Background: Osteocalcin (OCN) is an osteoblast-derived hormone regulating glucose homeostasis. OCN secretion is related to the production of insulin and of adipokines in a bidirectional relationship. Preclinical data suggest that OCN regulates endothelial function, but data in humans are inconsistent. Aim: To evaluate whether OCN serum levels are related to adipose tissue distribution and to adipokines in people with autoimmune diabetes (AD), and their association with estimated CV risk. Methods: Body composition was evaluated with dual-energy X-ray absorptiometry (DXA) in 62 subjects (median age 49.4 [23-79], disease duration 15 [1-64] years, HbA1c 7.9 [5.7-10.7]%, BMI 25.8 [17.2-46.8] kg/m2) with AD. Fat distribution was assessed by upper body fat deposition index (UBFDI), calculated as the ratio between upper body and lower body fat. Adipokines (vaspin, leptin, adiponectin), as well as OCN, were measured by ELISA in serum samples collected at fasting. CV risk was assessed with the Steno type 1 risk engine score (ST1RES). Results: OCN was negatively associated with HbA1c (r=0.06 p=0.032), UBFDI (r=0.22 p 0.0023), Vaspin (r=0.09 p=0.013) and positively associated with adiponectin (r=0.16, p=0.013). People with higher CV risk showed lower OCN levels and higher UBFDI, a marker of unhealthy adipose tissue distribution (Fig. 1A-B). A logistic binary regression for ST1RES (low versus medium/high risk) showed significant associations of UBFDI and adiponectin with the medium/high risk category: Odds Ratio (OR) [95% confidence intervals (CI)] for 1 standard deviation increase: 3.58 [1.05-12.23], p=0.042, and 3.92 [1.15-13.36], p=0.029, respectively. The association of OCN with ST1RES disappeared after correction for such variables. Conclusion: OCN serum levels decrease with increasing HbA1c levels in AD, supporting the hypothesis that hyperglycemia impact bone turn-over and OCN release. The negative correlation of OCN with UBFDI and vaspin, and the positive association with adiponectin, suggest that OCN is implicated in pathways promoting an healthy expansion of adipose tissue, indirectly relating OCN with CV risk.
