Reversing Diabetic Peripheral Neuropathy Through Exercise

通过运动逆转糖尿病周围神经病变

• 批准号: 9730470
• 负责人: Ryan Brown
• 金额: $ 73.32万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9730470
• 关键词: Adipose tissue; Aerobic; Affect; Amputation; Anisotropy; Architecture; Asses; Blood capillaries; Cardiovascular Physiology; Cardiovascular system; Chronic; Complications of Diabetes Mellitus; Control Groups; Cutaneous; Data; Diabetes Mellitus; Diffusion; Diffusion Magnetic Resonance Imaging; Endothelium; Exercise; Fatty acid glycerol esters; Fracture; Gait; Health Professional; Imaging Techniques; Imaging technology; Impairment; Infiltration; Intervention; Intramuscular; Lead; Leg; Lower Extremity; Magnetic Resonance Imaging; Measures; Metabolic; Michigan; Mitochondria; Monitor; Muscle; Muscle function; Muscular Atrophy; Nerve; Neurons; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Oxidative Stress; Patient-Focused Outcomes; Patients; Peripheral Nerves; Peripheral Nervous System Diseases; Phosphorus; Physical Exercise; Physiological; Plasma; Positioning Attribute; Randomized; Reproducibility; Research Personnel; Role; Signal Transduction; Skeletal Muscle; Structure; Supervision; Symptoms; Testing; Wound Infection; base; blood oxygen level dependent; chronic infection; control trial; diabetic; effective therapy; equilibration disorder; exercise intervention; exercise program; fall risk; glycemic control; imaging approach; improved; innovation; insight; instrument; insulin sensitivity; muscular structure; nerve injury; nerve supply; neurotrophic factor; novel; prevent; rapid technique; reinnervation; response; screening; symptom treatment; wound healing

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.

项目摘要 该项目提出了一种创新的多核MRI方法，以获取对运动的机理洞察力 - 糖尿病患者的低腿肌肉功能和周围神经完整性的相关适应性 周围神经病（DPN）。 DPN的重要结果是外周神经完整性的丧失， 神经源性肌肉萎缩，脂肪浸润和肌肉耐力的丧失。这些协同作用有助于 步态改变，平衡受损和跌落风险增加，这会导致骨折，愈合不良，伤口良好， 和经常需要截肢的慢性感染。没有疗法可以预防或扭转 DPN的进度。初步单组研究表明，有一个10周的中等强度监督 锻炼计划受DPN患者的耐受性良好，并改善了神经功能，皮肤神经， 以及心血管和大血管内皮功能。但是，这些影响的生理基础 定义很差。我们的团队独特地使用新颖的多核MRI技术来了解如何 运动影响DPN患者的骨骼肌和周围神经完整性和功能。我们将 为有氧和增强组件开出一个为期10周的运动计划，向50例DPN患者开出 谁将获得卫生专业人员的个人监督。另外50名DPN患者将是随机的 分配给非行进对照组。我们假设I）锻炼将改善外围神经 完整性（分数各向异性将增加，明显的扩散系数将随着测量而降低 使用扩散张量成像），ii）运动将降低血浆的氧化应激水平，iii）运动将 改善DPN症状，并通过密歇根州神经病筛查仪器进行评估。我们的第二个目标是 确定运动对DPN患者低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功能，如氧化能力的增加所定义 （使用磷-MRI测量），ii）锻炼将改善腿微血管功能，如 峰值微血管反应的增加（使用BOLD-MRI测量），iii）运动将减少 肌内脂肪并增加无脂肪的肌肉水平（使用Ideal-MRI测量）。高级多核 MRI可以为DPN患者的运动相关适应提供机械洞察力。这些包括 肌肉内脂肪含量，MV和代谢功能的变化以及外周的变化 神经功能和完整性。了解这些改编有望揭示改善DPN的新方法 运动干预后的症状，更好地预测患者的预后并开发更有效的治疗方法 对于DPN。

项目成果

Lower-Limb Non-Parametric Functional Muscle Network: Test-Retest Reliability Analysis

• DOI: 10.1109/tnsre.2023.3291748
• 发表时间: 2023-07
• 期刊: IEEE Transactions on Neural Systems and Rehabilitation Engineering
• 影响因子: 4.9
• 作者: Graduate Student Member Ieee Rory O’Keeffe;Jinghui Yang;Graduate Student Member Ieee Sarmad Mehrdad;Smita Rao;S. M. I. S. Farokh Atashzar-S.-M.-I.-S.-Farokh-Atashzar-2225980810