Glycated CD59 as a novel biomarker of gestational diabetes mellitus

糖化 CD59 作为妊娠期糖尿病的新型生物标志物

• 批准号: 8523847
• 负责人: JOSE A HALPERIN
• 金额: $ 20.4万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8523847
• 关键词: Active Sites; Address; Admission activity; Affect; Age; Alloantigen; American; American College of Obstetricians and Gynecologists; Biological Assay; Biological Markers; Birth Weight; Birth trauma; Blood specimen; Body Weight; CD46 Antigen; Caring; Clinical; Clinical Data; Clinical Research; Collection; Complement; Complement Membrane Attack Complex; Complications of Diabetes Mellitus; Cross-Sectional Studies; Data; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Equipment; Failure; Fasting; Fetal Macrosomia; Fetus; First Pregnancy Trimester; Freezing; Functional disorder; Gestational Age; Gestational Diabetes; Glucose; Glucose Intolerance; Glycosylated hemoglobin A; Goals; Gold; Graft Rejection; Hospitals; Human; Hyperglycemia; Hyperinsulinism; Hypoglycemia; Immune response; Immune system; Individual; Intake; Laboratories; Laboratory Research; Link; Liquid substance; Measures; Mediating; Membrane Proteins; Methods; Monoclonal Antibodies; Mutation; NIH Program Announcements; Nausea and Vomiting; Neonatal Intensive Care Units; OGTT; Organ; Organ Transplantation; Pathogenesis; Patients; Perinatal; Play; Population Heterogeneity; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Prenatal care; Prevention; Professional Organizations; Publications; Reagent; Reproducibility; Research Project Grants; Risk; Role; Sampling; Sensitivity and Specificity; Serum; Site; Source; Testing; Third Pregnancy Trimester; Time; Tissues; Translations; United States; Urine; Validation; Woman; Work; adverse outcome; base; clinical practice; clinically relevant; cohort; complement system; design; diabetic; fetal; genetic regulatory protein; glucose tolerance; glycation; innovation; meetings; non-diabetic; novel; pregnant; prevent; programs; prospective; public health priorities; screening; standard of care; success; tool; trophoblast

DESCRIPTION (provided by applicant): The goal of this proposal is to assess glycated CD59 in human serum as a pathogenically relevant early bio-marker for screening of gestational diabetes mellitus (GDM). This proposal is highly translational and addresses major Public Health priorities because 1) diabetes affects H 25 million Americans, 2) and GDM is a major source of adverse pregnancy outcomes including macrosomia and pre-eclampsia. The proposed work opens the possibility of using glyCD59 as a biomarker for GDM, an innovative departure from the use of OGTT, a cumbersome, costly and time-consuming test with poor reproducibility and many times unwanted effects including nausea and vomiting. A simpler, easy to use, patient friendly marker that is also involved in the pathogenesis of diabetes and its complications may help fulfill an important clinical need in the widespread screening for GDM and prevention of associated adverse outcomes. 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 that allow quantification of glycated hCD59 in human fluids and tissues. Specifically, we have demonstrated that 1) glycated CD59 is present in target organs of diabetic complications, and 2) glyCD59 can be readily measured in normal urine and serum. Furthermore, our preliminary data show that glyCD59 is a) significantly increased (3-4 fold) in the serum of diabetic and pre-diabetics individuals, and b) seems to respond faster than HbA1c to changes in glycemic load within an individual All necessary tools and expertise to accomplish our aim are available in the laboratory of the applicant and expert collaborators, including monoclonal antibodies specific for glycated CD59 and assay calibrators, access to large and diverse population of pregnant women undergoing pre-natal care at BWH, and diagnostic tools, equipment and expertise to necessary to conduct all studies proposed in the application. Successful accomplishment of our aims would represent a major advancement in screening and early diagnosis of GDM.

描述（由申请方提供）：本提案的目的是评估人血清中糖化CD 59作为筛查妊娠期糖尿病（GDM）的病理相关早期生物标志物。该提案具有高度转化性，并解决了主要的公共卫生优先事项，因为1）糖尿病影响2500万美国人，2）GDM是不良妊娠结局（包括巨大儿和先兆子痫）的主要来源。拟议的工作开辟了使用glyCD 59作为GDM生物标志物的可能性，这是对OGTT使用的创新偏离，OGTT是一种繁琐，昂贵和耗时的测试，重现性差，并且多次出现不必要的影响，包括恶心和呕吐。一种更简单，易于使用，患者友好的标记物，也参与了糖尿病及其并发症的发病机制，可能有助于满足广泛筛查GDM和预防相关不良后果的重要临床需求。申请人已经1）发现人CD 59通过糖化失活，2）提供了补体系统与糖尿病并发症的发病机制之间的联系的证据，和3）开发了允许定量人体液和组织中糖化的hCD 59的关键试剂。具体而言，我们已经证明1）糖化CD 59存在于糖尿病并发症的靶器官中，2）glyCD 59可以在正常尿液和血清中容易地测量。此外，我们的初步数据显示，glyCD 59 a）显著增加，（3-4倍），和B）似乎比HbA 1c更快地响应个体内血糖负荷的变化。在申请人和专家合作者的实验室中可获得实现我们的目标的所有必要工具和专业知识，包括糖化CD 59特异性单克隆抗体和测定校准品，接触在BWH接受产前护理的大量不同孕妇人群，以及进行申请中提议的所有研究所需的诊断工具、设备和专业知识。我们目标的成功实现将代表GDM筛查和早期诊断的重大进展。