Impaired Wound Healing in Diabetic Foot Ulceration

描述(由申请人提供)：糖尿病足溃疡(DFU)是一个严重损害患者生活质量的主要问题，导致延长住院时间，并可能需要进行重大截肢。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，这些皮肤微循环和肌肉代谢的异常是导致无法治愈足底糖尿病足部溃疡的原因。此外，我们假设创面愈合率与循环内皮祖细胞(EPC)的数量有关。为了验证我们的假设，我们计划对患有足底溃疡的糖尿病患者进行为期12周的跟踪调查。据估计，在这段时间内，35%-45%的这类人群将实现伤口完全愈合。同时纳入1组低危糖尿病足部溃疡患者和一组健康对照组，与足部溃疡组进行比较。我们将在基线、4、8和12周使用医学高光谱成像(MHSI)和循环内皮祖细胞(EPC)评估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周使用3T MRI稀有技术评估足部肌肉代谢。我们假设高光谱组织氧饱和度(SHSIO2)、肌肉代谢和循环内皮祖细胞将在有足部溃疡风险的糖尿病患者中降低，这种降低在无法治愈溃疡的患者中将更加明显。我们进一步假设，在那些没有治愈溃疡的患者中，与伤口愈合所需的血管生成反应相关的氧气输送和氧气提取的增加将不那么显著。我们相信，这项建议包括跨学科、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，这些策略将极大地提高我们管理这种情况的效率。此外，我们相信这将有助于理解心血管疾病与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.