Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy

The placenta participates in maternal insulin sensitivity changes during pregnancy, however mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75g oral glucose tolerance tests at ∼26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using IlluminaEPIC arrays. Using linear regression models to quantify associations at 720,077 CpGs, adjusted for maternal age, gravidity, smoking, body mass index, child sex and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P