Exercise-Facilitated NeuroRehabilitation in Diabetic Neuropathy

糖尿病神经病变的运动促进神经康复

• 批准号: 7748894
• 负责人: Morris Fisher
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7748894
• 关键词: Accounting; Acetylcarnitine; Address; Adult; Advanced Glycosylation End Products; Aerobic; Aerobic Exercise; Affect; Age; Aging; Aldehyde Reductase; American; Amputation; Animals; Blinded; Blindness; Blood flow; Body mass index; Caring; Chronic; Clinical; Clinical Research; Clinical Trials; Complications of Diabetes Mellitus; Conduct Clinical Trials; Data; Deterioration; Development; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Disease; Distal; Effectiveness; Epidemic; Esthesia; Exercise; Fiber; Functional disorder; Glucose; Goals; Health; Health Promotion; Health Surveys; Healthcare; Hexosamines; Homeostasis; Hospitals; Human; Hyperglycemia; Individual; Institution; Insulin-Dependent Diabetes Mellitus; Intervention; Isotonic Exercise; Kidney Diseases; Kidney Failure; Leg; Length; Life Style; Limb structure; Maintenance; Measurable; Measures; Medical; Medical center; Metabolic; Metabolism; Morbidity - disease rate; Motor; Muscle; National Institute of Diabetes and Digestive and Kidney Diseases; Nerve; Nerve Fibers; Nerve Growth Factors; Neural Conduction; Neuraxis; Neurologic Examination; Neurological outcome; Neuropathy; Neurorehabilitation; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outcome Measure; Oxidation-Reduction; Oxygen; Pain; Pain management; Patient Care; Patients; Perception; Peripheral Nerves; Peripheral Nervous System Diseases; Peripheral Vascular Diseases; Physical Examination; Physical activity; Physical therapy exercises; Polyneuropathy; Population; Prevalence; Prophylactic treatment; Proteins; Protocols documentation; Public Health; Publishing; Quality of life; Randomized; Recording of previous events; Recovery; Recruitment Activity; Rehabilitation therapy; Reporting; Research Methodology; Resources; Retinal Diseases; Risk; Savings; Secondary to; Sensory; Services; Signal Transduction Pathway; Site; Staging; Symptoms; System; Testing; Therapeutic; Therapeutic Intervention; Tissues; Torque; Training; Training Programs; Treadmill Tests; Triad Acrylic Resin; United States; Veterans; Visit; Visual Analogue Pain Scale; Walking; Western World; Work; aged; atherogenesis; autonomic nerve; cost; density; design; diabetes management; diabetes prevention program; diabetes risk; diabetic; diabetic patient; diet and exercise; experience; follow-up; glycation; glycemic control; group intervention; improved; infrared spectroscopy; inhibitor/antagonist; innovation; mortality; muscle strength; nerve injury; neuromechanism; novel therapeutics; nutrition; oxidation; painful neuropathy; palliative; patient population; polyol; primary outcome; programs; prophylactic; prospective; public health relevance; quadriceps muscle; relating to nervous system; response; secondary outcome; strength training; sural; tibialis anterior muscle; tissue oxygenation; treatment strategy; uptake

DESCRIPTION (provided by applicant): ABSTRACT Purpose: A single-site, randomized, blinded, prospective clinical trial is proposed to determine the significance of a combined isokinetic strength and aerobic exercise training program on the rehabilitation of peripheral nerve function in type 2 diabetic veterans with neuropathy. Background and Significance: Obesity is a major factor in the increasing rates of diabetes and its related complications. Diabetes affects greater than 7% of the population. Veterans are at even greater risk, with approximately 16% currently receiving treatment at Department of Veterans Affairs Medical Centers for diabetes. More than half of affected veterans experience debilitating complications of diabetes, including peripheral neuropathy (PN). Exercise training, in combination with pharmacologic intervention, is now recognized as a cornerstone of management for diabetes. Therapeutic interventions currently available for the treatment of PN in diabetic patients are limited, however, to pain management and stringent glycemic control. Exercise is reported to significantly decrease peripheral nerve microvascular complications common among chronic diabetics. Our preliminary findings demonstrate that exercise intervention improves peripheral nerve function in the diabetic veteran with PN. Intervention strategies, such as proposed in this application, offer a unique and novel therapeutic option for the rehabilitation of the neuro-compromised diabetic veteran. Methods & Research Plan: One-hundred subjects will be recruited for this 24-week study. Subjects each will be randomly assigned to aerobic, isokinetic strength training, combined aerobic and strength training, or non-exercise (control) intervention groups. Isokinetic strength training (Biodex System 3), aerobic exercise training (treadmill), or the combination of strength and aerobic training will be administered 3x per week for the initial 12 weeks. Control subjects will receive 12 clinical visits over the course of the initial 12 weeks. The effects of exercise training type, compared with control subjects, on recovery of peripheral nerve function will be rigorously determined from baseline, 12- and 24-week testing using electrodiagnostic primary outcome measures, Quantitative Sensory Testing, and a battery of validated qualitative and quantitative secondary outcome measures that include an incremental symptom-limited treadmill test, peak torque, Total Neuropathy Score, visual analogue pain scale, and quality of life SF-36V Health Survey. Sustainability of effect will be determined at 24-weeks.The individual effects of exercise training type, compared with control subjects, on tissue oxygenation will be determined from baseline, 12- and 24-week testing by non-invasive quantitated infrared spectroscopy using an InSpectraTM Tissue Spectrometer. Expected Outcomes: This study will objectively and critically determine the type and combination of exercise needed to rehabilitate the neuro-compromised diabetic Veteran. Guided exercise protocols may prove to be practical therapeutic options for the prophylactic management of diabetic subjects with neuropathy. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE: RELEVANCE TO PUBLIC HEALTH. HEALTH CARE SIGNIFICANCE OF PROBLEM: Diabetes mellitus afflicts more than 20 million Americans and is the main cause of kidney failure, new onset blindness, and neuropathy-associated limb amputations in adults.(7) Type 2 diabetes accounts for up to 95% of all diabetic cases and affects 7% of the U.S. population age 20 and older. Type 2 diabetes and its associated complications is strongly associated with obesity, secondary to physical inactivity and over-nutrition. The prevalence of type 2 diabetes has conservatively tripled in the last 30 years. Individuals with a body mass index (BMI) of 30 or more have a 5-fold greater risk of diabetes compared to subjects with BMI of 25 or less. In a major clinical trial conducted by the Diabetes Prevention Program (DPP), exercise reduced the risk of getting type 2 diabetes by 58%.(12) It is well established that exercise is a safe and integral approach to the management of patients with diabetes.(10-12) However, the management of neuropathy in type 2 diabetic patients remains palliative. Exercise significantly decreases peripheral nerve microvascular complications in the diabetic patient.(13) Therapeutic interventions that improve blood flow to peripheral nerves, such as exercise, are expected to slow or perhaps reverse the progression of neuropathy in the diabetic patient.(14) In a one-year study of lifestyle (diet and exercise) intervention, Smith et al.(34) observed a modest improvement in intraepidermal nerve fiber density with decreased neuropathic pain and improved sural sensory responses. Recently, we reported improved measures of peripheral nerve function in diabetic patients following a 24-week program of moderate aerobic exercise.(15) Muscle strength in symptomatic diabetic neuropathic patients, however, is markedly reduced when compared to control subjects and non-neuropathic diabetic patients.(56) This may represent a ceiling to the effectiveness of aerobic exercise one may observe among diabetic subjects. To address this concern, we considered different forms of exercise, such as isokinetic in comparison to isotonic, as a way to maximize the amount of muscle activation per unit of work.(57) While there are no published data demonstrating effectiveness of isokinetic training on recovery of peripheral nerve function in diabetic subjects, we argue that an exercise program utilizing strength and aerobic training, as proposed in this application, is strongly anticipated to produce measurable and meaningful therapeutic benefits to the diabetic veteran with neuropathy. RELEVANCE TO VETERAN HEALTH: Approximately 16% of U.S. Veterans are treated for diabetes.(1) At least 8-10% of the treated VA population now suffers with diabetic neuropathy. For these patients, improved treatment is expected to produce an improved quality of life, a decrease in the disabling burden of diabetic nerve dysfunction, and a diminished need for medical care. Although specific costs for treating diabetic neuropathies are not available, the potential savings with better management of diabetic neuropathies is evident given the large number of such patients cared for by the VA. With an aging Veteran population, the number of diabetic neuropathic patients in need of VA medical services is expected to increase considerably.

描述（由申请人提供）： 摘要目的：提出了一项单位，随机，盲目的前瞻性临床试验，以确定在2型糖尿病患者患有神经病的2型糖尿病退伍军人中，同动强度和有氧运动训练计划的合并意义。背景和意义：肥胖是糖尿病及其相关并发症发生率增加的主要因素。糖尿病会影响超过7％的人口。退伍军人面临更大的风险，目前约有16％在退伍军人事务部医疗中心接受糖尿病的治疗。超过一半的受影响的退伍军人经历了包括周围神经病（PN）在内的糖尿病并发症的衰弱并发症。与药理学干预结合使用运动训练，现在被认为是糖尿病管理的基石。但是，目前可用于治疗糖尿病患者PN的治疗干预措施受到疼痛管理和严格的血糖控制的限制。据报道，运动可显着降低慢性糖尿病患者常见的周围神经微血管并发症。我们的初步发现表明，运动干预可改善PN糖尿病退伍军人的周围神经功能。干预策略，例如本应用程序中提出的，为康复神经受损糖尿病退伍军人提供了独特而新颖的治疗选择。方法与研究计划：这项为期24周的研究将招募100名受试者。每个受试者将被随机分配给有氧，同动力训练，有氧和力量训练或非运动（对照）干预组。同动力强度训练（Biodex System 3），有氧运动训练（跑步机）或强度和有氧训练的组合将在最初的12周内每周3倍。控制受试者将在最初的12周内进行12次临床访问。与对照组相比，运动训练类型的影响，对外周神经功能的恢复，将通过基线，12周和24周的测试来确定使用电诊断的主要结果指标，定量感觉测试，定量和定量的二级结局测量，包括一个不断的症状效果，峰值测试，直率型号，直率的评分，直接效果，直率的测试，直接效果，直接效果，直率，直接效果，直率，直接效果，直率均匀尺寸，直率的评分， Life SF-36V健康调查。效应的可持续性将在24周内确定。与对照组相比，将使用InspectRATM组织光谱仪通过非侵入性定量的红外光谱仪来确定运动训练类型对组织氧合的各个影响。预期的结果：这项研究将客观和批判性地确定恢复神经功能障碍糖尿病经验所需的运动的类型和组合。指导运动方案可能被证明是对神经病的糖尿病患者进行预防治疗的实用治疗选择。 公共卫生相关性： 项目叙述：与公共卫生有关。 问题的医疗保健意义：糖尿病的糖尿病超过2000万美国人，是肾脏衰竭，新发作失明和成人神经病相关的肢体截肢的主要原因。（7）2型糖尿病占所有糖尿病病例中的95％，并影响了美国人群7％的7％。 2型糖尿病及其相关的并发症与肥胖症密切相关，其继发于身体不活动和过度营养。在过去30年中，2型糖尿病的患病率保守了两倍。与BMI相比，体重指数（BMI）为30或更多的人患糖尿病的风险高5倍。在预防糖尿病预防计划（DPP）进行的一项重大临床试验中，运动的风险降低了2型糖尿病的风险。（12）（12）可以很好地确定，运动是对糖尿病患者治疗的安全且积分的方法。（10-12）但是，2型糖尿病患者在2型糖尿病患者中的治疗仍然存在。运动显着降低糖尿病患者周围神经微血管并发症。（13）预计将血液流向血液流向外周神经的治疗干预措施，例如运动，有望减慢或可能逆转糖尿病患者中神经性病的进展。神经纤维密度随着神经性疼痛的减轻和改善的表情感觉反应而降低。最近，我们报道了在24周的中度有氧运动计划后，糖尿病患者的外周神经功能的方法改善了。（15）与对照组受试者和非神经性糖尿病患者相比，有症状性糖尿病神经性患者的肌肉力量显着降低，这可能代表一个主题。为了解决这一问题，我们考虑了不同形式的锻炼，例如与等官相比，是一种方法，是一种最大程度地提高每单位工作单位的肌肉激活量。（57）虽然没有公开的数据表明，同性恋培训在糖尿病学科中恢复的同性恋培训对恢复外围神经功能的恢复的有效性，我们认为锻炼的训练，我们认为这种锻炼的训练，并提出了这种锻炼的力量，并提出了这种训练，并提出了实力，并提出了实力，以实现这种训练，并提出了实力，并提出了辅助培训，并提出了实力，并提出了辅助训练，并提出了实力，并且可以实现这种训练。神经病对糖尿病老兵的有意义的治疗益处。与退伍军人健康有关：大约16％的美国退伍军人接受糖尿病治疗。（1）至少8-10％的VA治疗人群现在患有糖尿病神经病。对于这些患者，预计治疗的改善将改善生活质量，减少糖尿病神经功能障碍的残疾负担，并减少对医疗服务的需求。尽管无法获得治疗糖尿病神经病的特定成本，但鉴于VA所照顾的大量患者，显然可以更好地治疗糖尿病神经病。随着老化的资深人群，需要VA医疗服务的糖尿病神经性患者数量将大大增加。