Structured Exercise in Obese Diabetic Patients with Chronic Kidney Disease: A Ran

描述（由申请人提供）： 翻译后摘要：结构化运动在肥胖糖尿病患者慢性肾脏疾病：一项随机对照试验。 2型糖尿病、肥胖和慢性肾脏病（CKD）患者通常身体不活跃，死亡率高，并且可能从运动计划中受益。然而，还没有随机对照试验来确定运动训练在这一人群中的益处。本研究旨在证实这一假设，即通过运动训练增加肥胖糖尿病患者的能量消耗将导致以下益处：1。肾脏益处，包括蛋白尿减少和肾小球滤过率（GFR）稳定2。心血管益处，包括降低血压、降低心率和增加运动耐量。3.改善血糖控制（降低糖化血红蛋白），血脂控制（降低胆固醇，改善动脉粥样硬化）4。改善身体组成（体重减轻，增加瘦体重和减少脂肪量）。5.炎症（通过高敏C反应蛋白评估）、内皮功能障碍（通过血流介导的扩张评估）和氧化应激（通过还原型谷胱甘肽评估）减少。6.提高与健康相关的生活质量。 为了准备这项提议，我们进行了一项为期2 - 4周的随机对照可行性研究，比较有氧运动加最佳药物管理与单独药物管理在2型糖尿病、肥胖（BMI > 30 kg/m2）和2-4期CKD（eGFR 15-90 mL/min/1.73m2）伴持续性蛋白尿> 200 mg/g患者中的效果。被随机分配到运动组的受试者每周进行三次有氧训练，持续6周，然后进行18周的监督性家庭运动。运动训练导致运动持续时间、静息收缩压和蛋白尿的显著改善。 我们现在提出一个更大规模的随机对照试验，以确定运动对糖尿病肾病患者的肾功能，心血管健康，炎症和氧化应激的影响。这是一项为期52周的随机对照研究。随机分配至运动组的受试者将接受12周的结构化运动训练，随后接受40周的监督性家庭运动（研究总持续时间为1年）。主要结局变量为12周和52周时蛋白尿（白蛋白尿和总蛋白尿）减少。血压（BP）、糖化血红蛋白、血脂、C反应蛋白（CRP）水平、体重和成分将是次要结局变量。此外，我们将检查内皮功能障碍（通过血流介导的扩张）和氧化应激（血浆和尿液丙二醛）的指标。此外，由于血压是肾脏结局的重要决定因素，我们将利用VA远程医疗计划来监测所有受试者的家庭血压。我们还将进行生活质量（QoL）评价，因为这些数据对于本项目很重要，以便确定运动可以在该人群中产生有意义的健康感知改善，以及共存疾病指数（ICED）来测量合并症，以确定合并症是否对研究结果有任何影响。还将使用流行病学研究中心抑郁量表（CES-D）确定抑郁（协变量）对研究结局和研究目标依从性的影响。 本研究将直接探讨结构化运动计划对心血管并发症高危患者人群的影响。我们将特别讨论一个新的想法，即运动不仅可以改善心血管健康，而且还可以改善糖尿病引起的肾脏并发症。

DESCRIPTION (provided by applicant): Abstract: Structured exercise in obese diabetic patients with chronic kidney disease: a randomized controlled trial. Patients with type 2 diabetes, obesity, and chronic kidney disease (CKD) are generally physically inactive, have a high mortality rate, and may benefit from an exercise program. However, there have been no randomized controlled trials to determine the benefits of exercise training in this population. This study seeks to substantiate the hypothesis that increasing energy expenditure by exercise training in the obese diabetic patient with CKD will result in the following benefits: 1. Renal benefits, including reduction in proteinuria and stabilization of glomerular filtration rate (GFR) 2. Cardiovascular benefits, including decreased blood pressure, decreased heart rate, and increased exercise tolerance. 3. Improved glucose control (lower glycated hemoglobin), lipid control (decreased cholesterol with improved atherogenic profile) 4. Improved body composition (weight loss, increased lean body mass and decreased fat mass). 5. Decreased inflammation (assessed by high-sensitivity C-reactive protein), endothelial dysfunction (assessed by flow-mediated dilatation), and oxidative stress (assessed by reduced glutathione). 6. Increased health-related quality of life. In preparation for this proposal, we performed a 24-week randomized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes, obesity (BMI > 30 kg/m2), and stage 2-4 CKD (eGFR 15-90 mL/min/1.73m2) with persistent proteinuria of > 200 mg/g. Subjects randomized to exercise underwent thrice weekly aerobic training for 6 followed by 18 weeks of supervised home exercise. Exercise training resulted in a significant improvement in exercise duration, resting systolic blood pressure, and proteinuria. We now propose a larger-scale randomized controlled trial to determine the effects of exercise on renal functions, cardiovascular fitness, inflammation, and oxidative stress in diabetic patients with CKD. This will be a 52-week randomized controlled study. Subjects randomized to exercise will undergo 12 weeks of structured exercise training followed by 40 weeks of supervised home exercise (total duration of study 1 year). The primary outcome variable will be a decrease in proteinuria (albuminuria and total proteinuria) at 12 and 52 weeks. Blood pressure (BP), glycated hemoglobin, lipid profile, C-reactive protein (CRP) levels, and body weight and composition will be secondary outcome variables. In addition we will examine indices of endothelial dysfunction (by flow-mediated dilatation) and oxidative stress (plasma and urine malondialdehyde). Moreover, since blood pressure is such an important determinant of renal outcomes, we will take advantage of the VA Telehealth program to monitor home BPs in all subjects. We will also perform Quality of Life (QoL) evaluations, as such data are important for this project in order to establish that exercise can produce a meaningful improvement in perception of health in this population, as well as the Index of Coexistent Diseases (ICED) to measure comorbidities to determine if comorbid conditions had any influence on the outcomes of the study. The Center for Epidemiologic Studies Depression Scale (CES-D) will also be used to determine the influence of depression (covariate) on study outcomes and adherence with the study objectives. This study will directly address the effects of a structured exercise program in a patient population at high risk for cardiovascular complications. We will specifically address the novel idea that exercise will not only improve cardiovascular fitness but will also ameliorate the renal complications resulting from diabetes.