Inflammatory response to sleep apnea in obese subjects

阻塞性睡眠呼吸暂停（OSA）与心血管事件的风险增加有关。是否 这种关联的机制直接归因于OSA的促动脉粥样硬化作用，或者主要是 与肥胖症有关，目前尚不清楚。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。在肥胖和阻塞性睡眠呼吸暂停患者中， 与OSA相关的炎症可能会促进炎症和胰岛素抵抗。我们的主要目的是测试 假设OSA在肥胖和中度肥胖患者的炎症状态中起主要作用， 严重OSA，因此通过持续气道正压通气（CPAP）消除呼吸暂停 这些患者的治疗将大大减少炎症（通过C反应蛋白或CRP测量） 比单独减肥，这两种疗法相结合，将有累加效应，减少 炎症。我们的第二个目的是验证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治疗将具有 对降低胰岛素抵抗的作用比单独治疗更大。我们的第三个目标是测试 假设OSA和肥胖独立地导致血管内皮功能障碍， 对炎症和胰岛素抵抗的影响，因此将减肥和CPAP治疗相结合 将比单独的任何一种疗法更能改善内皮功能。为了实现这些目标，我们计划 将201名患有肥胖和中重度OSA且基线CRP>1.0 mg/L的受试者随机分为1）体重 单用CPAP治疗;或3）体重减轻加CPAP治疗6个月。我们将 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 (by肱动脉血流研究），以及第6、12和24周。我们建议本研究设计将 为分离肥胖和OSA对心血管风险的独立影响提供了最好的方法。

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 hypothesize 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.