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.

Public Health Relevance

Both diabetes and sleep apnea are strong risk factors for cardiovascular disease. It is not yet well understood whether having both diabetes and sleep apnea further increases the risk for heart disease beyond either one alone. This is important because sleep apnea commonly occurs in diabetes with roughly half of diabetic pa- tients also having moderate to severe sleep apnea. In this study, we will establish the combined effect of sleep apnea and diabetes on cardiovascular function by comparing the effects of diabetes alone, sleep apnea alone, and both diseases together. In addition, we will assess the extent to which measures of cardiovascular function improve after treating sleep apnea in patients with both sleep apnea and diabetes. These studies will provide an opportunity to train the next generation of sleep scientists in patient-oriented research and will also allow an evaluation of whether screening and treating sleep apnea may be a clinically effective way to reduce the risk of heart and vascular disease in patients with diabetes.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Special Emphasis Panel (MPOR (JA))
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Brown, Marishka
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University of Pittsburgh
Internal Medicine/Medicine
Domestic Higher Education
United States
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