VASCULAR REACTIVITY IN METABOLIC SYNDROME AND DIABETIC PATIENTS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 代谢综合征是一种高度流行的疾病，由几个主要的聚集因素组成，这些因素增加了发生心血管疾病(CVD)的风险。[41-43]新陈代谢综合征的特征将在后面的方案中讨论，然而，胰岛素抵抗、糖耐量减低和/或糖尿病(DM)是有助于诊断新陈代谢综合征的因素。但是，如果 患者单独患有糖尿病，那么他/她仍然有患心血管疾病的风险，因为胰岛素抵抗本身与血管变化有关。[38，39]可以看到这些干扰一直延伸到微血管水平。此外，这些血管障碍还会导致神经损伤和神经病变。 糖尿病周围神经病变(DPN)是一种由于长期暴露在高血糖环境中而引起的疾病。有趣的是，神经病还可以调节血管的反应性，从而改变循环。[44]因此，重要的是监测患者的微血管变化，以评估他们的疾病进展和 心血管风险。微血管障碍包括微动脉反应性异常、毛细血管再充盈、通透性和血流异常。[45]这些变化在代谢综合征和糖尿病患者中都很明显。有不同程度的这些干扰，小血管结构和 功能可以在生命的早期和疾病的早期观察到。[45]因此，筛查易患糖尿病、代谢综合征或心血管疾病的患者的微血管变化应该提供一种方法来评估向给定疾病状态的进展以及该进展 疾病。因此，研究患者的微血管变化可能对疾病患者和高危患者具有临床重要性；然而，在临床上还没有确定的、非侵入性的、准确的和简单的方法来测量这些变化。临床医生可以在门诊非侵入性地测量微血管系统的变化(例如，通过量化微血管系统中脱氧血红蛋白和氧合血红蛋白浓度对代谢应激的反应)的工具，可以对患者进行更早的检测和长期监测。这将为预防措施留出更多时间 护理和治疗。 这项研究项目与贝克曼激光研究所的合作伙伴合作，旨在评估一种名为漫反射光谱(DOS)的新技术可以用于非侵入性测量患者微血管系统变化的假设。DOS是一种测量 近红外光在肌肉等组织中的光学吸收和散射特性，以量化氧化和脱氧血红蛋白、水和脂质的绝对浓度。它提供了与组织灌注、代谢变化和组织损伤指标相关的微血管的定量和功能信息。它在乳腺癌领域显示出了希望，我们试图评估DOS作为一种测量代谢综合征和DM患者微血管变化的手段的潜力，以评估CVD风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Metabolic Syndrome is a highly prevalent condition that is comprised of several major clustering factors that increase the risk for developing cardiovascular disease (CVD). [41-43] The hallmarks of Metabolic Syndrome are discussed later in the protocol, however, insulin resistance, glucose intolerance, and/or Diabetes Mellitus (DM) are contributing factors to a diagnosis of Metabolic Syndrome. However, if the patient has DM alone, then he/she is still at risk for developing CVD, as insulin resistance on its own is associated with vascular changes. [38, 39] These disturbances can be seen down to the level of the microvasculature. Further, these vascular disturbances also lead to nerve damage and neuropathy. Diabetic Peripheral Neuropathy (DPN) is a condition brought on by prolonged exposure to high blood glucose. Interestingly, neuropathy can also modulate vascular reactivity and hence alter circulation. [44] Thus, it is important to monitor microvascular changes in patients to assess their disease progression and cardiovascular risks. Microvascular disturbances include abnormalities in arteriolar reactivity, capillary recruitment, permeability, and blood flow. [45] These changes are evident in both Metabolic Syndrome and DM patients. There are varying degrees of these disruptions, and the defects in small vessel structure and function can be observed very early in life and early in disease. [45] Therefore screening for microvascular changes in patients predisposed to the development of DM, Metabolic Syndrome, or CVD should provide a means to evaluate both progression towards a given disease state as well as the advancement of that disease. Thus, studying microvascular changes in patients may be of clinical importance in diseased patients as well as at-risk patients; however, there are no established, non-invasive, accurate, and easy ways to measure these changes at clinics. A tool that would allow clinicians to non-invasively measure changes in the microvasculature (for example, by quantifying the change in concentrations of deoxyhemoglobin and oxyhemoglobin in the microvasculature in response to metabolic stress) in an outpatient clinic, could allow for earlier detection and long-term monitoring of patients. This would allow more time for preventative care and treatment. This research project, in collaboration with partners at the Beckman Laser Institute, aims to evaluate the hypothesis that a novel technology known as Diffuse Optical Spectroscopy (DOS) can be used to non-invasively measure changes in the microvasculature of patients. DOS is a technique that measures the optical absorption and scattering properties of near-infrared light in tissues such as muscle in order to quantify the absolute concentration of oxygenated and deoxygenated hemoglobin, water, and lipids. It provides quantitative and functional information on the microvasculature related to tissue perfusion, metabolic changes, and indicators of tissue damage. It has shown promise in the field of breast cancer, and we seek to evaluate the potential of DOS as a means to measure microvascular changes in Metabolic Syndrome and DM patients in order to assess CVD risk.