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阿托伐他汀对糖尿病患者及2型糖尿病高危人群内皮功能的影响。

The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes.

作者信息

Economides Panayiotis A, Caselli Antonella, Tiani Elizabeth, Khaodhiar Lalita, Horton Edward S, Veves Aristidis

机构信息

Joslin Diabetes Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston Massachusetts 02215, USA.

出版信息

J Clin Endocrinol Metab. 2004 Feb;89(2):740-7. doi: 10.1210/jc.2003-031116.

Abstract

We have investigated the effect of atorvastatin on the endothelial function of patients with diabetes and subjects at risk for type 2 diabetes in a 12-wk, prospective, randomized, placebo-controlled, double-blind clinical trial. The flow- mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (endothelium independent) in the brachial artery and the vascular reactivity at the forearm skin were measured. FMD improved in the atorvastatin-treated, at-risk subjects [median (25-75 percentile), 7.2% (2.9-9.6%) at exit visit vs. 6.6% (2.9-9.5%) at baseline; P < 0.05]. A similar improvement of FMD was found in atorvastatin-treated diabetic patients [median (25-75 percentile), 5.6 (3.9-7.9) at exit visit vs. 4.2 (3.2-7.2) at baseline; P = 0.07]. No changes were observed in nitroglycerin-induced dilation and the microcirculation reactivity measurements in either group. In the at-risk group, there was a decrease in the C-reactive protein [median (25-75 percentile), 0.12 mg/dl (0.07-0.27 mg/dl) at exit visit vs. 0.24 mg/dl (0.07-0.35 mg/dl) at baseline; P < 0.05] and TNF alpha [median (25-75 percentile), 2.6 pg/ml (1.8-4.1 pg/ml) at exit visit vs. 4.4 pg/ml (3.6-6.0 pg/ml) at baseline; P < 0.05] in the atorvastatin-treated patients, whereas in the diabetes group, a decrease in endothelin-1 (mean +/- SD, 0.97 +/- 0.29 pg/ml at exit visit vs. 1.19 +/- 0.42 pg/ml at baseline; P < 0.05) and plasminogen activator inhibitor-1 [median (25-75 percentile), 18 ng/ml (9-24 ng/ml) at exit visit vs. 27 ng/ml (7-41 ng/ml) at baseline; P < 0.05] were observed. We conclude that atorvastatin improves endothelial function and decreases levels of markers of endothelial activation and inflammation.

摘要

我们在一项为期12周的前瞻性、随机、安慰剂对照、双盲临床试验中,研究了阿托伐他汀对糖尿病患者及2型糖尿病高危人群内皮功能的影响。测量了肱动脉的血流介导的血管舒张功能(FMD;内皮依赖性)、硝酸甘油诱导的血管舒张功能(内皮非依赖性)以及前臂皮肤的血管反应性。在接受阿托伐他汀治疗的高危人群中,FMD有所改善[末次访视时中位数(第25 - 75百分位数)为7.2%(2.9 - 9.6%),基线时为6.6%(2.9 - 9.5%);P < 0.05]。在接受阿托伐他汀治疗的糖尿病患者中也发现了类似的FMD改善[末次访视时中位数(第25 - 75百分位数)为5.6(3.9 - 7.9),基线时为4.2(3.2 - 7.2);P = 0.07]。两组中硝酸甘油诱导的血管舒张功能及微循环反应性测量均未观察到变化。在高危组中,接受阿托伐他汀治疗的患者C反应蛋白降低[末次访视时中位数(第25 - 75百分位数)为0.12 mg/dl(0.07 - 0.27 mg/dl),基线时为0.24 mg/dl(0.07 - 0.35 mg/dl);P < 0.05],肿瘤坏死因子α也降低[末次访视时中位数(第25 - 75百分位数)为2.6 pg/ml(1.8 - 4.1 pg/ml),基线时为4.4 pg/ml(3.6 - 6.0 pg/ml);P < 0.05],而在糖尿病组中,内皮素 - 1降低(末次访视时均值±标准差为0.9±0.29 pg/ml,基线时为1.19±0.42 pg/ml;P < 0.05),纤溶酶原激活物抑制剂 - 1也降低[末次访视时中位数(第25 - 75百分位数)为18 ng/ml(9 - 24 ng/ml),基线时为27 ng/ml(7 - 41 ng/ml);P < 0.05]。我们得出结论,阿托伐他汀可改善内皮功能,并降低内皮激活和炎症标志物水平。

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