GEMFIBROZIL TREATMENT INCREASES LOW-DENSITY-LIPOPROTEIN PARTICLE-SIZEIN TYPE-2 DIABETES-MELLITUS BUT DOES NOT ALTER IN-VITRO OXIDIZABILITY

The aim of this study was to determine the effect of the lipid modifyi ng agent gemfibrozil on lipid and coagulation risk factors in patients with Type 2 diabetes mellitus (Type 2 DM). Twenty-six subjects with T ype 2 DM and dyslipidaemia were treated for 24 weeks with either gemfi brozil 600 mg orally twice daily or placebo in a double-blind randomiz ed trial. Lipid profiles, fibrinogen, Factor VII, and plasminogen acti vator inhibitor-1 (PAI-1) were measured by routine laboratory methods. Low density lipoprotein (LDL) size was determined by gradient gel ele ctrophoresis and the resistance of LDL to copper-induced oxidation was assessed by measuring absorbance at 234 nm. Gemfibrozil significantly reduced total cholesterol (-0.9 (-0.48, -1.32) mmol l(-1); p <0.05) a nd triglycerides (-2.7 (-1.55, -1.35) mmol l (1); p < 0.001) vs placeb o. The fall in triglyceride was reflected by a fall in VLDL cholestero l levels in the gemfibrozil treated group vs placebo (-1.31 mmol I (1) ; p < 0.001). LDL-cholesterol level did not change but LDL particle si ze increased by 0.5 nm (0.01, 0.93); P <0.02. The increase in particle size was inversely correlated with the change of triglyceride level ( r = -0.79, p < 0.0001) but did not result in any reduction of suscepti bility to copper-induced oxidation. There were no significant changes in the coagulation parameters studied. Because of its ability to corre ct the lipid abnormalities associated with Type 2 DM particularly hype rtriglyceridaemia, gemfibrozil provides a useful therapeutic option in the management of diabetic dyslipidaemia but it does not alter in vit ro oxidizability of LDL. (C) 1998 John Wiley & Sons, Ltd.