FGF23 concentration and APOL1 genotype are novel predictors of mortality in African Americans with type 2 diabetes

Abstract

OBJECTIVE Cardiovascular and renal complications contribute to higher mortality in patients with diabetes.We assessed novel and conventional predictors ofmortality in African American-Diabetes Heart Study (AA-DHS) participants. RESEARCH DESIGN AND METHODS Associations between mortality and subclinical atherosclerosis, urine albumin-to- creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), plasma fibroblast growth factor 23 (FGF23) concentration, African ancestry proportion, and apolipoprotein L1 genotypes (APOL1) were assessed in 513 African Americans with type 2 diabetes; analyses were performed using Cox proportional hazards models. RESULTS At baseline, participants were 55.6% female with median (25th, 75th percentile) age 55 years (49.0, 62.0), diabetes duration 8 years (5.0, 13.0), glycosylated hemoglobin 60.7 mmol/mol (48.6, 76.0), eGFR 91.3 mL/min/1.73 m2 (76.4, 111.3), UACR 12.5 mg/mmol (4.2, 51.2), and coronary artery calcium 28.5 mg Ca2+ (1.0, 348.6); 11.5% had two APOL1 renal-risk variants. After 6.6-year follow-up (5.8, 7.5), 54 deathswere recorded. Higher levels of coronary artery calcified plaque, carotid artery calcified plaque, albuminuria, and FGF23 were associated with higher mortality after adjustment for age, sex, and African ancestry proportion. A penalized Cox regression that included all covariates and predictors associated with mortality identified male sex (hazard ratio [HR] 4.17 [95% CI 1.96-9.09]), higher FGF23 (HR 2.10 [95% CI 1.59- 2.78]), and absence of APOL1 renal-risk genotypes (HR 0.07 [95% CI 0.01-0.69]) as the strongest predictors of mortality. CONCLUSIONS Accounting for conventional risk factors, higher FGF23 concentrations and APOL1 non-renal-risk genotypes associatedwith highermortality in African Americanswith diabetes. These data add to growing evidence supporting FGF23 association with mortality; mechanisms whereby these novel predictors impact survival remain to be determined.