载脂蛋白 B-48 作为 2 型糖尿病肥胖患者内皮功能的决定因素：非诺贝特治疗的影响。

Apolipoprotein B-48 as a determinant of endothelial function in obese subjects with type 2 diabetes mellitus: effect of fenofibrate treatment.

机构信息

Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.

出版信息

Atherosclerosis. 2012 Apr;221(2):484-9. doi: 10.1016/j.atherosclerosis.2012.01.029. Epub 2012 Jan 26.

DOI:10.1016/j.atherosclerosis.2012.01.029

PMID:22341868

Abstract

OBJECTIVE

Elevated triglyceride-rich lipoproteins may contribute to endothelial dysfunction in obese diabetic subjects. We investigated the association between plasma concentrations of chylomicron-related particles and endothelial function, and the corresponding responses to fenofibrate treatment.

METHODS

Plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol concentrations were measured in 28 obese subjects with T2DM. Flow-mediated endothelium-dependent dilation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) in the brachial artery during reactive hyperaemia were examined by high-resolution ultrasound technique.

RESULTS

In univariate analysis, plasma apoB-48 and RLP-cholesterol concentrations were inversely associated with brachial artery FMD (r = -0.425 and -0.423, respectively, P<0.05), but not with GTNMD. In regression models including BMI and HOMA score, plasma apoB-48 was an independent predictors (P<0.05) of brachial artery FMD (β coefficient = -0.384). Replacing HOMA-IR score with plasma triglyceride, adiponectin or CRP concentrations did not alter the findings. The subjects were then randomized to a 12-week treatment period of either 200mg micronized fenofibrate or matching placebo. Compared with the placebo group, fenofibrate treatment (200mg daily for 12 weeks) achieved significant increase in FMD (+34%) and reduction in plasma triglyceride (-42%), apoB-48 (-52%) and RLP-cholesterol (-51%) concentrations. The increase in FMD with fenofibrate was significantly associated with the corresponding decrease in plasma apoB-48 (r = -0.644, P<0.02) concentrations.

CONCLUSIONS

Our findings demonstrate an association between changes in lipid metabolism and improvement in endothelial function in patients with diabetic dyslipidaemia treated with fenofibrate that may involve the effect of apoB-48 on endothelium-dependent vasodilator function.

摘要

目的

富含甘油三酯的脂蛋白升高可能导致肥胖糖尿病患者的内皮功能障碍。我们研究了乳糜微粒相关颗粒的血浆浓度与内皮功能之间的关系，以及它们对非诺贝特治疗的相应反应。

方法

在 28 例 T2DM 肥胖患者中测量了血浆载脂蛋白（apo）B-48 和残粒样颗粒（RLP）-胆固醇浓度。肱动脉反应性充血期间，采用高分辨率超声技术检测血流介导的内皮依赖性扩张（FMD）和甘油三酯介导的扩张（GTNMD）。

结果

在单因素分析中，血浆 apoB-48 和 RLP-胆固醇浓度与肱动脉 FMD 呈负相关（r=-0.425 和-0.423，分别，P<0.05），但与 GTNMD 无关。在包括 BMI 和 HOMA 评分的回归模型中，血浆 apoB-48 是肱动脉 FMD 的独立预测因子（P<0.05）（β系数=-0.384）。用血浆甘油三酯、脂联素或 CRP 浓度替代 HOMA-IR 评分不会改变研究结果。然后，将这些患者随机分为接受 12 周 200mg 微粒化非诺贝特或匹配安慰剂治疗的两组。与安慰剂组相比，非诺贝特治疗（每天 200mg，持续 12 周）可显著增加 FMD（增加 34%），降低血浆甘油三酯（减少 42%）、apoB-48（减少 52%）和 RLP-胆固醇（减少 51%）浓度。非诺贝特治疗时 FMD 的增加与血浆 apoB-48 浓度的相应降低显著相关（r=-0.644，P<0.02）。