title: Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels.
abstract: OBJECTIVE
  Bone-derived undercarboxylated osteocalcin regulates insulin secretion and sensitivity in mice, and reduced serum total osteocalcin (TOC) is associated with diabetes in humans. However, the relationship between TOC levels and other cardiovascular risk factors is uncertain. We sought to determine whether serum TOC is associated with metabolic syndrome and its components in older men.
  
  
  METHODS
  Cross-sectional analysis from a population-based cohort of men aged >or=70 years.
  
  
  METHODS
  Early morning sera were assayed for TOC. Insulin resistance was estimated using a homeostatic model (HOMA2-IR). Metabolic syndrome was defined according to NCEP-ATPIII criteria.
  
  
  RESULTS
  TOC was assayed in 4047 men. Men who were not fasting and reported having bone fractures, Paget's disease, or bisphosphonate, glucocorticoid, or warfarin use were excluded, leaving 2765 men with metabolic syndrome present in 797 (28.8%). TOC was inversely associated with waist circumference, glucose, and triglyceride levels and HOMA2-IR (all P<0.001), and was lower in men with metabolic syndrome (mean+/-S.E.M.: 20.1+/-0.4 vs 21.4+/-0.2 microg/l, P=0.002). In multivariate analysis, men with TOC of 13.25-16.55 and <13.25 microg/l had 1.5- to 2-fold increased risk of metabolic syndrome compared with men with levels >or=30 microg/l. TOC remained associated with metabolic syndrome after adjustment for individual components, but not after adjusting for both waist circumference and glucose.
  
  
  CONCLUSIONS
  Increased waist circumference, reduced TOC, elevated glucose, and triglyceride levels are inter-related in aging men. Osteocalcin may lie in the causal pathway between central adiposity and insulin resistance. Further research is required to evaluate whether interventions which raise osteocalcin levels might decrease cardiovascular risk.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia. byeap@cyllene.uwa.edu.au
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
authors.forename: S A Paul
authors.initials: SA
authors.lastname: Chubb
authors.forename: Leon
authors.initials: L
authors.lastname: Flicker
authors.forename: Kieran A
authors.initials: KA
authors.lastname: McCaul
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ebeling
authors.forename: John P
authors.initials: JP
authors.lastname: Beilby
authors.forename: Paul E
authors.initials: PE
authors.lastname: Norman
mesh_terms: D050154:Adiposity; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D015675:Osteocalcin / Q000097:blood*; D014280:Triglycerides / Q000097:blood*; D055105:Waist Circumference
chemical_list: D014280:Triglycerides; D015675:Osteocalcin