The influence of insulin-related genetic variants on fetal growth, fetal blood flow, and placental weight in a prospective pregnancy cohort
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The influence of insulin-related genetic variants on fetal growth, fetal blood flow, and placental weight in a prospective pregnancy cohort. / Reim, Pauline K.; Engelbrechtsen, Line; Gybel-Brask, Dorte; Schnurr, Theresia M.; Kelstrup, Louise; Høgdall, Estrid V.; Hansen, Torben.
In: Scientific Reports, Vol. 13, 19638, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The influence of insulin-related genetic variants on fetal growth, fetal blood flow, and placental weight in a prospective pregnancy cohort
AU - Reim, Pauline K.
AU - Engelbrechtsen, Line
AU - Gybel-Brask, Dorte
AU - Schnurr, Theresia M.
AU - Kelstrup, Louise
AU - Høgdall, Estrid V.
AU - Hansen, Torben
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-023-46910-6
DO - 10.1038/s41598-023-46910-6
M3 - Journal article
C2 - 37949941
AN - SCOPUS:85176209452
VL - 13
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 19638
ER -
ID: 378805647