Autonomic Function in Obstructive Sleep Apnea

描述（由申请人提供）：糖尿病（DM）和阻塞性睡眠呼吸暂停（OSA）的患病率随着当前美国肥胖的流行而迅速增加。糖尿病和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。这些疾病之间也存在其他联系，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）的患病率明显较高相关。目前的模型是OSA引起继发于间歇性缺氧的交感神经活动增加。然而，关于OSA是否通过高血糖导致自主神经功能障碍，或者是否通过高血糖损害自主神经系统导致睡眠呼吸暂停存在争议。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。本课题旨在回答以下问题：1)自主神经功能障碍是否独立于IGR发生在OSA中；2)持续气道正压（CPAP）治疗对葡萄糖调节和自主神经功能的影响。我的具体目标是：1)明确OSA患者的自主神经功能障碍是与OSA直接相关还是继发于IGR；2)确定IGR是否与OSA患者周围神经功能障碍相关；3)通过为期6个月的纵向研究评估CPAP对血糖和自主神经功能的影响。我建议的训练部分将包括学习自主神经和周围神经生理学评估的新方法，以及设计和实施纵向研究。作为培训的一部分，我将学习诸如心率变异性的频谱分析和皮肤活检中表皮内神经纤维密度的评估等技术。我的导师，博士。贝丝·马洛和斯蒂芬·戴维斯，以及顾问医生。伊娃·费尔德曼和大卫·罗伯逊。这个职业发展奖将使我实现成为一名专攻神经肌肉疾病的临床科学家的长期目标。

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.