Serum osteocalcin level is positively associated with insulin sensitivity and secretion in patients with type 2 diabetes.

Bone is being recognized as an endocrine organ. Although previous animal studies showed that osteocalcin stimulated the expression of insulin in islets and of adiponectin in adipocytes with increased insulin secretion and sensitivity, the associations of serum osteocalcin with those parameters remain unclear in humans. In this cross-sectional study, we employed 101 postmenopausal women and 152 men with type 2 diabetes, who have not taken drugs for diabetes or osteoporosis. We also examined 75 g oral glucose tolerance test (OGTT) in 18 postmenopausal women and 20 men who visited our clinic for medical check-up for diabetes. In both postmenopausal women and men, multiple regression analysis adjusted for age, body mass index, and serum creatinine showed that serum osteocalcin level was significantly and negatively associated with fasting plasma glucose, HbA(1c), %Trunk fat, and homeostasis model assessment (HOMA) for insulin resistance (p<0.05), and positively with HOMA for beta-cell function (p<0.05). In addition, significant positive association of serum osteocalcin level with serum adiponectin level was found in postmenopausal women (p<0.05), but not in men. In the OGTT examinations, subjects were divided into tertiles by their serum osteocalcin levels in each gender. Postmenopausal women in the lowest tertile showed hyperglycemia and hyperinsulinemia compared to those in the highest tertile after oral glucose loading (p<0.05). Men in the lowest tertile also exhibited hyperinsulinemia (p<0.05), while hyperglycemia was not found. These findings indicate that serum osteocalcin level is positively associated with insulin sensitivity and secretion in Japanese patients with type 2 diabetes.