The Long-term Influence of Persistent Organic Pollutants Exposure During and After Pregnancy on Metabolic Decline in Women After Pregnancies Complicated by Gestational Diabetes
妊娠期间和妊娠后持久性有机污染物暴露对妊娠合并妊娠糖尿病女性代谢下降的长期影响
基本信息
- 批准号:10256678
- 负责人:
- 金额:$ 46.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-08 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:Adipose tissueAffectAgingAmino AcidsAnimal ModelAnimalsArchivesBeta CellBiologicalBiological AssayBody BurdenBody CompositionBody fatBreast FeedingCell physiologyChemicalsDataDefectDevelopmentDiabetes MellitusDietElderlyEndocrine DisruptorsEnvironmentEpidemicExposure toFastingFlame RetardantsFunctional disorderFutureGeneral PopulationGenetic Predisposition to DiseaseGestational DiabetesGlucoseGoalsGoldHealthHispanicsHumanIncidenceIndividualInsulin ResistanceInternationalInvestigationJointsKnowledgeLinkLong-Term EffectsMeasuresMetabolicMetabolic PathwayMethodsMinorityModelingMothersNon-Insulin-Dependent Diabetes MellitusOGTTObesityParentsPathogenesisPhysical activityPlasmaPoisonPolychlorinated BiphenylsPostpartum PeriodPredispositionPregnancyPregnancy TrimestersPregnant WomenProspective StudiesProspective cohortPublic HealthPublishingRecording of previous eventsRegulationResearchRisk FactorsRoleSamplingStructure of beta Cell of isletThird Pregnancy TrimesterTimeVisitWeight GainWomancohortdiabetes pathogenesisdiabetes riskdiabetogenicepidemiology studyfollow-uphealth disparityhigh riskinsulin sensitivityinterestintravenous glucose tolerance testlifetime risklipid metabolismlipophilicitymetabolomicsnovelorganochlorine pesticidepersistent organic pollutantspredictive signaturepreventpreventive interventionprospectivepublic health prioritiesresponseunhealthy lifestyleyoung woman
项目摘要
ABSTRACT
Preventing diabetes has become a national priority for public health. Women with gestational diabetes mellitus
(GDM) history carry a significantly higher risk of developing type 2 diabetes (T2D) over their lifetime. Therefore,
GDM has been used as a unique model to identify early metabolic defects such as insulin resistance and β-cell
dysfunction that precede the development of diabetes in young women. Beyond well-known risk factors including
unhealthy lifestyle and genetic susceptibility, there is a growing concern over exposures to endocrine disrupting
chemicals, such as persistent organic pollutants (POPs), as novel risk factors for T2D. The goal of this study is
to investigate long-term effects of exposure to POPs during a woman’s vulnerable time windows of pregnancy
and the postpartum period on the metabolic trajectory that leads to T2D in women after GDM pregnancies.
Mounting evidence from animal models and human studies suggests that POPs exposure can adversely affect
insulin sensitivity and β-cell function thereby increasing T2D risk. However, previous epidemiological studies of
POPs and diabetes were mostly cross-sectional and have limitations of only examining the effect of a single
chemical compound or chemical class. Little is known about the joint effects of exposure to POPs mixture on the
metabolic decline and T2D. Importantly, no studies have assessed the long-term effects of POPs exposure
during pregnancy and postpartum period on metabolic decline and development of T2D in women’s later life,
beyond the effects of other risk factors such as aging and weight gain. To fill these knowledge gaps, we propose
to measure plasma concentrations of 60 priori-selected potentially diabetogenic POPs as the internal POPs
exposure level in women during pregnancy and postpartum period. The broad objectives of this project are to
investigate long-term effects of POPs exposure during and after pregnancy on the longitudinal decline of insulin
sensitivity and β-cell function as well as diabetes incidence in women after delivery. The study will be built upon
a unique prospective cohort of 102 women who had GDM during pregnancy and were followed from pregnancy
to 12 years after delivery. Insulin sensitivity and β-cell function were assessed in the original cohort using the
gold-standard method of intravenous glucose tolerance test at the 3rd trimester of pregnancy and every 15
months up to 12 years after delivery. To further investigate the biological mechanism linking POPs exposure and
long-term metabolic decline, we will further investigate the longitudinal metabolomic profiles from fasting plasma
samples collected at the 3rd trimester of pregnancy, postpartum and every 15-month visit up to 12 years. We
propose to use these metabolomic profiles as signatures of the biological response to the POPs exposure during
pregnancy and identify those that predict metabolic decline and T2D incidence. This project will advance our
knowledge in the role of POPs exposure during critical exposure windows of pregnancy and the postpartum
period in perturbing metabolic pathways and inducing diabetes pathophysiology and T2D incidence in women.
摘要
项目成果
期刊论文数量(0)
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Zhanghua Chen的其他文献
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{{ truncateString('Zhanghua Chen', 18)}}的其他基金
Circulating levels of Persistent Organic Pollutants and Subclinical Atherosclerosis progression in Postmenopausal women
持久性有机污染物的循环水平和绝经后妇女亚临床动脉粥样硬化进展
- 批准号:
10707102 - 财政年份:2022
- 资助金额:
$ 46.66万 - 项目类别:
HEPA Filtration on Reducing Cardiometabolic Risk During Wildfires
HEPA 过滤可降低野火期间的心脏代谢风险
- 批准号:
10838186 - 财政年份:2022
- 资助金额:
$ 46.66万 - 项目类别:
Slowing Atherothrombosis Progression through Indoor Air Filtration: A Crossover Trial in Hispanic and non-Hispanic Adults with Ischemic Heart Disease History
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- 批准号:
10688095 - 财政年份:2022
- 资助金额:
$ 46.66万 - 项目类别:
The Long-term Influence of Persistent Organic Pollutants Exposure During and After Pregnancy on Metabolic Decline in Women After Pregnancies Complicated by Gestational Diabetes
妊娠期间和妊娠后持久性有机污染物暴露对妊娠合并妊娠糖尿病女性代谢下降的长期影响
- 批准号:
10653028 - 财政年份:2020
- 资助金额:
$ 46.66万 - 项目类别:
The Long-term Influence of Persistent Organic Pollutants Exposure During and After Pregnancy on Metabolic Decline in Women After Pregnancies Complicated by Gestational Diabetes
妊娠期间和妊娠后持久性有机污染物暴露对妊娠合并妊娠糖尿病女性代谢下降的长期影响
- 批准号:
10450096 - 财政年份:2020
- 资助金额:
$ 46.66万 - 项目类别:
Metabolomic Signatures Linking Air Pollution, Obesity and Diabetes
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- 批准号:
9920725 - 财政年份:2017
- 资助金额:
$ 46.66万 - 项目类别:
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