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有关。这种联系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，本身就与炎症状态和胰岛素抵抗有关。在同时患有肥胖和OSA的个体中，与OSA相关的反复低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一假设，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(CPAP)治疗消除呼吸暂停将比单独减肥更能减少炎症(以C-反应蛋白或CRP衡量)，并且这两种治疗方法在减轻炎症方面将具有相加的效果。我们的第二个目标是检验这一假设，即OSA和肥胖独立导致这些患者的胰岛素抵抗状态，因此，减肥和CPAP联合治疗在降低胰岛素抵抗方面的效果将比单独使用任何一种疗法更大。我们的第三个目标是验证这一假设，即OSA和肥胖通过其对炎症和胰岛素抵抗的影响而独立地导致血管内皮功能障碍，因此联合减肥和CPAP疗法将比单独使用任何一种疗法更能改善血管内皮功能。为了达到这些目标，我们计划随机选择201名肥胖和中重度阻塞性睡眠呼吸暂停综合症患者，并将基线C反应蛋白和GT；1.0 mg/gT；分为1)单用Yapy减肥；2)单用CPAP治疗；或3)减肥加CPAP治疗6个月。我们将在基线、6周、12周和24周测量C反应蛋白、胰岛素抵抗(糖耐量试验曲线下面积)和内皮功能(通过臂动脉血流研究)。我们认为，这项研究设计将提供最好的方法来区分肥胖和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.