Obstructive Sleep Apnea Increases Cardiovascular Risk in Type 2 Diabetes

阻塞性睡眠呼吸暂停会增加 2 型糖尿病的心血管风险

• 批准号: 8606770
• 负责人: Sanjay R Patel
• 金额: $ 79.92万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8606770
• 关键词: Animals; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Clinical Trials; Collaborations; Comorbidity; Data; Development; Diabetes Mellitus; Discipline; Disease; Double-Blind Method; Elasticity; Epidemiology; Generations; Human; Iontophoresis; Lead; Life Style; Lipids; Magnetic Resonance Imaging; Mediating; Microcirculation; Neurocognitive; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obstructive Sleep Apnea; Patients; Poly(ADP-ribose) Polymerases; Prevalence; Public Health; Randomized; Randomized Clinical Trials; Research Design; Research Personnel; Risk; Role; Skin; Solid; Suggestion; Techniques; Testing; Ultrasonography; Vascular Diseases; Ventricular Function; Work; brachial artery; cardiovascular disorder risk; cardiovascular risk factor; clinical effect; endothelial dysfunction; frontier; glycemic control; improved; insight; macrovascular disease; nCPAP Ventilation; nitrosative stress; novel; novel therapeutic intervention; primary outcome; prospective; public health relevance; vascular risk factor

DESCRIPTION (provided by applicant): Despite improvements in the management of cardiovascular disease in type 2 diabetes, its prevalence remain still unacceptably high while numerous recent studies have indicated that improvements of glycemic control beyond a certain point have minimal, if any, effects on the macrovascular disease. This has led to the suggestion that targeting coexisting conditions, such as OSA, may be the new frontier in the effort to reduce risk of cardiovascular disease in diabetes. OSA was initially thought to be a marker of comorbidities related to an unfit lifestyle but is currently considered a real vascular risk factor. Thus, both animal and human epidemiological and interventional studies have shown that OSA can lead to development of cardiovascular disease. There is also a strong possibility that a synergistic interaction exists between OSA and diabetes significantly increasing cardiovascular risk, but before solid conclusions can be reached, the alternative hypothesis, namely that two diseases may offset one another or that risk may be limited by ceiling effects of the two diseases should be explored in more detail. The main hypothesis of the current application is that OSA and diabetes additively or synergistically increase the proinflammatory state that leads to endothelial dysfunction and the development of cardiovascular disease. We also hypothesize that appropriate treatment of OSA will improve vascular function in both the micro- and macrocirculation. Finally, we will test the hypothesis that this improvement is associated with a reduction of the proinflammatory state. In order to test our hypothesis, we will prospectively examine the effect of OSA treatment in the vascular function and the proinflammatory state of patients with DM and OSA. In order to test our hypothesis, the study will have three aims. The first aim will establish the combined effect of OSA and DM on cardiovascular function by comparing the effects of DM, OSA, and DM plus OSA on the ventricular function, aortic elasticity, vascular reactivity and proinflammatory status. The second aim involves a prospective, randomized clinical trial which will examine the effect of nasal continuous positive airway pressure (CPAP) treatment on the cardiovascular risk. The third aim will identify possible mechanisms through which OSA treatment reduces cardiovascular risk. The current proposal will encompass the collaboration of investigators working in various disciplines and has the potential to create very strong synergy and will lead to the generation of novel and very clinically useful data. Thus, it will be one of the very first ones in providing insight regarding the contributory effects of OSA in vascular disease in T2DM and the possible beneficial effects of OSA treatment. In that sense, it can have an immediate clinical effect as it may represent as paradigm shift in the way that OSA is viewed and managed by the professionals who treat T2DM patients. In addition, the proposed mechanistic studies have the potential to lead to new therapeutic approaches in the management of T2DM patients with OSA. PUBLIC HEALTH RELEVANCE: A strong synergistic interaction exists between OSA and diabetes significantly increasing cardiovascular risk, but before solid conclusions can be reached, the alternative hypothesis, namely that two diseases may offset one another or that risk may be limited by ceiling effects of the two diseases should be explored in more detail. We will establish the combined effect of OSA and DM on cardiovascular function by comparing the effects of DM, OSA, and DM plus OSA on the ventricular function, aortic elasticity, vascular reactivity and proinflammatory status. We will also investigate the effect of OSA treatment in the vascular function and the proinflammatory state of patients with DM and OSA.

描述（由申请人提供）：尽管 2 型糖尿病心血管疾病的治疗有所改善，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，血糖控制的改善超过某一点，对大血管疾病的影响即使有，也是微乎其微的。因此有人提出，针对 OSA 等共存疾病可能是降低糖尿病患者心血管疾病风险的新领域。 OSA 最初被认为是与不健康生活方式相关的合并症的标志，但目前被认为是真正的血管危险因素。因此，动物和人类流行病学和介入研究均表明 OSA 可导致心血管疾病的发生。 OSA 和糖尿病之间也很有可能存在协同相互作用，显着增加心血管风险，但在得出可靠结论之前，应更详细地探讨另一种假设，即两种疾病可能相互抵消，或者风险可能受到两种疾病上限效应的限制。当前申请的主要假设是OSA和糖尿病相加或协同增加促炎状态，导致内皮功能障碍和心血管疾病的发展。我们还假设适当的 OSA 治疗将改善微循环和大循环的血管功能。最后，我们将检验这一假设，即这种改善与促炎症状态的减少有关。为了检验我们的假设，我们将前瞻性地研究 OSA 治疗对 DM 和 OSA 患者血管功能和促炎症状态的影响。为了检验我们的假设，该研究将有三个目标。第一个目标是通过比较 DM、OSA 以及 DM 加 OSA 对心室功能、主动脉弹性、血管反应性和促炎状态的影响，确定 OSA 和 DM 对心血管功能的综合影响。第二个目标涉及一项前瞻性随机临床试验，该试验将检查经鼻持续气道正压通气 (CPAP) 治疗对心血管风险的影响。第三个目标是确定 OSA 治疗降低心血管风险的可能机制。目前的提案将涵盖不同学科研究人员的合作，有可能产生非常强大的协同作用，并将产生新颖且非常临床有用的数据。因此，它将是最早深入了解 OSA 对 T2DM 血管疾病的影响以及 OSA 治疗可能产生的有益效果的研究之一。从这个意义上说，它可以产生立竿见影的临床效果，因为它可能代表治疗 T2DM 患者的专业人员看待和管理 OSA 的方式的范式转变。此外，所提出的机制研究有可能为患有 OSA 的 T2DM 患者带来新的治疗方法。 公共卫生相关性：OSA 和糖尿病之间存在强烈的协同相互作用，显着增加心血管风险，但在得出可靠结论之前，应更详细地探讨另一种假设，即两种疾病可能相互抵消，或者风险可能受到两种疾病上限效应的限制。我们将通过比较 DM、OSA 以及 DM 加 OSA 对心室功能、主动脉弹性、血管反应性和促炎状态的影响，确定 OSA 和 DM 对心血管功能的联合影响。我们还将研究 OSA 治疗对 DM 和 OSA 患者血管功能和促炎症状态的影响。