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.
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