Blood Levels of Glycated CD59, a Novel Biomarker to Assess Pregnancy-induced Glucose Intolerance

糖化 CD59 的血液水平，一种评估妊娠引起的葡萄糖不耐受的新型生物标志物

• 批准号: 10382406
• 负责人: JOSE A HALPERIN
• 金额: $ 69.78万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382406
• 关键词: Address; Admission activity; Advisory Committees; Affect; Agreement; Aneuploidy; Biological Assay; Biological Markers; Birth trauma; Blood; Blood specimen; Cardiovascular system; Caring; Categories; Cell membrane; Cesarean section; Clinical; Complement; Complications of Diabetes Mellitus; Consumption; Cross-Sectional Studies; Data; Diabetes Mellitus; Diagnosis; Diagnostic tests; Dystocia; Early Diagnosis; Early Intervention; Enzyme-Linked Immunosorbent Assay; Epidemic; Equipment; Fetal Growth Retardation; Fetus; Frequencies; Fructosamine; Funding; Future; Gene Expression; Gestational Age; Gestational Diabetes; Glucose; Glucose Intolerance; Glycosylated hemoglobin A; Goals; Gold; Grant; Guidelines; Human; Hyperglycemia; Hyperinsulinism; Incidence; Individual; Infant; Insulin; International; Intervention; Laboratories; Link; Measurement; Measures; Metabolic; Methods; Modeling; Molecular; Monoclonal Antibodies; Mothers; Neonatal Hypoglycemia; Newborn Infant; OGTT; Obesity; Oral; Outcome; Pathogenesis; Pharmaceutical Preparations; Pilot Projects; Plasma; Population Heterogeneity; Pre-Eclampsia; Pregnancy; Pregnant Women; Prenatal care; Prevalence; Preventive service; Prospective Studies; Public Health; Publications; Publishing; Reagent; Reproducibility; Research; Resources; Risk; Sampling; Second Pregnancy Trimester; Seminal; Sensitivity and Specificity; Shoulder; Testing; Therapeutic Intervention; Time; United States National Institutes of Health; Validation; Visit; Woman; adverse outcome; adverse pregnancy outcome; base; clinical practice; cohort; complement system; cost effective; diagnosis standard; diagnostic screening; diagnostic tool; early detection biomarkers; early pregnancy; early screening; epidemiology study; fetal; genetic regulatory protein; glycation; malformation; maternal hyperglycemia; maternal outcome; non-diabetic; novel marker; perinatal complications; perinatal outcomes; pregnant; public health priorities; rate of change; screening; standard of care; tool

Project Summary/Abstract – The goal of this proposal is to validate glycated CD59 (GCD59) in human blood as a novel biomarker to screen for studies of pregnancy-induced glucose intolerance. This proposal is highly translational and addresses major Public Health priorities because: 1) women with pregnancy-induced glucose intolerance and their fetus are at an increased risk of adverse clinical outcomes and perinatal complications, 2) the frequency of pregnancy-induced glucose intolerance is increasing at alarming rates, 3) epidemiological studies have shown that appropriate treatment reduces the associated risks for the mother and newborn, and 4) the glucose load tests, currently the gold standard identifying pregnancy-induced glucose intolerance, are expensive, time consuming, non-physiologic and unpleasant, have poor reproducibility on repeat testing. These facts highlight why there is agreement that a simpler, shorter, easier-to-use, cost-effective, sensitive and specific test would be a much better tool to screen for pregnancy-induced glucose intolerance. The applicants have 1) discovered that human CD59 is inactivated by glycation, 2) provided evidence for a link between the complement system and the pathogenesis of the complications of diabetes, and 3) developed key reagents and established a specific and sensitive assay that allows quantification of GCD59 in blood. With this assay, we have conducted pilot studies in pregnant women undergoing glucose- loading tests to screen for GDM. The results showed that a single measurement of plasma GCD59 at week ≈ 24-26 predicted pregnancy-induced glucose intolerance and GDM with high specificity and sensitivity (ROC AUC: 0.93). Based on these robust preliminary data and available resources, we now propose the highly focused aim of prospectively studying a large cohort of pregnant women to assess the utility of GCD59 as a simple, easy-to-use test for early prediction of pregnancy-induced glucose intolerance. All necessary tools and expertise to accomplish our aims are available in the laboratory of the applicant and expert collaborators, including monoclonal antibodies specific for GCD59 and assay calibrators, access to plasma samples from a large and diverse population of pregnant women undergoing standard of care screening for GDM, diagnostic tools, equipment and expertise necessary to conduct all studies proposed in the application. Successful accomplishment of our aim will provide a clinically useful and independent predictor to investigate pregnancy-induced glucose intolerance that could simplify the earlier screening and diagnosis of this condition.

项目摘要/摘要 - 该提案的目的是验证人血中的糖化CD59（GCD59）作为一种新型生物标志物 筛选妊娠诱导的葡萄糖肠的研究。该提议被高度翻译，并且 解决主要公共卫生优先事项，因为：1）怀孕诱发的麸质intlerance的妇女 他们的胎儿有不良临床结局和围产期并发症的风险增加，2） 妊娠诱导的葡萄糖intlerance的频率正在以惊人的速度增加，3）流行病学研究 已经表明，适当的治疗可降低母亲和新生儿的相关风险，以及4） 葡萄糖负荷测试，目前是识别妊娠诱导的葡萄糖intlerance的黄金标准，是 昂贵，耗时，非生理学和不愉快的重复测试繁殖差。 这些事实强调了为什么有人同意更简单，更短，更易于使用，成本效益，敏感和 特定的测试将是筛选妊娠诱导的葡萄糖肠的更好工具。 申请人有1）发现人CD59被糖基化灭活，2）提供了证据 完成系统与糖尿病并发症的发病机理之间的联系，3） 开发了关键试剂，并建立了特定而敏感的评估，允许量化GCD59 在血液中。通过此测定，我们对接受葡萄糖的孕妇进行了试点研究 加载测试以筛选GDM。结果表明，在≈周时血浆GCD59进行了单一测量。 24-26预测具有高特异性和敏感性的妊娠诱导的葡萄糖intlerance和GDM（ROC AUC：0.93）。基于这些强大的初步数据和可用资源，我们现在提出了高度的建议 前瞻性研究大量孕妇以评估GCD59的效用的目的 简单，易于使用的测试，用于早期预测怀孕引起的葡萄糖肠。 实现我们目标的所有必要工具和专业知识都可以在申请人的实验室中获得， 专家合作者，包括针对GCD59和测定校准器的单克隆抗体 来自洲际护理标准的大量孕妇的血浆样本 筛选GDM，诊断工具，设备和专业知识，以进行所有提议的研究 在应用程序中。 成功实现我们的目标将为临床上有用且独立的预测指标 研究妊娠引起的葡萄糖耐药，这可以简化早期的筛查和诊断 这种情况。