Markers for T2DM, Risk of T2DM & Aptamer Array Diagnosis

T2DM 标志物、T2DM 风险

基本信息

批准号：
7140649
负责人：
EDWARD A DRATZ
金额：
$ 13.75万
依托单位：
MONTANA STATE UNIVERSITY - BOZEMAN
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2008-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7140649
关键词：
biomarker clinical research diabetes risk diagnosis design /evaluation diagnostic tests early diagnosis fluorescent dye /probe human subject liquid chromatography mass spectrometry metabolism disorder diagnosis noninsulin dependent diabetes mellitus oligonucleotides posttranslational modifications protein isoforms proteomics two dimensional gel electrophoresis

项目摘要

DESCRIPTION (provided by applicant): The immediate goal of this project is to identify new biomarker proteins for type 2 diabetes and early detection of risk of type 2 diabetes and to test a new photoaptamer array marker analysis system. The longer term goal is to foster and validate the measurement of new markers for the risk of type 2 diabetes (and markers found by others) in a robust and reliable photoaptamer array diagnostic platform. The hypothesis underlying this work is that a deep, global search for protein markers will reveal patterns of multiple markers that will signal type 2 diabetes (and other disease) risk states significantly earlier and much more reliably than current diagnostics, without requiring perturbations such as glucose administration and extensive multipoint tolerance measures. Global proteomics methods are well suited for disease marker discovery but appear to be too expensive for direct diagnosis, while the photoaptamer systems appear to be extremely well suited for providing routine, reliable, high-throughput diagnosis. We plan to search more deeply into the blood serum proteome for biomarkers and biomarker isoforms than has been accomplished previously, using new ultrasensitive multiplex fluorescent detection dyes developed at Montana State University-in a 2D gel format with liquid state IEF prefractionation. This improved methodology provides a powerful means to detect differences in expression of proteins between samples and is especially powerful for measuring changes in modified protein isoforms. We will complement and compare the 2D gel analysis with high resolution 2D-LC/MS/MS on the same fractions, using isotopic cysteine and lysine tags for measuring changes in protein and peptide expression. A clinical group at the U Mass Medical Center, Worcester (that is seeking to develop more effective lifestyle modification strategies for people at risk of type 2 diabetes) is providing samples from well characterized patients and controls. This project brings together our academic group that is developing and applying new targeted proteomics detection technologies with outstanding groups of investigators from industry that are contributing advanced technology resources and a powerful diagnostic platform. Relevance to public health: Approximately 5 million people in the US are thought to have undiagnosed Type 2 diabetes and the numbers appear to be growing. At the time of diagnosis of Type 2 diabetes many patients already have severe complications of diabetes and are a greatly increased risk of heart disease. Available screening methods, such as the oral glucose tolerance test appear to be of modest effectiveness, are expensive and difficult to carry out and there is little evidence of benefit from screening asymptomatic adults for undiagnosed diabetes with current technology. This project aims to identify diagostic targets and to foster the development more facile, inexpensive, sensitive, and reliable clinical tests.

描述（由申请人提供）：该项目的直接目标是识别 2 型糖尿病的新生物标志物蛋白并早期检测 2 型糖尿病的风险，并测试新的光适体阵列标志物分析系统。长期目标是在强大且可靠的光适体阵列诊断平台中培育和验证 2 型糖尿病风险新标记物（以及其他人发现的标记物）的测量。这项工作的假设是，对蛋白质标记物进行深入、全面的搜索将揭示多种标记物的模式，这些标记物将比当前的诊断更早、更可靠地发出 2 型糖尿病（和其他疾病）风险状态的信号，而无需葡萄糖等扰动管理和广泛的多点容忍措施。全球蛋白质组学方法非常适合疾病标志物发现，但对于直接诊断来说似乎过于昂贵，而光适体系统似乎非常适合提供常规、可靠、高通量的诊断。我们计划使用蒙大拿州立大学开发的新型超灵敏多重荧光检测染料（采用液态 IEF 预分级的 2D 凝胶形式），比以前更深入地研究血清蛋白质组中的生物标志物和生物标志物亚型。这种改进的方法提供了一种强大的手段来检测样品之间蛋白质表达的差异，并且对于测量修饰的蛋白质亚型的变化尤其有效。我们将使用同位素半胱氨酸和赖氨酸标签来补充和比较相同组分上的高分辨率 2D-LC/MS/MS 的 2D 凝胶分析，以测量蛋白质和肽表达的变化。伍斯特大学麻省大学医疗中心的一个临床小组（正在寻求为有 2 型糖尿病风险的人制定更有效的生活方式改变策略）正在提供来自特征明确的患者和对照的样本。该项目汇集了我们正在开发和应用新的靶向蛋白质组学检测技术的学术团队与来自行业的优秀研究人员团队，他们贡献了先进的技术资源和强大的诊断平台。与公共卫生的相关性：美国大约有 500 万人被认为患有未确诊的 2 型糖尿病，而且这个数字似乎还在增长。在诊断 2 型糖尿病时，许多患者已经患有严重的糖尿病并发症，并且患心脏病的风险大大增加。现有的筛查方法，例如口服葡萄糖耐量测试，似乎效果不大，价格昂贵且难以实施，而且几乎没有证据表明利用现有技术对无症状成年人进行未确诊糖尿病的筛查有益处。该项目旨在确定诊断目标并促进开发更简便、廉价、灵敏和可靠的临床测试。