Impaired Wound Healing in Diabetic Foot Ulceration

描述（由申请人提供）：糖尿病足溃疡（DFU）是一个严重的问题，严重损害患者的生活质量，导致住院时间延长，可能需要大截肢。我们单位以前的工作表明，糖尿病患者的皮肤血流量和氧合减少，足部肌肉的能量储备减少。这项研究的主要假设是，皮肤微循环和肌肉代谢的这些异常是导致足底糖尿病足溃疡愈合失败的原因。此外，我们假设伤口愈合的速度与循环内皮祖细胞（EPCs）的数量有关。为了探讨我们的假设，我们计划随访糖尿病患者足底溃疡12周。据估计，35%-45%的这一人群将在此期间实现完全伤口愈合。还将入组一组足部溃疡低风险的糖尿病患者和一组健康对照受试者，以便与足部溃疡组进行比较。我们将在基线、4、8和12周时使用医学高光谱成像（MHSI）和循环内皮祖细胞（EPC）评价皮肤微循环血管反应性、局部组织氧输送和氧提取，并在0和12周时使用3 T MRI RARE技术评价足部肌肉代谢。我们假设，高光谱组织氧饱和度（SHSIO 2），肌肉代谢和循环EPCs将减少糖尿病患者的足部溃疡的风险，这种减少将更加明显的患者谁不能治愈他们的溃疡。我们进一步假设，与伤口愈合所需的血管生成反应相关的氧输送和氧提取的增加在溃疡不愈合的患者中将不太明显。我们认为，该提案包括跨学科，翻译和临床组成部分，将增加我们在一个非常重要的领域的知识，并将帮助我们更好地了解DFU伤口愈合的病理生理学。我们还相信，这些知识的积累将为开发新的治疗策略铺平道路，这将大大提高我们管理这种疾病的疗效。此外，我们相信这将有助于了解心血管疾病和伤口愈合之间的关系。

DESCRIPTION (provided by applicant): Diabetic foot ulceration (DFU) is a major problem that significantly impairs the quality of life of the patient, leads to prolonged hospitalization and may require a major amputation. Previous work from our unit has shown that there is reduction in skin blood flow and oxygenation and reduced energy reserves of the foot muscles in diabetes. The main hypothesis for this study is that these abnormalities in the skin microcirculation and muscle metabolism are responsible for the failure to heal plantar diabetic foot ulcers. In addition, we hypothesize that the rate of wound healing is associated with the number of circulating endothelial progenitor cells (EPCs). In order to explore our hypotheses, we plan to follow up diabetic patients with plantar foot ulceration for a 12-week period. It is estimated that 35%-45% of this population will achieve complete wound healing during this period. 1 group of diabetic patients at low risk of foot ulceration and a group of healthy control subjects will also be enrolled so comparisons with the group with foot ulceration can be made. We will evaluate skin microcirculation vascular reactivity, localized tissue oxygen delivery and oxygen extraction, using Medical Hyperspectral Imaging (MHSI) and circulating Endothelial Progenitor Cells (EPCs) at baseline, 4, 8, and 12 weeks and foot muscle metabolism, using a 3T MRI RARE technique, at 0 and 12 weeks. We hypothesize that hyperspectral tissue oxygen saturation (SHSIO2), muscle metabolism and circulating EPCs will be reduced in the diabetic patients at risk of foot ulceration and that this reduction will be more pronounced in the patients who fail to heal their ulcers. We further hypothesize that the increase in oxygen delivery and oxygen extraction related to the angiogenic response required for wound healing will be less prominently observed in those patients who do not heal their ulcers. We believe that this proposal includes interdisciplinary, translational and clinical components that will increase our knowledge in a very important field and will help us to better understand the pathophysiology of wound healing in DFU. We also believe that the accumulation of such knowledge will pave the way to the development of new therapeutic strategies that will greatly enhance our efficacy in managing this condition. In addition, we believe that it will be helpful in understanding the relationship between cardiovascular disease and wound healing.