非诺贝特可改善他汀类药物治疗的 2 型糖尿病患者肱动脉和前臂阻力小动脉的内皮功能。

Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated Type 2 diabetic patients.

机构信息

School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, GPO Box X2213, Perth WA 6847, Australia.

出版信息

Clin Sci (Lond). 2010 Feb 23;118(10):607-15. doi: 10.1042/CS20090568.

DOI:10.1042/CS20090568

PMID:20047560

Abstract

Dyslipidaemia contributes to endothelial dysfunction and CVD (cardiovascular disease) in Type 2 diabetes mellitus. While statin therapy reduces CVD in these patients, residual risk remains high. Fenofibrate corrects atherogenic dyslipidaemia, but it is unclear whether adding fenofibrate to statin therapy lowers CVD risk. We investigated whether fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. In a cross-over study, 15 statin-treated Type 2 diabetic patients, with LDL (low-density lipoprotein)-cholesterol <2.6 mmol/l and endothelial dysfunction [brachial artery FMD (flow-mediated dilatation) <6.0%] were randomized, double-blind, to fenofibrate 145 mg/day or matching placebo for 12 weeks, with 4 weeks washout between treatment periods. Brachial artery FMD and endothelium-independent NMD (nitrate-mediated dilatation) were measured by ultrasonography at the start and end of each treatment period. PIFBF (post-ischaemic forearm blood flow), a measure of microcirculatory endothelial function, and serum lipids, lipoproteins and apo (apolipoprotein) concentrations were also measured. Compared with placebo, fenofibrate increased FMD (mean absolute 2.1+/-0.6 compared with -0.3+/-0.6%, P=0.04), but did not alter NMD (P=0.75). Fenofibrate also increased maximal PIFBF {median 3.5 [IQR (interquartile range) 5.8] compared with 0.3 (2.1) ml/100 ml/min, P=0.001} and flow debt repayment [median 1.0 (IQR 3.5) compared with -1.5 (3.0) ml/100 ml, P=0.01]. Fenofibrate lowered serum cholesterol, triacylgycerols (triglycerides), LDL-cholesterol, apoB-100 and apoC-III (P < or = 0.03), but did not alter HDL (high-density lipoprotein)-cholesterol or apoA-I. Improvement in FMD was inversely associated with on-treatment LDL-cholesterol (r=-0.61, P=0.02) and apoB-100 (r=-0.54, P=0.04) concentrations. Fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. This may relate partly to enhanced reduction in LDL-cholesterol and apoB-100 concentrations.

摘要

血脂异常导致 2 型糖尿病患者的内皮功能障碍和心血管疾病（CVD）。虽然他汀类药物治疗可降低这些患者的 CVD 风险，但仍存在较高的残余风险。非诺贝特可纠正致动脉粥样硬化性血脂异常，但尚不清楚在他汀类药物治疗的基础上加用非诺贝特是否会降低 CVD 风险。我们研究了非诺贝特是否可改善他汀类药物治疗的 2 型糖尿病患者的内皮功能障碍。在一项交叉研究中，15 名 LDL-胆固醇<2.6 mmol/L 且内皮功能障碍[肱动脉 FMD（血流介导的扩张）<6.0%]的他汀类药物治疗的 2 型糖尿病患者，随机、双盲、接受非诺贝特 145mg/天或匹配安慰剂治疗 12 周，在治疗期间之间有 4 周洗脱期。在每个治疗期开始和结束时，通过超声测量肱动脉 FMD 和内皮非依赖性 NMD（硝酸盐介导的扩张）。还测量了前臂缺血后血流（PIFBF），这是一种微血管内皮功能的测量指标，以及血清脂质、脂蛋白和载脂蛋白（apo）浓度。与安慰剂相比，非诺贝特增加了 FMD（平均绝对增加 2.1±0.6%，而非 0.3±0.6%，P=0.04），但未改变 NMD（P=0.75）。非诺贝特还增加了最大 PIFBF[中位数 3.5（IQR（四分位间距）5.8），而非 0.3（2.1）ml/100ml/min，P=0.001]和流量债务偿还[中位数 1.0（IQR 3.5），而非-1.5（3.0）ml/100ml，P=0.01]。非诺贝特降低了血清胆固醇、三酰甘油（甘油三酯）、LDL-胆固醇、apoB-100 和 apoC-III（P≤0.03），但不改变 HDL-胆固醇或 apoA-I。FMD 的改善与治疗中的 LDL-胆固醇（r=-0.61，P=0.02）和 apoB-100（r=-0.54，P=0.04）浓度呈负相关。非诺贝特可改善他汀类药物治疗的 2 型糖尿病患者的内皮功能障碍。这可能部分与 LDL-胆固醇和 apoB-100 浓度的降低有关。