Circulating Osteocalcin Levels Were Not Significantly Associated With The Risk Of Incident Type 2 Diabetes Mellitus In Elderly Japanese Men: The Fujiwara-Kyo Osteoporosis Risk In Men (Formen) Cohort Study

Introduction: Cross-sectional studies have shown that patients with type 2 diabetes mellitus (T2DM) have low circulating levels of osteocalcin (OC) and undercarboxylated OC (ucOC). This longitudinal study aimed to examine whether low OC or ucOC levels at baseline are associated with the risk of incident T2DM. Methods: We examined 1700 community-dwelling Japanese men (>65 years) after excluding those with history of diseases (other than T2DM) or medications that affect bone and glucose metabolism. T2DM was defined as fasting plasma glucose (FPG) >126 mg/dl or glycated hemoglobin A1c (HbA1c) >6.5%. Participants without prevalent T2DM at baseline were invited to follow-up surveys 5 and 10 years after baseline. Results: Among the participants, 309 with prevalent T2DM showed significantly lower serum OC and ucOC levels at baseline than those without. After excluding these participants, 46 and 57 participants with incident T2DM were identified in the first and second follow-up surveys, respectively. These participants did not show significantly different OC and ucOC levels at baseline relative to those without T2DM, although their FPG and HbA1c levels at baseline were significantly higher compared to those without incident T2DM. Increase in glycemic indices preceded decrease in OC and ucOC levels. OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM identified in the follow-up surveys. Conclusions: OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM. Our results do not support the findings of animal studies that ucOC is a hormone regulating glucose metabolism.