Responses to CPAP treatment in obese and lean sleep apnea patients

肥胖和阻塞性睡眠呼吸暂停(OSA)是胰岛素抵抗的独立危险因素 高血压和心血管疾病。这两种疾病都与交感神经增加和 炎症活动和氧化应激增加，被认为是他们共同的临床症状的媒介 后果。由于先前对CPAP治疗阻塞性睡眠呼吸暂停综合征患者的干预研究结果相互矛盾， 我们仍然不知道对肥胖OSA患者的治疗是否对这些危险因素有实质性的好处。在……里面 目的1，为了确定肥胖对阻塞性睡眠呼吸暂停患者CPAP治疗反应的影响，我们将 比较CPAP后白天嗜睡、胰岛素抵抗和动脉血压的反应 根据腹部内脏脂肪组织的数量分层治疗肥胖和消瘦的阻塞性睡眠呼吸暂停患者 脂肪堆积与交感神经活性增加、炎症和氧化应激有关，以及更多 比BMI更能预测心血管和代谢的不良后果。目标2将决定 两组CPAP治疗对交感神经活性及炎症和氧化应激的影响 生物标志物。我们的总体假设是，根据OSA的严重性进行调整，并从以下方面获得规范数据 内脏肥胖量相当的非OSA受试者(目标3)，两个OSA组将有 在白天嗜睡方面有类似的改善，但心血管和新陈代谢的改善 对于内脏脂肪组织增加的OSA患者，CPAP治疗后会减少。我们 预计虽然交感神经活动的标志物会有更大的绝对变化， CPAP治疗后肥胖OSA患者与瘦弱OSA患者的炎症和氧化应激比较 肥胖患者的胰岛素水平仍然会异常高，从而导致胰岛素改善的减少。 肥胖与瘦型阻塞性睡眠呼吸暂停患者的阻力、动脉血压和血管健康。相关性： 肥胖患者患睡眠呼吸暂停的风险增加。肥胖和睡眠呼吸暂停都能感觉到 增加患糖尿病、高血压和心血管疾病的风险。拟议中的研究将开始 确定治疗患有睡眠呼吸暂停的肥胖患者是否有助于降低这些风险。如果有益的效果 与患有睡眠呼吸暂停的消瘦患者相比，肥胖患者的CPAP治疗次数减少，然后治疗 肥胖患者的睡眠呼吸暂停需要与有效的肥胖管理相结合。

Obesity and obstructive sleep apnea (OSA) are independent risk factors for insulin resistance, systemic hypertension and cardiovascular disease. Both disorders are associated with increased sympathetic and inflammatory activity, and increased oxidative stress, presumed mediators of their shared clinical consequences. Due to conflicting results of previous intervention studies treating OSA patients with CPAP, we still do not know if treatment of obese OSA patients has a substantial benefit on these risk factors. In Aim 1, to determine the effects of obesity on the response to CPAP treatment in OSA patients, we will compare responses in daytime sleepiness, insulin resistance, and arterial blood pressure following CPAP treatment in obese and lean OSA patients, stratified by the amount of abdominal visceral adipose tissue, a fat depot associated with increased sympathetic activity, inflammation, and oxidative stress, and a more powerful predictor than BMI of adverse cardiovascular and metabolic outcomes. Aim 2 will determine the effect of CPAP treatment in these two groups on sympathetic activity, and inflammatory and oxidative stress biomarkers. Our overall hypothesis is that, adjusting for OSA severity and obtaining normative data from non-OSA subjects with comparable amounts of visceral adiposity (Aim 3), the two OSA groups will have comparable improvements in daytime sleepiness, but that the cardiovascular and metabolic improvements following CPAP therapy will be decreased in OSA patients with increased visceral adipose tissue. We anticipate that although there will be a greater absolute change in markers of sympathetic activity, inflammation and oxidative stress in obese compared to lean OSA patients following CPAP treatment, the levels will still be abnormally high in the obese patients resulting in the decreased improvements in insulin resistance, arterial blood pressure, and vascular health in obese versus lean OSA patients. Relevance: Obese patients are at increased risk of developing sleep apnea. Both obesity and sleep apnea are felt to increase the risk of diabetes, hypertension, and cardiovascular disease. The proposed research will begin to determine if treating obese patients with sleep apnea helps to reduce these risks. If the beneficial effects of CPAP treatment are reduced in obese compared to lean patients with sleep apnea, then treatment of sleep apnea in obese patients needs to be combined with effective management of their obesity.