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

描述(由申请人提供)： 摘要：肥胖糖尿病合并慢性肾脏疾病患者的结构性运动：一项随机对照试验。患有2型糖尿病、肥胖症和慢性肾脏病(CKD)的患者通常身体不活跃，死亡率很高，可能会从锻炼计划中受益。然而，还没有随机对照试验来确定运动训练对这一人群的好处。这项研究试图证实这样的假设，即通过运动训练增加肥胖糖尿病合并CKD患者的能量消耗将导致以下益处：1.肾脏益处，包括减少蛋白尿和稳定肾小球滤过率(GFR)；2.心血管益处，包括降低血压、降低心率和提高运动耐量。3.改善血糖控制(降低糖化血红蛋白)，改善血脂控制(降低胆固醇，改善动脉粥样硬化特征)4.改善身体成分(体重减轻，增加瘦体重，减少脂肪质量)。5.减少炎症(通过高敏C-反应蛋白评估)、内皮功能障碍(通过流动介导的扩张评估)和氧化应激(通过还原型谷胱甘肽评估)。6.提高与健康相关的生活质量。为了准备这项建议，我们进行了一项为期24周的随机对照可行性研究，比较有氧运动加最优医疗管理与单纯医疗管理对2型糖尿病、肥胖症(BMI&GT；30 kg/m2)和2-4CKD(EGFR 15-90mL/min/1.73m2)、持续性蛋白尿&gt；200 mg/g的患者的影响。随机选择锻炼的受试者每周进行三次有氧训练，共6次，然后进行18周的有监督的家庭锻炼。运动训练可显著改善运动持续时间、静息收缩压和蛋白尿。我们现在提出了一项更大规模的随机对照试验，以确定运动对患有CKD的糖尿病患者的肾功能、心血管健康、炎症和氧化应激的影响。这将是一项为期52周的随机对照研究。随机接受锻炼的受试者将接受12周的有组织的运动训练，然后是40周的有监督的家庭锻炼(研究总持续时间为1年)。主要的结果变量将是12周和52周时蛋白尿(蛋白尿和总蛋白尿)的减少。血压(BP)、糖化血红蛋白、血脂、C反应蛋白(CRP)水平以及体重和成分将是次要的结果变量。此外，我们还将检测内皮功能障碍指数(通过血流介导的扩张)和氧化应激指数(血浆和尿丙二醛)。此外，由于血压是肾脏预后的重要决定因素，我们将利用退伍军人事务部远程健康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)评估，因为这些数据对于这个项目很重要，以确定锻炼可以在这一人群中产生有意义的健康认知改善，以及共存性疾病指数(ICED)来衡量并存疾病，以确定并存状况是否对研究结果有任何影响。流行病学研究中心抑郁量表(CES-D)也将被用来确定抑郁症(协变量)对研究结果的影响和对研究目标的遵守。这项研究将直接讨论有组织的锻炼计划对心血管并发症高危人群的影响。我们将具体讨论运动不仅可以改善心血管健康，还可以改善糖尿病引起的肾脏并发症这一新想法。

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.