The overall goal of this application is to determine whether decreased resiliency of the HPA axis, (as reflected by increased evening cortisol levels) and/or sleep disturbances (and the associated decreased amounts of slow-wave sleep (SWS) and growth hormone (GH) secretion) adversely affect components of glucose tolerance. Studies to be performed in healthy young subjects will involve the manipulation of stress responses and/or one of its major neuroendocrine correlates (cortisol levels), as well as of sleep and/or one of its major neuroendocrine correlates (GH secretion). These manipulations will include: activation of the HPA axis by exposure to physical exercise or brief psychological stressors, entrainment of insulin secretion and insulin sensitivity to exogenously controlled oscillations of cortisol levels, acute partial sleep deprivation, chronic sleep curtailment and sleep extension, suppression and restoration of nocturnal GH secretion. Studies in middle-aged non-obese adults, who have shallow sleep, decreased GH secretion but normal cortisol profiles will test the hypothesis that the restoration of deep sleep by pharmacological treatment will increase nocturnal GH secretion and improve components of glucose tolerance on the next day. Studies in young obese subjects, who have normal sleep, decreased GH secretion and elevated evening cortisol levels will test the hypotheses that the abnormal diurnal variation in glucose tolerance associated with obesity is partially caused by the elevation of evening cortisol levels and that the restoration of sleep onset GH secretion by bedtime injection of exogenous GH will have beneficial effects on glucose regulation. In all studies, the primary output measures will be components of glucose tolerance, including beta-cell responsivity, insulin sensitivity, glucose effectiveness and insulin clearance. Taken together, the results of these studies should demonstrate the interactive roles of sleep quality and resilience to stress in the maintenance of normal glucose tolerance, and determine whether approaches to correct age-related reductions in sleep quality could prevent or delay the development of impaired glucose tolerance.

R01DK041814

1989-07-01

2005-04-30