Quantitative biomarkers of T1D peripheral neuropathy using functional imaging

 描述（由申请人提供）：糖尿病影响全球估计3.74亿人，其中包括2500多万美国人。糖尿病患者存在多种并发症的风险，包括心脏病、肾脏疾病（肾病）、眼部疾病（糖尿病视网膜病变）和糖尿病足（周围神经病变）。15%的糖尿病患者在其一生中会因周围神经病变而患上足部溃疡。足溃疡是糖尿病患者下肢截肢的主要原因（85%）。VisionQuest Biomedical LLC和新墨西哥州大学（UNM）组成了一个团队，研究患有和未诊断出周围神经病变的糖尿病患者人群，以便更好地了解一个人在寒冷刺激后的自动温度调节如何反映周围神经病变的神经元变化。该研究将使用标准的临床检查，如单丝感觉测试，以及不太标准的检查技术，如交感神经皮肤反应，与动态红外功能成像进行比较。功能性红外成像技术已被开发和应用，我们的小组作为试点研究的一部分。原型功能性热成像设备已经在许多受试者身上进行了测试，这些受试者显示出其测量足底热调节能力的强烈迹象，并证明了其作为生物标志物的潜力，用于准确定量1型（T1 D）或2型糖尿病（T2 D）的DPN变化/进展。我们的初步实验数据结果产生了非常令人信服的证据，热功能技术可以检测正常对照和糖尿病患者之间的差异/或周围神经病变的风险。有三个具体的目标要完成在这个赠款申请。第一个目的是建立一个规范的范围内的功能反应的热刺激测量的红外成像设备，通过研究50个控制对象。在第二个目标中，我们将研究50名糖尿病患者诊断为周围神经病变的热衍生功能信号的变化。第三个目标是应用目标1中开发的方案，对50名诊断为糖尿病但无周围神经病变的受试者进行临床研究。诸如恢复时间、恢复模式（时间和空间两者）的特征将与临床诊断测量相关联，诸如神经传导速度测试和踝臂指数测试。临床检查将由我们的合作足科医生进行。

 DESCRIPTION (provided by applicant): Diabetes affects an estimated 374 million people worldwide, including more than 25 million Americans. Diabetic patients are at risk for a wide array of complications, including heart disease, kidney disease (nephropathy), ocular diseases (diabetic retinopathy), and diabetic foot (peripheral neuropathy). Fifteen percent of diabetics wil develop a foot ulcer as a result of peripheral neuropathy during their lifetime. Foot ulcers are th main cause (85%) of lower extremity amputation in patients with diabetes. VisionQuest Biomedical LLC and the University of New Mexico (UNM) have formed a team to study a population of diabetics with and without diagnosed peripheral neuropathy in order to gain a better understanding of how a person's auto-thermo-regulation after a cold provocation reflects neuronal changes in peripheral neuropathy. The study will use standard clinical examinations, such as monofilament sensory tests, as well as less standard exam techniques, such as sympathetic skin response, to compare with dynamic infrared functional imaging. The functional infrared imaging techniques have been developed and applied by our group as part of a pilot study. A prototype functional thermal imaging device has been tested on a number of subjects that shows strong indications of its capacity to measure thermal regulation in the plantar foot, and demonstrates potential as a biomarker for accurate quantification of DPN changes/progression in type 1 (T1D) or type 2 diabetes (T2D). Our preliminary experimental data results produced highly compelling evidence that thermal-functional technology can detect differences between normal controls and diabetics with/or at risk for peripheral neuropathy. There are three specific aims to be accomplished in this grant application. The first aim is to establish a normative range for the functional response to thermal stimulus as measured by an infrared imaging device by studying 50 control subjects. In the second aim, we will study the variation in the thermally derived functional signal in 50 diabetics with diagnosed peripheral neuropathy. The third aim is to apply the protocol developed in Aim 1 to conduct a clinical study with 50 diagnosed subjects with diabetes without peripheral neuropathy. Features, such as recovery time, recovery pattern (both temporal and spatial), will be correlated with clinical diagnostic measurements, such as nerve conduction velocity tests and ankle-brachial index tests. Clinical examinations will be performed by our collaborating podiatrist.