Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risks for a major adverse cardiovascular event (MACE) and death in patients with type 2 diabetes and normal to mildly impaired kidney function, according to new study findings published in Diabetes Care.
Martin H. de Borst, MD, PhD, of the University of Groningen in the Netherlands, and colleagues analyzed plasma c-terminal FGF23 levels in 310 patient with type 2 diabetes (mean age 62 years; 58% men) with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 or higher from the Diabetes and Lifestyle Cohort Twente (DIALECT). During 5.8 years of follow-up, 47 patients experienced a MACE and 28 patients died. Each doubling of FGF23 was significantly associated with a 1.7- and 2.8-fold increased risk for MACE and all-cause mortality, respectively, in adjusted analyses.
In a subset of patients with eGFR of 90 mL/min/1.73 m2 or higher, each doubling of FGF23 was significantly associated with a 3.3-fold higher risk for all-cause mortality in adjusted analyses. The association with MACE was attenuated, likely due to underpowering, according to the investigators.
The researchers adjusted Cox regression models for a range of confounders including age, sex, body mass index, C-reactive protein, triglycerides, medications (for diabetes, hypertension, and cholesterol), urinary phosphate, urea excretion, plasma albumin, and urinary albumin-to-creatinine ratio.
High FGF23 level has been consistently associated with cardiovascular morbidity and mortality in patients with chronic kidney disease, Dr de Borst and his colleagues noted. The new observational data extend previous research.
“Our data provide a rationale for future studies on the specific role of FGF23 in patients with type 2 diabetes and normal kidney function.”
Yeung SMH, Binnenmars SH, Gant CM, et al. Fibroblast growth factor 23 and mortality in patients with type 2 diabetes and normal or mildly impaired kidney function [published online September 5, 2019]. Diabetes Care. doi:10.2337/dc19-0528