The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced β-cell function in middle-aged male subjects

Background: Recent human studies support the notion that serum osteocalcin increases β-cell proliferation and insulin secretion, and improves insulin sensitivity. However, no study has examined the effects of serum osteocalcin γ -carboxylation status on these associations or determined the role of uncarboxylated osteocalcin in glucose metabolism in humans. Methods: The aim of this study was to determine the association between uncarboxylated osteocalcin and β-cell function and insulin sensitivity in humans. As many as 199 men, aged 25-60 years (mean age, 47 years), who had never been treated with glucose lowering agents, were enrolled in this cross-sectional study. OGTT was performed and other metabolic parameters, such as, BMI, BP, lipid profiles, and both uncarboxylated and carboxylated osteocalcin plasma levels were measured. Results: When subjects were divided into tertiles by uncarboxylated and carboxylated osteocalcin plasma concentrations, subjects in the upper tertile of each showed lower fasting and post-challenge glucose levels after adjusting for age and BMI (P < 0.05). The upper uncarboxylated osteocalcin tertile was associated with higher HOMA-B% levels, which are representative of β-cell function (P < 0.05), and the upper carboxylated osteocalcin tertile was associated with lower HOMA-IR values, which are representative of insulin resistance (P < 0.05). Conclusions: Elevated levels of both carboxylated and uncarboxylated forms of osteocalcin were associated with improved glucose tolerance. Moreover, the uncarboxylated form of osteocalcin was found to be associated with enhanced β-cell function, and the carboxylated form was associated with improved insulin sensitivity in middle-aged male subjects.