title: Gemfibrozil treatment increases low-density lipoprotein particle size in Type 2 diabetes mellitus but does not alter in vitro oxidizability.
abstract: The aim of this study was to determine the effect of the lipid modifying agent gemfibrozil on lipid and coagulation risk factors in patients with Type 2 diabetes mellitus (Type 2 DM). Twenty-six subjects with Type 2 DM and dyslipidaemia were treated for 24 weeks with either gemfibrozil 600 mg orally twice daily or placebo in a double-blind randomized trial. Lipid profiles, fibrinogen, Factor VII, and plasminogen activator inhibitor-1 (PAI-1) were measured by routine laboratory methods. Low density lipoprotein (LDL) size was determined by gradient gel electrophoresis 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) and triglycerides (-2.7 (-1.55, -1.35) mmol l(-1); p < 0.001) vs placebo. The fall in triglyceride was reflected by a fall in VLDL cholesterol levels in the gemfibrozil treated group vs placebo (-1.31 mmol l(-1); p < 0.001). LDL-cholesterol level did not change but LDL particle size 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 susceptibility to copper-induced oxidation. There were no significant changes in the coagulation parameters studied. Because of its ability to correct the lipid abnormalities associated with Type 2 DM particularly hypertriglyceridaemia, gemfibrozil provides a useful therapeutic option in the management of diabetic dyslipidaemia but it does not alter in vitro oxidizability of LDL.
authors.affiliation: The University of Melbourne Department of Medicine, St Vincent's Hospital, Victoria, Australia.
authors.forename: D N
authors.initials: DN
authors.lastname: O'Neal
authors.forename: R C
authors.initials: RC
authors.lastname: O'Brien
authors.forename: K L
authors.initials: KL
authors.lastname: Timmins
authors.forename: G D
authors.initials: GD
authors.lastname: Grieve
authors.forename: K P
authors.initials: KP
authors.lastname: Lau
authors.forename: G C
authors.initials: GC
authors.lastname: Nicholson
authors.forename: M A
authors.initials: MA
authors.lastname: Kotowicz
authors.forename: J D
authors.initials: JD
authors.lastname: Best
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015248:Gemfibrozil / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D010084:Oxidation-Reduction
chemical_list: D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D015248:Gemfibrozil