NEUROPATHY ASSOCIATED WITH IMPAIRED GLUCOSE TOLERANCE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 感觉神经病，通常伴有疼痛，是一种常见的神经系统疾病。在发达国家，II型（胰岛素抵抗）糖尿病是感觉神经病变最常见的原因。我们发现，35-50%的前瞻性评估的原发性疼痛性周围神经病变患者有糖耐量受损（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，并已被证明具有心血管发病的独立风险。这是一个显着更高的频率IGT比报告在大型流行病学研究的年龄匹配的一般人群（14%）。我们推测，IGT所确定的餐后高血糖导致或促成了一种疼痛的小纤维神经病变，这种神经病变与早期坦率糖尿病中观察到的神经病变难以区分，并且早期积极治疗IGT患者以使高血糖正常化将减缓或预防神经病变的进展。这项临床初步研究将为以后对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疗法或降糖药治疗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相关的神经病变的临床、电诊断和组织学表型。 使用经验证的终点指标定义IGT相关神经病变进展的自然史，以及 建议使用表皮内神经纤维计数（IENF）作为小纤维损失的测量。

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.