阿托伐他汀降低2型糖尿病患者含载脂蛋白B脂蛋白和高密度脂蛋白中的载脂蛋白C-III：一种降低血浆甘油三酯的潜在机制。

Atorvastatin decreases apolipoprotein C-III in apolipoprotein B-containing lipoprotein and HDL in type 2 diabetes: a potential mechanism to lower plasma triglycerides.

作者信息

Dallinga-Thie Geesje M, Berk-Planken Ingrid I L, Bootsma Aart H, Jansen Hans

机构信息

Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.

出版信息

Diabetes Care. 2004 Jun;27(6):1358-64. doi: 10.2337/diacare.27.6.1358.

DOI:10.2337/diacare.27.6.1358

PMID:15161788

Abstract

OBJECTIVE

Apolipoprotein (apo)C-III is a constituent of HDL (HDL apoC-III) and of apoB-containing lipoproteins (LpB:C-III). It slows the clearance of triglyceride-rich lipoproteins (TRLs) by inhibition of the activity of the enzyme lipoprotein lipase (LPL) and by interference with lipoprotein binding to cell-surface receptors. Elevated plasma LpB:C-III is an independent risk factor for cardiovascular disease. We studied the effect of atorvastatin on plasma LpB:C-III and HDL apoC-III.

RESEARCH DESIGN AND METHODS

We studied the effect of 30 weeks' treatment with 10 and 80 mg atorvastatin on plasma apoC-III levels in a randomized, double-blind, placebo-controlled trial involving 217 patients with type 2 diabetes and fasting plasma triglycerides between 1.5 and 6.0 mmol/l.

RESULTS

Baseline levels of total plasma apoC-III, HDL apoC-III, and LpB:C-III were 41.5 +/- 10.0, 17.7 +/- 5.5, and 23.8 +/- 7.7 mg/l, respectively. Plasma apoC-III was strongly correlated with plasma triglycerides (r = 0.74, P < 0.001). Atorvastatin 10- and 80-mg treatment significantly decreased plasma apoC-III (atorvastatin 10 mg, 21%, and 80 mg, 27%), HDL apoC-III (atorvastatin 10 mg, 22%, and 80 mg, 28%) and LpB:C-III (atorvastatin 10 mg, 23%, and 80 mg, 28%; all P < 0.001). The decrease in plasma apoC-III, mainly in LpB:C-III, strongly correlated with a decrease in triglycerides (atorvastatin 10 mg, r = 0.70, and 80 mg, r = 0.78; P < 0.001). Atorvastatin treatment also leads to a reduction in the HDL apoC-III-to-HDL cholesterol and HDL apoC-III-to-apoA-I ratios, indicating a change in the number of apoC-III per HDL particle (atorvastatin 10 mg, -21%, and 80 mg, -31%; P < 0.001).

CONCLUSIONS

Atorvastatin treatment resulted in a significant dose-dependent reduction in plasma apoC-III, HDL apoC-III, and LpB:C-III levels in patients with type 2 diabetes. These data indicate a potentially important antiatherogenic effect of statin treatment and may explain (part of) the triglyceride-lowering effect of atorvastatin.

摘要

目的

载脂蛋白（apo）C-III是高密度脂蛋白（HDL apoC-III）和含apoB脂蛋白（LpB:C-III）的组成成分。它通过抑制脂蛋白脂肪酶（LPL）的活性以及干扰脂蛋白与细胞表面受体的结合，减缓富含甘油三酯脂蛋白（TRL）的清除。血浆LpB:C-III升高是心血管疾病的独立危险因素。我们研究了阿托伐他汀对血浆LpB:C-III和HDL apoC-III的影响。

研究设计与方法

在一项随机、双盲、安慰剂对照试验中，我们研究了10毫克和80毫克阿托伐他汀治疗30周对217例2型糖尿病且空腹血浆甘油三酯在1.5至6.0毫摩尔/升之间患者血浆apoC-III水平的影响。

结果

血浆总apoC-III、HDL apoC-III和LpB:C-III的基线水平分别为41.5±10.0、17.7±5.5和23.8±7.7毫克/升。血浆apoC-III与血浆甘油三酯密切相关（r = 0.74，P < 0.001）。10毫克和80毫克阿托伐他汀治疗显著降低了血浆apoC-III（10毫克阿托伐他汀降低21%，80毫克降低27%）、HDL apoC-III（10毫克阿托伐他汀降低22%，80毫克降低28%）和LpB:C-III（10毫克阿托伐他汀降低23%，80毫克降低28%；所有P < 0.001）。血浆apoC-III的降低，主要是LpB:C-III的降低，与甘油三酯的降低密切相关（10毫克阿托伐他汀，r = 0.70；80毫克阿托伐他汀，r = 0.78；P < 0.001）。阿托伐他汀治疗还导致HDL apoC-III与HDL胆固醇以及HDL apoC-III与apoA-I的比值降低，表明每个HDL颗粒中apoC-III数量的变化（10毫克阿托伐他汀降低-21%，80毫克降低-31%；P < 0.001）。