吡格列酮对代谢综合征糖耐量异常患者血管内皮功能的影响

Effects of Pioglitazone on endothelial function in patients with metabolic syndrome

目的:研究吡格列酮对罹患多重心血管危险因素的非糖尿病的代谢综合征(metabolic syndrome,MS)糖耐量异常患者血管内皮功能的影响。方法:162例患MS的受试者入选并最终完成本研究,根据胰岛素敏感度指数检测(quantitative insulin sensitivity check index,QUICKI)甄别受试者胰岛素敏感性,分为胰岛素敏感组和抵抗组,患者接受基础治疗外加用吡格列酮治疗8周,45 mg/d,设立安慰剂对照组。进行血管内皮功能一氧化氮(nitric oxide,NO)和QUICKI、高敏C反应蛋白(high sensitive C-reactive protein,hs-CRP)及体内氧化水平[丙二醛(malondialdehyde,MDA);还原型谷胱甘肽(reduced glutathione,GSH)]检测。结果:吡格列酮治疗组QUICKI增加(P<0.01);NO显著上升(P<0.01);hs-CRP降低(P<0.01);MDA水平降低(P<0.01),GSH轻度升高(P>0.05)。胰岛素抵抗组干预后部分患者胰岛素抵抗改善,未改善者的NO,MDA,hs-CRP也有显著改善(P<0.01)。结论:吡格列酮干预能提高MS病患者体内胰岛素敏感性,显著改善血管内皮功能,但吡格列酮治疗的血管益处并非完全依赖其对胰岛素敏感性的影响,也与其抗炎、抗氧化作用有关。

Objective： Endothelial dysfunction plays a key role in the pathogenesis of the atherosclerosis.Pioglitazone has been shown to exert multiple antiatherosclerotic actions in diabetic patients.This study examined whether Pioglitazone improves endothelial function in metabolic syndromic patients with impaired glucose tolerance.Methods： The study had a double-blind,placebo-controlled design.Insulin sensitivity was assessed by the Quantitative Insulin Sensitivity Check Index（QUICKI）,and 162 patients were further classified as insulin sensitive or insulin resistant group.The subjects reveived standard medicine therapy were treated with or without Pioglitazone（45 mg/d） for 8 weeks.All patients were subjected to following assessments： the serum levels of nitric oxide（NO）,malondialdehyde（MDA）,reduced glutathione（GSH） and high sensitive C-reactive protein（hs-CRP）.Results： Treatment with Pioglitazone significantly improved insulin sensitivity（QUICKI,P0.01） and the plasma levels of NO（P0.01）,MDA（P0.01） and hs-CRP（P0.01） in patients with metabolic syndrome.Importantly,the forementioned parameters were still improved in a subgroup of which QUICKI was less than 0.34（the insulin-resistent group）（P0.01）.Conclusion： In metabolic syndromic patients with impaired glucose tolerance,Pioglitazone treatment enhances insulin sensitivity,inhibits inflammation,lowers oxidation in vivo and improves endothelial function.These effects do not appear to be closely related,suggesting that Pioglitazone may have beneficial vascular properties independent of its effect on insulin sensitivity.