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: 10599099
• 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 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599099
• 关键词: Address; Admission activity; Affect; Agreement; Aneuploidy; Biological Assay; Biological Markers; Birth trauma; Blood; Blood specimen; Cardiovascular Diseases; Caring; Categories; Cell membrane; Cesarean section; Classification; 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; 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; Prospective Studies; Public Health; Publications; Publishing; Reagent; Recommendation; Reproducibility; Research; Resources; Risk; Sampling; Second Pregnancy Trimester; Seminal; Sensitivity and Specificity; Shoulder; Testing; Therapeutic Intervention; Time; United States National Institutes of Health; United States Preventative Services Task Force; Validation; Visit; Woman; adverse outcome; adverse pregnancy outcome; clinical practice; cohort; complement system; cost effective; diagnosis standard; diagnostic tool; early detection biomarkers; early pregnancy; early screening; epidemiology study; fetal; gene function; genetic regulatory protein; glycation; imprint; malformation; maternal hyperglycemia; maternal outcome; non-diabetic; novel marker; perinatal complications; perinatal outcomes; 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

项目成果

Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes-A Scoping Review.

• DOI: 10.3390/jcm10071533
• 发表时间: 2021-04-06
• 期刊: Journal of clinical medicine
• 影响因子: 3.9
• 作者: Bogdanet D;Reddin C;Murphy D;Doheny HC;Halperin JA;Dunne F;O'Shea PM
• 通讯作者: O'Shea PM

The Diagnostic Accuracy of Second Trimester Plasma Glycated CD59 (pGCD59) to Identify Women with Gestational Diabetes Mellitus Based on the 75 g OGTT Using the WHO Criteria: A Prospective Study of Non-Diabetic Pregnant Women in Ireland.

• DOI: 10.3390/jcm11133895
• 发表时间: 2022-07-04
• 期刊: Journal of clinical medicine
• 影响因子: 3.9

Plasma-glycated CD59 as an early biomarker for gestational diabetes mellitus: prospective cohort study protocol.

• DOI: 10.1136/bmjopen-2021-054773
• 发表时间: 2022-04-20
• 期刊: BMJ OPEN
• 影响因子: 2.9
• 作者: Andrews, Chloe;Toth-Castillo, Michelle;Aktas, Huseyin;Fernandez, Miguel-Angel Luque;Wong, Steven Koon;Sen, Sarbattama;Halperin, Jose
• 通讯作者: Halperin, Jose