Faculty of Health Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Maersk Tower, Blegdamsvej 3B, 8th Floor, 2200, Copenhagen, Denmark.
Department of Gynaecology and Obstetrics, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Sci Rep. 2023 Nov 10;13(1):19638. doi: 10.1038/s41598-023-46910-6.
The fetal insulin hypothesis proposes that low birthweight and type 2 diabetes (T2D) in adulthood may be two phenotypes of the same genotype. In this study we aimed to explore this theory further by testing the effects of GWAS-identified genetic variants related to insulin release and sensitivity on fetal growth and blood flow from week 20 of gestation to birth and on placental weight at birth. We calculated genetic risk scores (GRS) of first phase insulin release (FPIR), fasting insulin (FI), combined insulin resistance and dyslipidaemia (IR + DLD) and insulin sensitivity (IS) in a study population of 665 genotyped newborns. Two-dimensional ultrasound measurements with estimation of fetal weight and blood flow were carried out at week 20, 25, and 32 of gestation in all 665 pregnancies. Birthweight and placental weight were registered at birth. Associations between the GRSs and fetal growth, blood flow and placental weight were investigated using linear mixed models. The FPIR GRS was directly associated with fetal growth from week 20 to birth, and both the FI GRS, IR + DLD GRS, and IS GRS were associated with placental weight at birth. Our findings indicate that insulin-related genetic variants might primarily affect fetal growth via the placenta.
胎儿胰岛素假说提出，低出生体重和成年 2 型糖尿病（T2D）可能是同一基因型的两种表型。在这项研究中，我们旨在通过测试与胰岛素释放和敏感性相关的 GWAS 鉴定的遗传变异对胎儿生长和从妊娠 20 周开始至出生的血流以及出生时胎盘重量的影响，进一步探讨这一理论。我们在一个由 665 名基因分型新生儿组成的研究人群中计算了第一相胰岛素释放（FPIR）、空腹胰岛素（FI）、胰岛素抵抗和血脂异常综合（IR+DLD）和胰岛素敏感性（IS）的遗传风险评分（GRS）。在所有 665 例妊娠中，在妊娠 20、25 和 32 周进行二维超声测量，并估计胎儿体重和血流。在出生时记录出生体重和胎盘重量。使用线性混合模型研究 GRS 与胎儿生长、血流和胎盘重量之间的关系。FPIR GRS 与从 20 周妊娠到出生的胎儿生长直接相关，FI GRS、IR+DLD GRS 和 IS GRS 均与出生时的胎盘重量相关。我们的研究结果表明，与胰岛素相关的遗传变异可能主要通过胎盘影响胎儿生长。
