In type 2 diabetes, rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glucose control
In type 2 diabetes, rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glucose control
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DOI：
10.2337/diacare.27.2.484
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发表时间：
2004-02-01
期刊：
影响因子：
16.2
通讯作者：
Gross, P
中科院分区：
文献类型：
--
作者：
Pistrosch, F;Passauer, J;Gross, P
目的-胰岛素抵抗是动脉硬化和心血管死亡的独立危险因素.然而，胰岛素抵抗导致动脉硬化的机制尚不清楚。可以想象，可能涉及内皮功能障碍。因此，我们问是否治疗胰岛素抵抗改善任何内皮dysfunctions.RESEARCH设计和方法-我们进行了一项双盲交叉试验的12例患者最近诊断为2型糖尿病。他们接受罗格列酮4 mg b.i.d.治疗。治疗12周，那格列奈60 mg b.i.d.以随机顺序持续相同的周数。为了评估内皮功能障碍的程度，我们使用静脉闭塞体积描记法。我们研究了血管舒张反应乙酰胆碱（ACh）与和无外源性胰岛素。将药剂注入肱动脉。此外，我们还通过正葡萄糖钳夹技术测定了胰岛素抵抗。与那格列奈相比，罗格列酮改善了60%的胰岛素抵抗。在使用rosightazone治疗后，ACh反应显著增加（使用rosightazone和那格列奈后，最大前臂血流量分别为12.8 ± 1.3 ml/100 ml和8.8 ± 1.3 ml/100 ml; P < 0.05），但未达到健康对照组的水平（14.0 ± 0.7 ml/100 ml）。罗格列酮组同时输注外源性胰岛素进一步增加ACh反应。一氧化氮合酶拮抗剂N-单甲基-L-精氨酸-乙酸酯（L-NMMA）在很大程度上阻止了rosightazone后增加的血管舒张，无论是否存在胰岛素。胰岛素敏感性和血流反应相关（P < 0.01）。结论：胰岛素抵抗是2型糖尿病内皮功能障碍的主要原因。内皮功能障碍和胰岛素抵抗都可以通过罗格列酮治疗。
OBJECTIVE - Insulin resistance is an independent risk factor for arteriosclerosis and cardiovascular mortality. However, the mechanism by which insulin resistance contributes to arteriosclerosis is unknown. Conceivably, endothelial dysfunction could be involved. Therefore, we asked whether therapy for insulin resistance ameliorates any endothelial dysfunction.RESEARCH DESIGN AND METHODS - We performed a double-blind cross-over trial of 12 patients with recently diagnosed type 2 diabetes. They received rosiglitazone 4 mg b.i.d. for 12 weeks and nateglinide 60 mg b.i.d. for the same number of weeks in random order. To assess the degree of endothelial dysfunction, we used venous occlusion plethysmography. We studied vasodilation in response to acetylcholine (ACh) with and without exogenous insulin. The agents were infused into the brachial artery. Furthermore, we determined insulin resistance by euglycemic clamp.RESULTS - Glycemic control was comparable under rosiglitazone and nateglinide. Rosiglitazone ameliorated insulin resistance by 60% compared with nateglinide. ACh response was significantly increased after rosightazone treatment (maximum forearm blood flow 12.8 +/- 1.3 vs. 8.8 +/- 1.3 ml/100 ml after rosightazone and nateglinide, respectively; P < 0.05) but did not attain the level of healthy control subjects (14.0 +/- 0.7 ml/100 ml). Coinfusion of exogenous insulin increased ACh response further in the rosiglitazone group. N-monomethyl-L-arginine-acetate (L-NMMA), an antagonist of nitric oxide synthase, largely prevented the increased vasodilation after rosightazone, regardless of the presence or absence of insulin. Insulin sensitivity and blood flow response were found to be correlated (P < 0.01).CONCLUSIONS - Insulin resistance is a major contributor toward endothelial dysfunction in type 2 diabetes. Both endothelial dysfunction and insulin resistance are amenable to treatment by rosiglitazone.