Diabetes mellitus complicating pregnancy: a study of maternal vascular endothelial dysfunction and of placental terminal villous ultrastructure

Abstract

Insulin dependant diabetes is metabolic disorder associated with vascular endothelial dysfunction. Pregnancy, in a woman with diabetes, is associated with an increased risk of maternal vascular complications, such as pre-eclampsia and progression of microvascular disease. These vascular complications are in part mediated though inflammatory effects on the vessel wall. Insulin dependent diabetes is also associated with an increased risk of fetal complications including intrauterine hypoxia and stillbirth. Maternal vascular dysfunction may alter the feto-placental environment and be associated with aberrant placental vascular development. We therefore aimed to determine: (1) if pregnancy in the insulin dependent (type I) diabetic woman is associated with increased maternal endothelial dysfunction, and (2) if the ultrastructure of the terminal placental villus, the functional exchange unit, is altered in these pregnancies.As an index of maternal vascular function circulating concentrations of defined endothelial-derived cell adhesion molecules were assessed. An ELISA was used to quantify the concentrations of these cell adhesion molecules, throughout diabetic and control pregnancies and in matched non-pregnant women. The circulating concentrations of the cell adhesion molecules: E-selectin and ICAM-1 were increased in non-pregnant diabetic subjects compared to non-pregnant controls. These cell adhesion molecules interact with neutrophils and provide evidence of endothelial dysfunction in our population of non-pregnant diabetic women. In contrast, during pregnancy there was no difference in the circulating concentrations of E-selectin or ICAM-1 between diabetic and control groups. The concentration of E-selectin was significantly reduced when measured in the pregnant compared to the non-pregnant diabetic cohorts. Circulating concentrations of von Willebrand factor, an established index of endothelial dysfunction, were also comparable in diabetic and control pregnant cohorts. These findings suggest that pregnancy, in our population of diabetic women, may actually be a time of vascular well-being. We hypothesize that this is a reflection of the improved glycaemic control achieved by these women during pregnancy.