Corticosteroid-mediated programming and the pathogenesis of obesity and diabetes

Epidemiological studies have shown that low birthweight is associated with increased risk of development of diabetes and obesity in later life. Over-exposure of the developing fetus to glucocorticoids is one of the major hypotheses that has been proposed to explain this association. In animal models, a range of manipulations that increase fetal glucocorticoid load, 'programme' permanent changes in glucose and insulin metabolism and adiposity. This may be mediated by alterations in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In humans, low birthweight is associated with increased circulating glucocorticoid levels, and an increased cortisol response to physiological and psychosocial stressors, in child- and adulthood. This activation of the HPA axis is also associated with increased risk of development of diabetes and obesity in later life.