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

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.

• Authors: Kwok Leung Ong, Kerry-Anne Rye, Rachel O'Connell, Alicia J Jenkins, Chris Brown, Aimin Xu, David R Sullivan, Philip J Barter, Anthony C Keech, FIELD study investigators
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 97 Issue 12 Pg. 4701-8 (Dec 2012) ISSN: 1945-7197 [Electronic] United States
• PMID: 23144467 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hypolipidemic Agents
• Placebos
• RBP4 protein, human
• Retinol-Binding Proteins, Plasma
• fibroblast growth factor 21
• Fibroblast Growth Factors
• Fenofibrate

Topics

• Aged
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy, metabolism)
• Diabetic Cardiomyopathies (blood, diagnosis, etiology, metabolism)
• Double-Blind Method
• Female
• Fenofibrate (pharmacology, therapeutic use)
• Fibroblast Growth Factors (blood, metabolism)
• Humans
• Hypolipidemic Agents (pharmacology, therapeutic use)
• Male
• Middle Aged
• Placebos
• Retinol-Binding Proteins, Plasma (analysis, metabolism)
• Risk Factors
• Time Factors
• Up-Regulation (drug effects)