FGF23 Concentration and Genotype Are Novel Predictors of Mortality in African Americans With Type 2 Diabetes.

Chan GC, Divers J, Russell GB, Langefeld CD, Wagenknecht LE, Hsu FC, Xu J, Smith SC, Palmer ND, Hicks PJ, Bowden DW, Register TC, Ma L, Carr JJ, Freedman BI
Diabetes Care. 2018 41 (1): 178-186

PMID: 29113983 · PMCID: PMC5741152 · DOI:10.2337/dc17-0820

OBJECTIVE - Cardiovascular and renal complications contribute to higher mortality in patients with diabetes. We assessed novel and conventional predictors of mortality 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 () 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 m (76.4, 111.3), UACR 12.5 mg/mmol (4.2, 51.2), and coronary artery calcium 28.5 mg Ca (1.0, 348.6); 11.5% had two renal-risk variants. After 6.6-year follow-up (5.8, 7.5), 54 deaths were 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 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 non-renal-risk genotypes associated with higher mortality in African Americans with diabetes. These data add to growing evidence supporting FGF23 association with mortality; mechanisms whereby these novel predictors impact survival remain to be determined.

© 2017 by the American Diabetes Association.

MeSH Terms (19)

African Americans Albuminuria Apolipoprotein L1 Atherosclerosis Cohort Studies Creatinine Diabetes Mellitus, Type 2 Female Fibroblast Growth Factors Follow-Up Studies Genotyping Techniques Glomerular Filtration Rate Glycated Hemoglobin A Humans Kidney Function Tests Male Middle Aged Proportional Hazards Models Risk Factors

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