Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women
Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women
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DOI：
10.2337/diabetes.51.9.2796
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发表时间：
2002-09-01
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
2型糖尿病通常是由于在慢性胰岛素抵抗的情况下胰腺β细胞功能的进行性衰竭而引起的。我们测试了长期改善胰岛素抵抗是否会保护胰腺β细胞功能，延迟或预防高危西班牙裔女性2型糖尿病的发生。既往患有妊娠期糖尿病的妇女被随机分配至安慰剂组（n = 133）或胰岛素增敏药物曲格列酮组（400 mg/天; n = 133），以双盲方式给药。每3个月测量一次空腹血糖，每年进行一次口服葡萄糖耐量试验（OGTT）以检测糖尿病。在基线和3个月后进行静脉葡萄糖耐量试验（IVGTT），以确定与糖尿病保护相关的早期代谢变化。在试验期间未发生糖尿病的女性在研究药物停止后8个月返回进行OGTT和IVGTT。在盲法药物治疗的中位随访30个月期间，236名至少返回一次随访的女性中，安慰剂组和曲格列酮组的平均年糖尿病发病率分别为12.1%和5.4%（P < 0.01）。曲格列酮组的糖尿病保护1）与随机化后3个月内源性胰岛素需求的降低程度密切相关，2）在研究药物停止后持续8个月，3）与胰岛素抵抗的β细胞代偿的保留相关。曲格列酮治疗可延迟或预防高危西班牙裔女性2型糖尿病的发生。保护作用与胰腺β细胞功能的保存有关，并且似乎是通过慢性胰岛素抵抗对β细胞的分泌需求减少介导的。
Type 2 diabetes frequently results from progressive failure of pancreatic beta-cell function in the presence of chronic insulin resistance. We tested whether chronic amelioration of insulin resistance would preserve pancreatic beta-cell function and delay or prevent the onset of type 2 diabetes in high-risk Hispanic women. Women with previous gestational diabetes were randomized to placebo (n = 133) or the insulin-sensitizing drug troglitazone (400 mg/day; n = 133) administered in double-blind fashion. Fasting plasma glucose was measured every 3 months, and oral glucose tolerance tests (OGTTs) were performed annually to detect diabetes. Intravenous glucose tolerance tests (IVGTTs) were performed at baseline and 3 months later to identify early metabolic changes associated with any protection from diabetes. Women who did not develop diabetes during the trial returned for OGTTs and IVGTTs 8 months after study medications were stopped. During a median follow-up of 30 months on blinded medication, average annual diabetes incidence rates in the 236 women who returned for at least one follow-up visit were 12.1 and 5.4% in women assigned to placebo and troglitazone, respectively (P < 0.01). Protection from diabetes in the troglitazone group 1) was closely related to the degree of reduction in endogenous insulin requirements 3 months after randomization, 2) persisted 8 months after study medications were stopped, and 3) was associated with preservation of beta-cell compensation for insulin resistance. Treatment with troglitazone delayed or prevented the onset of type 2 diabetes in high-risk Hispanic women. The protective effect was associated with the preservation of pancreatic beta-cell function and appeared to be mediated by a reduction in the secretory demands placed on beta-cells by chronic insulin resistance.