Reversing Diabetic Peripheral Neuropathy Through Exercise

项目摘要 该项目提出了一种创新的多核磁共振方法，以获得对演习的机械性洞察- 糖尿病患者小腿肌肉功能和周围神经完整性的相关适应 周围神经病(DPN)。DPN的一个重要后果是周围神经完整性的丧失， 神经性肌肉萎缩、脂肪渗透和肌肉耐力丧失。这些协同作用有助于 步态改变，平衡受损，摔倒的风险增加，这可能导致骨折，愈合不良的伤口， 以及经常需要截肢的慢性感染。没有任何治疗方法可以预防或逆转 DPN的进展。初步的单组研究表明，在10周的中等强度监督下 DPN患者对运动计划的耐受性很好，可以改善神经功能，皮肤神经， 以及心血管和大血管内皮功能。然而，这些效应的生理基础 定义不明确。我们的团队处于独特的地位，可以使用新的多核磁共振技术来了解 运动影响DPN患者骨骼肌和周围神经的完整性和功能。我们会 给50名DPN患者开一个为期10周的运动计划，包括有氧和强化两部分 世卫组织将接受卫生专业人员的亲自监督。另有50名DPN患者将随机 分配给非运动对照组。我们假设i)锻炼会改善周围神经。 完整性(分数各向异性将增加，表观扩散系数将减小 使用扩散张量成像)，ii)运动将降低血浆氧化应激水平，iii)运动将 用密歇根神经病变筛查仪评估改善DPN症状。我们的第二个目标是 了解运动对糖尿病周围神经营养不良患者小腿肌肉结构和功能的影响。我们假设 I)运动将增加腿部线粒体的功能，其定义是氧化能力的增加 (使用磷核磁共振测量)，ii)运动将改善腿部微血管功能，如 峰值微血管反应增加(使用BOLD-MRI测量)，以及III)运动将减少 增加肌肉内脂肪和增加脱脂肌肉的水平(使用理想核磁共振测量)。先进的多核- MRI可以提供对DPN患者运动相关适应的机械性洞察。这些措施包括 骨骼肌和外周肌肉的肌内脂肪含量、MV和代谢功能的变化 神经功能和完整性。了解这些适应有望揭示改进DPN的新方法 运动干预后的症状，更好地预测患者的结果，并开发更有效的治疗方法 对DPN来说。

Project Summary This project proposes an innovative multinuclear MRI approach to gain mechanistic insight into the exercise- associated adaptations in lower leg muscle function and peripheral nerve integrity of patients with diabetic peripheral neuropathy (DPN). A significant consequence of DPN is loss of peripheral nerve integrity, neurogenic muscle atrophy, fatty infiltration, and loss of muscle endurance. These synergistically contribute to altered gait, impaired balance, and increased fall risk, which can lead to bone fractures, poorly healing wounds, and chronic infections that often require an amputation. There are no therapies to prevent or reverse the progress of DPN. Preliminary single-group studies showed that a 10-week moderate-intensity supervised exercise program is well tolerated by patients with DPN, and improves nerve function, cutaneous innervation, and cardiovascular and macrovascular endothelial functions. However, the physiological basis of these effects is poorly defined. Our team is uniquely positioned to use novel multinuclear MRI technology to understand how exercise affects skeletal muscle and peripheral nerve integrity and function in patients with DPN. We will prescribe a 10-week exercise program, with both aerobic and strengthening components, to 50 DPN patients who will receive personal supervision from health professionals. Another 50 DPN patients will be randomly assigned to the non-exercising control group. We hypothesize that i) exercise will improve peripheral nerve integrity (fractional anisotropy will increase, and the apparent diffusion coefficient will decrease as measured using diffusion tensor imaging), ii) exercise will decrease plasma levels of oxidative stress, iii) exercise will improve DPN symptoms, assessed with the Michigan Neuropathy Screening Instrument. Our second aim is to determine the effect of exercise on lower leg muscle structure and function in DPN patients. We hypothesize that i) exercise will increase leg mitochondrial function, as defined by an increase in oxidative capacity (measured using phosphorus-MRI), ii) exercise will improve leg microvascular function, as defined by an increase in peak microvascular response (measured using BOLD-MRI), and iii) exercise will decrease intramuscular fat and increase levels of fat-free muscle (measured using IDEAL-MRI). Advanced multinuclear- MRI can provide mechanistic insight into exercise-related adaptations in patients with DPN. These include changes in intramuscular fat content, MV and metabolic functions of the skeletal muscle, as well as peripheral nerve function and integrity. Understanding these adaptations promises to reveal new ways to improve DPN symptoms after exercise interventions, better predict patient outcomes, and develop more effective treatments for DPN.