Impaired Glucose Tolerance Causes Neuropathy

描述（由申请人提供）：感觉神经病，通常伴有疼痛，是一种常见的神经系统患者。 在发达国家，2型糖尿病是感觉神经病变最常见的原因。 我们发现，72例前瞻性评估的特发性周围神经病变患者中有36例糖耐量受损（IGT）。 这是一个显着更高的频率IGT（50%）比在大型流行病学研究报告的年龄匹配的一般人群（14%）。 IGT，定义为2小时口服葡萄糖耐量试验（OGTT）在140和200 mg/dl之间，代表葡萄糖代谢的中间缺陷，与胰岛素抵抗综合征相关，并已被证明具有心血管发病的独立风险。 IGT患者几乎一致具有疼痛性感觉神经病变，将其与早期糖尿病神经病变的表型联系起来。 最近完成的糖尿病预防计划（DPP）表明，强化饮食和运动调整可以减缓从IGT到糖尿病的进展。 糖尿病控制和并发症试验（DCCT）清楚地表明，神经病变的发作和严重程度与糖尿病的血糖控制相关。 在DCCT中，高血糖症的积极治疗预防或减缓了神经病变的进展。 我们推测，餐后高血糖症，确定IGT，导致或有助于疼痛，小纤维神经病变，这是无法区分的早期坦率的糖尿病，积极治疗，以正常的高血糖症将减缓或防止神经病变的进展。 本临床初步研究的目的是为IGT和神经病变患者的前瞻性临床试验奠定基础，以确定单独或联合降糖药进行强化运动和饮食咨询是否可以稳定或逆转神经病变。 我们有三个具体目标：1。 使用年龄和体重指数匹配的慢性疼痛对照受试者证实IGT和神经病变之间的统计学关联。 描述IGT相关神经病变的临床、电诊断和组织学表型。使用两种有效的神经病变严重程度测量方法（冷阈值和神经传导速度）确定IGT相关神经病变的进展，并验证表皮内神经纤维计数作为小纤维神经病变进展的测量方法。

DESCRIPTION (provided by the applicant): Sensory neuropathy, often with pain, is a common neurologic patient. In developed countries, type-2 diabetes is the most frequently-defined cause of sensory neuropathy. We have found that 36 of 72 prospectively evaluated patients with otherwise idiopathic peripheral neuropathy have Impaired Glucose Tolerance (IGT). This is a significantly greater frequency of IGT (50%) than reported in large epidemiological studies of the age-matched general population (14%). IGT, defined as a 2-hour Oral Glucose Tolerance Test (OGTT) between 140 and 200 mg/dl, represents an intermediate defect in glucose metabolism, which correlates with insulin resistance syndrome, and has been shown to carry an independent risk for cardiovascular morbidity. Patients with IGT almost uniformly have a painful sensory neuropathy, linking them to the phenotype of early diabetic neuropathy. The recently completed Diabetes Prevention Program (DPP) shows that intensive diet and exercise modification can slow progression from IGT to diabetes. The Diabetes Control and Complications Trial (DCCT) clearly shows that neuropathy onset and severity correlates with glycemic control in diabetes. In the DCCT, aggressive treatment of hyperglycemia prevented or slowed the progression of neuropathy. We hypothesize that the post-prandial hyperglycemia, identified by IGT, causes or contributes to a painful, small fiber neuropathy, which is indistinguishable from that observed in early frank diabetes, and that aggressive treatment to normalize hyperglycemia will slow or prevent progression of neuropathy. The purpose of this Clinical Pilot Study is to lay the groundwork for a prospective clinical trial in patients with IGT, and neuropathy, to determine if intensive exercise and diet counseling alone, or with a glucose-lowering agent, can stabilize or reverse neuropathy. We have three specific aims:1. Confirm the statistical association between IGT and neuropathy using control subjects with chronic pain, matched for age and body mass index.2. Characterize the clinical, electrodiagnostic, and histologic phenotype of neuropathy associated with IGT.Define the progression of neuropathy associated with IGT using two validated measures of neuropathy severity (cold detectiort threshold and nerve conduction velocity), and validate the use of intraepidermal nerve fiber countin as a measure of small fiber neuropath progression.