Buchanan T A, Xiang A H, Peters R K, Kjos S L, Berkowitz K, Marroquin A, Goico J, Ochoa C, Azen S P
Department of Medicine, University of Southern California School of Medicine, Los Angeles, USA.
Diabetes. 2000 May;49(5):782-8. doi: 10.2337/diabetes.49.5.782.
The purpose of this study was to examine the response of pancreatic beta-cells to changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose tolerance and a history of gestational diabetes before and after 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin sensitivity was assessed by minimal model analysis, and beta-cell insulin release was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt) during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during OGTTs. Beta-cell compensation for insulin resistance was assessed as the product (disposition index) of minimal model insulin sensitivity and each of the 3 measures of beta-cell insulin release. In the placebo group, there was no significant change in insulin sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment resulted in a significant increase in insulin sensitivity, as reported previously. In response, AIRg did not change significantly, so that the disposition index for AIRg increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so that the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with placebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significantly from baseline or compared with placebo during troglitazone treatment. The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tolerance.
本研究的目的是检测2型糖尿病高危女性胰腺β细胞对胰岛素敏感性变化的反应。对葡萄糖耐量受损且有妊娠期糖尿病史的拉丁裔女性，在接受每日400mg曲格列酮治疗12周前后（n = 13）以及接受安慰剂治疗12周前后（n = 12），分别进行口服葡萄糖耐量试验（OGTT）和频繁采样静脉葡萄糖耐量试验（FSIGT）。通过最小模型分析评估胰岛素敏感性，在FSIGT期间，将β细胞胰岛素释放评估为对葡萄糖（AIRg）和甲苯磺丁脲（AIRt）的急性胰岛素反应，在OGTT期间评估为30分钟增量胰岛素反应（30分钟dINS）。将最小模型胰岛素敏感性与β细胞胰岛素释放的3种测量方法中的每一种的乘积（处置指数）作为β细胞对胰岛素抵抗的代偿情况进行评估。在安慰剂组中，胰岛素敏感性、胰岛素释放的任何测量指标、β细胞对胰岛素抵抗的代偿情况或葡萄糖耐量均无显著变化。如先前报道，曲格列酮治疗导致胰岛素敏感性显著增加。作为反应，AIRg没有显著变化，因此AIRg的处置指数较基线显著增加（P = 0.004），且与安慰剂相比（P = 0.02）。在曲格列酮治疗期间，随着胰岛素敏感性改善，AIRt（P = 0.001）和30分钟dINS（P = 0.02）下降，因此β细胞功能的这些测量指标中的每一个的处置指数与基线相比（P > 0.20）或与安慰剂相比（P > 0.3）均无显著变化。最小模型分析显示，曲格列酮治疗期间胰岛素敏感性相对于基线的变化中，89%是由血浆胰岛素浓度降低所致。在曲格列酮治疗期间，口服或静脉葡萄糖耐量相对于基线或与安慰剂相比均无显著变化。2型糖尿病高危女性β细胞对改善的胰岛素敏感性的主要反应是胰岛素释放减少，以维持近乎恒定的葡萄糖耐量。
