Lower Uncarboxylated Osteocalcin Concentrations in Children with Prediabetes Is Associated with β-Cell Function

• Published in: The journal of clinical endocrinology and metabolism 2011-07, Vol.96 (7), p.E1092-E1099
• Main Authors: Pollock, Norman K, Bernard, Paul J, Gower, Barbara A, Gundberg, Caren M, Wenger, Karl, Misra, Sudipta, Bassali, Reda W, Davis, Catherine L
• Format: Article
• Language: English
• Subjects: Adipose tissue; Age; Beta cells; Blood Glucose; Body weight; Child; Children; Data processing; Disposition; Female; Glucose tolerance; Glucose Tolerance Test; Homeostasis; Hot Topics in Translational Endocrinology; Humans; Insulin; Insulin Resistance - physiology; Insulin-Secreting Cells - physiology; Magnetic resonance imaging; Male; Obesity; Osteocalcin; Osteocalcin - blood; Prediabetic State - blood; Prediabetic State - physiopathology; Races; Sex
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2010-2731

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.