Diabetes in pregnancy: importance of ethnicity, timing of onset and modes of prevention

Abstract

Gestational diabetes mellitus (GDM) is associated with adverse risks to the mother and developing baby. Managing GDM has significant cost implications both in terms of the resources required to adequately treat the condition as well as those needed to address secondary complications. Preventing GDM therefore has several theoretical benefits.

Factors contributing to GDM development and the associated complications, most notably fetal macrosomia, are explored in this thesis with an emphasis on the effect of ethnicity. An original analysis of 4562 women presented here demonstrated significant variations in baseline maternal demographics, measures of glycaemia, fetal birth weight and adjusted birth weight centile across five different ethnic groups. An ethnic group dependent effect on the interaction between glucose and fetal birth weight was additionally found that persisted following adjustment for maternal early pregnancy body mass index.

While maternal weight and ethnicity are considerations in addressing materno-fetal risk, length of exposure to glucose is also important and increases adverse outcomes as illustrated by the results of a case control study of 200 pregnant women presented here. However, despite identification and treatment of women who develop hyperglycaemia early in pregnancy, increased premature delivery rates and higher still birth rates were observed implicating the importance of preventing hyperglycaemia in pregnancy.

One of the principle risk factors identified for early development of hyperglycaemia, was a previous pregnancy complicated by GDM. The final part of this thesis focuses on the rationale for an original trial designed to establish if metformin therapy, commenced early pregnancy, could prevent GDM recurring in women with previously affected pregnancies. While the impact of metformin in mitigating risk cannot be commented on, the low macrosomia rates and postnatal complication rates observed in this trial relative to pregnant women with previous GDM, continue to suggest the importance of addressing factors early in pregnancy.