Department of Medicine, University of Hong Kong, Hong Kong.
Department of Medicine, University of Hong Kong, Hong Kong.
Atherosclerosis. 2017 Aug;263:24-28. doi: 10.1016/j.atherosclerosis.2017.05.031. Epub 2017 May 25.
Pre-β1 HDL, being a major acceptor of free cholesterol from cells, plays an important role in reverse cholesterol transport. This study was performed to determine whether abnormalities in pre-β1 HDL concentration were present in type 2 diabetes irrespective of their HDL-cholesterol levels, and the impact on cholesterol efflux.
640 type 2 diabetic patients with or without cardiovascular disease (CVD) and 360 non-diabetic controls matched for serum HDL-cholesterol levels were recruited. Plasma pre-β1 HDL was measured by ELISA, and cholesterol efflux to serum, mediated by ATP-binding cassette transporter A1 (ABCA1), was determined by measuring the transfer of [3H]cholesterol from cultured cells expressing ABCA1 to the medium containing the tested serum.
Despite the diabetic subjects having matched HDL-cholesterol and total apoA1 as controls, plasma pre-β1 HDL was significantly reduced in both male (p < 0.01) and female diabetic patients (p < 0.05), and patients with CVD had the lowest pre-β1 HDL level. Serum capacity to induce ABCA1-mediated cholesterol efflux was impaired in the diabetic group (p < 0.01) and cholesterol efflux correlated with pre-β1 HDL (Pearson's r = 0.38, p < 0.01), and this association remained significantly even after controlling for age, gender, body mass index, diabetes status, smoking, apoA1, triglyceride and LDL.
Plasma pre-β1 HDL level was significantly decreased in type 2 diabetes and was associated with a reduction in cholesterol efflux mediated by ABCA1. Our data would suggest that low pre-β1 HDL might cause impairment in reverse cholesterol transport in type 2 diabetes.
前β1 高密度脂蛋白（HDL）作为细胞内游离胆固醇的主要接受体，在胆固醇逆转运中发挥重要作用。本研究旨在确定 2 型糖尿病患者是否存在前β1 HDL 浓度异常，而不论其 HDL-胆固醇水平如何，并探讨其对胆固醇流出的影响。
本研究共纳入 640 例 2 型糖尿病合并或不合并心血管疾病（CVD）患者和 360 例按血清 HDL-胆固醇水平匹配的非糖尿病对照者。采用 ELISA 法检测血浆前β1 HDL，通过测定载脂蛋白 A1（ABCA1）介导的胆固醇从表达 ABCA1 的培养细胞转移到含有受试血清的培养基中的转移来确定胆固醇流出至血清的能力。
尽管糖尿病患者的 HDL-胆固醇和总载脂蛋白 A1 与对照组相匹配，但男性（p<0.01）和女性（p<0.05）糖尿病患者的血浆前β1 HDL 水平均显著降低，且 CVD 患者的前β1 HDL 水平最低。糖尿病组血清诱导 ABCA1 介导的胆固醇流出能力受损（p<0.01），胆固醇流出与前β1 HDL 相关（Pearson 相关系数 r=0.38，p<0.01），即使在校正年龄、性别、体重指数、糖尿病状态、吸烟、载脂蛋白 A1、甘油三酯和 LDL 后，这种相关性仍然显著。
2 型糖尿病患者的血浆前β1 HDL 水平显著降低，与 ABCA1 介导的胆固醇流出减少相关。我们的数据表明，低前β1 HDL 可能导致 2 型糖尿病患者胆固醇逆转运受损。
