Harmer, JA and Keech, AC and Veillard, AS and Skilton, MR and Marwick, TH and Watts, GF and Meredith, IT and Celermajer, DS, for the FIELD Vascular Study Investigators, Fenofibrate effects on arterial endothelial function in adults with type 2 diabetes mellitus: A FIELD substudy, Atherosclerosis, 242, (1) pp. 295-302. ISSN 0021-9150 (2015) [Refereed Article]
Copyright 2015 Elsevier Ireland Ltd.
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.
|Item Type:||Refereed Article|
|Keywords:||arterial endothelial function, atherosclerosis, cardiovascular disease, diabetes mellitus, fenofibrate, randomised controlled trial|
|Research Division:||Medical and Health Sciences|
|Research Group:||Cardiorespiratory Medicine and Haematology|
|Research Field:||Cardiology (incl. Cardiovascular Diseases)|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Cardiovascular System and Diseases|
|Author:||Marwick, TH (Professor Tom Marwick)|
|Web of Science® Times Cited:||6|
|Deposited By:||Menzies Institute for Medical Research|
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