Mounting evidence suggests that a hyperglycemic intrauterine environment increases the risk of cardiometabolic disease and cognitive dysfunction in the offspring. Animal studies also indicate an intergenerational inheritance of these adverse effects. This is concerning given that 7-14% of pregnancies worldwide are complicated by diabetes. Hereof T1D is the most severe, whereas gestational diabetes (GDM) is the most prevalent. However, our understanding of the pathophysiologic pathways involved is limited and knowledge gaps exist regarding whether the risk increases during the life-course and whether a transfer through multiple generations may also take place in humans. A dose-response association with levels of maternal hyperglycemia during pregnancy has been proposed and indications of epigenetic changes have been found, but conclusions from previous studies regarding direct adverse effects of intrauterine hyperglycemia are often challenged by confounding from maternal overweight, genetic predisposition and socioeconomic factors. Consistent with animal studies, a recent study in adolescents born to women with GDM has demonstrated both functional and anatomical alterations in hypothalamic and hippocampal areas of the brain. The changes found were associated with impaired brain insulin action and altered eating behavior, which can potentially be restored with pharmacological and lifestyle interventions.
This presentation will discuss literature based on both animal and human studies but pay special attention to data from two large Danish human cohorts as well as from the Danish national registers.