Natural History of Peripheral Diabetic Neuropathy

描述（由申请人提供）：目前没有可以客观评价小神经纤维功能的客观测量。目前使用的技术是主观的方法，依赖于患者的合作，这导致高度的可变性。这阻碍了新的治疗方法的评估，可以具体影响糖尿病神经病变的小神经纤维，如神经营养因子。本提案的主要目的是评估神经轴突相关的血管舒张测量在量化C伤害性纤维的功能和在至少三年的时间内跟踪糖尿病相关功能障碍的进展中的功效。为此，我们计划随访150例糖尿病患者和25例健康对照者。所有参与者将每18个月见一次面，至少36个月。每次访视期间，将使用当前采用的方法评估神经病变，包括评估神经病变症状评分（NSS）、神经病变损害评分（NIS）、振动感知阈值（VPT）、热测试和Semmes-Weinstein单丝。在每次访视期间，将测量神经轴突反射相关血管舒张，这是一项可评价C-伤害性纤维功能的客观测量。将神经轴突相关血管舒张测量的变化与当前可用方法中观察到的变化进行比较。希望本研究能回答以下问题：1.糖尿病神经病变中小神经纤维功能下降的速度是多少？2.神经轴突相关的血管舒张测量是否适用于参与临床试验的糖尿病患者的长期随访，以检查新治疗的疗效？3.临床试验所需的患者数量和所需的时间长度是多少？

DESCRIPTION (provided by applicant): There are currently no objective measurements that can objectively evaluate the function of small nerve fibers. The currently used techniques are subjective methods that rely on the patient's collaboration and this results to a high degree of variability. This hampers the assessment of new treatments that can specifically affect the small nerve fibers in diabetic neuropathy, such as neurotrophic factors. The main objective of the present proposal is to evaluate the efficacy of nerve axon-related vasodilation measurement in quantifying the function of C nociceptive fibers and following the progression of diabetes-related dysfunction over a period of at least three years. To this end, we plan to follow up 150 diabetic patients without and with mild neuropathy and 25 healthy control subjects. All participants will be seen every 18 months for a minimum of 36 months. During each visit, neuropathy will be assessed using currently employed methods that include the assessment of the Neuropathy Symptom Score (NSS), Neuropathy Impairment Score (NIS), Vibration Perception Threshold (VPT), thermal testing and Semmes-Weinstein monofilaments. The nerve axon reflex related vasodilation, an objective measurement that can evaluate the function of the C-nociceptive fibers, will be measured during each visit. The changes in the nerve axon-related vasodilation measurement will be compared to the changes that will be observed in the currently available methods. It is hoped that this study will provide answers to the following questions: 1. What is the rate of decline of the small nerve fiber function in diabetic neuropathy? 2. Is the nerve axon-related vasodilation measurement suitable for the long term follow-up of diabetic patients who participate in clinical trials that examine the efficacy of new treatments? 3. What are the required numbers of patients and the required length of time so a clinical trial is properly powered?