The influence of insulin-related genetic variants on fetal growth, fetal blood flow, and placental weight in a prospective pregnancy cohort

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...

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Bibliographic Details
Published in:Scientific reports 2023-11, Vol.13 (1), p.19638-19638, Article 19638
Main Authors: Reim, Pauline K., Engelbrechtsen, Line, Gybel-Brask, Dorte, Schnurr, Theresia M., Kelstrup, Louise, Høgdall, Estrid V., Hansen, Torben
Format: Article
Language:English
Subjects:
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Birth weight
Blood flow
Diabetes mellitus (non-insulin dependent)
Dyslipidemia
Fetuses
Genetic diversity
Genetic variance
Genotypes
Gestation
Humanities and Social Sciences
Insulin resistance
multidisciplinary
Neonates
Phenotypes
Placenta
Population studies
Science
Science (multidisciplinary)
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-46910-6