Autonomic Function in Obstructive Sleep Apnea

描述(申请人提供)：随着目前美国肥胖症的流行，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。糖尿病和阻塞性睡眠呼吸暂停综合征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(在本研究中统称为IGR的未确诊糖尿病、糖耐量受损或空腹血糖受损)的患病率显著增加有关。目前的模型是，OSA引起继发于间歇性低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，或者是否通过高血糖对自主神经系统的损害导致睡眠呼吸暂停，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。这项建议的目的是回答以下问题：1)OSA患者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)确定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OSA IGR患者是否存在相关的周围神经功能障碍；3)在一项为期6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，以及设计和实施一项纵向研究。作为培训的一部分，我将学习一些技术，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。我的导师贝丝·马洛博士和斯蒂芬·戴维斯博士以及顾问伊娃·费尔德曼博士和大卫·罗伯逊博士将跟随我的进步。这个职业发展奖将使我实现我的长期目标，成为一名专门研究神经肌肉疾病的临床医生和科学家。

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.