Osteocalcin is Needed to Protect Against Metabolic Syndrome
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 osteocalcin and other cardiovascular risk factors is uncertain. We sought to determine whether TOC is associated with metabolic syndrome and its components in older men. Design Cross-sectional analysis from a population-based cohort of men aged >/=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 4,047 men. Men not fasted and those reporting bone fractures, Paget's disease, or bisphosphonate, glucocorticoid or warfarin use were excluded, leaving 2,765 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+/-SE: 20.1+/-0.4 vs 21.4+/-0.2 mug/L, p=0.002). In multivariate analysis, men with TOC of 13.25-16.55 and <13.25 mug/L had 1.5 to 2-fold increased risk of metabolic syndrome compared to men with levels >/=30 mug/L. Osteocalcin 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 osteocalcin, elevated glucose and triglyceride levels are inter-related in ageing 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.
Yeap B, Chubb SA, Flicker L, McCaul K, Ebeling P, Beilby J, Norman PE. Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia and triglyceride levels. Eur J Endocrinol. 2010 May B Yeap, School of Medicine and Pharmacology, University of Western Australia, Perth, 6160, Australia.