title: 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.
  
  
  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.
authors.affiliation: Hospital Universitari Joan XXIII de Tarragona, Institut d'Investigacions Sanitàries Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; Department of Endocrinology and Nutrition, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Llauradó
authors.affiliation: Hospital Universitari Joan XXIII de Tarragona, Institut d'Investigacions Sanitàries Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Megia
authors.affiliation: Department of Endocrinology and Nutrition, Hospital de Sabadell, Corporació Sanitària i Universitària Parc Taulí (Universitat Autònoma de Barcelona), Sabadell, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Cano
authors.affiliation: Department of Endocrinology and Nutrition, Hospital de Sabadell, Corporació Sanitària i Universitària Parc Taulí (Universitat Autònoma de Barcelona), Sabadell, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Giménez-Palop
authors.affiliation: Hospital Universitari Joan XXIII de Tarragona, Institut d'Investigacions Sanitàries Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Simón
authors.affiliation: Department of Ophthalmology, Hospital de Sabadell, Corporació Sanitària i Universitària Parc Taulí (Universitat Autònoma de Barcelona), Sabadell, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: González-Sastre
authors.affiliation: Biochemistry Department, UDIAT, Corporació Sanitària i Universitària Parc Taulí (Universitat Autònoma de Barcelona), Sabadell, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Berlanga
authors.affiliation: Hospital Universitari Joan XXIII de Tarragona, Institut d'Investigacions Sanitàries Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernández-Veledo
authors.affiliation: Hospital Universitari Joan XXIII de Tarragona, Institut d'Investigacions Sanitàries Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.affiliation: Department of Endocrinology and Nutrition, Hospital de Sabadell, Corporació Sanitària i Universitària Parc Taulí (Universitat Autònoma de Barcelona), Sabadell, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: José-Miguel
authors.initials: JM
authors.lastname: González-Clemente
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D008903:Minerals / Q000378:metabolism*; D063177:Pulse Wave Analysis; D059289:Vascular Stiffness; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; D008903:Minerals; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D