Circulating osteocalcin level is associated with improved glucose tolerance, insulin secretion and sensitivity independent of the plasma adiponectin level

Summary In agreement with the results of animal studies, the plasma osteocalcin level is positively associated with improved glucose tolerance and insulin secretion and sensitivity. In addition, the plasma osteocalcin level is inversely associated with the development of diabetes; however, the plasma adiponectin level may not be involved in osteocalcin-mediated energy metabolism in humans. Introduction Recent animal studies have suggested crosstalk between bone and energy metabolism through osteocalcin. The aims of this study were to determine whether or not osteocalcin is associated with the improved glucose tolerance and insulin secretion and sensitivity, and whether or not the association is dependent on the plasma adiponectin level in humans. Methods Four hundred twenty-five subjects, 19–82 years of age (mean age, 53 years), were enrolled. An oral glucose tolerance test (OGTT) and OGTT-based methods that were validated against the euglycemic clamp were determined. Total osteocalcin, leptin, and total adiponectin levels were measured. Results The plasma levels of total osteocalcin were significantly different between the normal glucose tolerance, pre-diabetes, and diabetes groups. The glucose levels and homeostasis model assessment insulin resistance values varied inversely with the osteocalcin tertiles, and OGTT-based insulin secretion (HOMA-B%, disposition index) and insulin sensitivity indices (Stumvoll’s and OGIS indices) were increased with the tertiles. Although the plasma adiponectin level was positively correlated with the osteocalcin level, no changes in the association were noted between the plasma osteocalcin level and the glucose tolerance or insulin secretion and sensitivity indices after adjustment for the plasma adiponectin level. Based on multiple logistic regression analysis, the plasma osteocalcin level was inversely associated with the development of type 2 diabetes mellitus independent of age, gender, body mass index, and fasting plasma glucose and plasma adiponectin levels. Conclusions Circulating osteocalcin level is associated with improved glucose tolerance and insulin secretion and sensitivity independent of the plasma adiponectin level in humans.