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

Norman K. Pollock, Paul J. Bernard, Barbara A. Gower, Caren M. Gundberg, Karl Wenger, Sudipta Misra, Reda W. Bassali, Catherine L. Davis

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Context: 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. Objective: 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). Methods: 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 (DIOGTT)] and uncarboxylated and carboxylated forms of osteocalcin. Visceral adipose tissue (VAT) was assessed using magnetic resonance imaging. Results: After controlling for age, sex and race, lower uncarboxylated osteocalcin concentrations, Matsuda index, insulinogenic index, and DIOGTT 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 DIOGTT (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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)E1092-E1099
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number7
DOIs
StatePublished - Jul 1 2011

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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