Insulin sensitivity and secretion in children and adolescents with hypothalamic obesity following treatment for craniopharyngioma

Background Craniopharyngioma (CP), a tumour occurring in the hypothalamic-pituitary area, results in morbid obesity in 25-60% of affected children. It has been suggested that abnormalities of insulin secretion and/or insulin action due to hypothalamic injury may be associated with weight gain and the metabolic syndrome in this population. Aim To evaluate: (i) insulin secretion (IS) and insulin sensitivity (Si); (ii) features of the metabolic syndrome (MS) and (iii) factors involved in risk for diabetes and heart disease in obese youth treated for CP. Methods Obese subjects treated for CP were compared to BMI-matched control subjects. All subjects underwent anthropometric, blood pressure, resting energy expenditure and body fat assessment. Cholesterol and inflammatory markers, oral glucose tolerance test (OGTT) and frequent sampling intravenous glucose tolerance test (FSIGT), with calculation of IS and Si, were performed. Results Fifteen CP subjects and 15 controls (C) were studied. There were no differences between CP and C for age, gender, BMI or pubertal status. MS was present in 10/15 CP and 3/15 C (P = 0·03), including impaired glucose tolerance (IGT) in 6/15 CP and 0/15 C (P = 0·02). Measures of IS, including first and second phase IS, and insulin area-under-the-curve (AUC_ins) during OGTT, were significantly higher in CP. Si, measured by frequent sampled intravenous glucose tolerance test (Si-FSIGT), was significantly lower in CP subjects (0·96 ± 0·34 vs. 1·67 ± 0·7; P = 0·01). AUC _ins was negatively correlated with Si-FSIGT (r = -0·62; P = 0·003). Conclusion Children with CP and hypothalamic obesity have more features of MS, increased IS and IGT prevalence and lower Si compared with BMI-matched controls.