Mentored Patient Oriented Research in Sleep and Metabolic Disease

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 DESCRIPTION (provided by applicant): Immediate Goals: To examine the role of obstructive sleep apnea (OSA) as a cardiovascular risk factor in diabetes with a long term goal of assessing the relevance of screening and treating OSA in type 2 diabetes patient populations. Career Development Goals: To provide sufficient time for mentoring and develop further skills in mentoring. Research Project: Despite improvements in the management of cardiovascular disease in type 2 diabetes, its prevalence remain unacceptably high while numerous recent studies have indicated that improvements of glycemic control beyond a certain point have minimal, if any, effects on macro-vascular complications. This has led to the suggestion that targeting coexisting conditions, such as OSA, may be the new frontier in the effort to reduce cardiovascular risk in diabetes. Studies in animal models as well as human studies demonstrate that OSA is an independent risk factor for cardiovascular disease. Preliminary data suggest there is at least an additive if not synergistic interaction between OSA and diabetes, but before solid conclusions can be reached, the alternative hypothesis, namely that the two diseases may offset one another or that risk may be limited by ceiling effects needs to be explored in more detail. The main hypothesis of the current application is that OSA and diabetes synergistically increase endothelial dysfunction and as a result cardiovascular disease risk. We also hypothesize that appropriate treatment of OSA will improve vascular function in both the micro- and macro-circulation in a diabetic population. We will test these hypotheses by first assessing cardiovascular health including ventricular mass, aortic elasticity, brachial artery reactivity, an micro-vascular flow cross-sectionally in subjects with type 2 diabetes alone, OSA alone, type 2 diabetes plus OSA, and healthy controls. Next, we will assess the same cardiovascular outcomes in a population with type 2 diabetes plus OSA randomized to 3 months of OSA therapy with active versus placebo treatment using continuous positive airway pressure. Finally, we will explore potential cellular mechanisms for OSA to impact cardiovascular function in diabetic patients by exploring expression and activation of the protein tyrosine phosphatase 1b (PTP1B) pathway.