Birth weight, infant growth and insulin resistance
Birth weight, infant growth and insulin resistance
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DOI：
10.1530/eje.0.151u131
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发表时间：
2004-11-01
影响因子：
5.8
通讯作者：
Dunger, DB
中科院分区：
文献类型：
--
作者：
Ong, KK;Dunger, DB
出生时的大小和出生后早期的生长速度是人类围产期生存的重要决定因素;它们还预测生长克里思、成年身高和肥胖、2型糖尿病和心血管疾病的长期风险。雅芳妊娠和儿童纵向研究（ALSPAC）的结果表明，胎儿生长受到胎儿基因和母亲-子宫-胎盘因素的影响。重要的母体-胎盘因素包括产次、吸烟和体重增加，但也包括母体或胎儿胎盘中的母体遗传因素，包括线粒体DNA 16189变体和H19。这些母体遗传因素特别影响较小的，生长受限的婴儿，如第一次怀孕。胎儿基因包括胰岛素基因（INS）VNTR（可变数目串联重复序列），我们最近证实这与出生大小和脐带血IGF-II水平有关;在出生后的生活中，INS VNTR III/III基因型仍然与身体大小相关，包括体重指数和腰围，女孩的胰岛素敏感性也较低。然而，在出生时，可以看到显着的基因-环境相互作用。快速“追赶”早期出生后体重增加遵循母亲子宫的约束，并强烈预测后来的儿童肥胖和胰岛素抵抗，在这些孩子中，那些与INS VNTR I类等位基因更obesity.Genetic因素，影响早期生长可能赋予了一些早期生存优势，在人类历史上的营养不良时期。随着营养的丰富和肥胖率的上升，这些遗传因素及其与影响儿童生长的母亲和儿童环境因素的相互作用现在可能有助于成人疾病风险的早期发展。对它们的认识可能有助于制定有针对性的早期干预措施，以防止进展为成人疾病。
Size at birth and early postnatal growth rates are important determinants of human perinatal survival; they also predict the tempo of growth, adult height and long-term risks for obesity, type 2 diabetes and cardiovascular disease.Results from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) show that fetal growth is influenced by both fetal genes and maternal-uterine-placental factors. Important maternal-placental factors include parity, smoking and weight gain, but also maternal genetic factors in the mother or fetal placenta, including the mitochondrial DNA 16189 variant and H19. These maternal genetic factors particularly influence smaller, growth-restrained infants, as in first pregnancies. Fetal genes include the insulin gene (INS) VNTR (variable number of tandem repeat), which we recently confirmed to be associated with birth size and cord blood IGF-II levels; these fetal gene effects are more evident in the absence of maternal-uterine growth restraint.During postnatal life, the INS VNTR III/III genotype remains associated with body size, including body mass index and waist circumference, and also lower insulin sensitivity among girls. However, as at birth, significant gene-environment interactions are seen. Rapid 'catch-up' early postnatal weight gain follows maternal-uterine restraint, and strongly predicts later childhood obesity and insulin resistance; among these children, those with INS VNTR class I alleles are more obese.Genetic factors that influence early growth may have conferred some early survival advantage in human history during times of undernutrition. With abundant nutrition and rising obesity rates, these genetic factors and their interactions with maternal and childhood environmental factors that influence childhood growth may now contribute to the early development of adult disease risk. Their recognition may help the development of targeted early interventions to prevent the progression towards adult disease.