title: The peroxisome proliferator-activated receptor alpha agonist fenofibrate has no effect on insulin sensitivity compared to atorvastatin in type 2 diabetes mellitus; a randomised, double-blind controlled trial.
abstract: OBJECTIVE
  Assess insulin sensitivity after treatment with a selective PPAR-alpha agonist compared to an HMG CoA reductase inhibitor in human subjects with type 2 diabetes mellitus.
  
  
  METHODS
  Thirteen subjects with Type 2 diabetes mellitus were studied in a double-blind crossover design with 4-week placebo run-in and washout and 12-week treatment periods, randomised to micronised fenofibrate 267 mg or atorvastatin 10mg daily followed by the alternate drug in the second period. Insulin resistance was measured using the isoglycaemic hyperinsulinaemic clamp method with isotope dilution.
  
  
  RESULTS
  Weight, physical activity and other medications did not change. Total cholesterol (mean +/- standard error) was 4.60+/-0.21 versus 3.9+/-0.22 mmol/L after fenofibrate and atorvastatin respectively, p<0.05. LDL was 2.70+/-0.19 versus 1.95+/-0.23 mmol/L, p<0.05 and triglyceride 1.64+/-0.23 versus 1.84+/-0.26 mmol/L, p<0.05. Insulin-stimulated whole-body glucose disposal (35.4+/-3.1 versus 33.2+/-3.0 μmol/kg/min) and nadir endogenous glucose production (6.2+/-1.4 versus 7.0+/-1.1 μmol/kg/min) revealed no significant differences in effects of the treatments.
  
  
  CONCLUSIONS
  In human subjects with Type 2 diabetes mellitus there were characteristic differences in lipid profile changes but no difference in insulin sensitivity after treatment with micronised fenofibrate compared to atorvastatin. This study finds no evidence of increased insulin sensitivity using this selective PPAR-alpha agonist over a commonly used statin at these doses.
authors.affiliation: Regional Centre for Endocrinology & Diabetes, Royal Victoria Hospital, Grosvenor Road, Belfast, Northern Ireland, BT12 6BA, UK. Electronic address: neil.black@westerntrust.hscni.net.
authors.forename: R Neil A
authors.initials: RN
authors.lastname: Black
authors.affiliation: Regional Centre for Endocrinology & Diabetes, Royal Victoria Hospital, Grosvenor Road, Belfast, Northern Ireland, BT12 6BA, UK.
authors.forename: Cieran N
authors.initials: CN
authors.lastname: Ennis
authors.affiliation: Nutrition and Metabolism Group, The Queen's University of Belfast, Belfast, UK.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.affiliation: Regional Centre for Endocrinology & Diabetes, Royal Victoria Hospital, Grosvenor Road, Belfast, Northern Ireland, BT12 6BA, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hunter
authors.affiliation: Regional Centre for Endocrinology & Diabetes, Royal Victoria Hospital, Grosvenor Road, Belfast, Northern Ireland, BT12 6BA, UK.
authors.forename: A Brew
authors.initials: AB
authors.lastname: Atkinson
authors.affiliation: Regional Centre for Endocrinology & Diabetes, Royal Victoria Hospital, Grosvenor Road, Belfast, Northern Ireland, BT12 6BA, UK.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Bell
mesh_terms: D000069059:Atorvastatin; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D011345:Fenofibrate / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000819:agonists*; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007328:Insulin; D047493:PPAR alpha; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin; D011345:Fenofibrate
keywords: Fibrate; Insulin resistance; Peroxisome proliferator-activated receptor alpha; Statin; Type 2 diabetes mellitus