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J Clin Endocrinol Metab. 2012 Dec;97(12):4701-8. doi: 10.1210/jc.2012-2267. Epub 2012 Nov 8.

Long-term fenofibrate therapy increases fibroblast growth factor 21 and retinol-binding protein 4 in subjects with type 2 diabetes.

Author information

1
Lipid Research Group, Heart Research Institute, Sydney, New South Wales 2042, Australia. ongk@hri.org.au

Abstract

CONTEXT:

Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α agonist that showed beneficial effects on total cardiovascular risk in patients with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

OBJECTIVE:

This study aimed to investigate the long-term effect of fenofibrate therapy on three novel biomarkers of cardiovascular risk, namely adipocyte-fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF21), and retinol-binding protein 4 (RBP4), which are all downstream targets of PPAR-α or PPAR-γ, in patients with type 2 diabetes.

DESIGN, SETTING, AND PATIENTS:

A total of 216 patients (108 in the fenofibrate group and 108 in the placebo group) were randomly selected from the FIELD study cohort. A-FABP, FGF21, and RBP4 levels were measured in serum samples at both baseline and the fifth year of the study.

RESULTS:

Relative to the placebo group, the changes of serum FGF21 and RBP4 levels were 85% (P < 0.001) and 10% (P = 0.032) higher in the fenofibrate group, respectively, over 5 yr. Fenofibrate treatment had no detectable effect on serum A-FABP level (P > 0.05). The effect of fenofibrate treatment on serum FGF21, but not RBP4, remained significant after adjusting for fenofibrate-induced changes in glycosylated hemoglobin, total cholesterol, triglycerides, apolipoprotein A-II, fibrinogen, plasma creatinine, and homocysteine (P = 0.002).

CONCLUSIONS:

Long-term fenofibrate treatment could increase serum FGF21 levels over 5 yr in patients with type 2 diabetes. Additional studies are needed to investigate the potential role of FGF21 in the fenofibrate-mediated reduction of cardiovascular risk.

PMID:
23144467
DOI:
10.1210/jc.2012-2267
[Indexed for MEDLINE]
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