Endocrine Abstracts

Background: Childhood obesity is an increasing health problem, affecting over 40 million children aged 0–5 years worldwide. It is associated with premature onset of diabetes and cardiovascular disease in adulthood. Pathologically elevated cortisol is known to induce obesity and cardio-metabolic complications, suggesting cortisol is implicated in the onset of obesity. Indeed, recent pilot-studies showed an increase in hair cortisol concentrations in obese adults and adolescents. Additionally, polymorphisms in the glucocorticoid receptor (GR) gene increasing glucocorticoid (GC) sensitivity have been associated with metabolically adverse body composition.

Aim: To explore the role of GCs in the onset of obesity, we studied the associations of long-term GC exposure and genetically determined GC sensitivity with obesity and body fat distribution in children.

Methods: Average cortisol and cortisone concentrations over a 3-month period were measured by LC–MS/MS in scalp hair of 3019 6-year-old children participating in the Generation R study, a population-based cohort-study. Four polymorphisms (GR-9Beta, ER22-23EK, N363S, Bcl1) in the GR gene affecting GC sensitivity were genotyped. Anthropometrics were measured and DEXA scans were performed. World Obesity Federation criteria for weight-cutoffs were used.

Results: A total of 4.3% of the children were obese and 13.4% overweight. Long-term cortisol concentrations were associated with obesity (OR 10.3, P<0.001) and overweight (OR 1.5, P<0.05). Cortisone showed the same trend for obesity (OR 2.1, P<0.05), and overweight (OR 1.4, P=0.08). Cortisol and cortisone showed a positive linear association with BMI (P<0.001 and P<0.01), fat mass index (kg/height²) (P<0.01 and P<0.001) and android/gynecoid fat mass ratio (P=0.04 and P<0.001). Fat mass index was increased in homozygous Bcl1− carriers (P=0.03). We found no effects of other polymorphisms.

Conclusion: Long-term GC levels are strongly associated with an increased risk of childhood obesity, and show linear associations with adverse fat distribution. The contribution of GR gene polymorphisms to body composition at the age of 6 years seems limited.

Disclosure: The Thrasher Research Fund, TRF11643.