title: Fenofibrate effects on arterial endothelial function in adults with type 2 diabetes mellitus: A FIELD substudy.
abstract: OBJECTIVE
  Dislipidaemia in type 2 diabetes mellitus contributes to arterial endothelial dysfunction and an increased risk of cardiovascular disease. Fenofibrate, a lipid-regulating peroxisome proliferator-activated receptor-α (PPARα) agonist, has been shown to reduce vascular complications in adults with type 2 diabetes. However, the mechanisms for such benefit are not well understood. We examined the effects of fenofibrate on brachial artery endothelial function in adults with type 2 diabetes.
  
  
  METHODS
  In a prospectively designed substudy of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, we assessed arterial flow-mediated dilatation (FMD; endothelium-dependent dilatation) and dilator responses to glyceryl trinitrate (GTN, an endothelium-independent dilator) in a subset of 193 representative adults. Traditional risk factors were assessed at baseline, 4 months and 2 years after randomised treatment allocation to fenofibrate (200 mg daily) or placebo. The prespecified primary study endpoint was the difference in FMD between treatment groups at 4 months.
  
  
  RESULTS
  Fenofibrate was associated with a significant improvement at 4 months compared with placebo (+1.05% (absolute); P=0.03); GTN-dilator responses were unchanged (P=0.77). After 2 years, FMD was similar in both groups (P=0.46). In multivariable models, none of the fenofibrate-related changes in lipoproteins and lipids were significantly associated with improved FMD on fenofibrate at 4 months.
  
  
  CONCLUSIONS
  Treatment with fenofibrate significantly improved arterial endothelial function after 4 months. However, the effect was no longer apparent after 2 years. The long-term beneficial vascular effects of fenofibrate in type 2 diabetes are likely to be mediated via mechanisms other than improvement in endothelium-dependent dilatation of conduit arteries, and may differ for the microcirculation.
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: jhar2154@uni.sydney.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Harmer
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Keech
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Veillard
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Skilton
authors.affiliation: Menzies Research Institute Tasmania, Hobart, TAS, Australia.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Marwick
authors.affiliation: Department of Medicine, University of Western Australia, Perth, WA, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Department of Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Meredith
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
mesh_terms: D000368:Aged; D001315:Australia; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005387:Finland; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D005996:Nitroglycerin / Q000494:pharmacology; D011446:Prospective Studies; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000960:Hypolipidemic Agents; D014665:Vasodilator Agents; D005996:Nitroglycerin; D011345:Fenofibrate
keywords: Arterial endothelial function; Atherosclerosis; Cardiovascular disease; Diabetes mellitus; Fenofibrate; Randomised controlled trial