(Circulation. 2000;101:1773.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Ciprofibrate Therapy Improves Endothelial Function and Reduces Postprandial Lipemia and Oxidative Stress in Type 2 Diabetes Mellitus
From the Cardiovascular Sciences Research Group, University Hospital of Wales, Cardiff (M.E., R.A.A., G.R.E., S.D., S.K.J., M.J.L., M.P.F., A.R.); Department of Biomedical Sciences, University of Wales Institute, Cardiff (K.M.); and Department of Biochemistry, Liverpool John Moores University, Liverpool, UK (J.G.).
Correspondence to Dr L.M. Evans, Department of Diabetes and Endocrinology, C/O Ward B7, University Hospital of Wales, Heath Park, Cardiff, Wales CF4 4XW. E-mail morgancl{at}cf.ac.uk
Background—Exaggerated postprandial lipemia (PPL) is a factor in atherogenesis, involving endothelial dysfunction and enhanced oxidative stress. We examined the effect of ciprofibrate therapy on these parameters in type 2 diabetes mellitus.
Methods and Results—Twenty patients entered a 3-month, double-blind, placebo-controlled study. Each subject was studied fasting and after a fatty meal, at baseline, and after 3 months of treatment. Glucose and lipid profiles were measured over an 8-hour postprandial period. Endothelial function (flow-mediated endothelium-dependent vasodilatation [FMD]) and oxidative stress (electron paramagnetic resonance spectroscopy) were measured after fasting and 4 hours postprandially. At baseline, both groups exhibited similar PPL and deterioration in endothelial function. After ciprofibrate, fasting and postprandial FMD values were significantly higher (from 3.8±1.8% and 1.8±1.3% to 4.8±1.1% and 3.4±1.1%; P<0.05). This was mirrored by a fall in fasting and postprandial triglycerides (3.1±2.1 and 6.6±4.1 mmol/L to 1.5±0.8 and 2.8±1.3 mmol/L, P<0.05). Fasting and postprandial HDL cholesterol was also elevated (0.9±0.1 and 0.8±0.1 mmol/L and 1.2±0.2 and 1.2±0.1 mmol/L, P<0.05). There were no changes in total or LDL cholesterol. Fasting and postprandial triglyceride enrichment of all lipoproteins was attenuated, with cholesterol depletion of VLDL and enrichment of HDL. There were similar postprandial increases in oxidative stress in both groups at baseline, which was significantly attenuated by ciprofibrate (0.3±0.6 versus 1.5±1.1 U, P<0.05).
Conclusions—This study demonstrates that fibrate therapy improves fasting and postprandial endothelial function in type 2 diabetes. Attenuation of PPL and the associated oxidative stress, with increased HDL cholesterol levels, may be important.
Key Words: diabetes mellitus • lipemia • endothelium • stress
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