Inflammatory response to sleep apnea in obese subjects

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）与心血管事件风险增加相关。这种关联的机制是否直接归因于OSA的促动脉粥样硬化作用或主要与肥胖有关尚不清楚。肥胖在OSA患者中很常见，并且本身与炎症状态和胰岛素抵抗相关。在患有肥胖和OSA的个体中，与OSA相关的重复缺氧可能会促进炎症和胰岛素抵抗。我们的主要目的是检验这样一个假设，即OSA在肥胖和中重度OSA患者的炎症状态中起主要作用，因此在这些患者中通过持续气道正压通气（CPAP）治疗消除呼吸暂停将更大程度地减少炎症（通过C-反应蛋白或CRP测量）比单独减肥更有效，这两种疗法联合使用将对减轻炎症产生叠加效应。我们的第二个目的是检验这一假设，即OSA和肥胖独立地导致这些患者的胰岛素抵抗状态，因此联合减肥和CPAP治疗将比单独使用任何一种治疗对降低胰岛素抵抗具有更大的作用。我们的第三个目的是检验OSA和肥胖通过其对炎症和胰岛素抵抗的影响独立地导致血管内皮功能障碍的假设，因此结合减肥和CPAP治疗将比单独使用任何一种治疗更能改善内皮功能。为了实现这些目标，我们计划将201名患有肥胖症和中重度OSA且基线CRP>1.0 mg/L的受试者随机分为1）单独使用Yellow减肥; 2）单独使用CPAP治疗;或3）减肥加CPAP治疗6个月。我们将在基线和第6、12和24周测量CRP、胰岛素抵抗（葡萄糖耐量试验曲线下面积）和内皮功能（通过肱动脉血流研究）。我们建议，这项研究设计将提供最好的方法来分离肥胖和OSA对心血管风险的独立影响。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is associated with an increased risk for cardiovascular events. Whether the mechanism for this association is directly attributable to pro-atherosclerotic effects of OSA or primarily related to obesity is not known. Obesity is common in patients with OSA, and is itself associated with an inflammatory state and insulin resistance. In individuals with both obesity and OSA, the repetitive hypoxia associated with OSA may promote inflammation and insulin resistance. Our primary aim is to test the hypothesis that OSA plays a primary role in the inflammatory state of patients with obesity and moderate-severe OSA, and that therefore the elimination of apnea by continuous positive airway pressure (CPAP) therapy in these patients will more greatly reduce inflammation (measured by C-reactive protein or CRP) than weight loss alone, and that combining these two therapies will have additive effects on reducing inflammation.; Our second aim is to test the hypothesis that OSA and obesity independently contribute to the insulin resistant state in these patients, and thus combined weight loss and CPAP therapy will have greater effects on lowering insulin resistance than either therapy alone. Our third aim is to test the hypothesis that OSA and obesity contribute independently to vascular endothelial dysfunction, through their effects on inflammation and insulin resistance, and that therefore combining weight loss and CPAP therapy will improve endothelial function more than either therapy alone. To address these aims, we plan to randomize 201 subjects with obesity and moderate-severe OSA, and baseline CRP>1.0 mg/L to 1) weight loss theYapy alone; 2) CPAP therapy alone; or 3) weight loss plus CPAP therapy for 6 months. We will measure CRP, insulin resistance (area under the curve of a glucose tolerance test), and endothelial function (by brachial artery flow studies) at baseline, and weeks 6, 12, and 24. We propose that this study design will provide the best way to separate the independent effects of obesity and OSA on cardiovascular risk.