title: Association between serum ferritin and osteocalcin as a potential mechanism explaining the iron-induced insulin resistance.
abstract: BACKGROUND
  Increased iron stores are associated with increased risk of type 2 diabetes, however, the mechanisms underlying these associations are poorly understood. Because a reduction of circulating osteocalcin levels after iron overload have been demonstrated in cell cultures, and osteocalcin is related to glucose and insulin metabolism, the iron-induced osteocalcin reductions could contribute to explain the role of iron metabolism in the development of type 2 diabetes mellitus.
  
  
  OBJECTIVE
  To analyzed the associations between serum total and uncarboxylated osteocalcin and adiponectin concentrations with serum ferritin and soluble transferrin receptor (sTfR) in elderly subjects.
  
  
  METHODS
  We evaluated a total of 423 subjects from the PREDIMED cohort in a population-based cross-sectional analysis. Extensive clinical, nutritional and laboratory measurements, including total and uncarboxylated osteocalcin, adiponectin, ferritin and sTfR were recorded.
  
  
  RESULTS
  Serum ferritin was positively correlated with increased glucose and insulin circulating levels but also with HOMA-IR, and was inversely associated with total osteocalcin and adiponectin. A regression analysis revealed that serum ferritin and transferrin receptor levels were significantly associated with a decrease in total and uncarboxylated osteocalcin. Serum sTfR levels were associated with lower uncarboxylated osteocalcin levels in the whole-study subjects and remained significant only in the IFG (impaired fasting glucose) individuals.
  
  
  CONCLUSIONS
  We described, for the first time, an inverse association between serum ferritin and sTfR with osteocalcin and extend previous results on adiponectin, thus supporting that factors related to iron metabolism could contribute to the insulin resistance and the development of type 2 diabetes mellitus.
  
  
  BACKGROUND
  Controlled-Trials.com ISRCTN35739639 <http://www.controlled-trials.com/ISRCTN35739639>.
authors.affiliation: Human Nutrition Unit and Preventive Medicine Unit, Faculty of Medicine and Health Sciences, IISPV, Universitat Rovira i Virgili, Reus, Spain ; CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III (ISCIII), Madrid, Spain.
authors.forename: Martí
authors.initials: M
authors.lastname: Juanola-Falgarona
authors.forename: José
authors.initials: J
authors.lastname: Cándido-Fernández
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvadó
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martínez-González
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
authors.forename: Miquel
authors.initials: M
authors.lastname: Fiol
authors.forename: Victoria
authors.initials: V
authors.lastname: Arija-Val
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005293:Ferritins; D006801:Humans; D007333:Insulin Resistance; D007501:Iron / Q000097:blood*; D019190:Iron Overload / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D011990:Receptors, Transferrin / Q000097:blood
chemical_list: D011990:Receptors, Transferrin; D015675:Osteocalcin; D005293:Ferritins; D007501:Iron