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

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.