Long Term Effects of Diet and Exercise on Early Diabetic Neuropathy

描述 2型糖尿病在老龄化人口中是一个日益严重的问题，特别是在退伍军人中。目前，还没有有效的治疗方法来预防或逆转糖尿病神经病变。由康复研发资助的一项正在进行的临床试验--改善早期糖尿病患者的神经病变和活动能力(INMED)--将在以家庭为基础的定制饮食和体力活动计划中确定，可以防止神经病变的进展，并改善血糖调节受损的参与者的活动能力。本研究的主要终点是测量表皮内神经纤维密度(IENFD)以测量神经病变的进展，并测量限时6分钟步行(6 MW)以测量参与者的活动能力。尽管INMED的研究可能表明，量身定制的生活方式干预(饮食建议、量身定做的运动和活动干预)可以改善或防止神经病的进展，但尚不清楚这种好处是否会持续到干预期间之后，从而对受试者产生持续的好处。这些信息对确定生活方式干预的长期有效性将是重要的。目前的研究是对IMMED应答者的随访研究，IMMED应答者被定义为IENFD或6 mW比基线有改善的参与者。在INMED研究结束后，48名受试者将在没有特定干预的情况下再跟踪一年，看看根据6 mW和IENFD确定的量身定制的饮食和运动计划是否对神经病变和/或活动的进展有持续、长期的好处。主要终点将是额外一年结束时的6兆瓦，次要终点将是额外一年后的IENFD，额外6个月后将是6兆瓦。还将收集信息以确定(1)参与者是否在没有干预的情况下继续锻炼，(2)如果运动量在没有持续咨询的情况下减少，(3)他们是否继续保持在INMED研究中观察到的相同的改善速度，以及(4)在INMED研究之后，神经病临床测量的改善是否持续。申请者Lindsay Zilliox博士是马里兰大学神经病学系的助理教授，在完成奖学金培训两年后，他的目标是成为一名独立的VA临床研究人员。到目前为止，她的临床培训还没有包括专门的研究培训时间。这两年的CDA-1将使她能够完成课程，通过巴尔的摩马里兰大学获得临床研究理学硕士学位。她还将继续接受一组退伍军人管理局高级调查人员的指导，这些调查人员将提供多样化的研究经验。她的主要导师将是詹姆斯·罗素博士，他是一名成功的退伍军人管理局临床研究人员，对糖尿病神经病变有共同的研究兴趣，在过去几年里一直与齐利奥克斯博士合作，并与她共同撰写了三篇同行评议的期刊文章。此外，她还将通过尼尔·亚历山大博士的指导，获得行动能力评估和运动干预领域的经验和培训。她还将获得皮肤活检的操作和解释方面的专业知识，以确定表皮内神经纤维的密度，这在周围神经病研究领域是必不可少的。 公共卫生相关性： 2型糖尿病在所有老年人中是一个日益严重的问题，特别是退伍军人。大多数患有糖尿病的退伍军人身体健康状况不佳，如果他们有神经病变，他们的损伤更严重，功能受限。对糖尿病相关的两种常见残疾进行持续、长期的干预；行动能力和神经病变可能会对健康结果产生重大影响，这对所有患有糖尿病的老年退伍军人都很重要。这些结果包括预防灾难性的糖尿病并发症，保持个人独立性，提高生活质量，以及随着时间的推移降低医疗和个人护理成本。如果拟议的研究确定生活方式干预在行动能力和神经病变进展以及体力活动水平方面具有长期、持续的好处，这种干预将是可复制的，并能够覆盖到综合退伍军人健康系统中的大量患有糖尿病的老年退伍军人。

DESCRIPTION Type two diabetes mellitus is a growing problem in the aging population, especially among Veterans. Currently, there is no effective therapy to prevent or reverse diabetic neuropathy. An ongoing clinical trial, Improving Neuropathy and Mobility in Subjects with Early Diabetes (INMED), funded by Rehabilitation R&D, will determine in a home based, tailored diet and physical activity program can prevent the progression of neuropathy and improve mobility in participants with impaired glucose regulation. The primary endpoints in this study are measurements of the intraepidermal nerve fiber density (IENFD) to measure the progression of neuropathy and a timed six-minute walk (6MW) as a measurement of the participants' mobility. Although the INMED study may show that a tailored lifestyle intervention (dietary advice, tailored exercise and mobility intervention) improves or prevents the progression of neuropathy, it is unknown if this benefit lasts beyond the period of the intervention and thus would have a sustained benefit to the subject. This information will be important in determining the long-term validity of the lifestyle intervention. The current study is a follow up study of the IMMED responders, defined as participants who had an improvement in the IENFD or 6MW compared to baseline. 48 subjects would be followed for an additional year without a specific intervention after the conclusion of the INMED study to see if there would be a sustained, long-term benefit of a tailored diet and exercise program on the progression of neuropathy and/or mobility as determined by the 6MW and the IENFD. The primary endpoint would be the 6MW at the conclusion of the additional year and the secondary endpoints would be the IENFD after the additional year and the 6MW after an additional 6 months. Information would also be collected to determine (1) if the participants continue to exercise without intervention, (2) if the amount o exercise decreases without ongoing counseling, (3) if they continue to maintain the same rate of improvement observed in the INMED study, and (4) if improvements in clinical measures of neuropathy are sustained beyond the INMED study. The applicant, Dr. Lindsay Zilliox, is an Assistant Professor in the Department of Neurology at the University of Maryland within two years of completing fellowship training who aims to become an independent VA clinical researcher. Her clinical training to this point has not included dedicated time for research training. This 2 year CDA-1 will allow her to complete coursework to earn a Master's of Science in Clinical Research through the University of Maryland, Baltimore. She will also continue to be mentored by a group of senior VA investigators that will provide a diverse research experience. Her primary mentor will be Dr. James Russell, who is a successful VA clinical researcher who shares a research interest in diabetic neuropathy and has worked with Dr. Zilliox over the past several years and co-authored three peer-reviewed journal articles with her. In addition she will gain experience and training in the field of mobility assessment and exercise interventions through mentorship from Dr. Neil Alexander. She will also gain expertise in the performance and interpretation of skin biopsies for the determination of intraepidermal nerve fiber density, which is essential in the field if peripheral neuropathy research. PUBLIC HEALTH RELEVANCE: Type two diabetes is a growing problem among all older adults, particularly Veterans. The majority of Veterans with diabetes are in poor physical health and they are significantly more impaired, with functional limitations, if they have neuropathy. An intervention with sustained, long-term benefits on two of the common disabilities associated with diabetes; mobility and neuropathy will potentially have major effects on health outcomes that are important to all older Veteran with diabetes. These outcomes include prevention of catastrophic diabetic complications, maintenance of personal independence, improved quality of life, and decreased costs for medical and personal care over time. If the proposed research determines that a lifestyle intervention has long term, sustained benefits on mobility and neuropathy progression as well as on levels of physical activity this intervention will be replicable and able to reach th large number of older Veterans with diabetes within the integrated VA Health System.