Response of pancreatic β-cells to improved insulin sensitivity in women at high risk for type 2 diabetes
Response of pancreatic β-cells to improved insulin sensitivity in women at high risk for type 2 diabetes
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DOI：
10.2337/diabetes.49.5.782
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发表时间：
2000-05-01
期刊：
影响因子：
7.7
通讯作者：
Azen, SP
中科院分区：
文献类型：
--
作者：
Buchanan, TA;Xiang, AH;Azen, SP
本研究的目的是研究胰腺β细胞对2型糖尿病高危女性胰岛素敏感性变化的反应。对葡萄糖耐量受损且有妊娠糖尿病史的拉丁裔妇女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（FSIGTs），并在给予400mg /天曲格列酮（n = 13）或安慰剂（n = 12）治疗前后12周，通过最小模型分析评估胰岛素敏感性。在FSIGTs期间，β细胞胰岛素释放被评估为对葡萄糖（AIR(g)）和甲苯丁胺（AIR(t)）的急性胰岛素反应，在ogtt期间，被评估为30分钟胰岛素增量反应（30分钟dINS）。β细胞对胰岛素抵抗的补偿被评估为最小模型胰岛素敏感性的产物（处置指数）和β细胞胰岛素释放的3种测量中的每一种。在安慰剂组中，胰岛素敏感性、胰岛素释放、β细胞对胰岛素抵抗的补偿或葡萄糖耐量的任何测量都没有显著变化。如前所述，曲格列酮治疗导致胰岛素敏感性显著增加。作为回应，AIR(g)没有显著变化，因此与安慰剂相比，AIR(g)的处置指数较基线显著增加（P = 0.004）。在曲格列酮治疗期间，AIR(t) （P = 0.001）和30分钟dINS （P = 0.02）随着胰岛素敏感性的改善而下降，因此这些β细胞功能测量的处置指数与基线相比（P > 0.20）或与安慰剂相比（P > 0.3）没有显著变化。最小模型分析显示，在曲格列酮治疗期间，89%的胰岛素敏感性变化是由血浆胰岛素浓度降低引起的。在曲格列酮治疗期间，口服和静脉注射葡萄糖耐量与基线或安慰剂相比都没有显著变化。在2型糖尿病高危妇女中，β细胞对胰岛素敏感性改善的主要反应是胰岛素释放减少，以维持几乎恒定的葡萄糖耐量。
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 (AIR(g)) and tolbutamide (AIR(t)) 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, AIR(g) did not change significantly so that the disposition index for AIR(g) increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIR(t) (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 significant ly 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.