The effect of diabetes, neuropathy and arterial disease in lower extremity energy

描述（由申请人提供）：糖尿病导致大量糖尿病患者出现下肢问题。外周动脉疾病（PAD）可影响高达29%的糖尿病患者，而其中绝大多数患者存在微循环功能变化。这些异常与周围神经病变（躯体和自主神经）的存在相结合，导致足部溃疡的发展，目前每年导致超过80，000例下肢截肢。因此，与下肢病变主要局限于大动脉的非糖尿病状态相比，糖尿病的病变更广泛，影响微循环和外周神经系统。最终结果是终末器官功能障碍加重，主要是在局部皮肤和肌肉水平。目前，没有可用的技术可以评估糖尿病下肢疾病的进展和各种治疗干预的结果。因此，周围神经病变和微血管疾病的影响在很大程度上被忽视，导致对疾病严重程度的评估不足。主要假设是磁共振波谱（MRS）和血氧水平依赖性（BOLD）测量将能够令人满意地识别下肢肌肉能量储备和组织缺氧的变化。当前提案的主要目的是开发新技术，以评估糖尿病、周围神经病变和血管疾病在休息状态和分级运动期间对小腿中段下肢肌肉功能的影响。我们还将评估18个月期间患有PAD的糖尿病患者和没有PAD和/或神经病变的糖尿病患者的肌肉能量储备的变化。为了实现我们的目标，我们将采用3特斯拉MRI通过MRS研究磷代谢物和使用BOLD技术的肌肉氧合来评估肌肉代谢。公共卫生相关性：在本研究中，我们建议采用磁共振波谱（MRS）和血氧水平依赖性（BOLD）测量测量小腿肌肉的糖尿病患者和无外周动脉疾病的变化。我们相信该项目有潜力开发一种新技术，可以评估糖尿病和血管疾病对下肢肌肉功能的终末器官影响。像这样的技术既可以用于临床实践，也可以用于治疗试验。

DESCRIPTION (provided by applicant): Diabetes causes lower extremity problems in a large number of diabetic patients. Peripheral arterial disease (PAD) can affect up to 29% of all diabetic patients while functional changes in the microcirculation are present in the vast majority of them. These abnormalities in combination with the presence of peripheral neuropathy, both somatic and autonomic, are responsible for the development of foot ulceration which currently results in more than 80,000 lower extremity amputations per year. Thus, in contrast to the non-diabetic state where pathology in the lower extremity is mainly confined in the large arteries, the pathology in diabetes is more widespread, affecting the microcirculation and the peripheral nervous system. The final outcome is an accentuated end-organ dysfunction, mainly at the local skin and muscle level. Currently, there are no techniques available that can evaluate the progression of diabetic lower extremity disease and the outcome of various therapeutic interventions. As a result, the impact of peripheral neuropathy and microvascular disease is largely ignored, leading to inadequate assessment of the severity of the disease. The primary hypothesis is that Magnetic Resonance Spectroscopic (MRS) and Blood Oxygenation Level-Dependent (BOLD) measurements will be able to satisfactorily identify changes in lower extremity muscle energy reserves and tissue hypoxia. The main aim of the current proposal is to develop new techniques that will evaluate the effect of diabetes, peripheral neuropathy and vascular disease in the muscle function of the lower extremity at the mid-calf level both during resting conditions and during graded exercise. We will also evaluate changes in muscle energy reserves over a 18-month period in diabetic patients with PAD and diabetic patients without PAD and/or neuropathy. In order to achieve our goal, we will employ a 3 Tesla MRI to assess the muscle metabolism through MRS studies of the phosphorous metabolites and the muscle oxygenation using the BOLD technique. PUBLIC HEALTH RELEVANCE: In the present study, we propose to employ Magnetic Resonance Spectroscopic (MRS) and blood oxygenation level-dependent (BOLD) measurements to measure changes in the calf muscles of diabetic patients with and without peripheral arterial disease. We believe that this project has the potential to develop a new technique that can evaluate the end-organ impact of diabetes and vascular disease in the lower extremity muscle function. A technique like this can be used in both clinical practice and the conduct of therapeutic trials.