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。无论是 这种联系的机制直接归因于OSA的促动脉粥样硬化作用或主要是 与肥胖有关的因素尚不清楚。肥胖在阻塞性睡眠呼吸暂停综合征患者中很常见，其本身与 炎症状态和胰岛素抵抗。在同时患有肥胖症和阻塞性睡眠呼吸暂停综合症的个体中，重复的低氧 与OSA相关的可能会促进炎症和胰岛素抵抗。我们的主要目标是测试 假设OSA在肥胖和中度肥胖患者的炎症状态中起主要作用 严重的阻塞性睡眠呼吸暂停，因此通过持续气道正压(CPAP)消除呼吸暂停 这些患者的治疗将更显著地减少炎症(以C反应蛋白或CRP衡量) 这两种疗法结合在一起会对减肥有相加的效果 我们的第二个目标是测试阻塞性睡眠呼吸暂停综合征和肥胖独立作用的假说。 这些患者的胰岛素抵抗状态，因此联合减肥和CPAP治疗将会有 在降低胰岛素抵抗方面比任何一种单独治疗都有更大的效果。我们的第三个目标是测试 假设阻塞性睡眠呼吸暂停综合征和肥胖是血管内皮功能障碍的独立原因，这是通过他们的 对炎症和胰岛素抵抗的影响，因此结合减肥和CPAP治疗 将比任何一种单独治疗更能改善内皮功能。为达致这些目标，我们计划 将201名肥胖和中重度阻塞性睡眠呼吸暂停患者随机分为两组，每组1)体重，C反应蛋白和血糖为1.0毫克/L 2)单纯CPAP治疗；或3)减肥加CPAP治疗6个月。我们会 测量C反应蛋白、胰岛素抵抗(葡萄糖耐量试验曲线下面积)和内皮功能 (通过臂动脉血流研究)在基线、6周、12周和24周。我们建议这项研究设计将 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。

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.