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).