Ezetimibe beneficially influences fasting and postprandial triglyceride-rich lipoproteins in type 2 diabetes
Ezetimibe beneficially influences fasting and postprandial triglyceride-rich lipoproteins in type 2 diabetes
复制标题
DOI：
10.1016/j.atherosclerosis.2011.03.012
复制
发表时间：
2011-07-01
期刊：
影响因子：
5.3
通讯作者：
Rivellese, Angela A.
中科院分区：
文献类型：
--
作者：
Bozzetto, Lutgarda;Annuzzi, Giovanni;Rivellese, Angela A.
简介：2型糖尿病与餐后富含甘油三酯的脂蛋白的致动脉粥样硬化异常有关。本研究评估依折麦布是否通过抑制肠道胆固醇吸收影响空腹和标准餐后的乳糜微粒和VLDL颗粒。通过双盲交叉设计，15例2型糖尿病和高胆固醇血症受试者随机接受依折麦布10 mg +辛伐他汀20 mg（埃泽+ S）或安慰剂+辛伐他汀20 mg（P + S）治疗6周6周洗脱期后，交叉至另一种治疗（NCT 00699023）。在每个阶段结束时，血浆和脂蛋白组分中的脂质、apoB-48和apoB-100浓度（通过不连续密度梯度超离心分离）在高脂肪测试餐之前和之后6小时内测定。与P + S相比，埃泽+ S可诱导：（a）除LDL胆固醇水平显著降低外，（B）乳糜微粒脂质含量在空腹和餐后均显著降低（4.4 +/- 2.7对比8.3 +/- 8.7 mg/dl x 6 h总AUC，胆固醇，p < 0.05; 6小时甘油三酯浓度为18 +/- 12 vs. 29 +/- 24 mg/dl，p < 0.05），（c）乳糜微粒餐后apoB-48显著降低（0.03 +/- 0.03对0.09 +/- 0.08 mg/l，4小时，p < 0.05），和（d）VLDL、IDL和LDL的胆固醇含量的空腹和餐后显著降低，结论：与辛伐他汀单独治疗相比，依折麦布和辛伐他汀联合治疗6周对2型糖尿病患者空腹和餐后脂蛋白谱产生积极影响，有利于产生低胆固醇乳糜微粒和VLDL颗粒，这些颗粒具有较低的致动脉粥样硬化潜力。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Introduction: Type 2 diabetes is associated with atherogenic abnormalities of postprandial triglyceride-rich lipoproteins. This study evaluated whether ezetimibe, by inhibiting intestinal cholesterol absorption, influences chylomicrons and VLDL particles at fasting and after a standard meal.Methods: By a double blind cross-over design 15 subjects with type 2 diabetes and hypercholesterolaemia followed in random order a 6-week treatment with ezetimibe 10 mg + simvastatin 20 mg (EZE + S) or placebo + simvastatin 20 mg (P + S) and, after a 6-week wash-out period, crossed over to the other treatment (NCT00699023). At the end of each period lipids, apoB-48, and apoB-100 concentrations in plasma and lipoprotein fractions (separated by discontinuous density gradient ultracentrifugation) were determined before and over 6 h following a high-fat test meal.Results: Compared with P + S, EZE + S induced, (a) beside a greater decrease in LDL cholesterol, (b) a significant decrease in chylomicron lipid content both at fasting and postprandially (4.4 +/- 2.7 vs. 8.3 +/- 8.7 mg/dl x 6 h total AUC for cholesterol, p < 0.05; 18 +/- 12 vs. 29 +/- 24 mg/dl triglyceride concentrations at 6 h, p < 0.05), (c) a significant decrease in chylomicron postprandial apoB-48 (0.03 +/- 0.03 vs. 0.09 +/- 0.08 mg/l at 4 h, p < 0.05), and (d) significant fasting and postprandial decreases in the cholesterol content of VLDL, IDL, and LDL, as shown by the significant reduction of the cholesterol/triglyceride ratio in these lipoproteins.Conclusions: A 6-week treatment with ezetimibe and simvastatin, compared to simvastatin alone, positively influences lipoprotein profile both at fasting and postprandially in type 2 diabetic patients by favouring the production of cholesterol-poor chylomicrons and VLDL particles that have less atherogenic potential. (C) 2011 Elsevier Ireland Ltd. All rights reserved.