title: The association between sclerostin and incident type 2 diabetes risk: a cohort study.
abstract: OBJECTIVE
  To determine whether sclerostin is associated with fasting glucose, insulin levels, insulin resistance or increased risk of incident type 2 diabetes.
  
  
  BACKGROUND
  Type 2 diabetic patients have a higher risk of fractures. Recent studies suggest sclerostin, a regulator of osteoblast activity, is associated with diabetes.
  
  
  METHODS
  Sclerostin levels were obtained from 1778 individuals with no history of type 2 diabetes participating in the population-based Canadian Multicentre Osteoporosis Study (CaMos) cohort. Participants were followed until diagnosis of type 2 diabetes, death or end of the study period (31 December 2013). The relationship of sclerostin with fasting glucose, insulin levels and homoeostatic model assessment-insulin resistance (HOMA-IR) was studied in linear regression models. Cox proportional hazards models were used to determine the association of sclerostin levels and the risk of incident type 2 diabetes during a mean 7·5 years of follow-up.
  
  
  RESULTS
  Fasting glucose, fasting insulin levels and HOMA-IR were weakly correlated with sclerostin levels (Spearman's correlation coefficient: 0·11, P < 0·05; -0·09, P < 0·05; and -0·07, P = 0·02, respectively). Multiple linear regression analyses confirmed a significant association between sclerostin and fasting insulin and HOMA-IR but no significant association with fasting glucose levels. Sclerostin levels were not found to be significantly associated with the risk of incident type 2 diabetes (HR: 1·30; 95% CI: 0·37-4·57).
  
  
  CONCLUSIONS
  We observed an association between sclerostin levels with fasting insulin levels and HOMA-IR, but there was no clear association with type 2 diabetes risk. Further studies are needed to understand the role of sclerostin in type 2 diabetes.
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.|Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: O H Y
authors.identifier: http://orcid.org/0000-0003-4877-557X
authors.initials: OH
authors.lastname: Yu
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.|Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Richards
authors.affiliation: CaMos Coordinating Centre, McGill University, Montreal, QC, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Berger
authors.affiliation: Division of Endocrinology & Metabolism, St Michael's University of Toronto, Toronto, ON, Canada.
authors.forename: R G
authors.initials: RG
authors.lastname: Josse
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: W D
authors.initials: WD
authors.lastname: Leslie
authors.affiliation: Department of Medicine, McGill University and McGill University Health Centre, Montreal, QC, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Goltzman
authors.affiliation: Division of Endocrinology & Metabolism, Dalhousie University, Halifax, NS, Canada.
authors.forename: S M
authors.initials: SM
authors.lastname: Kaiser
authors.affiliation: Discipline of Medicine-Endocrinology, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: C S
authors.initials: CS
authors.lastname: Kovacs
authors.affiliation: A Priori Medical Sciences Inc., Victoria, BC, Canada.
authors.forename: K S
authors.initials: KS
authors.lastname: Davison
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D002170:Canada; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005215:Fasting / Q000097:blood; D005819:Genetic Markers; D006706:Homeostasis; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008875:Middle Aged; D012306:Risk
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D007328:Insulin; C422903:SOST protein, human