NEUROPATHY ASSOCIATED WITH IMPAIRED GLUCOSE TOLERANCE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。感觉神经病变是一种常见的神经系统疾病，常伴有疼痛。在发达国家，2型糖尿病是感觉神经病变最常见的病因。在大约40%的神经病变患者中，无法确定病因(？特发性神经病吗?)我们和其他研究表明，35-50%的特发性神经病变患者有糖耐量（IGT）受损，而年龄匹配的普通人群中这一比例为14%。IGT的定义是2小时口服葡萄糖耐量试验（OGTT）后的葡萄糖水平在140 - 200mg /dL之间，空腹血糖低于126mg /dL。IGT患者几乎都有疼痛性感觉神经病变，这与早期糖尿病神经病变的表型有关。糖尿病控制和并发症试验（DCCT）清楚地表明，神经病变的发病和严重程度与1型糖尿病的血糖控制有关。在DCCT中，积极治疗高血糖可以预防或减缓神经病变的进展，而糖尿病预防计划（DPP）表明，强化饮食和运动调整可以防止IGT进展为糖尿病，并为IGT患者制定了护理标准。我们假设，发作性高血糖导致的神经病变在临床上与糖尿病患者观察到的难以区分，并且积极治疗使血糖水平正常化对于减缓这些患者的神经病变进展是必要的。为了验证这一假设，我们提出了一项前瞻性对照试验，以确定强化饮食和运动咨询治疗是否可以稳定或逆转IGT患者的神经病变

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 2 diabetes is the most frequent defined cause of sensory neuropathy. In approximately 40% of patients with neuropathy, no cause can be defined (?idiopathic neuropathy?). We and others have shown that 35-50% of patients with otherwise idiopathic neuropathy have impaired glucose tolerance (IGT), compared to 14% of the age matched general population. IGT is defined as a glucose level after a 2 hour oral glucose tolerance test (OGTT) between 140 and 200 mg/dL and a fasting plasma glucose less than 126 mg/dL. Patients with IGT almost uniformly have a painful sensory neuropathy, linking them to the phenotype of early diabetic neuropathy. The Diabetes Control and Complications Trial (DCCT) clearly showed that neuropathy onset and severity correlates with glycemic control in type I diabetes. In the DCCT, aggressive treatment of hyperglycemia prevented or slowed the progression of neuropathy, while the Diabetes Prevention Program (DPP) shows that intensive diet and exercise modification can prevent progression from IGT to diabetes and sets a standard of care for IGT patients. We hypothesize that episodic hyperglycemia contributes to a neuropathy that is clinically indistinguishable from that observed in patients with frank diabetes, and that aggressive treatment to normalize blood glucose levels will be necessary to slow progression of neuropathy in these patients. To test this hypothesis, we propose a prospective controlled trial to determine if treatment with intensive diet and exercise counseling can stabilize or reverse neuropathy in IGT patients