The Association between Serum under carboxylated Osteocalcin Level and Type-2 Diabetes Mellitus: Results from the Kyushu and Okinawa Population Study

Objectives: Diabetes can affect bone via obesity, hyperglycemia, hyperinsulinemia, and hypoinsulinemia. Osteocalcin (OC) is a non-collagenous protein of the bone that contributes to bone formation. A population-based study was done to examine the relationship between the serum level of under carboxylated osteocalcin (ucOC) and diabetes. Methods: A cross-sectional study was done in 2,062 women aged 40 to 69 years living in a suburban Japanese town. Serum ucOC level by electro chemiluminescent immunoassay, Fasting Plasma Glucose (FPG), and glycohemoglobin A1c (HbA1c) were measured for each participant. Participants who were previously diagnosed with diabetes or who were receiving its treatment were defined as having pre-existing diabetes. Participants without pre-existing diabetes who had a FPG level >7.0 mmol/L or HbA1c level of ≥6.5 % were defined as having newly diagnosed diabetes. Results: The median serum ucOC level of 1,433 postmenopausal women (5.2 ng/mL) was significantly higher than that of 629 premenopausal women (3.1 ng/mL) (P<0.0001). The distribution of postmenopausal women with pre-existing diabetes, newly diagnosed diabetes, and non-diabetes was 38 (2.7%), 88 (6.1%), and 1,307 (91.2%), respectively. The median serum ucOC levels of the 3- groups of postmenopausal women significantly decreased with worsened glucose metabolism (pre-existing diabetes 3.38, newly diagnosed diabetes 4.51, and non-diabetes 5.51 ng/mL) (P<0.0001). Multivariate regression analysis showed the FPG and HbA1c values to be negative factors independently associated with the serum ucOC level of postmenopausal women. Conclusions: These findings indicate that the serum ucOC levels decrease in postmenopausal diabetic women, suggesting a relationship between diabetes and osteoporosis.