Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with beta-cell function

Although animal studies suggest that it is the uncarboxylated rather than carboxylated form of osteocalcin that affects glucose homeostasis, the human data are scant and equivocal.

This study investigated associations of uncarboxylated and carboxylated forms of osteocalcin with insulin sensitivity and β-cell function in 140 overweight prepubertal children (43% female, 46% black, 84% obese) with normal glucose levels (n = 99) and prediabetes (n = 41).

An oral glucose tolerance test was used to identify prediabetes and for measurement of insulin sensitivity (Matsuda index), β-cell function [oral glucose tolerance test derived insulinogenic index and disposition index (DI(OGTT))] and uncarboxylated and carboxylated forms of osteocalcin. Visceral adipose tissue (VAT) was assessed using magnetic resonance imaging.

After controlling for age, sex and race, lower uncarboxylated osteocalcin concentrations, Matsuda index, insulinogenic index, and DI(OGTT) and higher VAT levels were found in the prediabetes vs. normal-glucose group (all P < 0.03). Carboxylated osteocalcin levels were not different between groups. Multiple linear regression adjusting for age, sex, race, and VAT revealed that uncarboxylated osteocalcin was associated with insulinogenic index and DI(OGTT) (β = 0.34, 0.36, respectively, both P < 0.04) in the prediabetes group but not the normal-glucose group. In both the normal-glucose and prediabetes groups, carboxylated osteocalcin was associated with insulin sensitivity (β = 0.26, 0.47, respectively, both P < 0.02).

These data suggest that the lower uncarboxylated osteocalcin concentrations found in children with prediabetes may be associated with β-cell dysfunction. In addition, our findings between carboxylated osteocalcin and insulin sensitivity suggest that carboxylated osteocalcin plays a role in human glucose homeostasis.