The Effect of High Intensity Interval Training and Surgical Weight Loss On Distal Symmetric Polyneuropathy Outcomes

项目概要/摘要 远端对称性多发性神经病（DSP）影响超过15%的40岁以上的美国人。这种高度 流行病损害患者的生活质量，引起疼痛，并导致福尔斯。DSP引起的患者 患糖尿病的人患溃疡和下肢截肢的风险特别高。尽管人口众多 受这种疾病的影响和导致的显著发病率，没有疾病修饰疗法存在， 防止神经损伤。神经性疼痛药物可以减轻DSP引起的疼痛，但不能防止神经性疼痛。 损害已证实加强血糖控制可预防1型糖尿病患者的DSP，但 对2型糖尿病患者影响不大。因此，迫切需要开发疾病修饰剂， DSP患者和有DSP风险的患者的治疗。 我们提出了两种潜在的疾病修饰疗法，即运动和/或减肥。确定 运动对DSP结果的影响，我们计划将患者随机分为高强度间歇训练（HIIT）或 例行运动咨询我们选择HIIT作为我们的锻炼方案，因为数据支持增加 肥胖和糖尿病患者的依从性。这种创新的干预措施也有新的数据， 支持改善糖尿病患者的代谢结果。我们假设运动会使 对DSP结局的影响最大，因为之前的三项非对照研究记录了大量 在那些接受治疗的患者中表皮内神经纤维密度和皮肤再生能力的改善 运动养生很少或没有减肥。相比之下，在一项非对照研究中，我们发现稳定的IENFD 经过两年的医学减肥虽然IENFD的自然史是在那些 对于糖尿病和糖尿病前期，尽管体重明显减轻，但IENFD没有改善。我们提出 通过研究减肥手术人群来确定体重减轻对DSP结局的影响，其中55%的 的患者一旦获得手术审查委员会的批准就可以进行手术。我们将对HIIT进行分层 1：1随机分配至接受手术的患者和不接受手术的患者。这种非随机设计将 允许比较手术与HIIT的效果，而不需要昂贵的随机手术 干预试验。手术减肥对DSP结局的影响可能比医疗体重更强 由于体重减轻的幅度和可持续性，我们还将能够研究 结合手术减肥和HIIT 拟议的目标有可能为DSP确定有希望的运动和/或减肥干预措施。 这项2期研究可能会导致一个明确的3期试验，这可能会导致第一种疾病， DSP的改良治疗。鉴于与DSP相关的高患病率和大量发病率， 迫切需要进行干预。

Project Summary/abstract Distal symmetric polyneuropathy (DSP) affects upwards of 15% of Americans over the age of 40. This highly prevalent condition impairs patient's quality of life, causes pain, and results in falls. Patients with DSP caused by diabetes are at particular risk for ulcerations and lower extremity amputations. Despite the large population affected by this disease and the significant morbidity that results, no disease modifying therapies exist to prevent nerve injury. Neuropathic pain medications can reduce the pain from DSP, but do not prevent nerve damage. Enhanced glucose control has been proven to prevent DSP in patients with type 1 diabetes, but has only a small effect on patients with type 2 diabetes. As a result, a critical need exists to develop disease modify therapies for patients with and at risk for DSP. We propose two potential disease modifying therapies, namely exercise and/or weight loss. To determine the impact of exercise on DSP outcomes, we plan to randomize patients to high intensity interval training (HIIT) or routine exercise counseling. We chose HIIT as our exercise regimen because of data supporting increased compliance in patients with obesity and diabetes. This innovative intervention also has emerging data to support improved metabolic outcomes in patients with diabetes. We hypothesize that exercise will have the largest effect on DSP outcomes because of three previous uncontrolled studies documenting substantial improvement in intraepidermal nerve fiber density and cutaneous regenerative capacity in those receiving an exercise regimen with little to no weight loss. By comparison, in an uncontrolled study, we found stable IENFD after two years of significant medical weight loss. While the natural history of IENFD is to decrease in those with diabetes and pre-diabetes, improvement in IENFD was not seen despite robust weight loss. We propose to determine the effect of weight loss on DSP outcomes by studying a bariatric surgery population where 55% of the patients have surgery once they are approved by the surgery review committee. We will stratify HIIT randomization 1:1 to those that do and those that do not undergo surgery. This non-randomized design will allow comparison of the effect of surgery to HIIT without the need for an expensive, randomized surgical intervention trial. Surgical weight loss may have a more robust effect on DSP outcomes than medical weight loss because of the magnitude and sustainability of weight loss. We will also be able to investigate the effect of combining surgical weight loss and HIIT. The proposed aims have the potential to identify promising exercise and/or weight loss interventions for DSP. This phase 2 study may lead to a definitive phase 3 trial, which would possibly result in the first disease modifying therapy for DSP. Given the high prevalence and substantial morbidity associated with DSP, such an intervention is desperately needed.