Plasma Fibroblast Growth Factor-21 Levels Are Positively Associated With Metabolic Syndrome, Insulin Resistance And Systemic Inflammation

Background: Fibroblast growth factor 21 (FGF-21) is a metabolic regulator of glucose and lipid metabolism, and in animal models has been shown to improve glucose tolerance and insulin sensitivity. Small scale studies in humans suggest an association of circulating FGF-21 levels with obesity and insulin resistance. However, its relationship to metabolic syndrome, systemic inflammation and subclinical atherosclerosis are not well characterized. Objective: We aimed to elucidate the relationship between plasma FGF-21 levels with determinants of metabolic syndrome, lipoprotein metabolism, glucose homeostasis, systemic inflammation and coronary artery calcification Methods & Results: Plasma FGF-21 levels were measured in 1702 subjects in three independently-recruited cross-sectional studies that included: 1) subjects with type 2 diabetes mellitus but without clinical CAD (n=699); 2) healthy non-diabetic subjects with a family history of premature coronary artery disease (n=587); and 3) healthy subjects with one or more metabolic syndrome risk factors (n=416). In all three studies, FGF-21 levels were directly correlated with LDL-C (p Conclusion: Higher FGF-21 levels were positively associated with several features of the metabolic syndrome, including markers of systemic inflammation, but not with CAC. While this finding seems paradoxical, it may be secondary to compensatory response or resistance to FGF-21. Further clinical studies are necessary to provide insight into the complex role of FGF-21 in humans.