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

项目摘要/摘要 远端对称性多发性神经病(DSP)影响着超过15%的40岁以上的美国人。如此之高 流行的疾病损害患者的生活质量，导致疼痛，并导致跌倒。由DSP引起的患者 糖尿病引起的疾病尤其容易导致溃疡和截肢。尽管人口众多 受这种疾病和由此导致的显著发病率的影响，目前还不存在疾病修饰疗法 防止神经损伤。神经病理性止痛药可以减轻DSP引起的疼痛，但不能预防神经病变。 损坏。加强血糖控制已被证明可以预防1型糖尿病患者的DSP，但 对2型糖尿病患者只有很小的影响。因此，迫切需要开发疾病改良剂 治疗患有和有患DSP风险的患者。 我们提出了两种可能的疾病改善疗法，即运动和/或减肥。要确定 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 例行的运动咨询。我们选择HIIT作为我们的锻炼方案是因为数据支持增加了 肥胖和糖尿病患者的依从性。这种创新的干预也有新的数据来 支持改善糖尿病患者的代谢结果。我们假设演习将会有 对DSP结果的最大影响是因为之前的三项非对照研究记录了大量 接受针灸治疗的患者表皮内神经纤维密度和皮肤再生能力的改善 运动养生法几乎不会减轻体重。相比之下，在一项非对照研究中，我们发现了稳定的IENFD 在经历了两年的重大医学减肥之后。而IENFD的自然历史是在那些 对于糖尿病和糖尿病前期患者，尽管体重大幅下降，但IENFD的改善并不明显。我们建议 通过对55%的减肥手术人群的研究，确定体重减轻对DSP结果的影响 的患者一旦获得手术审查委员会的批准就进行了手术。我们将对HIIT进行分层 随机化1：1对接受手术和不接受手术的患者进行比较。这种非随机化的设计将 允许比较手术和HIIT的效果，而不需要昂贵的随机手术 干预试验。手术减重可能比药物减重对治疗效果的影响更大。 体重下降是因为减肥的幅度和可持续性。我们还将能够调查 结合手术减肥和HIIT。 建议的目标有可能为DSP确定有前景的运动和/或减肥干预措施。 这项2期研究可能会导致最终的3期试验，这可能会导致第一种疾病 对数字信号处理器的改良治疗。鉴于与数字信号处理器相关的高患病率和高发病率，这样的 干预是迫切需要的。

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.