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
基本信息
- 批准号:10382406
- 负责人:
- 金额:$ 69.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAdmission activityAdvisory CommitteesAffectAgreementAneuploidyBiological AssayBiological MarkersBirth traumaBloodBlood specimenCardiovascular systemCaringCategoriesCell membraneCesarean sectionClinicalComplementComplications of Diabetes MellitusConsumptionCross-Sectional StudiesDataDiabetes MellitusDiagnosisDiagnostic testsDystociaEarly DiagnosisEarly InterventionEnzyme-Linked Immunosorbent AssayEpidemicEquipmentFetal Growth RetardationFetusFrequenciesFructosamineFundingFutureGene ExpressionGestational AgeGestational DiabetesGlucoseGlucose IntoleranceGlycosylated hemoglobin AGoalsGoldGrantGuidelinesHumanHyperglycemiaHyperinsulinismIncidenceIndividualInfantInsulinInternationalInterventionLaboratoriesLinkMeasurementMeasuresMetabolicMethodsModelingMolecularMonoclonal AntibodiesMothersNeonatal HypoglycemiaNewborn InfantOGTTObesityOralOutcomePathogenesisPharmaceutical PreparationsPilot ProjectsPlasmaPopulation HeterogeneityPre-EclampsiaPregnancyPregnant WomenPrenatal carePrevalencePreventive serviceProspective StudiesPublic HealthPublicationsPublishingReagentReproducibilityResearchResourcesRiskSamplingSecond Pregnancy TrimesterSeminalSensitivity and SpecificityShoulderTestingTherapeutic InterventionTimeUnited States National Institutes of HealthValidationVisitWomanadverse outcomeadverse pregnancy outcomebaseclinical practicecohortcomplement systemcost effectivediagnosis standarddiagnostic screeningdiagnostic toolearly detection biomarkersearly pregnancyearly screeningepidemiology studyfetalgenetic regulatory proteinglycationmalformationmaternal hyperglycemiamaternal outcomenon-diabeticnovel markerperinatal complicationsperinatal outcomespregnantpublic health prioritiesrate of changescreeningstandard of caretool
项目摘要
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-
这项提案的目标是验证人类血液中的糖化CD59(GCD59)作为一种新的生物标志物
对妊娠期葡萄糖耐量异常的研究进行筛查。这项建议具有很高的翻译性和
解决主要的公共卫生优先事项,因为:1)患有妊娠期糖耐量异常的妇女
和他们的胎儿处于不良临床结局和围产期并发症的风险增加,2)
3)流行病学研究显示,妊娠期糖耐量低减的频率正在以惊人的速度增加
已经表明,适当的治疗可以降低母亲和新生儿的相关风险,以及4)
葡萄糖负荷测试是目前确定妊娠期葡萄糖耐量异常的金标准,它是
昂贵、耗时、非生理学和令人不快,重复测试的重复性较差。
这些事实突显了为什么人们一致认为,一种更简单、更短、更容易使用、具有成本效益、敏感和
特定的测试将是筛查妊娠诱导的葡萄糖耐量异常的更好的工具。
申请者已经1)发现人类CD59被糖基化灭活,2)提供了证据
补体系统与糖尿病并发症发病机制之间的联系,以及3)
开发了关键试剂,并建立了一种特异和敏感的分析方法,可以对GCD59进行定量
在鲜血中。通过这项测试,我们在接受葡萄糖治疗的孕妇中进行了初步研究。
将测试加载到GDM筛查。结果显示,在≈周单次测量血浆GCD59
24-26预测妊娠期糖耐量异常和妊娠期糖尿病具有较高的特异性和敏感性(ROC
AUC:0.93)。基于这些稳健的初步数据和可用的资源,我们现在建议高度
重点是前瞻性研究一大批孕妇,以评估GCD59作为一种
简便易行的试验用于早期预测妊娠期糖耐量异常。
申请人的实验室可提供实现我们目标所需的所有工具和专业知识
专家合作者,包括针对GCD59的单抗和检测校准器,可以访问
接受标准护理的大量多样化孕妇的血浆样本
进行所有拟议研究所需的GDM筛查、诊断工具、设备和专业知识
在应用程序中。
我们的目标的成功实现将提供一个临床上有用的独立预测指标
调查妊娠期糖耐量异常,可简化早期筛查和诊断
这种情况。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOSE A HALPERIN其他文献
JOSE A HALPERIN的其他文献
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{{ truncateString('JOSE A HALPERIN', 18)}}的其他基金
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:
9902416 - 财政年份:2019
- 资助金额:
$ 69.78万 - 项目类别:
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 - 财政年份:2019
- 资助金额:
$ 69.78万 - 项目类别:
Human Studies on Blood Levels of Glycated CD59 as a Biomarker in Diabetes
糖化 CD59 血液水平作为糖尿病生物标志物的人体研究
- 批准号:
9116831 - 财政年份:2014
- 资助金额:
$ 69.78万 - 项目类别:
Human Studies on Blood Levels of Glycated CD59 as a Biomarker in Diabetes
糖化 CD59 血液水平作为糖尿病生物标志物的人体研究
- 批准号:
8668411 - 财政年份:2014
- 资助金额:
$ 69.78万 - 项目类别:
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:
8374166 - 财政年份:2012
- 资助金额:
$ 69.78万 - 项目类别:
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 - 财政年份:2012
- 资助金额:
$ 69.78万 - 项目类别:
Glycation inactivation of human CD59 and diabetic complications
人 CD59 的糖基化失活和糖尿病并发症
- 批准号:
8234691 - 财政年份:2011
- 资助金额:
$ 69.78万 - 项目类别:
Glycation inactivation of human CD59 and diabetic complications
人 CD59 的糖基化失活与糖尿病并发症
- 批准号:
8766558 - 财政年份:2011
- 资助金额:
$ 69.78万 - 项目类别:
Glycation inactivation of human CD59 and diabetic complications
人 CD59 的糖基化失活和糖尿病并发症
- 批准号:
8399044 - 财政年份:2011
- 资助金额:
$ 69.78万 - 项目类别:
Glycation inactivation of human CD59 and diabetic complications
人 CD59 的糖基化失活与糖尿病并发症
- 批准号:
8575096 - 财政年份:2011
- 资助金额:
$ 69.78万 - 项目类别: