The Impact of the Metabolic Syndrome on Neuropathy

描述(由申请者提供)：神经病是一种痛苦和虚弱的疾病，影响着超过1500万美国人。令人惊讶的是，即使经过广泛的评估，仍有超过30%的患者被贴上特发性的标签。对于那些神经病变最常见的原因是糖尿病的患者，控制血糖仍然是唯一有效的治疗方法。不幸的是，尽管血糖控制良好，超过40%的糖尿病患者仍会发展为神经病变。这些观察结果强调，需要确定神经病变的可改变的危险因素，这些危险因素可能是“特发性”神经病变的原因，以及除了高血糖外，还会导致糖尿病神经病变的因素。代谢综合征成分可能是神经病中这些重要的可改变的危险因素。这种综合征由多个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，这些成分中的一个或多个与神经病变的发展有关，但这些研究受到显著的设计限制。大多数研究在设计上只是横断面的，并且只关注糖尿病人群。此外，这些研究没有应用神经病变的标准化定义，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，并在两个特定目标中确定哪些代谢综合征成分与神经病变相关。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和瘦身对照人群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成分与神经病变有关。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果测量。纵向成分的优势在于，我们可以研究饮食和运动方案后代谢综合征成分的动态变化与神经病变结局指标变化的关系。这个项目的总体目标是确定神经病变发展的可改变的危险因素，这将导致介入临床。 预防和/或治疗神经病的试验。这项建议对我的职业发展至关重要。我将成为一名独立的临床研究员，在内分泌疾病状态下的神经学并发症方面拥有专业知识。生物统计学家和流行病学的正式培训和实践经验将不仅为成功完成这一项目，而且也为今后的调查奠定基础。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，并无缝地过渡到干预研究，这将 为神经病患者带来新的治疗方法。Eva Feldman博士和Charles Burant博士是这个项目的理想导师，他们在神经病和代谢表型方面的专业知识互补。密歇根大学的大量资源，包括神经病中心、研究体重管理诊所、密歇根临床与健康研究所和公共卫生学院，将对 成功地完成了这项提案。

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.