Autonomic Function in Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停的自主神经功能

• 批准号: 7795692
• 负责人: Amanda C Peltier
• 金额: $ 16.56万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795692
• 关键词: Autonomic Dysfunction; Autonomic nervous system; Biopsy; Cardiovascular Diseases; Continuous Positive Airway Pressure; Diabetes Mellitus; Diagnosis; Disease; Epidemic; Evaluation; Fiber; Frequencies; Functional disorder; Glucose; Goals; High Prevalence; Hyperglycemia; Hypoxia; Impaired fasting glycaemia; Impairment; Individual; Insulin Resistance; K-Series Research Career Programs; Learning; Link; Longitudinal Studies; Measures; Mediating; Mentors; Methodology; Modeling; Nerve Fibers; Neuromuscular Diseases; Obesity; Obstructive Sleep Apnea; Patients; Peripheral Nerves; Physiology; Prevalence; Recruitment Activity; Research Personnel; Risk; Scientist; Secondary to; Skin; Sleep Apnea Syndromes; Sleep Deprivation; Study Subject; Sudden Death; Techniques; Training; United States; blood glucose regulation; cohort; density; design; diabetic; glucose metabolism; heart rate variability; impaired glucose tolerance; programs

DESCRIPTION (provided by applicant): The prevalence of diabetes mellitus (DM) and obstructive sleep apnea (OSA) are increasing rapidly with the current epidemic of obesity in the United States. Both DM and OSA are associated with autonomic dysfunction, increasing the risk of sudden death and cardiovascular disease in these disorders. Additional links between these disorders exist as well, as OSA is associated with a significantly higher prevalence of impaired glucose regulation (undiagnosed diabetes, impaired glucose tolerance, or impaired fasting glucose collectively called IGR for the purpose of this study). The current model is that OSA causes increased sympathetic activity secondary to intermittent hypoxia. Controversy exists, however, as to whether OSA causes autonomic dysfunction via hyperglycemia, or whether damage to the autonomic nervous system through hyperglycemia causes sleep apnea. My hypothesis is that IGR resulting from OSA is an independent cause of autonomic dysfunction in these patients. The goals of this proposal are to answer the questions: 1) Does autonomic dysfunction occur in OSA independently of IGR and 2) What is the effect of continuous positive airway pressure (CPAP) therapy on glucose regulation and autonomic function. My specific aims are 1) Define whether autonomic dysfunction in patients with OSA is directly associated with OSA or is secondary to IGR; 2) Determine if there is associated peripheral nerve dysfunction in OSA subjects with IGR; and 3) Evaluate the effect of CPAP on glucose and autonomic function in a six-month longitudinal study. The training component of my proposal will consist of learning new methodology in assessment of autonomic and peripheral nerve physiology, and in designing and implementing a longitudinal study. As part of my training, I will learn techniques such as spectral analysis of heart rate variability and evaluation of intraepidermal nerve fiber density in skin biopsies. My progress will be followed by my mentors, Drs. Beth Malow and Stephen Davis, and by consultants Drs. Eva Feldman and David Robertson. This career development award will allow me to achieve my long-term goal of becoming a clinician-scientist specializing in neuromuscular disorders.

描述（由申请人提供）：随着美国目前肥胖症的流行，糖尿病（DM）和阻塞性睡眠呼吸暂停（OSA）的患病率正在迅速增加。 DM 和 OSA 都与自主神经功能障碍有关，增加了这些疾病中猝死和心血管疾病的风险。这些疾病之间还存在其他联系，因为 OSA 与血糖调节受损（未确诊的糖尿病、糖耐量受损或空腹血糖受损，在本研究中统称为 IGR）的患病率显着升高相关。目前的模型是 OSA 会导致继发于间歇性缺氧的交感神经活动增加。然而，对于 OSA 是否通过高血糖导致自主神经功能障碍，或者高血糖对自主神经系统的损害是否会导致睡眠呼吸暂停，仍存在争议。我的假设是 OSA 引起的 IGR 是这些患者自主神经功能障碍的独立原因。该提案的目标是回答以下问题：1) OSA 中自主神经功能障碍是否独立于 IGR 发生；2) 持续气道正压 (CPAP) 治疗对血糖调节和自主神经功能有何影响。我的具体目标是 1) 明确 OSA 患者的自主神经功能障碍是否与 OSA 直接相关，还是继发于 IGR； 2) 确定伴有 IGR 的 OSA 受试者是否存在相关的周围神经功能障碍； 3) 在一项为期六个月的纵向研究中评估 CPAP 对血糖和自主神经功能的影响。我的建议的培训部分将包括学习评估自主神经和周围神经生理学的新方法，以及设计和实施纵向研究。作为培训的一部分，我将学习心率变异性频谱分析和皮肤活检中表皮内神经纤维密度评估等技术。我的导师 Drs 将关注我的进步。贝丝·马洛（Beth Malow）和斯蒂芬·戴维斯（Stephen Davis）以及顾问博士。伊娃·费尔德曼和大卫·罗伯逊。这个职业发展奖将使我能够实现成为一名专门研究神经肌肉疾病的临床医生科学家的长期目标。