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
预防糖尿病已成为国家公共卫生的优先事项。妊娠期糖尿病孕妇
(GDM)糖尿病史携带着在其一生中发展为2型糖尿病(T2D)显著更高风险。因此,我们认为,
妊娠期糖尿病是一种独特的模型,可用于早期代谢缺陷如胰岛素抵抗和β细胞
年轻女性患糖尿病之前的功能障碍。除了众所周知的风险因素,
由于不健康的生活方式和遗传易感性,人们越来越关注内分泌干扰物的暴露。
化学品,如持久性有机污染物(POP),作为T2D的新风险因素。本研究的目的是
调查妇女在怀孕的脆弱时间窗内接触持久性有机污染物的长期影响
和产后期的代谢轨迹,导致2型糖尿病的妇女怀孕后。
动物模型和人类研究提供的越来越多的证据表明,接触持久性有机污染物会对环境产生不利影响,
胰岛素敏感性和β细胞功能,从而增加T2 D风险。然而,以前的流行病学研究,
持久性有机污染物和糖尿病大多是横截面的,并有局限性,只检查一个单一的影响,
化合物或化学类别。关于接触持久性有机污染物混合物对环境的联合影响,
代谢下降和T2D。重要的是,没有研究评估了持久性有机污染物暴露的长期影响
在怀孕期间和产后期间对代谢下降和女性晚年T2D的发展的影响,
超出了其他风险因素的影响,如衰老和体重增加。为了填补这些知识空白,我们建议
测量60种优先选择的潜在致糖尿病的持久性有机污染物作为体内持久性有机污染物的血浆浓度
妇女在怀孕和产后期间的接触水平。该项目的主要目标是
研究妊娠期间和妊娠后接触持久性有机污染物对胰岛素纵向下降的长期影响
敏感性和β细胞功能以及产后妇女糖尿病发病率。这项研究将建立在
一个独特的前瞻性队列,102名妇女在怀孕期间患有GDM,并从怀孕开始进行随访
到分娩后12年。胰岛素敏感性和β细胞功能在最初的队列中使用
金标准法静脉葡萄糖耐量试验在妊娠晚期和每15
分娩后12个月至12年。进一步调查持久性有机污染物接触与
长期代谢下降,我们将进一步研究空腹血浆中的纵向代谢组学特征,
在妊娠晚期、产后和12年内每15个月随访时采集样本。我们
建议使用这些代谢组学特征作为在以下情况下对持久性有机污染物接触的生物反应的特征:
妊娠,并确定那些预测代谢下降和T2D发病率。该项目将推动我们的
了解持久性有机污染物接触在怀孕和产后关键接触窗口期的作用
在扰乱代谢途径和诱导糖尿病病理生理学和女性T2D发病率的时期。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Zhanghua Chen其他文献
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
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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
通过室内空气过滤减缓动脉粥样硬化血栓形成的进展:对有缺血性心脏病史的西班牙裔和非西班牙裔成年人进行的交叉试验
- 批准号:
10688095 - 财政年份:2022
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$ 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
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Metabolomic Signatures Linking Air Pollution, Obesity and Diabetes
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9920725 - 财政年份:2017
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