Falling Insulin Requirements and Placental Dysfunction in Women with Pre-Existing Diabetes During Pregnancy

Abstract

The second half of pregnancy is characterized by a 50-70% rise in insulin resistance due to placental mediated hormone production. In women with pre-existing diabetes, this period corresponds to an increase in insulin requirements. However, less is known about the significance of a large fall in insulin requirements, when and whether this adversely impacts maternal and fetal outcomes. Falling insulin requirements (FIR) in late pregnancy has been thought to be a marker of placental insufficiency prompting admission to hospital for maternal and fetal monitoring as well as emergency delivery in some cases. However, the limited cohort studies which have looked at this group of patients failed to show any difference in maternal or fetal outcomes. Furthermore, no previous studies have directly associated FIR with evidence of placental insufficiency and it remains unclear why some women have large falls in insulin requirements and what the underlying pathophysiology is. In this thesis, through two clinical studies, the association of FIR with placental insufficiency and maternal and fetal outcomes was assessed. In addition, the pathophysiology of FIR was investigated.