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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL127307-03
Application #
9283627
Study Section
Special Emphasis Panel (MPOR (JA))
Program Officer
Brown, Marishka
Project Start
2015-08-15
Project End
2020-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
3
Fiscal Year
2017
Total Cost
$115,372
Indirect Cost
$8,546
Name
University of Pittsburgh
Department
Type
Domestic Higher Education
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Simonelli, Guido; Dudley, Katherine A; Weng, Jia et al. (2017) Neighborhood Factors as Predictors of Poor Sleep in the Sueño Ancillary Study of the Hispanic Community Health Study/Study of Latinos. Sleep 40:
Dudley, Katherine A; Weng, Jia; Sotres-Alvarez, Daniela et al. (2017) Actigraphic Sleep Patterns of U.S. Hispanics: The Hispanic Community Health Study/Study of Latinos. Sleep 40:
Ye, Lichuan; Antonelli, Mary T; Willis, Danny G et al. (2017) Couples' experiences with continuous positive airway pressure treatment: a dyadic perspective. Sleep Health 3:362-367
Alcántara, Carmela; Patel, Sanjay R; Carnethon, Mercedes et al. (2017) Stress and Sleep: Results from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. SSM Popul Health 3:713-721
Donovan, Lucas M; Rueschman, Michael; Weng, Jia et al. (2017) The effectiveness of an obstructive sleep apnea screening and treatment program in patients with type 2 diabetes. Diabetes Res Clin Pract 134:145-152
Johnson, Dayna A; Simonelli, Guido; Moore, Kari et al. (2017) The Neighborhood Social Environment and Objective Measures of Sleep in the Multi-Ethnic Study of Atherosclerosis. Sleep 40:
Spilsbury, James C; Patel, Sanjay R; Morris, Nathan et al. (2017) Household chaos and sleep-disturbing behavior of family members: results of a pilot study of African American early adolescents. Sleep Health 3:84-89
Donovan, Lucas M; Patel, Sanjay R (2017) Making the Most of Simplified Sleep Apnea Testing. Ann Intern Med 166:366-367
Simonelli, Guido; Dudley, Katherine A; Weng, Jia et al. (2016) Neighborhood Factors as Predictors of Poor Sleep in the Sueño Ancillary Study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Sleep :