FGF-23/Vitamin D Axis in Type 1 Diabetes: The Potential Role of Mineral Metabolism in Arterial Stiffness

PLoS One. 2015 Oct 13;10(10):e0140222. doi: 10.1371/journal.pone.0140222. eCollection 2015.

Abstract

Objective: To investigate the usefulness of Fibroblast Growth Factor 23 (FGF-23) and vitamin D as possible biomarkers of pre-clinical atherosclerosis, assessed as arterial stiffness (AS), in a group of subjects with type 1 diabetes (T1DM) and no previous cardiovascular events.

Research design and methods: 68 T1DM patients and 68 age- and sex-matched controls were evaluated for 1) age, sex, diabetes duration, physical activity, smoking, alcohol intake, BMI, blood pressure, fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR) and lipid profile; 2) microvascular complications; 3) blood concentrations of FGF-23 and mineral metabolism parameters (calcium, phosphate, parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D)); 4) AS, assessed as aortic pulse wave velocity (aPWV); and 5) low-grade inflammation (hsCRP, IL-6, sTNFαR1, sTNFαR2) and endothelial dysfunction (ED) markers (ICAM-1, VCAM-1, E-Selectin).

Results: Patients with T1DM had higher aPWV compared with controls (p<0.001), but they did not present differences in 25(OH)D (70.3(50.4-86.2)nmol/L vs. 70.7(59.7-83.0)nmol/L; p = 0.462) and in FGF-23 plasma concentrations (70.1(38.4-151.9)RU/mL vs. 77.6(51.8-113.9)RU/mL; p = 0.329). In T1DM patients, higher concentrations of FGF-23 were positively associated with aPWV after adjusting for eGFR and classical cardiovascular risk factors (model 1: ß = 0.202, p = 0.026), other mineral metabolism parameters (model 2: ß = 0.214, p = 0.015), microvascular complications, low-grade inflammation and ED markers (model 3: ß = 0.170, p = 0.045). Lower 25(OH)D concentrations were also associated with higher aPWV after adjusting for all the above-mentioned factors (model 3: ß = -0.241, p = 0.015).

Conclusions: We conclude that both FGF-23 plasma concentrations (positively) and 25(OH)D serum concentrations (negatively) are associated with AS in patients with T1DM and no previous cardiovascular events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Humans
  • Male
  • Minerals / metabolism*
  • Pulse Wave Analysis
  • Vascular Stiffness*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood

Substances

  • FGF23 protein, human
  • Minerals
  • Vitamin D
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • 25-hydroxyvitamin D

Grants and funding

Financial support was provided by a grant from the Fondo de Investigación Sanitaria (FIS) (PS09/01360 and PI12/00954) by Instituto de Salud Carlos III (Spain) and the Fundació La Marató de TV3-2008 (Project N° 081410). The study was also cofunded by Fondos FEDER and CIBER de Diabetes y Enfermedades Metabólicas asociadas CIBERDEM (CB07/08/0012), SAF2012-36186 and CP10/00438 to SF-V (Spanish Ministry of Economy and Competitiveness). CIBERDEM de Diabetes y Enfermedades Metabólicas asociadas (CB07708/0012) is an initiative of the Instituto de Salud Carlos III. GL was supported by a “Rio Hortega” research fellowship (CM12/00044) from the Instituto de Salud Carlos III (Spain). SF-V acknowledges support from the "Miguel Servet" tenure track program (CP10/00438), from the Fondo de Investigación Sanitaria (FIS), co-financed by the European Regional Development Fund (ERDF).