Long-Term Fenofibrate Therapy Increases Fibroblast Growth Factor 21 and Retinol-Binding Protein 4 in Subjects with Type 2 Diabetes

• Published in: The journal of clinical endocrinology and metabolism Vol. 97; no. 12; pp. 4701 - 4708
• Main Authors: Ong, Kwok Leung, Rye, Kerry-Anne, O'Connell, Rachel, Jenkins, Alicia J., Brown, Chris, Xu, Aimin, Sullivan, David R., Barter, Philip J., Keech, Anthony C.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.12.2012; Endocrine Society
• Subjects: Aged; Apolipoprotein A; Apolipoprotein A-II; Biological and medical sciences; Cardiovascular diseases; Cholesterol; Creatinine; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Diabetic Cardiomyopathies - blood; Diabetic Cardiomyopathies - diagnosis; Diabetic Cardiomyopathies - etiology; Diabetic Cardiomyopathies - metabolism; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acid-binding protein; Feeding. Feeding behavior; Female; Fenofibrate; Fenofibrate - pharmacology; Fenofibrate - therapeutic use; Fibrinogen; Fibroblast Growth Factors - blood; Fibroblast Growth Factors - metabolism; Fibroblasts; Fundamental and applied biological sciences. Psychology; Growth factors; Hemoglobin; Homocysteine; Humans; Hypolipidemic Agents - pharmacology; Hypolipidemic Agents - therapeutic use; Male; Medical sciences; Middle Aged; Peroxisome proliferator-activated receptors; Placebos; Proteins; Retinol-binding protein; Retinol-Binding Proteins, Plasma - analysis; Retinol-Binding Proteins, Plasma - metabolism; Risk Factors; Time Factors; Triglycerides; Up-Regulation - drug effects; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Vitamin A; Endocrinopathy; Type 2 diabetes; Human; Fibroblast growth factor; Obesity; Nutrition; Fibrate derivatives; Nutrition disorder; Metabolic diseases; Increase; Adipokine; Long term; Fenofibrate; Treatment; Endocrinology; Nutritional status; Antilipemic agent
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2012-2267

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.