Effect of Osteocalcin on Insulin Sensitivity, Insulin Secretion, and Beta-cell Compensation in Mexican Americans.

Context: Previous animal studies show association between osteocalcin (OC) and type 2 diabetes-related quantitative traits (QTs), with some suggesting these effects being mediated by adipokines. Replication in humans have been inconsistent.

Objective: We aimed to assess the association between osteocalcin and type 2 diabetes-related QTs, and the roles of adipokines on the association between osteocalcin and glucose metabolism.

Methods: We used data from the BetaGene study, which is a cross-sectional family-based study of Mexican-Americans from Los Angeles County. We tested the association between type 2 diabetes-related QTs and OC, including inactive (OC-inactive) and active (OC-active) forms, in 867 Mexican-Americans without type 2 diabetes from 342 families. We also assessed the potential mediating effect of adipokines on these relationships.

Results: OC-active was negatively associated with insulin sensitivity (SI; p = 2.1×10-3) and positively associated with insulinogenic index (p = 2.8×10-3). Acute insulin response (AIR) was marginally significantly associated with OC-active (p = 0.07). Measures of beta-cell compensation for insulin resistance were not associated with OC. There was no evidence of mediation by adipokines.

Conclusions: We conclude OC-active is associated with SI, without mediation by adipokines or body fat. As there was no association with measures of beta-cell compensation for insulin resistance, the association between OC-active and insulin secretion reflects the compensatory response to SI.