Abstract
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 β 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 (β coefficient: 2.87; 95% CI: 0.23, 5.52; P = 0.033), and changes in ucOC were linked to a decrease in HOMA-IR (β 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.
