SLEEP DISORDERED BREATHING, METABOLIC SYNDROME, AND VASCULAR FUNCTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。胰岛素抵抗和代谢综合征与血管内皮功能障碍和动脉粥样硬化有共同的危险因素和致病机制。睡眠呼吸障碍（SDB）可能以复杂的方式与这一致病区域相关，既可能是结果（通过肥胖），也可能是原因（通过低氧血症、氧化应激和交感超负荷）。本研究的主要目的是在威斯康星睡眠队列（WSC）研究（SPID 8813）的参与者样本中研究SDB与代谢综合征和血管功能障碍发生率之间的纵向关联，该研究是一组中年个体，在过去15年中反复进行了完全睡眠研究，每个参与者最多4个，间隔4年。在WSC至少两次访问的总共600名参与者将被招募到研究中。该组包括a)约150例突发代谢综合征，b)随机抽取约450-470名队列成员。这些参与者将接受非侵入性血管功能测量，包括：(1)肱动脉反应性；(2)脑动脉对高碳酸血症的反应性；(3)视网膜小动脉/静脉比值。此外，我们将测量低氧应激（VEGF）、氧化应激（尿异前列腺素）、交感神经和下丘脑-垂体-肾上腺轴功能（心率变异性、尿去甲肾上腺素、尿皮质醇）的标志物。拟议的研究将验证最近或过去的SDB预测代谢综合征的发生，并与胰岛素抵抗程度（HOMA-IR）和血管或内皮功能障碍有关的假设。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. [from CRISP website (edited)] Insulin resistance and the metabolic syndrome share risk factors and disease-causing mechanisms with vascular endothelial dysfunction and atherosclerosis. Sleep disordered breathing (SDB) might be associated with this diesease-causing area in complex ways, both as a result (via obesity) and as a cause (via hypoxemia, oxidative stress, and sympathetic overload). The primary objective of this study is to study the longitudinal association between SDB and the incidence of the metabolic syndrome and vascular dysfunction in a sample of participants in the Wisconsin Sleep Cohort (WSC) Study (SPID 8813), a group of middle-age individuals who have undergone repeated full sleep studies over the last 15 years, up to four in each participants, four years apart. A total of 600 participants with at least 2 visits in the WSC will be recruited into the study. This group includes a) about 150 cases of incident metabolic syndrome, and b) a random sample of about 450-470 members of the cohort. These participants will undergo non-invasive measures of vascular function including: (1) brachial artery reactivity; (2) cerebral artery responsiveness to hypercapnia; and (3) retinal arteriolar/venular ratio. In addition, we will measure markers of hypoxic stress (VEGF), oxidative stress (urinary isoprostane), and sympathetic and hypothalamic-pituitary-adrenal axis function (heart rate variability, urinary norepinephrine, urinary cortisol). The proposed study will test the hypothesis that recent or past SDB predicts incident metabolic syndrome and is related to the degree of insulin resistance (HOMA-IR), and vascular or endothelial dysfunction.