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

糖尿病、神经病变和动脉疾病对下肢能量的影响

• 批准号: 7743288
• 负责人: ARISTIDIS VEVES
• 金额: $ 25.38万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7743288
• 关键词: Affect; Amputation; Arteries; Asses; Development; Diabetes Mellitus; Diabetic Angiopathies; Disease; Disease Outcome; Exercise; Functional disorder; Goals; Hypoxia; Lower Extremity; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Microcirculation; Muscle; Muscle function; Neuropathy; Organ; Outcome; Pathology; Patients; Peripheral Nervous System; Peripheral Nervous System Diseases; Peripheral arterial disease; Phosphorous; Rest; Severity of illness; Skin; Techniques; Therapeutic Intervention; Therapy Clinical Trials; Tissues; Ulcer; Vascular Diseases; blood oxygen level dependent; clinical practice; diabetic; diabetic patient; foot; muscle metabolism; non-diabetic; public health relevance

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.

描述（由申请人提供）：糖尿病会导致大量糖尿病患者的下肢问题。周围动脉疾病（PAD）最多会影响所有糖尿病患者的29％，而微循环的功能变化在其中绝大多数。这些异常与体细胞和自主神经的外周神经病的存在相结合，是造成足部溃疡的发展，目前每年导致80,000多个下肢截肢。因此，与非糖尿病状态相比，下肢的病理主要局限于大动脉，糖尿病的病理更为广泛，影响了微循环和周围神经系统。最终结果是强调的末端功能障碍，主要是在局部皮肤和肌肉水平上。当前，尚无可用的技术来评估糖尿病下肢疾病的进展和各种治疗干预措施的结果。结果，周围神经病和微血管疾病的影响在很大程度上被忽略，导致对疾病严重程度的评估不足。主要假设是磁共振光谱（MRS）和血液氧合水平依赖性（BOLD）测量将能够令人满意地识别下肢肌肉能量储量和组织缺氧的变化。当前提案的主要目的是开发新技术，以评估糖尿病，周围神经病和血管疾病在下肢肌肉功能中，在休息状况和分级运动中，下肢的肌肉功能。我们还将评估未经PAD和糖尿病患者没有PAD和/或神经病的糖尿病患者的18个月内肌肉能量储量的变化。为了实现我们的目标，我们将使用3个特斯拉MRI通过MRS研究磷代谢产物和使用BOLD技术来评估肌肉代谢。公共卫生相关性：在本研究中，我们建议采用磁共振光谱（MRS）和血液氧合水平依赖性（BOLD）测量，以测量患有和没有周围动脉疾病的糖尿病患者小腿肌肉的变化。我们认为，该项目有可能开发一种新技术，可以评估糖尿病和血管疾病对下肢肌肉功能的最终影响。这样的技术都可以在临床实践和治疗试验的进行中使用。