Total and undercarboxylated osteocalcin predict changes in insulin sensitivity and β cell function in elderly men at high cardiovascular risk

Background: Osteocalcin has been related to insulin secretion in experimental models. Few prospective studies have evaluated the association between circulating osteocalcin concentrations and insulin secretion and sensitivity in humans. Objective: The objective was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin and insulin secretion and sensitivity in elderly men at high cardiovascular risk. Design: We examined cross-sectional and longitudinal associations between serum measurements of total osteocalcin and undercarboxylated osteocalcin (ucOC) with fasting glucose, fasting insulin, HOMA-IR, and HOMA beta cell function (HOMA-BCF) in 79 elderly men. We also examined the association between 2-y changes in osteocalcin and changes in fasting glucose, insulin, HOMA-IR, and HOMA-BCF. Results: In an adjusted multivariable linear regression analysis, increases in serum osteocalcin were significantly associated with an increase in HOMA-BCF (beta coefficient: 2.87; 95% CI: 0.23, 5.52; P = 0.033), and changes in ucOC were linked to a decrease in HOMA-IR (beta coefficient: -0.31; 95% CI: -0.60, 0.03; P = 0.032). Moreover, in subjects not taking oral antidiabetic drugs, baseline osteocalcin concentrations were positively associated with higher fasting insulin concentrations and HOMA-BCF even after adjustment for BMI, physical activity, intervention group, presence of type 2 diabetes mellitus, and baseline values of each dependent variable. Conclusions: Changes in serum osteocalcin and ucOC are associated with an improvement in insulin secretion and sensitivity, which suggests a possible role of bone in the development of type 2 diabetes. This trial is registered at clinicaltrials.gov as ISRCTN35739639. Am J Clin Nutr 2012;95:249-55.