Mentored Patient Oriented Research in Sleep and Metabolic Disease

指导以患者为导向的睡眠和代谢疾病研究

• 批准号: 9230624
• 负责人: Sanjay R Patel
• 金额: $ 11.54万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9230624
• 关键词: Age; Animal Model; Aorta; Blood Circulation; Blood Pressure; Blood Vessels; Body mass index; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Clinical Management; Clinical Trials; Comorbidity; Continuous Positive Airway Pressure; Data; Development; Diabetes Mellitus; Disease; Double-Blind Method; Elasticity; Evaluation; Experimental Designs; Functional disorder; Goals; Health; Heart; High Prevalence; Human; Hypercapnia; Hypoxia; Inflammation; Inflammatory; Insulin Resistance; Lead; Life Style; Lipids; Measures; Mediating; Mentors; Metabolic Diseases; Morbidity - disease rate; Neurocognitive; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obstructive Sleep Apnea; Outcome; Oxidative Stress; Pathway interactions; Patients; Placebo Control; Placebos; Play; Poly(ADP-ribose) Polymerases; Population; Prevalence; Public Health; Randomized; Recurrence; Research Project Grants; Risk; Risk Factors; Role; Scientist; Sleep; Sleep Apnea Syndromes; Sleep Fragmentations; Solid; Suggestion; Testing; Time; Training; Vascular Diseases; Ventricular; Work; blood pressure reduction; brachial artery; burden of illness; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; career development; diabetic; diabetic patient; endothelial dysfunction; frontier; glycemic control; heart disease risk; high risk; improved; improved functioning; mortality; next generation; nitrosative stress; patient oriented research; patient population; prospective; protein tyrosine phosphatase 1B; screening; sex; skills; treatment program

 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.

 描述（由申请人提供）：近期目标：检查阻塞性睡眠呼吸暂停（OSA）作为糖尿病心血管危险因素的作用，长期目标是评估筛查和治疗2型糖尿病患者人群中OSA的相关性。职业发展目标：提供足够的时间进行辅导，并进一步发展辅导技能。研究项目：尽管2型糖尿病心血管疾病的管理有所改善，但其患病率仍然高得令人无法接受，而最近的许多研究表明，血糖控制改善超过一定程度对大血管并发症的影响极小（如果有的话）。这导致了这样的建议，即针对共存的条件，如OSA，可能是努力降低糖尿病心血管风险的新前沿。动物模型研究和人类研究表明，OSA是心血管疾病的独立危险因素。初步数据表明，OSA和糖尿病之间至少有一种相加作用，如果不是协同作用的话，但在得出可靠的结论之前，需要更详细地探讨另一种假设，即两种疾病可能相互抵消，或者风险可能受到天花板效应的限制。本申请的主要假设是OSA和糖尿病协同增加内皮功能障碍，并因此增加心血管疾病风险。我们还假设，OSA的适当治疗将改善糖尿病患者微循环和大循环的血管功能。我们将首先评估心血管健康状况，包括心室质量、主动脉弹性、肱动脉反应性、2型糖尿病患者、OSA患者、2型糖尿病合并OSA患者和健康对照者的微血管横截面血流，以检验这些假设。接下来，我们将评估2型糖尿病合并OSA的人群中相同的心血管结局，这些人群随机接受3个月的OSA治疗，使用持续气道正压通气进行活性药物治疗与安慰剂治疗。最后，我们将通过探索蛋白酪氨酸磷酸酶1b（PTP1B）通路的表达和激活来探索OSA影响糖尿病患者心血管功能的潜在细胞机制。