Distinct Changes in Serum Fibroblast Growth Factor 21 Levels in Different Subtypes of Diabetes

Aims: Fibroblast growth factor (FGF) 21 is an endocrine factor with multiple beneficial effects on glucose and lipid metabolism in animals. This study aimed to investigate the association of serum FGF21 levels with type 1 diabetes, latent autoimmune diabetes in adults (LADA) and type 2 diabetes. Methods: Serum FGF21 levels were determined by ELISA in patients with type 1 diabetes (n = 76), LADA (n = 68), type 2 diabetes (n = 77), and their age-and sex-matched controls. The association of serum FGF21 with markers of autoimmunity was studied. Results: In type 1 diabetic patients, serum FGF21 levels were significantly lower than controls [108.3 (61.5-180.1) vs. 196.0 (103.7-330.9) pg/ml, P < 0.001]. In LADA patients, serum FGF21 levels were significantly lower than controls after adjustment for body mass index [210.9 (121.4-441.6) vs. 268.3 (159.5-443.6) pg/ml, P = 0.003]. By contrast, serum FGF21 levels in type 2 diabetic patients were significantly higher than controls [381.2 (244.7-531.3) vs. 301.4 (173.9-444.2) pg/ml, P = 0.006]. FGF21 levels increased progressively from type 1 diabetes, LADA, to type 2 diabetes (P < 0.001 for global trend). Furthermore, FGF21 levels correlated inversely with titers of glutamic acid decarboxylase and insulinoma-associated protein 2 autoantibodies in type 1 diabetic and LADA patients. Conclusions: Serum FGF21 level is increased in type 2 diabetes but decreased in type 1 diabetes and LADA. In autoimmune diabetes, the reduction in circulating FGF21 is closely associated with markers of pancreatic beta-cell autoimmunity. (J Clin Endocrinol Metab 97: E54-E58, 2012)