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

描述（由申请人提供）：睡眠不足会导致严重的健康问题，虽然这早已是我们的常识，但直到最近才受到科学的审视。许多发现是惊人的和可怕的。最重要的是，现在很明显，正常的睡眠和健康密切相关。睡眠不足或有睡眠呼吸障碍（SDB）的人有各种并发症的风险，包括空腹高血糖和全身炎症。SDB是一种慢性疾病，其特征是睡眠时上呼吸道反复塌陷。它是普通人群中的一种常见疾病，其患病率估计随着年龄的增长而稳步增加。此外，慢性睡眠不足也已成为一个普遍的问题，越来越多的各个年龄段的成年人晚上的睡眠时间比以往任何时候都少。最终，我们提出的研究的长期目标是了解SDB和慢性睡眠债务导致不良健康后果的机制。为了方便、节俭和科学的严谨性，我们将研究SDB和短睡眠时间与空腹高血糖、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）活性（皮质醇）的关系。为了加快我们的发现过程，我们将利用一项正在进行的流行病学研究（mrs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；(2)描述正常睡眠时间、葡萄糖代谢、全身炎症和HPA活性之间的横断面和纵向关联。mro研究是一项多中心队列研究，对老年男性进行了七年的密切跟踪。参与者还接受了活动描记术来评估通常的睡眠模式和多导睡眠描记术来评估SDB的存在和严重程度。此外，DXA和ct衍生的全身和区域脂肪分布的测量也分别可用。目前的建议旨在利用这一丰富的数据收集以及在多次诊所访问中收集的血清样本的可用性。总之，拟议的研究不仅将解决睡眠不足和SDB是否与糖代谢异常和全身性炎症相关，而且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医学疾病的基本生理机制产生重要见解。

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.