Cavaghan M K, Ehrmann D A, Byrne M M, Polonsky K S
Department of Medicine, The University of Chicago and Pritzker School of Medicine, Chicago, Illinois 60637, USA.
J Clin Invest. 1997 Aug 1;100(3):530-7. doi: 10.1172/JCI119562.
Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion. We sought to determine the role of beta cell function in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone (n = 14) or placebo (n = 7) in a randomized, double-blind design. Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (SI) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and beta cell glucose-sensing ability during an oscillatory glucose infusion. Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% (P = 0.03) and 39% (P = 0.003), respectively. SI increased from 1.3+/-0.3 to 2.6+/-0.4 x 10(-)5min-1pM-1 (P = 0.005). Average insulin secretion rates adjusted for SI over the glucose interval 5-11 mmol/liter were increased by 52% (P = 0.02), and the ability of the beta cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% (P = 0.04). No significant changes in these parameters were demonstrated in the placebo group. In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced beta cell response to glucose characteristic of subjects with IGT. This appears to be an important factor in the observed improvement in glucose tolerance.
糖耐量受损（IGT）与胰岛素分泌及作用缺陷相关，且转化为非胰岛素依赖型糖尿病（NIDDM）的风险很高。曲格列酮是一种胰岛素增敏剂，可降低NIDDM和IGT患者的血糖浓度，但尚不清楚其是否影响胰岛素分泌。我们试图确定β细胞功能在介导糖耐量改善中的作用。肥胖的IGT患者以随机、双盲设计接受为期12周的每日400mg曲格列酮治疗（n = 14）或安慰剂治疗（n = 7）。在基线和治疗后进行的研究测量包括：口服75g葡萄糖耐量试验的血糖和胰岛素反应、通过频繁采样静脉葡萄糖耐量试验评估的胰岛素敏感性指数（SI）、分级葡萄糖输注期间的胰岛素分泌率以及振荡葡萄糖输注期间的β细胞葡萄糖感应能力。曲格列酮使口服葡萄糖后的血糖和胰岛素综合反应分别降低了10%（P = 0.03）和39%（P = 0.003）。SI从1.3±0.3增加到2.6±0.4×10⁻⁵min⁻¹pM⁻¹（P = 0.005）。在5 - 11mmol/L葡萄糖区间内，经SI调整后的平均胰岛素分泌率增加了52%（P = 0.02），通过频谱功率分析评估，β细胞对外源性振荡葡萄糖输注的同步能力提高了49%（P = 0.04）。安慰剂组这些参数无显著变化。除了提高胰岛素敏感性外，我们还证明曲格列酮改善了IGT患者β细胞对葡萄糖反应降低的特征。这似乎是观察到的糖耐量改善的一个重要因素。
