Pediatric Obstructive Sleep Apnea and Metabolic Syndrome

该提案将通过导师、课程和培训，为PI提供临床研究方面的正式和非正式教育。 工作，研讨会，并追求一个以病人为导向的研究项目，检查之间的关系， 阻塞性睡眠呼吸暂停（OSAS）和代谢综合征。代谢综合征是2型糖尿病的前兆 糖尿病（T2 DM）和心血管疾病。独立于肥胖，OSAS是成人的一个危险因素， 胰岛素抵抗和高血压，代谢综合征的两个组成部分。内分泌改变 在成人OSAS中观察到了系统和炎症标志物， 代谢综合征，而脂肪组织中的紊乱，在激素和细胞因子的产生中活跃， 与代谢综合征有关儿童肥胖症的日益普遍， 2型糖尿病提示OSAS也应该被评估为与儿童代谢综合征的联系。我们 假设儿童OSAS患者睡眠和/或低氧血症的反复觉醒导致 炎症级联反应，包括脂肪因子的改变，以及增强的拟交感神经输出， 导致血压升高和胰岛素敏感性降低， 扭转这些混乱。我们将对肥胖和肥胖症患者进行多导睡眠图和详细的代谢研究， 非肥胖儿童和非肥胖儿童OSAS，这些研究将重复治疗后， 儿童OSAS，以解决我们的具体目标：1）确定儿童OSAS是否有 胰岛素敏感性降低与OSAS的严重程度相关，2）为了确定儿童是否患有 阻塞性睡眠呼吸暂停综合征（OSAS）可增加循环炎症标志物，干扰脂肪因子， 与胰岛素敏感性相关的儿茶酚胺分泌，和3）确定是否有效 OSAS的治疗逆转了胰岛素抵抗、代谢和炎症变化。PI，其 主要职业目标是成为一名具有儿科内分泌合并症专业知识的临床研究员 疾病，将利用这项研究作为职业发展的机制：1）巩固她的技能，作为一个临床 研究者通过与CHOP及其GCRC的儿科临床研究专家合作，2）参与 在宾夕法尼亚大学接受过临床研究、药理学和神经生物学方面的正规教育， 3）通过地方和全国会议继续进行糖尿病和内分泌学教育。

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.