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.

CONCLUSION:

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: Jason A Harmer, Anthony C Keech, Anne-Sophie Veillard, Michael R Skilton, Thomas H Marwick, Gerald F Watts, Ian T Meredith, David S Celermajer, FIELD Vascular Study Investigators
• Journal: Atherosclerosis (Atherosclerosis) Vol. 242 Issue 1 Pg. 295-302 (Sep 2015) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 26233916 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Hypolipidemic Agents
• Vasodilator Agents
• Nitroglycerin
• Fenofibrate

Topics

• Aged
• Australia
• Brachial Artery (diagnostic imaging, drug effects, physiopathology)
• Diabetes Mellitus, Type 2 (blood, diagnosis, drug therapy, physiopathology)
• Double-Blind Method
• Dyslipidemias (blood, diagnosis, drug therapy)
• Endothelium, Vascular (diagnostic imaging, drug effects, physiopathology)
• Female
• Fenofibrate (therapeutic use)
• Finland
• Humans
• Hypolipidemic Agents (therapeutic use)
• Male
• Middle Aged
• New Zealand
• Nitroglycerin (pharmacology)
• Prospective Studies
• Recovery of Function
• Time Factors
• Treatment Outcome
• Ultrasonography
• Vasodilation (drug effects)
• Vasodilator Agents (pharmacology)