The Impact of the Metabolic Syndrome on Neuropathy

代谢综合征对神经病变的影响

基本信息

批准号：
9301064
负责人：
Brian Christopher Callaghan
金额：
$ 18.74万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9301064
关键词：
Address Affect Age American Area Biopsy Blood Pressure Classification Clinic Clinical Clinical Trials Consensus Coupled Cross-Sectional Studies Development Diabetes Mellitus Diabetic Neuropathies Diagnosis Diagnostic tests Disease Distal Enrollment Epidemiology Etiology Evaluation Evolution Fiber Future Gender Glucose Goals Health High Density Lipoprotein Cholesterol Hypertriglyceridemia Idiopathic Neuropathy Individual Institutes Intervention Intervention Studies Investigation K-Series Research Career Programs Label Lead Leg Logistic Regressions Measures Mentors Metabolic syndrome Michigan Modeling Nerve Fibers Neurologic Neuropathy Non-Insulin-Dependent Diabetes Mellitus Obesity Observational Study Outcome Outcome Measure Pain Patients Pharmaceutical Preparations Phenotype Population Prediabetes syndrome Predictive Factor Prevalence Public Health Schools Relative Risks Research Research Design Research Infrastructure Research Personnel Risk Risk Factors Risk Reduction Serum Skin Standardization Syndrome Testing Thigh structure Thinness Time Training United States National Institutes of Health Universities University resources Weight maintenance regimen base blood glucose regulation cardiovascular disorder risk cardiovascular risk factor career development cohort density design diabetic diet and exercise effective therapy exercise regimen experience longitudinal analysis longitudinal design metabolic phenotype modifiable risk prevent primary outcome public health relevance sugar

项目摘要

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.

描述（由申请人提供）：神经病是一种痛苦且使人衰弱的疾病，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% 的患者被标记为特发性。对于那些患有神经病变最常见原因糖尿病的患者来说，血糖控制仍然是唯一有效的治疗方法。不幸的是，尽管血糖控制良好，仍有超过 40% 的糖尿病患者会出现神经病变。这些观察结果强调需要确定神经病的可改变的危险因素，这些因素可能是“特发性”神经病的原因，以及除了高血糖之外导致糖尿病神经病的因素。代谢综合征成分可能是神经病中这些重要的可改变危险因素。这种综合征由多种心血管危险因素组成，这些危险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展有关，但这些研究存在明显的设计局限性。大多数研究只是横断面设计，并且只关注糖尿病人群。此外，这些研究没有采用神经病的标准化定义，病例分类通常基于一项诊断测试。在这个职业发展奖中，我们建议量化代谢综合征对神经病的影响，并确定哪些代谢综合征成分与神经病相关，以实现两个具体目标。在目标 1 中，我们将通过广泛的神经病变表型分析，将代谢综合征队列中的神经病变患病率与瘦对照进行比较。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果测量。纵向成分的优点是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果指标变化的关系。该项目的总体目标是确定神经病发展的可改变的危险因素，从而导致介入临床预防和/或治疗神经病的试验。这个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，在内分泌疾病状态的神经系统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不仅将为成功完成该项目奠定基础，也将为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，并无缝过渡到介入研究，这将为神经病患者带来新的治疗方法。博士。伊娃·费尔德曼 (Eva Feldman) 和查尔斯·伯兰特 (Charles Burant) 在神经病和代谢表型方面具有互补的专业知识，是该项目的理想导师。密歇根大学的丰富资源，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以及公共卫生学院，将为顺利完成本提案。