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研究背景:伴有心血管危险因素的患者有内皮功能障碍,是导致动脉粥样硬化发病机制的关键因素之一, 在糖尿病患者中应用四氢噻唑产生了多种抗动脉粥样硬化的作用,本研究证实匹格列酮在伴有心血管危险因素的非糖尿病病人中提高内皮功能的假设。方法和结果:研究采用随机,双盲,安慰剂对照,交叉设计。入选80 名同时伴有高血压和高胆固醇血症的患者。胰岛素敏感性用定量胰岛素敏感检测指数(QUICK)评价。进一步将患者分为胰岛素敏感和胰岛素抵抗,在每个治疗阶段,患者每天服用匹格列酮45 mg或安慰剂共八周,在每8 周末,进行实验室检查。应用匹格列酮组血浆胰岛素水平显著下降,QUICK胰岛素敏感指数升高,HDL升高,甘油三酯、自由脂肪酸,和C-反应蛋白水平降低。匹格列酮治疗显著提高缓激肽的内皮依赖性舒张功能而不影响对硝普钠的反应。多变量分析显示:只有总胆固醇的变化预示匹格列酮提高内皮活性。结论:伴有心血管危险因素的非糖尿病病人中,匹格列酮治疗提高胰岛素敏感性,降低C-反应蛋白,提高内皮血管扩张功能。这些结果并不密切相关,提示匹格列酮对血管的有益作用独立于其对胰岛素敏感性和炎性的作用。
Background: Cardiovascular risk factors in patients with endothelial dysfunction, leading to the pathogenesis of atherosclerosis is one of the key factors in the application of tetrahydrothiazole in patients with diabetes have a variety of anti-atherosclerotic effect, the Studies confirm the hypothesis that pioglitazone improves endothelial function in nondiabetic patients with cardiovascular risk factors. Methods and Results: A randomized, double-blind, placebo-controlled, crossover design was used. Eighty-eight patients with hypertension and hypercholesterolemia were enrolled. Insulin sensitivity was measured using a quantitative insulin sensitivity test index (QUICK). Patients were further divided into insulin sensitivity and insulin resistance. During each treatment phase, patients took pioglitazone 45 mg or placebo for eight weeks daily and performed laboratory tests every 8 weeks. Plasma insulin levels were significantly decreased in pioglitazone-treated patients, QUICK insulin sensitivity index increased, HDL increased, and triglycerides, free fatty acids, and C-reactive protein levels decreased. Pioglitazone treatment significantly increased the endothelium-dependent vasodilation of bradykinin without affecting the response to sodium nitroprusside. Multivariate analysis showed that only changes in total cholesterol predicted that pioglitazone increased endothelial activity. CONCLUSIONS: In nondiabetic patients with cardiovascular risk factors, pioglitazone improves insulin sensitivity, decreases C-reactive protein, and improves endothelial vasodilation. These results are not closely related, suggesting that the beneficial effects of pioglitazone on blood vessels are independent of their effects on insulin sensitivity and inflammation.