Obstructive Sleep Apnea Increases Cardiovascular Risk in Type 2 Diabetes

描述（由申请人提供）：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，而许多最近的研究表明，血糖控制改善超过一定程度对大血管疾病的影响极小（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疾病风险的新前沿。OSA最初被认为是与不健康的生活方式相关的合并症的标志，但目前被认为是真实的血管危险因素。因此，动物和人类的流行病学和干预性研究表明，OSA可导致心血管疾病的发展。OSA和糖尿病之间存在协同作用显著增加心血管风险的可能性也很大，但在得出可靠结论之前，应更详细地探讨备择假设，即两种疾病可能相互抵消或风险可能受到两种疾病的天花板效应的限制。本申请的主要假设是OSA和糖尿病相加或协同地增加导致内皮功能障碍和心血管疾病发展的促炎状态。我们还假设，适当的治疗OSA将改善微循环和大循环的血管功能。最后，我们将测试的假设，这种改善是与减少促炎状态。为了验证我们的假设，我们将前瞻性地检查OSA治疗对DM和OSA患者的血管功能和促炎状态的影响。为了验证我们的假设，这项研究将有三个目标。第一个目的是通过比较DM、OSA和DM + 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作用。第二个目标是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。目前的提案将包括在不同学科工作的研究人员的合作，并有可能创造非常强大的协同作用，并将导致产生新的和非常临床有用的数据。因此，它将是第一个提供有关OSA在T2DM血管疾病中的贡献作用和OSA治疗可能的有益作用的见解。从这个意义上说，它可以具有立即的临床效果，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，提出的机制研究有可能导致新的治疗方法，在管理T2DM患者的OSA。 公共卫生相关性：OSA和糖尿病之间存在强烈的协同作用，显著增加心血管风险，但在得出可靠的结论之前，应更详细地探讨备择假设，即两种疾病可能相互抵消或风险可能受到两种疾病的天花板效应的限制。我们将通过比较DM、OSA和DM + 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作用。我们还将研究OSA治疗对糖尿病合并OSA患者血管功能和促炎状态的影响。

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.