Gestational Diabetes Mellitus and Developmental Programming

During normal pregnancy, increased insulin resistance acts as an adaptation to enhance materno-foetal nutrient transfer and meet the nutritional needs of the developing foetus, particularly in relation to glucose requirements. However, about 1 in 6 pregnancies worldwide is affected by the inability of the mother's metabolism to maintain normoglycaemia, with the combination of insulin resistance and insufficient insulin secretion resulting in gestational diabetes mellitus (GDM). A growing body of epidemiologic work demonstrates long-term implications for adverse offspring health resulting from exposure to GDM in utero. The effect of GDM on offspring obesity and cardiometabolic health may be partly influenced by maternal obesity; this suggests that improving glucose and weight control during early pregnancy, or better still before conception, has the potential to lessen the risk to the offspring. The consequences of GDM for microbiome modification in the offspring and the impact upon offspring immune dysregulation are actively developing research areas. Some studies have suggested that GDM impacts offspring neurodevelopmental and cognitive outcomes; confirmatory studies will need to separate the effect of GDM exposure from the complex interplay of social and environmental factors. Animal and human studies have demonstrated the role of epigenetic modifications in underpinning the predisposition to adverse health in offspring exposed to suboptimal hyperglycaemic in utero environment. To date, several epigenome-wide association studies in human have extended our knowledge on linking maternal diabetes-related DNA methylation marks with childhood adiposity-related outcomes. Identification of such epigenetic marks can help guide future research to develop candidate diagnostic biomarkers and preventive or therapeutic strategies. Longer-term interventions and longitudinal studies will be needed to better understand the causality, underlying mechanisms, or impact of GDM treatments to optimize the health of future generations.