E.W. "Al" Thrasher
Status: Funded - Closed
The role of the stress hormone cortisol in the development of obesity and the metabolic syndrome in children
Elisabeth van Rossum, M.D., Ph.D.
BACKGROUND: Worldwide childhood obesity has increased enormously resulting in adverse effects on blood pressure, cholesterol, and glucose levels, also called “metabolic syndrome”, ultimately leading to cardiovascular disease at young adult age. An important link in the risk of developing metabolic syndrome (MetS) at young age may be the stress hormone cortisol, since in pathological conditions high cortisol levels lead to obesity, diabetes, elevated blood pressure and high cholesterol.
GAP: The relationship between cortisol and the MetS in children is not known, partly due to inadequate tools for measuring long-term cortisol, which have been used up till now. In this study used the unique tools of measuring cortisol levels in scalp hair, accurately reflecting chronic cortisol levels, and additionally we studied genes determining cortisol sensitivity.
HYPOTHESIS: We hypothesize that chronic increased exposure to the stress hormone cortisol is related to the presence of obesity and the metabolic syndrome in children.
METHODS: Study 1: We performed a cross-sectional study of cortisol and cortisone concentrations over a 3-month period, measured by LC–MS/MS in scalp hair of 3019 6-year-old children participating in the Generation R study, a population-based prospective cohort study from fetal life onwards. Genotyping of Glucocorticoid Receptor (GR) gene polymorphisms was performed. Numerous clinical data were collected from these children since their prenatal phase, in particular data on body composition and metabolic syndrome..
Study 2: In addition, we developed normal values of cortisol and cortisone in children, and also studied the hair cortisol levels in 54 children aged 4-18 years with adrenal insufficiency treated with cortisol substitution (such as Addison’s disease, and congenital adrenal hyperplasia), and compared them to 54 healthy children, matched for gender and age.
RESULTS: Study 1: Of all children in Generation R, 4.3% was obese and 13.4% overweight. Cortisol was significantly associated with a 9-fold increased risk of obesity (OR: 9.4 (3.3–26.9), and increased risk of overweight (OR: 1.4 (1.0–2.0)). Cortisone was also associated with an increased risk of obesity (OR: 1.9 (1.0–3.5)). Cortisol and cortisone were significantly positively associated with body mass index, fat mass (FM) and android/gynecoid FM ratio. This indicates that more of the metabolically adverse abdominal fat is present when cortisol levels are chronically high. GR polymorphisms were not associated with adiposity parameters.
Study 2: Mean long-term cortisol levels were significantly higher in adrenal insufficiency patients compared to healthy children (mean 13.3 vs 8.2 pg/mg, p=0.02). Adrenal insufficiency patients also had a higher BMI (p<0.001) and waist circumference (WC) (p=0.02). Long-term cortisol was significantly associated with BMI (p=0.002) and WC (p=0.002), and explained 13% of the difference in BMI and 29% of the difference in WC between adrenal insufficiency patients and controls.
IMPACT: Study 1: Long-term cortisol concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. This may indicate that cortisol is already at young age an important risk factor of obesity and metabolic syndrome. Future research may reveal what the exact causes are of these increased cortisol levels, and whether increased cortisol may be a target for therapy.
Study 2: Cortisol (hydrocortisone) treated children with adrenal insufficiency have increased long-term cortisol levels and adverse anthropometric characteristics compared to healthy controls. Hair cortisol measurement seems of value in identifying overtreatment and thereby improve hydrocortisone replacement therapy in children.
Website Link: http://www.erasmusmc.nl/inwendige_geneeskunde/endocrinologie/organisatie/dokter/3762230/
Metabolic Syndrome, Obesity, Prospective Cohort, Diagnosis, Human