title: Comparison of effects of simvastatin alone versus fenofibrate alone versus simvastatin plus fenofibrate on lipoprotein subparticle profiles in diabetic patients with mixed dyslipidemia (from the Diabetes and Combined Lipid Therapy Regimen study).
abstract: Diabetes mellitus is a strong risk factor for atherosclerosis and is often characterized by dyslipidemia. Besides acting on traditional lipids, statins and fibrates may also exert beneficial effects on various pro- and antiatherogenic lipid subparticles. This analysis was undertaken to evaluate combination therapy on lipid subparticles in the Diabetes and Combined Lipid Therapy Regimen (DIACOR) study. Patients with type 2 diabetes mellitus and no histories of coronary heart disease were evaluated (n = 498). Eligible patients underwent a 6- to 8-week washout period of all lipid-lowering medications and were enrolled if they demonstrated mixed dyslipidemia (having >or=2 of the following 3 lipid parameters: low-density lipoprotein [LDL] cholesterol >or=100 mg/dl, triglycerides >or=200 mg/dl, and high-density lipoprotein cholesterol <40 mg/dl). Patients were randomized to simvastatin 20 mg, fenofibrate 160 mg, or combined simvastatin 20 mg and fenofibrate 160 mg. Lipid subparticles were assessed 12 weeks after randomization by the Vertical Auto Profile II method. A total of 300 patients (mean age 61.6 +/- 11.5 years, 55% men) were randomized. Combination therapy was superior in lowering LDL cholesterol pattern B (-33.9 mg/dl) and dense very low-density lipoprotein cholesterol (-10.0 mg/dl) and increasing high-density lipoprotein3 (+2.3 mg/dl) and exerted the greatest change in altering the LDL cholesterol size profile. A potential effect on lipoprotein(a) (-0.5 mg/dl) was also found. For those with triglycerides >170 mg/dl, combination therapy was superior in lowering dense very low density lipoprotein cholesterol (-10.7 mg/dl) and LDL cholesterol pattern B (-35.8 mg/dl), the lipids that tend to be formed in the presence of elevated triglycerides. In conclusion, in this trial of mixed dyslipidemic patients with diabetes, combination therapy was more effective in changing a variety of other cardiovascular risk markers.
authors.affiliation: Intermountain Medical Center and LDS Hospital, Salt Lake City, Utah, USA.
authors.forename: Heidi T
authors.initials: HT
authors.lastname: May
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Robert R
authors.initials: RR
authors.lastname: Pearson
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Jensen
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Horne
authors.forename: Farangis
authors.initials: F
authors.lastname: Lavasani
authors.forename: H Daniel
authors.initials: HD
authors.lastname: Yannicelli
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Muhlestein
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood
chemical_list: D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; D019821:Simvastatin; D011345:Fenofibrate