NEUROPATHY ASSOCIATED WITH IMPAIRED GLUCOSE TOLERANCE

点击翻译按钮获取中文摘要

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.