Association of osteocalcin with obesity, insulin resistance, and cardiovascular risk factors in young adults

Low levels of osteocalcin (OCN), an osteoblast-specific hormone, have recently been associated with insulin resistance (homeostasis model assessment-insulin resistance (HOMA-IR)) and obesity, particularly in older adults. The aim of this study was to determine whether low levels of OCN would be associated with insulin resistance, obesity, and greater cardiovascular (CV) risk in young adults just emerging from adolescence. Undercarboxylated OCN and carboxylated OCN levels were measured on stored serum samples (total OCN = undercarboxylated OCN carboxylated OCN) on 137 participants (67 males) at mean age 18.6 years (range 17-22 years). Insulin resistance was measured by hyperinsulinemic-euglycemic clamp (M_lbm). Multivariable regression analyses with ln(OCN) as the independent variable were adjusted for age, sex, ethnicity, and BMI as indicated. Total OCN was inversely related to BMI, waist circumference, systolic blood pressure (SBP), interleukin (IL)-6, and directly related to M_lbm; only SBP remained significant (with M_lbm P = 0.0560) after further adjustment for BMI. Carboxylated OCN was inversely related to BMI, waist circumference, SBP, low-density lipoprotein cholesterol (LDL-C), and directly related to adiponectin; SBP and adiponectin remained significant after further adjustment for BMI. There were no significant associations with undercarboxylated OCN. In summary, most associations with OCN were mediated via BMI. However, the significant associations of OCN with SBP, obesity, and adiponectin and borderline with M_lbm, suggest a potential role for OCN in the development of insulin resistance and CV risk that becomes more apparent with aging into older adulthood.