Hyperglycaemia in pregnancy: characterization, mitigation and implications for maternal and offspring health

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Promotion K. Hribar

This thesis Kaja Hribar investigates the pathophysiology of lean gestational diabetes mellitus (GDM) and its consequences for both mother and offspring. We use an innovative mouse model, combining a high-fat diet with streptozotocin to mimic hyperglycaemia during pregnancy. This resulted in an insulin-sensitive mouse model that developed hyperglycaemia during pregnancy, independent of obesity.

In the first part, we focus on maternal effects. We characterize the hyperglycemic phenotype and discover early markers of liver disease that correlate with the severity of hyperglycaemia. Furthermore, we demonstrate that even lean GDM can lead to postpartum development of metabolic dysfunction-associated steatotic liver disease (MASLD) and T2DM. We also explore the potential of cannabidiolic acid as a therapeutic intervention.

The second part concentrates on offspring outcomes. We observe that prenatal exposure to hyperglycaemia results in alterations in glucose regulation and insulin sensitivity in adult offspring. Moreover, we note changes in pancreatic islet morphology, providing a potential mechanism for the observed metabolic effects.

A crucial finding is the strong correlation between the severity of maternal hyperglycaemia and health outcomes for both mother and child. This emphasizes the importance of adequate glycaemic control during pregnancy.

This research deepens our understanding of lean GDM and its intergenerational consequences, highlighting the need for early detection, careful management of blood sugar levels, and potential interventions to mitigate long-term risks. It opens new avenues for future studies and the development of more effective prevention strategies and treatment modalities.