Sclerostin and its association with insulin resistance in children and adolescents

Abstract

Introduction: Recent studies have shown that sclerostin, which is mainly known as a negative regulator of bone formation, could play an important role in the crosstalk between bone and glucose metabolism. The aim of this study was to investigate the relationship between sclerostin, other bone and fat related factors as osteocalcin (OC), Receptor Activator of Nuclear Factor NF-қB ligand (RANKL), leptin and adiponectin with glucose metabolism and insulin action in children and adolescents with obesity compared with healthy children and adolescents.

Methods: Fifty-five obese children and adolescents, a mean age of 13.2 ± 3.4 yrs., BMI 28.89 ± 5.5 kg/m², and 26 healthy controls (mean age 13.0 ± 4.3 yrs., BMI 19.96 ± 3.1 kg/m²), sex-, and Tanner stage-matched were included into the study. Fasting blood samples for measurement of sclerostin, glucose, lipid profile, HbA1c, C-peptide, OC, RANKL, leptin and adiponectin, and vitamin D were taken at 8.00 AM.

Results: Sclerostin, osteocalcin, RANKL, and adiponectin levels did not differ between obese patients and the control group. Leptin and fasting insulin levels were significantly higher in obese subjects compared with controls (p < 0.01, p = 0.01, respectively). A positive correlation between sclerostin and OC (r = 0.417, p = 0.027) and negative correlations between sclerostin and HOMA-IR and between sclerostin and age (r = -0.24, p = 0.045, r = -0.23, p = 0.037, respectively) were found in all of the subjects. Sclerostin did not correlate with HbA1c, lipids, RANKL and fat-derived leptin and adiponectin. Partial correlation analysis adjusted for age, SDS-BMI and Tanner staging only revealed a negative correlation between sclerostin and HOMA-IR (r = -0.3, p = 0.01). In obese patients this correlation was stronger than in the whole group (r = -0.39, p = 0.005). Moreover, a negative correlation between sclerostin and insulin was found in obese patients (r = -0.39, p = 0.006). In the healthy cohort, sclerostin had a negative correlation only with C-peptide (r = -0.79, p = 0.02).

Conclusions: Sclerostin could play an important role in the regulation of glucose metabolism in children and adolescents, regardless of other fat and bone-derived factors. In obese young patients it's action could be associated with decreasing insulin resistance.

Keywords: Children and adolescents; Insulin action; Obesity; Sclerostin.