NEUROPATHY ASSOCIATED WITH IMPAIRED GLUCOSE TOLERANCE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 感觉神经病，通常伴有疼痛，是一种常见的神经学问题。在发达国家，II型(胰岛素抵抗)糖尿病是感觉神经病最常见的病因。我们发现，在前瞻性评估的特发性痛性周围神经病患者中，有35-50%患有糖耐量减低(IGT)，这是一种与胰岛素抵抗综合征相关的葡萄糖代谢中间缺陷，已被证明是心血管疾病的独立风险因素。这比在年龄匹配的普通人群的大型流行病学研究中报告的IGT发生率(14%)要高得多。我们假设，IGT发现的餐后高血糖会导致或导致疼痛的细小纤维神经病，这与早期弗兰克糖尿病时观察到的没有区别，早期积极治疗IGT患者以使高血糖正常化将减缓或防止神经病变的进展。这项临床先导性研究将为以后对IGT和神经病变患者进行前瞻性双盲安慰剂对照试验奠定基础，以确定强化饮食和运动治疗或葡萄糖缓释剂是否可以稳定或逆转神经病变。在这项初步研究中，我们将： 描述与IGT相关的神经病的临床、电诊断和组织学表型。 使用有效的终点测量定义IGT相关神经病变进展的自然病史，以及 验证使用表皮内神经纤维计数(IENF)作为衡量小纤维丢失的方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sensory neuropathy, often with pain, is a common neurologic problem. In developed countries, type II (insulin resistant) diabetes is the most frequently defined cause of sensory neuropathy. We have found that 35-50% of prospectively evaluated patients with otherwise idiopathic painful peripheral neuropathy have impaired glucose tolerance (IGT), an intermediate defect in glucose metabolism which correlates with insulin resistance syndrome, and has been shown to carry an independent risk for cardiovascular morbidity. This is a significantly greater frequency of IGT than reported in large epidemiologic studies of age matched general population (14%). We hypothesize that the postprandial hyperglycemia identified by IGT causes or contributes to a painful, small fiber neuropathy that is indistinguishable from that observed in early frank diabetes, and that early, aggressive treatment of IGT patients to normalize hyperglycemia will slow or prevent progression of neuropathy. This clinical pilot study will lay the groundwork for a later prospective double blind placebo controlled trial of patients with IGT and neuropathy to determine if treatment with intensive diet and exercise cousneling, or a glucose loweing agent can stabilize or reverse neuropathy. In this initial study we will: Characterize the clinical, electrodiagnostic, and histologic phenotype of neuropathy associated with IGT. Define the natural history of IGT associated neuropathy progression using validated endpoint measures, and Validate the use of intraepidermal nerve fiber counting (IENF) as a measure of small fiber loss.