Determinants of insulin resistance in children exposed to gestational diabetes in utero

Background The evolution of increased adiposity and cardiometabolic risk in offspring exposed to maternal gestational diabetes (GDM) is not well understood. Objective (a) To evaluate the impact of in utero exposure to GDM and maternal weight status on homeostasis model assessment of insulin resistance (HOMA-IR) in the offspring longitudinally from 1 to 3 years of age and (b) to compare body mass index (BMI) and HOMA-IR in GDM and non-GDM exposed offspring at 1 and 3 years of age. Methods A prospective cohort of children born to mothers with and without GDM underwent metabolic characterization between birth and 3 years of age. Results In the overall cohort, weight gain between birth and 3 years of age was positively associated with HOMA-IR (beta= 0.1491,P= .02), independent of maternal weight status. HOMA-IR was not different between GDM and non-GDM exposed children from 1 to 3 years of age; however, BMIzscore was greater in GDM exposed children at 3 years of age. Among non-GDM exposed children, male sex predicted a 35.1% lower HOMA-IR (P= .03). In GDM exposed offspring, a 1 unit increase in maternal insulin sensitivity predicted a 20.8% decrease in HOMA-IR (P= .002). Conclusions Overall, weight gain in the first 3 years of life was positively associated with HOMA-IR, while insulin sensitivity of mothers with GDM negatively predicted HOMA-IR in the offspring. Our findings indicate the need to target weight trajectories in early life, as well as maternal factors during gestation to improve metabolic outcomes in the offspring, particularly those exposed to GDM.