This proposal will provide the PI formal and informal education in clinical research through mentors, course work, seminars, and the pursuit of a patient-oriented research project examining the relationship between obstructive sleep apnea (OSAS) and metabolic syndrome. Metabolic syndrome is a precursor to Type 2 diabetes (T2DM) and cardiovascular disease. Independent of obesity, OSAS is a risk factor in adults for insulin resistance and hypertension, both components of metabolic syndrome. Alterations in the endocrine system and in inflammatory markers have been observed in adult OSAS and may directly contribute to metabolic syndrome while disturbances in adipose tissue, active in both hormone and cytokine production, have recently been implicated in metabolic syndrome. The increasing prevalence of pediatric obesity and T2DM suggests OSAS should also be evaluated as a link to metabolic syndrome in children. We hypothesize that the repeated arousals from sleep and/or hypoxemia of pediatric OSAS lead to an inflammatory cascade, including alterations in adipokines, and enhanced sympathomimetic output which contribute to blood pressure elevations and decreased insulin sensitivity and that treatment of OSAS reverses these disturbances. We will perform polysomnography and detailed metabolic studies in obese and non-obese children with and without OSAS, and these studies will be repeated following treatment of children with OSAS to address our SPECIFIC AIMS: 1) To determine whether children with OSAS have decreased insulin sensitivity that correlates with severity of OSAS, 2) To determine whether children with OSAS have increased circulating inflammatory markers, disturbances in adipokines, and elevated catecholamine secretion that correlate with insulin sensitivity, and 3) To determine whether effective treatment of OSAS reverses insulin resistance, metabolic, and inflammatory changes. The PI, whose primary career goal is to become a clinical researcher with expertise in endocrine co-morbidities of pediatric disease, will use this study as a mechanism for career development: 1) to solidify her skills as a clinical investigator by working with experts in pediatric clinical research at CHOP and its GCRC, 2) to participate in formal education in clinical research, pharmacology, and neurobiology at The University of Pennsylvania, and 3) to continue education in diabetes and endocrinology through local and national conferences.
