NT‐proBNP Mediates the Association Between FGF23 and All‐Cause Mortality in Individuals With Type 2 Diabetes

Abstract

Background FGF23 (fibroblast growth factor 23) is associated with a higher mortality risk in type 2 diabetes, but the mechanism is unclear. We aimed to study whether NT‐proBNP (N‐terminal pro‐brain natriuretic peptide) mediates the association between FGF23 and mortality. Methods and Results We analyzed C‐terminal FGF23 and NT‐proBNP levels in 399 patients with type 2 diabetes. Cox regression analyses were performed, followed by mediation analyses using Structural Equation Modeling. During follow‐up of 9.2 [7.6–11.3] years, 117 individuals died. FGF23 was associated with all‐cause mortality, independent of potential confounders (fully adjusted hazard ratio [HR], 2.32 [95% CI, 1.21–4.43], P =0.01). The association was lost upon further adjustment for NT‐proBNP (HR, 1.84; 95% CI, 0.91–3.73). NT‐proBNP accounted for 26% of the mediation effect between FGF23 and all‐cause mortality. Conclusions These findings suggest that a higher FGF23 level is associated with increased mortality in individuals with type 2 diabetes through an effect on volume homeostasis.