1963-P: Undercarboxylated Osteocalcin Is Correlated with Insulin Secretion in Japanese Individuals with Diabetes

Abstract

Background and Aims: Undercarboxylated osteocalcin (ucOC) is a secreted protein produced by osteoblasts. UcOC can regulate insulin secretion and insulin sensitivity in rodents. Pharmacological administration of ucOC enhances insulin secretion which could be mediated by GLP-1 in mice. However, pathophysiological roles of ucOC in glucose intolerance in human remain unknown. In this study, we aimed to investigate the association between ucOC and glucose metabolism in individuals with varying degrees of glucose tolerance. Materials and Methods: The 75-g oral glucose tolerance test was carried out in 75 Japanese individuals not taking diabetes medications [age: 65±11 (mean±SD); male/female: 34/41; BMI: 24.9±3.8]. Individuals were classified as normal (NGT), impaired glucose tolerance (IGT), and diabetes (DM) groups (each group: n=25). The insulinogenic index (IGI) as an index of insulin secretion, and QUICKI and the Matsuda Index (MI) as indices of insulin sensitivity were calculated. Fasting serum levels of ucOC and leptin were assayed by ECLIA and by ELISA, respectively. Normally-distributed loge-transformed (ln-)values were used for regression analysis in some cases. Results: Although fasting and 2h after glucose loading plasma glucose, HbA1c, IGI, QUICKI and MI were significantly different among the 3 groups, age, sex, BMI, and ucOC were not different. In simple regression analysis in each group, ln-ucOC was not correlated with QUICKI and ln-MI in all 3 groups. Interestingly, ln-ucOC was correlated with ln-IGI (r=0.422, P=0.0345) and HbA1c (r=-0.574, P=0.0022) only in DM. In multiple regression analysis in DM, ln-IGI was independently predicted by BMI (β=0.598) and ln-ucOC (β=0.641) (R2=0.488, P=0.0006) and by ln-leptin (β=0.624) and ln-ucOC (β=0.448) (R2=0.568, P<0.0001). Conclusion: UcOC was correlated with insulin secretion independently of adiposity in Japanese individuals with diabetes. Disclosure S. Funakoshi: None. S. Ohmi: None. E. Amano: None. Y. Terada: None. S. Fujimoto: None.