95-OR: Plasma miRNAs Levels at First Trimester of Pregnancy Predict Insulin Sensitivity Estimated at the Second Trimester of Pregnancy

Background: Gestational diabetes mellitus (GDM) is the most common pregnancy complication with a prevalence of 14% worldwide and has important consequences on both the mother and her child. GDM results from imbalance between insulin secretion capacity response and decreasing insulin sensitivity in pregnancy. MicroRNAs (miRNAs) are small (19-24nt) single-stranded RNA molecules involved in post-transcriptional regulation through binding to targeted mRNAs. MiRNAs are thought to regulate many physiological processes including glucose homeostasis.

Objective: Identify plasmatic miRNAs at the first trimester of pregnancy that predict insulin sensitivity (IS; as estimated with the Matsuda index) assessed between the 24^th and the 28^thweek of pregnancy. Methods: miRNAs were quantified by next generation sequencing in 443 plasma samples from the Gen3G birth-cohort. DESeq2 package was applied to identify miRNAs associated with IS. Glmnet package was used to compute lasso regression and find the minimum number of miRNAs predicting IS.

Results: On average, participants were 28.43 ± 4.3 (18-47) years old and had a BMI of 26.1 ± 6.1 (16.6-54.1) kg/m² at first trimester and had a Matsuda index of 8.41 ± 4.9 (0.77-37.53) at second trimester. A total of 106 miRNAs were associated with IS (p-adjusted for false discovery rate <0.1) when analyses were corrected for gestational age at blood collection, with 37 of them remaining significant after further correction for maternal age and BMI measured at first trimester. A lasso regression selected 27 of these miRNAs along with maternal age and BMI and overall explained 32% of the variability of IS at second trimester.

Conclusion: miRNAs quantified at first trimester of pregnancy are associated with and predictive of maternal IS estimated at second trimester. These miRNAs are likely involved in the pathophysiology of GDM and provide novel promising biomarkers for predicting glucose metabolism dysregulation in pregnancy.