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 atherogenesis, involving endothelial dysfunction and enhanced oxidative stress. We examined the effect of ciprofibrate therapy on these parameters in type 2 diabetes mellitus.


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.
Evans
M
M
Cardiovascular Sciences Research Group, University Hospital of Wales, Cardiff, UK. morgancl@cf.ac.uk
Anderson
R A
RA
Graham
J
J
Ellis
G R
GR
Morris
K
K
Davies
S
S
Jackson
S K
SK
Lewis
M J
MJ
Frenneaux
M P
MP
Rees
A
A
D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D008076:Cholesterol, HDL / Q000097:blood; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D058607:Fibric Acids; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D008055:Lipids; D014280:Triglycerides; D002995:Clofibric Acid; C019304:ciprofibrate