within normal limits in these "normoinsulinemic" relatives of NIDDM patients.
选取20名非胰岛素依赖型糖尿病（NIDDM）患者的血糖正常的一级亲属，与20名无糖尿病家族史的匹配对照者进行比较，采用静脉葡萄糖耐量试验并结合葡萄糖消失及胰岛素动力学的最小模型分析。两组的静脉葡萄糖耐量指数（Kg）相似（分别为1.60±0.14与1.59±0.18，×10⁻² min⁻¹，无显著性差异）。然而，亲属组的胰岛素敏感性（Si）降低（分别为3.49±0.43与4.80±0.61，×10⁻⁴ min⁻¹ per mU/liter，P = 0.05），而葡萄糖效能（Sg）升高（分别为1.93±0.14与1.52±0.16，×10⁻² min⁻¹，P < 0.05）。尽管存在胰岛素抵抗，但亲属组的空腹血浆胰岛素浓度（分别为7.63±0.48与6.88±0.45，mU/liter，无显著性差异）及第一时相胰岛素反应性（Phi1）（分别为3.56±0.53与4.13±0.62，mU/liter min⁻¹ per mg/dl，无显著性差异）均未升高。亲属组中Phi1随胰岛素抵抗程度降低，因此亲属组的Phi1×Si指数较低（分别为11.5±2.2与16.7±2.0，×10⁻⁴ min⁻² per mg/dl，P < 0.05）。重要的是，在基础肌肉活检中，葡萄糖效能与Kg及基础葡萄糖氧化相关，但与总葡萄糖转运体4（GLUT4）含量无关。总之，我们证实NIDDM患者的一级亲属存在胰岛素抵抗。然而，亲属组的胰岛素分泌因胰岛素抵抗程度而改变并降低，而葡萄糖效能升高。我们推测，葡萄糖效能增加使这些NIDDM患者的“正常胰岛素血症”亲属的葡萄糖耐量维持在正常范围内。
