Abstract 12743: Pioglitazone Decreases Plasma Fibroblast Growth Factor-21 Levels in Patients with Type 2 Diabetes

Abstract

Background: Fibroblast growth factor-21 (FGF21) is a potent metabolic regulator, which has been shown to improve lipid metabolism, glucose metabolism, and insulin sensitivity. Recently, FGF21 was shown to be a key mediator of the physiologic and pharmacologic actions of peroxisome proliferator-activated receptor-γ (PPAR γ) in animals. Thus, the effects of the PPARγ agonist, pioglitazone, may be associated with FGF21 expression. Therefore, we investigated whether pioglitazone would alter plasma FGF-21 levels in patients with type 2 diabetes (DM).

Methods and Results: ELISA results showed that baseline plasma FGF21 levels were significantly (p<0.01) higher in patients with DM (n=40, 427±388 ng/L) than in healthy volunteers (n=40, 102±97 ng/L). Patients were randomized to receive either pioglitazone (15 to 30 mg, n=19) or glimepiride (0.5 to 4 mg, n=21) for 4 months, with titrations to optimal dosages. Both treatments comparably reduced fasting plasma glucose and HbA1c values. Pioglitazone significantly reduced plasma FGF21 levels (352 ± 197 to 245 ± 145 ng/L, p<0.04) and significantly increased plasma adiponectin levels (5.3 ± 2.9 to 14.1 ± 7.3 µg/mL, p<0.01). Glimepiride had no effect on plasma FGF21 or adiponectin levels. In the pioglitazone treated group, the reduction in plasma FGF21 was correlated with the increase in plasma adiponectin in the pioglitazone treated group (r=-0.38, p<0.05).

Conclusions: These results suggest that the effects of pioglitazone on glucose metabolism may be associated with the action of FGF21.