Significant inverse association between serum osteocalcin and incident type 2 diabetes in a middle-aged cohort

Background Accumulating evidence indicates that osteocalcin links bone formation to glucose homeostasis. However, the correlation between osteocalcin and incident type 2 diabetes has been controversial based on the limited results of cohort studies. We examined the link between serum osteocalcin and glucose homeostasis including incident type 2 diabetes in a 3-year follow-up study. Methods This retrospective study enrolled 1870 middle-aged subjects (1279 men, 591 women) at Chinese PLA General Hospital who were followed-up for 3 years. Cox proportional hazards regression was used to determine whether incident type 2 diabetes was influenced by the osteocalcin concentrations measured with an electrochemiluminescence immunoassay. Results At baseline, the blood glucose levels and prevalence of metabolic syndrome varied inversely with the osteocalcin quartiles. During follow-up, type 2 diabetes developed in 80 of the 1870 subjects. The prevalence decreased with osteocalcin quartiles (P = 0.016). In models adjusted for metabolism-related parameters, osteocalcin was inversely associated with fasting plasma glucose {beta = -0.017 [95% confidence interval (CI), -0.034-0.00], P = 0.040}. Osteocalcin was inversely related to the risk of incident type 2 diabetes assessed using a model adjusted for glucose metabolic parameters, 25-hydroxy vitamin D3 and parathyroid hormone (hazard ratio [HR] = 0.09 [95% CI, 0.01-0.96], P = 0.046). The onset risk of diabetes in the first osteocalcin quartile was higher than in the fourth quartile (HR = 1.67 [95% CI, 0.96-3.48], P = 0.035). The correlation was strongly significant after fully adjusting for glucose related parameters and bone turnover (HR = 3.02 [95% CI, 1.25-7.32], P = 0.014). Conclusions Low serum osteocalcin concentrations at baseline were independently related to an increased risk of incident type 2 diabetes. Copyright (C) 2016 John Wiley & Sons, Ltd.