Sleep Apnea and Longitudinal Changes in Glycemia and Inflammation in Older Men

描述(申请人提供)：尽管睡眠质量和睡眠质量不足会导致严重的健康影响这一事实是我们共同智慧的一部分，但直到最近才受到科学的审视。许多调查结果都令人震惊和可怕。最重要的是，现在很明显，正常睡眠与健康密切相关。睡眠不足或患有睡眠呼吸紊乱(SDB)的人有患各种并发症的风险，包括空腹高血糖和全身炎症。SDB是一种慢性疾病，其特征是睡眠期间上呼吸道反复塌陷。这是普通人群中的一种常见疾病，患病率估计随着年龄的增长而稳步上升。此外，随着越来越多的所有年龄段的成年人夜间睡眠比以往任何时候都少，慢性睡眠不足也成为一个普遍问题。最终，我们提出的研究的长期目标是了解SDB和长期睡眠债务导致不利健康后果的机制。为了方便、节俭和科学严谨，我们将研究空腹高血糖、胰岛素抵抗、全身炎症标志物(即CRP、IL-6和TNF-1)、脂肪细胞因子分泌(瘦素)和下丘脑-垂体-肾上腺(HPA)活动(皮质醇)与SDB和短睡眠时间的关系。为了加快我们的发现进程，我们将利用正在进行的流行病学研究(MROS研究)的基础设施来解决以下两个具体目标：(1)评估SDB严重程度、葡萄糖代谢、全身炎症和HPA活性指标之间的横断面和纵向关联；以及(2)描绘通常睡眠时间、葡萄糖代谢、全身炎症和HPA活性之间的横断面和纵向关联。MROS研究是一项对老年男性进行的多中心队列研究，他们已经被密切跟踪了七年。参与者还接受了活动描记以评估通常的睡眠模式，并进行了多导睡眠描记以了解SDB的存在和严重程度。此外，还可以使用DXA和CT分别测量全身和局部脂肪分布。目前的建议旨在利用这一丰富的数据收集以及通过多次临床访问收集的血清样本的可用性。总之，拟议的研究不仅将探讨睡眠不足和SDB是否与糖代谢异常和全身炎症有关，而且还将对慢性睡眠不足和SDB可能导致高血压、2型糖尿病和心血管疾病等疾病的基本生理机制产生重要的见解。 公共卫生相关性：这项研究提案的总体目的是确定睡眠呼吸暂停和睡眠时间短是否与社区老年男性较高的空腹血糖和胰岛素水平有关。此外，我们还试图确定患有睡眠呼吸暂停和习惯性睡眠不足的男性是否存在皮质醇水平和其他炎症指标的异常，这些指标是心血管疾病的已知风险因素。

DESCRIPTION (provided by applicant): Though long part of our common wisdom, the fact that inadequate sleep quantity and quality lead to serious health implications have only recently come under scientific scrutiny. Many of the findings have been striking and frightful. Most germane, it is now evident that normal sleep and health are intimately related. People who sleep less or have sleep-disordered breathing (SDB) are at risk for a variety of complications including fasting hyperglycemia and systemic inflammation. SDB is a chronic condition characterized by recurrent collapse of the upper airway during sleep. It is a common disorder in the general population with prevalence estimates that steadily increase with age. In addition, chronic sleep loss has also become a pervasive problem with increasing number of adults of all ages sleeping less at night than ever before. Ultimately, the long-term goal of our proposed research is to understand the mechanisms by which SDB and chronic sleep debt lead to adverse health consequences. For the sake of expediency, frugality, and scientific rigor, we will examine how SDB and short sleep duration are associated with fasting hyperglycemia, insulin resistance, markers of systemic inflammation (i.e., CRP, IL-6, and TNF-1), adipocytokine secretion (leptin) and hypothalamic-pituitary-adrenal (HPA) activity (cortisol). To speed our process of discovery, we will utilize the infrastructure of on ongoing epidemiologic study (The MrOS study) to address the following two specific aims: (1) To assess the cross-sectional and longitudinal associations between indices of SDB severity, glucose metabolism, systemic inflammation, and HPA activity; and (2) To delineate the cross-sectional and longitudinal associations between usual sleep duration, glucose metabolism, systemic inflammation, and HPA activity. The MrOS study is a multi-center cohort study of older men who have been closely followed for seven-year period. Participants have also undergone actigraphy for assessments of usual sleep patterns and polysomnography for the presence and severity of SDB. In addition, DXA- and CT-derived measures of total body and regional fat distribution, respectively, are also available. The current proposal aims to utilize this rich collection of data along with the availability of serum samples which were collected over multiple clinic visits. Together, the proposed studies will address not only whether sleep deprivation and SDB are associated with abnormalities in glucose metabolism and systemic inflammation but will also yield important insight into the basic physiologic mechanisms by which chronic sleep debt and SDB may lead to medical conditions such as hypertension, type 2 diabetes mellitus, and cardiovascular disease. PUBLIC HEALTH RELEVANCE: The overall purpose this research proposal is to determine whether sleep apnea and short sleep duration are related to higher fasting glucose and insulin levels in older community-dwelling men. In addition, we also seek to determine whether men that have sleep apnea and habitually sleep less than other have abnormalities in their cortisol levels and other inflammatory markers that are known risk factors for cardiovascular disease.