VASCULAR REACTIVITY IN METABOLIC SYNDROME AND DIABETIC PATIENTS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子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，这些因素会增加患心血管疾病（CVD）的风险。[41-43]代谢综合征的特征将在方案的后面讨论，但是，胰岛素抵抗、葡萄糖耐受不良和/或糖尿病（DM）是代谢综合征诊断的促成因素。但如果 如果患者仅患有DM，那么他/她仍有发生CVD的风险，因为胰岛素抵抗本身与血管变化相关。[38这些干扰可以被看到下降到微脉管系统的水平。此外，这些血管紊乱还导致神经损伤和神经病变。 糖尿病周围神经病变（DPN）是一种由长期暴露于高血糖引起的疾病。有趣的是，神经病变也可以调节血管反应性，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其疾病进展， 心血管风险。微血管障碍包括小动脉反应性、毛细血管募集、渗透性和血流的异常。[45]这些变化在代谢综合征和DM患者中都很明显。存在不同程度的这些破坏，并且小血管结构和 可以在生命的早期和疾病的早期观察到功能。[45]因此，筛查易患DM、代谢综合征或CVD的患者的微血管变化应提供一种评估向给定疾病状态的进展以及该疾病状态的进展的手段。 疾病因此，研究患者的微血管变化可能在患病患者以及处于风险中的患者中具有临床重要性;然而，没有建立的、非侵入性的、准确的和容易的方法来在临床上测量这些变化。一种允许临床医生在门诊诊所中无创测量微血管系统变化的工具（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响应代谢应激的变化），可以允许对患者进行早期检测和长期监测。这将使更多的时间用于预防 护理和治疗。 该研究项目与贝克曼激光研究所的合作伙伴合作，旨在评估一种称为漫射光谱（DOS）的新技术可用于非侵入性测量患者微血管变化的假设。DOS是一种测量 近红外光在诸如肌肉的组织中的光学吸收和散射特性，以便量化氧合和脱氧血红蛋白、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系统的定量和功能信息。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.