Maternal BMI and Glycemia Impact the Fetal Metabolome.
Maternal BMI and Glycemia Impact the Fetal Metabolome.
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DOI：
10.2337/dc16-2452
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发表时间：
2017-07
期刊：
影响因子：
16.2
通讯作者：
HAPO Study Cooperative Research Group
中科院分区：
文献类型：
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作者：
Lowe WL Jr;Bain JR;Nodzenski M;Reisetter AC;Muehlbauer MJ;Stevens RD;Ilkayeva OR;Lowe LP;Metzger BE;Newgard CB;Scholtens DM;HAPO Study Cooperative Research Group
我们使用靶向代谢组学来确定母亲BMI和葡萄糖水平与脐带血代谢物的关系，以及脐带血代谢物与母亲-后代双体新生儿体重和肥胖的关系。对欧洲血统、非洲-加勒比、泰国和墨西哥裔美国新生儿（每个血统组400名）的脐带血血浆样本进行了靶向代谢组学分析，这些新生儿的母亲参加了高血糖和不良妊娠结局（HAPO）研究，并在出生时进行了人体测量。四个队列的荟萃分析显示，除了甘油三酯、天冬酰胺/天冬氨酸、精氨酸和酰基肉碱C14-OH/C12-DC外，所有脐带血代谢物分析与妊娠~ 28周母体空腹相同代谢物水平显著相关。荟萃分析还表明，无论是否调整母体血糖，母体BMI都与脐带血代谢物有关，包括支链氨基酸及其代谢物以及苯丙氨酸。1小时（非空腹）血糖与脐带血3-羟基丁酸及其肉碱酯（一种中链酰基肉碱）和甘油有关。许多脐带血代谢物与新生儿体重和皮肤褶皱数相关，包括甘油三酯负相关，3-羟基丁酸酯、肉碱酯和丝氨酸与新生儿结局呈正相关。母亲的BMI和血糖与新生儿代谢组的不同成分相关，与它们对新生儿出生时体重的独立影响一致。母体BMI与新生儿胰岛素抵抗和成人2型糖尿病风险的代谢特征相关。
We used targeted metabolomics to determine associations of maternal BMI and glucose levels with cord blood metabolites and associations of cord blood metabolites with newborn birth weight and adiposity in mother-offspring dyads. Targeted metabolomic assays were performed on cord blood plasma samples from European ancestry, Afro-Caribbean, Thai, and Mexican American newborns (400 from each ancestry group) whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and who had anthropometric measurements at birth. Meta-analysis across the four cohorts demonstrated significant correlation of all cord blood metabolites analyzed with maternal fasting levels of the same metabolites at ∼28 weeks’ gestation except for triglycerides, asparagine/aspartate, arginine, and the acylcarnitine C14-OH/C12-DC. Meta-analyses also demonstrated that maternal BMI with or without adjustment for maternal glucose was associated with cord blood metabolites including the branched-chain amino acids and their metabolites as well as phenylalanine. One-hour but not fasting glucose was associated with cord blood 3-hydroxybutyrate and its carnitine ester, a medium-chain acylcarnitine, and glycerol. A number of cord blood metabolites were associated with newborn birth weight and sum of skinfolds, including a negative association of triglycerides and positive association of 3-hydroxybutyrate, its carnitine ester, and serine with both newborn outcomes. Maternal BMI and glycemia are associated with different components of the newborn metabolome, consistent with their independent effects on newborn size at birth. Maternal BMI is associated with a newborn metabolic signature characteristic of insulin resistance and risk of type 2 diabetes in adults.