Quantitative biomarkers of T1D peripheral neuropathy using functional imaging

 描述(申请人提供)：全世界大约有3.74亿人患有糖尿病，其中包括超过2500万的美国人。糖尿病患者面临一系列并发症的风险，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%的糖尿病患者在一生中会因周围神经病变而发展为足部溃疡。足部溃疡是糖尿病患者截肢的主要原因(85%)。VisionQuest Biomedical LLC和新墨西哥大学(UNM)组成了一个团队，研究了一组有和没有被诊断为周围神经病变的糖尿病患者，以更好地了解一个人在冷刺激后的自动体温调节如何反映周围神经病变中的神经元变化。这项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，如交感皮肤反应，以与动态红外功能成像进行比较。作为先导研究的一部分，我们小组已经开发并应用了功能红外成像技术。一种原型功能热成像设备已经在许多受试者身上进行了测试，显示出其测量足底热调节的能力，并显示出作为准确量化1型(T1D)或2型糖尿病(T2D)DPN变化/进展的生物标志物的潜力。我们的初步实验数据结果产生了非常令人信服的证据，表明热功能技术可以检测出正常对照组和有/或有周围神经病变风险的糖尿病患者之间的差异。在这项赠款申请中，有三个具体目标需要实现。第一个目标是通过研究50名对照受试者，建立红外成像仪测量的热刺激功能反应的标准范围。在第二个目标中，我们将研究50名诊断为周围神经病变的糖尿病患者的热导出功能信号的变化。第三个目标是应用在目标1中开发的方案来对50名诊断为无周围神经病变的糖尿病患者进行临床研究。恢复时间、恢复模式(时间和空间)等特征将与神经传导速度测试和踝臂指数测试等临床诊断测量相关联。临床检查将由我们合作的足科医生进行。

 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.