Pediatric Obstructive Sleep Apnea and Metabolic Syndrome

这项建议将通过导师、课程提供临床研究的PI正式和非正式教育 工作、研讨会和追求以患者为中心的研究项目，检查两者之间的关系 阻塞性睡眠呼吸暂停(OSAS)和代谢综合征。代谢综合征是2型的先兆 糖尿病(T2 DM)和心血管疾病。与肥胖无关，阻塞性睡眠呼吸暂停综合征是成人患上 胰岛素抵抗和高血压，都是代谢综合征的组成部分。内分泌的变化 在成人OSAS中观察到系统和炎性标志物，并可能直接参与 代谢综合征，同时脂肪组织紊乱，激素和细胞因子产生活跃， 最近都与代谢综合征有牵连。儿童肥胖症的发病率不断上升， T2 DM提示，OSAS也应被评估为与儿童代谢综合征的联系。我们 假设儿童阻塞性睡眠呼吸暂停综合征反复从睡眠和/或低氧血症中唤醒导致 炎症性级联反应，包括脂肪因子的改变，以及增强的拟交感神经输出，这 有助于血压升高和胰岛素敏感性降低以及OSAS的治疗 扭转了这些骚乱。我们将对肥胖患者进行多导睡眠图和详细的代谢研究 患有和不患有阻塞性睡眠呼吸暂停综合征的非肥胖儿童，这些研究将在治疗后重复进行 OSAS儿童解决我们的具体目标：1)确定OSAS儿童是否有 与OSAS严重程度相关的胰岛素敏感性降低，2)确定患有 OSA增加了循环炎症标志物，脂肪因子紊乱，并升高 与胰岛素敏感性相关的儿茶酚胺分泌，以及3)确定是否有效 阻塞性睡眠呼吸暂停综合征的治疗可以逆转胰岛素抵抗、代谢和炎症变化。少年派，他的 主要职业目标是成为一名在儿科内分泌并存方面具有专长的临床研究人员。 疾病，将利用这项研究作为职业发展的机制：1)巩固她作为临床医生的技能 通过与CHOP及其GCRC的儿科临床研究专家合作进行研究，2)参与 在宾夕法尼亚大学接受临床研究、药理学和神经生物学的正规教育， 3)通过地方和国家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.