Differential effects of bariatric surgery on circulating GDF15 and FGF21 levels: Implications for glycemic status and weight loss outcomes.

Background: Type 2 diabetes (T2D) is a comorbidity commonly associated with obesity. Elevated concentrations of growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) are associated with these conditions, making both cytokines interesting candidates to combat them. This study aimed to analyse the relationship between changes in plasma GDF15 and FGF21 levels and the resolution of T2D or obesity improvements after bariatric surgery.

Methods: Plasma samples from 104 patients (52 with obesity and normoglycemia and 52 with obesity and impaired glucose tolerance or T2D) were analysed before and after Roux-en-Y-gastric bypass surgery.

Results: Plasma GDF15 levels increased significantly after bariatric surgery in patients with obesity and normoglycemia (p < 0.01), as well as in those with obesity and impaired glucose tolerance or T2D (p < 0.05). This increase was significant in patients analysed up to 8 months after surgery in both groups (p < 0.01) but not in those analysed between 8 to 15 months after surgery, suggesting that GDF15 concentrations exhibit an early increase after surgery but may return to baseline levels over time. In contrast, plasma FGF21 levels after bariatric surgery decreased significantly in patients with impaired glucose tolerance or T2D (p < 0.05). Pre-surgery FGF21 concentrations were negatively correlated with the percentage of excess weight loss and the percentage of fat loss.

Conclusions: GDF15 and FGF21 exhibit a different behaviour after Roux-en-Y-gastric bypass surgery, with FGF21 being more closely associated with glycemic status and weight loss. Elevated pre-surgery FGF21 concentrations could predict a higher difficulty in losing the excess weight after surgery.