First trimester plasma microRNAs levels predict Matsuda Index-estimated insulin sensitivity between 24th and 29th week of pregnancy

INTRODUCTION: Gestational diabetes mellitus (GDM) is a consequence of an imbalance between insulin sensitivity (IS) and secretion during pregnancy. MicroRNAs (miRNAs) are small and secreted RNA molecules stable in blood and known to regulate physiological processes including glucose homeostasis. The aim of this study was to identify plasmatic miRNAs detectable in early pregnancy predicting IS at 24th-29th week of pregnancy. RESEARCH DESIGN AND METHODS: We quantified circulating miRNAs in 421 women in plasma collected at 9.6±2.2 weeks of pregnancy using next-generation sequencing. RESULTS: we detected 2170 miRNAs: 39 (35 positively and 4 negatively) were associated with IS as estimated by the Matsuda Index at 26.4±1.0 weeks of pregnancy. Lasso regression identified 18 miRNAs independently predicting Matsuda Index-estimated IS. Together with gestational age, maternal age and body mass index at first trimester, they explain 36% of IS variance in late second trimester of pregnancy. These miRNAs regulate fatty acid biosynthesis and metabolism among other pathways. CONCLUSIONS: In summary, we have identified first trimester plasmatic miRNAs predictive of Matsuda Index-estimated IS in late second trimester of pregnancy. These miRNAs could also contribute to initiate and support IS adaptation to pregnancy potentially through lipid metabolism regulation.