Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus

Background-Exaggerated postprandial lipemia (PPL) is a factor in atherogene sis, involving endothelial dysfunction and enhanced oxidative stress. We ex amined the effect of ciprofibrate therapy on these parameters in type 2 dia betes mellitus. Methods and Results-Twenty patients entered a 3-month, double-blind, placeb o-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 (flo w-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 t o 1.5+/-0.8 and 2.8+/-1.3 mmol/L, P<0.05). Fasting and postprandial HDL cho lesterol was also elevated (0.9+/-0.1 and 0.8+/-0.1 mmol/L and 1.2+/-0.2 an d 1.2+/-0.1 mmol/L, P<0.05). There were no changes in total or LDL choleste rol. Easting and postprandial triglyceride enrichment of all lipoproteins w as attenuated, with cholesterol depletion of VLDL and enrichment of HDL. Th ere 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 a nd postprandial endothelial function in type 2 diabetes. Attenuation of PPL and the associated oxidative stress, with increased HDL cholesterol levels , may be important.