Metformin in Pregnancy: Fetal Consequences & Long-term Offspring Outcomes in a NHP Model
妊娠期二甲双胍:对胎儿的影响
基本信息
- 批准号:10683230
- 负责人:
- 金额:$ 142.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-17 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:4 year oldAccelerationAdolescentAmericanAnimal FeedAnimalsAutomobile DrivingBiogenesisBirth WeightClinicalClinical ResearchClinical TrialsConceptionsDataDevelopmentDiabetes MellitusDietEpidemicEpidemiologyEventExposure toFutureGestational DiabetesGrowthHigh Fat DietInsulin ResistanceIslet CellLactationLifeLiverLow Birth Weight InfantMacaca mulattaMeasuresMetabolicMetabolic PathwayMetabolic syndromeMetabolismMetagenomicsMetforminMitochondriaModelingMolecularMuscleMuscle FibersNon-Insulin-Dependent Diabetes MellitusNutrientObesityOrganOutcomePancreasPathway interactionsPerinatalPharmacodynamicsPhenotypePhysiologicalPhysiologyPlacebosPolycystic Ovary SyndromePrediabetes syndromePredispositionPregnancyPrimatesPubertyRiskSeriesSpecimenTestingWeaningWomanclinical implementationcohortdietary controlearly adolescenceearly life exposureepigenomicsexperimental studyfeedingfetaljuvenile animalmRNA Translationmetabolomicsmicrobialmother nutritionnext generationnonhuman primateobesity developmentoffspringpostnatalprenatal exposureprepregnancypreventprimary outcomesecondary outcometranscriptomicswestern diet
项目摘要
Metformin is prescribed to 50 million Americans annually, and is currently in widespread perinatal (pre-pregnancy,
during pregnancy, and post-natal) clinical use. Over the past decade, clinical indications and pragmatic use of metformin
have steadily expanded beyond the treatment of overt diabetes outside of pregnancy, and now include prediabetes and
obesity, polycystic ovary syndrome, type 2 diabetes, and gestational diabetes. With its expanded use, questions of
unintended long-term harm have arisen. The rationale underlying these concerns for metformin exposure during
development as a consequence of expanded maternal use arises from its basic pharmacodynamics and mechanisms of
action, which we and others hypothesize converge to disrupt important metabolic pathways during fetal life, which are
necessary to establish normal birth weight and appropriate early post-natal growth trajectory. When combined with a
maternal Western-style diet (WSD), fetal metformin exposure leads to accelerated early development of a pre-diabetic,
pre-obese phenotype with evidence of obesity and insulin resistance in early adolescence (puberty onset).
We are inspired by our preliminary data to pursue development of a non-human primate model of maternal
metformin use. Powered as a three-armed mechanistic-based clinical study, we will determine the impact of metformin
or placebo exposure from pre-pregnancy through lactation on the development of obesity and insulin resistance. This
study is adequately powered to test the hypothesis that maternal metformin use in isolation or in conjunction with a
maternal high fat diet renders low birthweight and aberrant catch-up growth, driving obesity and insulin resistance in
the offspring by onset of puberty (approximately 3-4 years of age). In Aim 1, we will determine if early life metformin
exposure in control and/or WSD-fed dams leads to low birthweight and aberrant catch-up growth, resulting in obesity
and insulin resistance in pubertal juvenile offspring. In Aim 2, we will determine what the impact of metformin exposure
in WSD-fed dams is on maternal, fetal (G145) and juvenile (to puberty onset) metabolic physiology. This will include core
measures of maternal and fetal organ metabolism (liver, muscle, gut and pancreas). In Aim 3, we will determine
whether weaning offspring onto a control diet can ameliorate or mitigate the effects of maternal metformin exposure in
WSD-fed dams. Finally, in Aim 4 we will determine how early metformin exposure wields its molecular impact on control
and WSD-induced alterations of core measures of maternal and fetal metabolism in the liver, gut, muscle, and pancreas.
Considering the recently emerged epidemiologic evidence and known mechanisms of actions of metformin, there is
a rational concern that rather than preventing developmental programming, metformin use during pregnancy may
have unintended consequences of accelerating obesity and the metabolic syndrome epidemic in the next generation.
The animal, specimen, and uniformly generated multi’omic data generated in the current proposal will collectively
inform ongoing clinical trials and future clinical implementation.
每年有5000万美国人开二甲双胍,目前在围产期(孕前)、
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kjersti Marie Aagaard其他文献
Kjersti Marie Aagaard的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kjersti Marie Aagaard', 18)}}的其他基金
Metformin in Pregnancy: Fetal Consequences & Long-term Offspring Outcomes in a NHP Model
妊娠期二甲双胍:对胎儿的影响
- 批准号:
10491266 - 财政年份:2021
- 资助金额:
$ 142.14万 - 项目类别:
Metformin in Pregnancy: Fetal Consequences & Long-term Offspring Outcomes in a NHP Model
妊娠期二甲双胍:对胎儿的影响
- 批准号:
10364417 - 财政年份:2021
- 资助金额:
$ 142.14万 - 项目类别:
Project 2: Investigating the role of PAH exposures associated with superfund site proximity in preterm birth etiology through placental transcriptomics and metagenomics
项目 2:通过胎盘转录组学和宏基因组学研究与超级基金地点邻近相关的 PAH 暴露在早产病因学中的作用
- 批准号:
10116393 - 财政年份:2020
- 资助金额:
$ 142.14万 - 项目类别:
Project 2: Investigating the role of PAH exposures associated with superfund site proximity in preterm birth etiology through placental transcriptomics and metagenomics
项目 2:通过胎盘转录组学和宏基因组学研究与超级基金地点邻近相关的 PAH 暴露在早产病因学中的作用
- 批准号:
10559699 - 财政年份:2020
- 资助金额:
$ 142.14万 - 项目类别:
Interrupting the Vicious Cycle of Obesity and Metabolic Syndrome
中断肥胖和代谢综合症的恶性循环
- 批准号:
9985360 - 财政年份:2019
- 资助金额:
$ 142.14万 - 项目类别:
A Multi'omics Approach towards Deciphering the Influence of the Microbiome on Pre
破译微生物组对预防的影响的多组学方法
- 批准号:
8862198 - 财政年份:2013
- 资助金额:
$ 142.14万 - 项目类别:
A Multi'omics Approach towards Deciphering the Influence of the Microbiome on Pre
破译微生物组对预防的影响的多组学方法
- 批准号:
8659859 - 财政年份:2013
- 资助金额:
$ 142.14万 - 项目类别:
A Multi'omics Approach towards Deciphering the Influence of the Microbiome on Pre
破译微生物组对预防的影响的多组学方法
- 批准号:
9091301 - 财政年份:2013
- 资助金额:
$ 142.14万 - 项目类别:
A Multi'omics Approach towards Deciphering the Influence of the Microbiome on Pre
破译微生物组对预防的影响的多组学方法
- 批准号:
8743311 - 财政年份:2013
- 资助金额:
$ 142.14万 - 项目类别:
相似海外基金
SHINE: Origin and Evolution of Compressible Fluctuations in the Solar Wind and Their Role in Solar Wind Heating and Acceleration
SHINE:太阳风可压缩脉动的起源和演化及其在太阳风加热和加速中的作用
- 批准号:
2400967 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Standard Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328975 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Continuing Grant
EXCESS: The role of excess topography and peak ground acceleration on earthquake-preconditioning of landslides
过量:过量地形和峰值地面加速度对滑坡地震预处理的作用
- 批准号:
NE/Y000080/1 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Research Grant
Market Entry Acceleration of the Murb Wind Turbine into Remote Telecoms Power
默布风力涡轮机加速进入远程电信电力市场
- 批准号:
10112700 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Collaborative R&D
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328973 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328972 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328974 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Continuing Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332916 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Standard Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332917 - 财政年份:2024
- 资助金额:
$ 142.14万 - 项目类别:
Standard Grant
Radiation GRMHD with Non-Thermal Particle Acceleration: Next-Generation Models of Black Hole Accretion Flows and Jets
具有非热粒子加速的辐射 GRMHD:黑洞吸积流和喷流的下一代模型
- 批准号:
2307983 - 财政年份:2023
- 资助金额:
$ 142.14万 - 项目类别:
Standard Grant














{{item.name}}会员




