Challenges and importance of metabolic management of gestational diabetes in the third trimester

Gestational diabetes (GDM), the most common maternal complication of pregnancy, currently affects 9.98% of all pregnant women in Germany with increasing prevalence. The majority of women with GDM achieve recommended blood glucose concentrations by implementing moderate dietary changes and physical activity. In contrast, care for women with obesity and preconceptional insulin resistance can be challenging, as very high insulin doses are required in some cases to achieve fasting glucose concentrations around 95 mg/dL (5.3 mmol/L). As an ultima ratio, additional metformin may be considered, which has the positive side-effect of reducing weight gain. Excessive weight gain further increases insulin requirements, which is then associated with even more weight gain. Weight gain affects fetal growth and also long-term weight development of children. The quality of metabolic control affects fetal growth particularly in the third trimester, when the fetal pancreas produces significant amounts of insulin in response to increased placental glucose transfer. Insulin is the most potent growth factor in pregnancy and promotes the development of subcutaneous adipose tissue in the fetus. This leads to the typical fetal asymmetric growth in diabetic pregnancies with high neonatal fat mass later on. In obesity, normalization of fetal growth by blood glucose control alone is limited because increased concentrations of maternal lipids also trigger fetal growth, which in turn can be positively influenced by insulin. Therefore, an indication for insulin therapy should be made more generously in maternal obesity.