烟酸缓释剂对 2 型糖尿病合并他汀类药物治疗的男性患者餐后脂蛋白 (a) 和载脂蛋白 B-100 脂蛋白代谢的影响。
Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus.
机构信息
From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
出版信息
Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2686-93. doi: 10.1161/ATVBAHA.115.306136. Epub 2015 Oct 29.
OBJECTIVE
The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration.
APPROACH AND RESULTS
The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL, -49.8%; intermediate-density lipoprotein, -44.7%; LDL, -46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%).
CONCLUSIONS
In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.
目的
在一项为期 12 周的随机交叉试验中，研究了缓释烟酸（ERN；1-2g/d）对 11 名接受他汀类药物治疗的 2 型糖尿病白人男性脂蛋白（a）（Lp(a)）和载脂蛋白（apo）B-100 代谢的影响。
方法和结果
通过静脉内给予 D3-亮氨酸、气相色谱-质谱联用和房室模型，在标准化口服脂肪负荷（87%脂肪）后，确定 Lp(a)和极低密度脂蛋白（VLDL）、中间密度脂蛋白和低密度脂蛋白（LDL）apoB-100 的动力学。ERN 显著降低空腹血浆总胆固醇、LDL 胆固醇和甘油三酯浓度。这些作用是在体重或胰岛素抵抗无显著变化的情况下实现的。ERN 显著降低血浆 Lp(a)浓度（-26.5%）和 apo(a)的产生率（-41.5%）和 Lp(a)-apoB-100（-32.1%）；在 Lp(a)浓度升高的个体中效果更大。ERN 显著降低 VLDL（-58.7%）、中间密度脂蛋白（-33.6%）和 LDL（-18.3%）apoB-100 浓度和相应的产生率（VLDL，-49.8%；中间密度脂蛋白，-44.7%；LDL，-46.1%）。VLDL apoB-100 颗粒的分泌数量增加了对口服脂肪负荷的反应。尽管如此，ERN 还是显著减少了 10 小时餐后期间的总 VLDL apoB-100 产生（-21.9%）。
结论
在接受他汀类药物治疗的 2 型糖尿病男性中，ERN 通过减少 apo(a)和 Lp(a)-apoB-100 的产生来降低血浆 Lp(a)浓度。ERN 还通过减少 VLDL 产生和这些颗粒从 VLDL 到 LDL 级联的转运来降低载脂蛋白 B-100 脂蛋白的浓度。我们的研究为 ERN 的脂质调节作用提供了进一步的机制见解。
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