Obstructive Sleep Apnea Increases Cardiovascular Risk in Type 2 Diabetes

描述(申请人提供)：尽管2型糖尿病的心血管疾病管理有所改善，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，血糖控制超过一定程度的改善对大血管疾病的影响很小，如果有的话。这导致有人提出，针对并存疾病，如阻塞性睡眠呼吸暂停，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共病的标志，但现在被认为是真正的血管风险因素。因此，动物和人类的流行病学和干预性研究都表明，OSA可导致心血管疾病的发生。OSA和糖尿病之间存在显著增加心血管风险的协同作用的可能性也很大，但在得出可靠的结论之前，应更详细地探讨另一种假设，即两种疾病可能相互抵消或风险可能受到两种疾病的上限效应的限制。目前应用的主要假说是OSA和糖尿病相加或协同增加促炎状态，从而导致内皮功能障碍和心血管疾病的发展。我们还假设OSA的适当治疗将改善微循环和大循环中的血管功能。最后，我们将检验这样一个假设，即这种改善与促炎状态的减少有关。为了验证我们的假设，我们将前瞻性地检查OSA治疗对糖尿病和OSA患者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。第二个目标涉及一项前瞻性、随机的临床试验，该试验将检验鼻腔持续正压(CPAP)治疗对心血管风险的影响。第三个目标将确定OSA治疗降低心血管风险的可能机制。目前的建议将包括在不同学科工作的研究人员的合作，并有可能产生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，它将是第一批提供有关OSA对T2 DM血管疾病的贡献作用以及OSA治疗可能的有益影响的洞察力的文章之一。从这个意义上说，它可以产生立竿见影的临床效果，因为它可能代表着治疗T2 DM患者的专业人员看待和管理OSA的方式发生了范式转变。此外，拟议的机制研究有可能为T2 DM合并OSA患者的治疗带来新的治疗方法。

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.