Maternal Obesity and Gestational Diabetes: Impact on Metabolome

孕产妇肥胖和妊娠糖尿病：对代谢组的影响

• 批准号: 8503043
• 负责人: William L Lowe
• 金额: $ 44.45万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8503043
• 关键词: Address; Adult; American; Amino Acids; Biological; Birth; Birth Weight; Body fat; Body mass index; C-Peptide; Caribbean region; Child; Childhood; Consensus; Data; Data Collection; Diabetes Mellitus; Diagnosis; Emerging Technologies; Enrollment; Environment; Environmental Exposure; European; Exhibits; Fasting; Fetal Development; Fetal Growth; Fetus; Frequencies; Funding; Future; Genetic; Gestational Diabetes; Glucose; Goals; Health; Human Resources; Hyperglycemia; Individual; International; Laboratories; Lipids; Mass Fragmentography; Mass Spectrum Analysis; Measures; Metabolic; Metabolic Diseases; Mexican Americans; Molecular Weight; Mothers; Neonatal; Newborn Infant; OGTT; Obesity; Observational Study; Outcome; Outcome Study; Physiological; Placenta; Pregnancy; Pregnancy Outcome; Protocols documentation; Resources; Risk; Sampling; Secondary to; Serum; Sum; Technology; Testing; Third Pregnancy Trimester; Time; Training; United States National Institutes of Health; Woman; acylcarnitine; base; cohort; fetal; glucose metabolism; glucose tolerance; impaired glucose tolerance; improved; instrument; insulin sensitivity; maternal diabetes; metabolomics; obesity risk; offspring; public health relevance; trait

DESCRIPTION (provided by applicant): Offspring of mothers with obesity and/or pre-existing or gestational diabetes mellitus (GDM) during pregnancy are at increased risk for obesity and altered glucose metabolism as children and adults, leading to a proposed "transgenerational cycle of obesity and diabetes" wherein maternal diabetes and/or obesity in pregnancy beget more diabetes and obesity. The mechanisms underlying these risks are not known, but the mother's metabolic profile impacts the intrauterine milieu of the developing fetus as glucose and other molecules cross the placenta and impact fetal growth and development. We are hypothesizing that analytes comprising distinct metabolic signatures will demonstrate association with newborn anthropometric traits as well as maternal glycemic and anthropometric traits and that offspring of mothers with GDM (defined using the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria) and/or obesity will exhibit a metabolic profile similar to that associated with newborn adiposity, regardless of their adiposity. We will address this hypothesis using metabolomics, a technology capable of defining the metabolic profile present in different physiologic or pathophysiologic conditions, and a unique resource, stored serum samples from ~23,000 mothers and their offspring who were enrolled in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. The General Aim of the proposed HAPO Metabolomics Study is to use a targeted mass spectrometry- based platform to measure amino acids, acylcarnitines, and conventional metabolites and a gas chromatography:mass spectrometry-based non-targeted platform to analyze a wide variety of metabolites to define the metabolic profile of 1,600 Northern European ancestry, Afro-Caribbean, Mexican-American and Thai mother-offspring pairs at ~28 weeks gestation (in mothers) and birth (in offspring). The following Specific Aims will be addressed. (i) To test the hypothesis that distinct metabolic signatures are independently associated with maternal metabolic traits (fasting, 1 hr., and 2 hr. glucose and insulin sensitivity) determined by an oral glucose tolerance test (OGTT) and body mass index (BMI) at the time of the OGTT. (ii) To test the hypothesis that the above metabolic profiles will be evident during pregnancy in mothers of newborns at increased risk for metabolic diseases by determining metabolic profiles for mothers that independently associate with GDM and obesity during pregnancy. (iii) To test the hypothesis that a distinct metabolic signature in mothers and newborns is associated with newborn anthropometric traits at birth including birth weight, sum of skinfolds, and percent body fat. (iv) To test the hypothesis that newborns at risk for metabolic diseases in childhood and/or adulthood secondary to maternal GDM and/or obesity have distinct metabolic profiles at birth by determining metabolic profiles in newborns that independently associate with GDM and maternal obesity during pregnancy. Together, these studies will have an important impact on our understanding of the metabolic underpinnings of the increased risk of metabolic diseases in newborns of mothers with hyperglycemia and/or obesity.

描述（由申请人提供）：怀孕期间患有肥胖和/或孕妇糖尿病（GDM）的母亲的后代有增加肥胖症的风险，以及儿童和成人作为儿童和成人的葡萄糖代谢改变的风险，导致肥胖和糖尿病的转变型抑制性疾病和/或肥胖的疾病，或者是饮食中的饮食症状和/或肥胖。肥胖。这些风险背后的机制尚不清楚，但是母亲的代谢形象会影响发育中的胎儿宫内环境，因为葡萄糖和其他分子穿越胎盘并影响胎儿的生长和发育。我们假设包括不同的代谢特征的分析将证明与新生儿人体测量学性状以及母体血糖和人体测量特征的关联，并且具有GDM的母亲的后代（定义的，使用新的国际糖尿病和妊娠研究小组（IADPSG）和/或或征询ATID ARITIAD CRITERIAID）定义的母亲（定义）肥胖，无论其肥胖如何。我们将使用代谢组学解决这一假设，该假设能够定义不同生理或病理生理状况中存在的代谢特征，以及独特的资源，从约23,000名母亲及其后代中存储的血清样本，这些血清样本及其后代被纳入高血糖和不良怀孕和不良妊娠结局（HAPO）研究。 The General Aim of the proposed HAPO Metabolomics Study is to use a targeted mass spectrometry- based platform to measure amino acids, acylcarnitines, and conventional metabolites and a gas chromatography:mass spectrometry-based non-targeted platform to analyze a wide variety of metabolites to define the metabolic profile of 1,600 Northern European ancestry, Afro-Caribbean, Mexican-American and泰国母亲在妊娠约28周（母亲）和出生（后代）的泰国母亲。将解决以下特定目标。 （i）检验以下假设：不同的代谢特征与母体代谢性状（禁食，1小时和2小时的葡萄糖和胰岛素敏感性）独立相关。 （ii）测试以下假设：在怀孕期间，新生儿母亲在怀孕期间将明显的新生特征通过确定与GDM和肥胖症在怀孕期间独立关联的母亲的代谢特征来增加代谢疾病的风险。 （iii）检验以下假设：母亲和新生儿中明显的代谢签名与新生儿人体测量特征有关，包括出生体重，皮肤折叠和体内脂肪百分比。 （iv）检验以下假设：在孕产妇GDM和/或肥胖继发的儿童和/或成年的新生儿在出生时通过确定新生儿的代谢特征在出生时具有独特的代谢特征，通过确定与GDM和孕妇在怀孕期间独立联系的新生特征。总之，这些研究将对我们对高血糖和/或肥胖母亲的新生儿中代谢风险增加的代谢基础的理解产生重要影响。