Possible pathophysiological mechanisms
Few studies have provided mechanistic insights about the link between maternal diabetes and increased cardiovascular disease in the offspring. It is well established that glucose crosses the placenta and fetal hyperglycaemia leads to insulin production, increase in hepatic glucose uptake and glycogen synthesis in the fetus (22). These metabolic changes are associated with glycogen uptake from myocardial cells and development of myocardial hypertrophy, which may vary in severity depending on glycaemic control during pregnancy. Animal studies have also shown that intrauterine exposure to hyperglycaemia can induce fetal myocardial hyperplasia and myocardial remodelling which can account for differences in morphology and endocardial deformation noted between fetuses of mothers with GDM and controls. In addition, experimental studies have indicated that fetuses of mothers with GDM may experience hypoxaemia, which can lead to myocardial cell damage, myocyte death and impaired ventricular function (23-25). Finally, depending on the timing of in utero exposure to the hyperglycaemic stimulus changes to critical developmental pathways can occur as a result of altered gene expression (26).