Correlations of Carboxylated and un(der)Carboxylated Osteocalcin with Parameters of Energy Metabolism in Subjects with and without Type 2 Diabetes

Abstract

Background: Osteocalcin is a vitamin K-dependent protein produced by osteoblasts. In systemic circulation, it is found in both carboxylated and un- or undercarboxylated forms. Experimental studies have revealed that un(der)carboxylated osteocalcin affects beneficially the energy metabolism in mice and rats. Clinical trials have confirmed the endocrine activity of osteocalcin in humans. However, it remains controversial as to which form of the protein is the one possessing hormonal function.
Aim: In an attempt to clarify the above question, we searched for associations of un(der)carboxylated and carboxylated osteocalcin with anthropometric and biochemical parameters in subjects with and without type 2 diabetes.
Methods: The current cross-sectional study included 46 diabetics and 19 non-diabetic participants. Circulating levels of carboxylated and un(der)carboxylated osteocalcin were measured through high-sensitive enzyme immunoassay kits. The energy metabolism was characterized by anthropometric measures, lipid profile, fasting blood glucose and glycated hemoglobin level. The level of lipid peroxidation was determined to assess oxidative stress.
Results: Carboxylated osteocalcin was negatively correlated with body mass index, waist circumference and waist-to-height ratio and positively associated with HDL-cholesterol in the entire sample and in the non-diabetic group. In the diabetic group carboxylated osteocalcin was associated with waist circumference and HDL-cholesterol. Un(der)carboxylated osteocalcin was negatively correlated with fasting blood glucose in the non-diabetic group.
Conclusion: Our study confirmed the connection of osteocalcin with parameters of metabolic disorders in humans. We found associations indicating beneficial metabolic effects for both forms of osteocalcin, the carboxylated one being more active.