The Impact of the Metabolic Syndrome on Neuropathy

描述（由申请人提供）：神经病是一种痛苦和衰弱的状况，影响超过1500万美国人。令人惊讶的是，超过30%的患者即使在广泛的评估后也被标记为特发性。对于那些最常见的神经病变，糖尿病的患者，血糖控制仍然是唯一有效的治疗方法。不幸的是，超过40%的糖尿病患者将发展神经病变，尽管良好的血糖控制。这些观察结果强调了需要确定神经病变的可改变的风险因素，这些因素可能是“特发性”神经病变的原因，以及除了高血糖导致糖尿病神经病变的因素。代谢综合征组分可能是神经病变中这些重要的可改变的危险因素。这种综合征由多种心血管危险因素组成，这些因素往往聚集在一起。过去的观察性研究表明，这些成分中的一种或多种与神经病变的发生有关，但这些研究存在显著的设计局限性。大多数研究仅采用横断面设计，仅关注糖尿病人群。此外，这些研究没有应用神经病的标准化定义，病例分类通常基于一种诊断测试。在这个职业发展奖中，我们建议量化代谢综合征对神经病变的影响，并确定哪些代谢综合征成分与神经病变相关，具体目标有两个。在目标1中，我们将利用广泛的神经病变表型比较代谢综合征队列与瘦对照组中神经病变的患病率。在目标2中，我们将采用横断面和纵向设计来确定哪些代谢综合征组分与神经病变相关。横断面设计的优点是在任何干预之前应用临床神经病变结局指标。纵向分量的优点是，我们可以研究饮食和运动方案后代谢综合征组分的动态变化与神经病变结局指标变化的关系。本项目的总体目标是确定神经病变发展的可改变的风险因素，这些风险因素将导致干预性临床治疗。 用于预防和/或治疗神经病的试验。这份工作对我的职业发展至关重要。我将成为一名独立的临床研究人员，在内分泌疾病状态的神经并发症方面具有专业知识。生物统计学家和流行病学的正式培训和实践经验将为成功完成本项目以及未来的调查奠定基础。我职业发展的临床试验部分将使我能够从这项研究中获得结果，并无缝过渡到干预性研究， 从而为神经病患者带来新的治疗方法。伊娃费尔德曼博士和查尔斯伯兰特是理想的适合作为导师为这个项目与他们的互补专业知识在神经病变和代谢表型。密歇根大学的巨大资源，包括神经病中心，调查体重管理诊所，密歇根临床和健康研究所，以及公共卫生学院，将大大有助于 圆满完成了这一提案。

DESCRIPTION (provided by applicant): Neuropathy is a painful and debilitating condition that affects over 15 million Americans. Surprisingly over 30% of patients are labeled as idiopathic even after an extensive evaluation. For those patients with the most common cause of neuropathy, diabetes, glucose control remains the only effective treatment. Unfortunately, greater than 40 percent of patients with diabetes will develop neuropathy despite good glucose control. These observations highlight the need to identify modifiable risk factors for neuropathy that may be the cause of "idiopathic" neuropathy and the factors that in addition to high serum glucose lead to diabetic neuropathy. Metabolic syndrome components may be these important modifiable risk factors in neuropathy. This syndrome is comprised of multiple cardiovascular risk factors that tend to cluster together. Past observational studies have implicated one or more of these components in the development of neuropathy, but these studies have suffered from significant design limitations. Most studies were only cross-sectional in design and focused only on diabetic populations. Furthermore, these studies did not apply a standardized definition of neuropathy, and case classification was often based on one diagnostic test. In this career development award, we propose to quantify the impact of the metabolic syndrome on neuropathy and to determine which metabolic syndrome components are associated with neuropathy in two specific aims. In aim 1, we will compare the prevalence of neuropathy in a metabolic syndrome cohort with lean controls by utilizing extensive neuropathy phenotyping. In aim 2, we will employ cross-sectional and longitudinal designs to identify which metabolic syndrome components are associated with neuropathy. The cross-sectional design has the advantage of applying clinical neuropathy outcome measures prior to any intervention. The advantage of the longitudinal component is that we can investigate the relationship of the dynamic changes in metabolic syndrome components after a diet and exercise regimen with changes in neuropathy outcome measures. The overall goal of this project is to identify modifiable risk factors for the development of neuropathy that will lead to interventional clinical trials to prevent and/or treat neuropathy. This proposal is essential to my career development. I will become an independent clinical researcher with expertise in neurologic complications from endocrinologic disease states. The biostatistician and epidemiologic formal training and practical experiences will set the stage for successful completion of not only this project, but also of future investigations. The clinical trial component of my career development will allow me to take the results from this study and seamlessly transition into interventional studies that will lead to new treatments for patients with neuropathy. Drs. Eva Feldman and Charles Burant are ideally suited as mentors for this project with their complementary expertise in neuropathy and metabolic phenotyping. The vast resources of the University of Michigan, including the Neuropathy Center, the Investigational Weight Management Clinic, the Michigan Institute for Clinical and Health Research, and the school of Public Health, will significantly contribute to the successful completion of this proposal.