吡格列酮对冠心病合并新发2型糖尿病患者内皮功能、胰岛素敏感性及血糖控制的影响。

Effects of pioglitazone on endothelial function, insulin sensitivity, and glucose control in subjects with coronary artery disease and new-onset type 2 diabetes.

作者信息

Sourij Harald, Zweiker Robert, Wascher Thomas C

机构信息

Department of Internal Medicine, Metabolism and Vascular Biology Unit, Medical University of Graz, Auenbruggerpl. 15, A-8036 Graz, Austria.

出版信息

Diabetes Care. 2006 May;29(5):1039-45. doi: 10.2337/diacare.2951039.

DOI:10.2337/diacare.2951039

PMID:16644634

Abstract

OBJECTIVE

About one of five patients with coronary artery disease (CAD) suffers from previously unknown, predominantly postprandial type 2 diabetes. In the process of atherogenesis and the subsequent increased cardiovascular mortality of diabetic patients, endothelial dysfunction is suspected to play an important role, and it is observed in diabetic as well as insulin-resistant states. Thus, the aim of our study was to investigate the effect of pioglitazone on endothelial dysfunction, insulin sensitivity, and glucose control in newly detected type 2 diabetic patients with CAD.

RESEARCH DESIGN AND METHODS

We investigated 42 patients (39 men and 3 women, age 60.25 +/- 7.5 years, HbA1c 6.1 +/- 0.5%) with manifest CAD and newly detected type 2 diabetes. A randomized, double-blind, placebo-controlled, parallel study with pioglitazone (30 mg/day for 12 weeks) was performed. At study entry and end, we performed an oral glucose tolerance test and measurements of endothelial dysfunction by photoplethysmographic pulse wave analysis.

RESULTS

Endothelial dysfunction was severely impaired at baseline in both groups. After 12 weeks, endothelial dysfunction was significantly better in the pioglitazone group (change of reflection index 6.5 +/- 5.1 vs. 1.6 +/- 2.9%, P = 0.002) compared with placebo. Insulin sensitivity, as assessed by homeostasis model assessment (2.20 +/- 1.62 vs. 3.61 +/- 1.87, P = 0.01), or the change of insulin sensitivity index from baseline to study end (0.021 +/- 0.023 vs. -0.003 +/- 0.012 micromol x kg(-1) x min(-1) per pmol/l, P = 0.0001) and beta-cell function (57.42 +/- 49.86 vs. 21.78 +/- 18.54 mU/l per mmol/l, P = 0.0014) significantly improved in the pioglitazone group, with no change observed after placebo.

CONCLUSIONS

Pioglitazone improves endothelial dysfunction independently from the observed benefits on insulin sensitivity and beta-cell function in patients with newly diagnosed type 2 diabetes and CAD.

摘要

目的

约五分之一的冠心病（CAD）患者患有此前未知的、主要为餐后发作的2型糖尿病。在动脉粥样硬化形成过程以及随后糖尿病患者心血管死亡率增加的过程中，内皮功能障碍被怀疑起着重要作用，并且在糖尿病以及胰岛素抵抗状态中均有观察到。因此，我们研究的目的是调查吡格列酮对新诊断的患有CAD的2型糖尿病患者内皮功能障碍、胰岛素敏感性和血糖控制的影响。

研究设计与方法

我们调查了42例患有明显CAD且新诊断为2型糖尿病的患者（39名男性和3名女性，年龄60.25±7.5岁，糖化血红蛋白6.1±0.5%）。进行了一项使用吡格列酮（30毫克/天，持续12周）的随机、双盲、安慰剂对照、平行研究。在研究开始和结束时，我们进行了口服葡萄糖耐量试验，并通过光电容积脉搏波分析测量内皮功能障碍。

结果

两组在基线时内皮功能障碍均严重受损。12周后，与安慰剂相比，吡格列酮组的内皮功能障碍明显改善（反射指数变化6.5±5.1%对1.6±2.9%，P = 0.002）。通过稳态模型评估评估的胰岛素敏感性（2.20±1.62对3.61±1.87，P = 0.01），或从基线到研究结束时胰岛素敏感性指数的变化（0.021±0.023对-0.003±0.012微摩尔·千克-1·分钟-1每皮摩尔/升，P = 0.0001）以及β细胞功能（57.42±49.86对21.78±18.54毫国际单位/升每毫摩尔/升，P = 0.0014）在吡格列酮组中显著改善，安慰剂组未观察到变化。