Plasma FGF23 and Calcified Atherosclerotic Plaque in African Americans with Type 2 Diabetes Mellitus

Am J Nephrol. 2015;42(6):391-401. doi: 10.1159/000443241. Epub 2015 Dec 23.

Abstract

Background: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial.

Methods: Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate.

Results: The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m2, urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up.

Conclusions: Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Albuminuria / blood
  • Albuminuria / complications
  • Black or African American
  • Blood Pressure
  • Bone Density
  • Carotid Arteries / physiopathology
  • Coronary Vessels / physiopathology
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / ethnology
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Glycated Hemoglobin / analysis
  • Humans
  • Iliac Artery / physiopathology
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Phosphates / chemistry
  • Plaque, Atherosclerotic / blood*
  • Plaque, Atherosclerotic / ethnology
  • Renin-Angiotensin System
  • Risk Factors
  • Tomography, X-Ray Computed
  • Vitamin D / blood

Substances

  • FGF23 protein, human
  • Glycated Hemoglobin A
  • Phosphates
  • hemoglobin A1c protein, human
  • Vitamin D
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23