Ciprofibrate reduces the postprandial generation of triglyceride-rich lipoproteins and attenuates the associated endothelial dysfunction and oxidative stress in non-insulin-dependent diabetes mellitus

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• 作者：Evans ; L.M. ; Anderson ; R.A. ; Davies ; J.S. ; Ellis ; G.R. ; Jackson ; S.K. ; Graham ; J. ; Lewis ; M.J. ; et. al.
• 刊名：Atherosclerosis
• 出版年：1999
• 期刊代码：28_00219150
• 类别：med
• 出版时间：August, 1999
• 卷：145
• 期：2
• 页码：434
• 文件大小：107 K

摘要

Introduction: Triglyceride-rich lipoproteins (TGRL) may be involved in atherogenesis by mechanisms including endothelial dysfunction and enhanced oxidative stress. Non-insulin-dependent diabetes mellitus (NIDDM) results in excess vascular disease and exaggerated excursions of postprandial TGRL. We studied the effect of fibrate therapy on the relationship between postprandial lipaemia (PPL), endothelial function (EF) and oxidative stress in NIDDM. Methods: Twenty NIDDM patients were studied following an overnight fast and 4 h after a fatty meal. Lipoproteins were separated using an iodixanol density gradient medium. Free radicals (FR) were directly measured using electron paramagnetic resonance spectroscopy. EF was assessed by measuring flow-mediated brachial artery dilatation (FMD). Subjects were randomised in a double-blind manner to 3 months of placebo (P) or ciprofibrate (C) (100 mg OD). Results (mean ± SD): Seventeen subjects completed the study. At base line, both groups exhibited similar changes in FMD [(%change) 3.8 ± 1.8%to 1.8 ± 1.3%(C) vs. 3.3 ± 1.7 to 1.7 ± 1.1%(P)]. Increase in FR [(arbitrary units) 2.9 ± 1.3 (C) vs. 3.1 ± 1.5 (P)]. Rise in plasma TG [(mmol/l) 2.8 ± 2.1 to 6.7 ± 6 (C) vs. 2.8 ± 1.7 to 7 ± 7.3 (P)] and TG enrichment of very low-density lipoprotein (VLDL) [(%TG content) 59.6 ± 4.6%to 73.4 ± 6.9%(C) vs. 61.2 ± 5.9%to 76.1 ± 9.8%(P)]. Following treatment fasting and PP, FMD improved in the treatment group with reductions in fasting and PP TG, VLDL-TG content and FR. FMD, 4.8 ± 1.1 to 3.4 ± 1.1%(C) vs. 3.4 ± 1.2 to 1.8 ± 1.1%(P) (P < 0.05). TG, 1.5 ± 0.8 to 2.8 ± 1.3 mmol/l (C) vs. 3.1 ± 2.1 to 6.6 ± 4.1(P) mmol/l (P < 0.05). VLDL-TG (%), 50.1 ± 6.2 to 59.5 ± 4.3%(C) vs. 60.6 ± 3.9 to 72.9 ± 6.9%(P) (P < 0.05). FR, 0.3 ± 0.6 (C) vs. 1.1 ± 0.9 (P) (P < 0.05). Conclusions: This study demonstrates that ciprofibrate may reduce the risk of vascular disease in NIDDM by mechanisms involving improved EF, attenuated PPL, enhanced catabolism of TGRL and reduced FR release.