Gestational diabetes: Metabolic damage occurs early in pregnancy

The prevalence of gestational diabetes (GDM) is increasing worldwide. The International Diabetes Federation (2015) estimates that, globally, one in seven births is affected by GDM. Maternal obesity is a key risk factor for GDM, and other risk factors include maternal age, ethnicity, family history of diabetes, maternal smoking, previous GDM, multiparity, previous adverse pregnancy outcomes and a previous large baby.

GDM is associated with multiple risks for the mother and fetus. These include maternal hypertensive disorders, greater rates of operative and interventional deliveries and attendant complications, polyhydramnios, stillbirth, fetal and perinatal death, fetal macrosomia, shoulder dystocia, congenital anomalies, and neonatal hypoglycaemia and other neonatal metabolic complications. Women with previous GDM also have a seven-fold increased risk of developing type 2 diabetes.

In addition to these complications, there is a potential increased risk of obesity in children born to mothers with GDM (Dabelea and Pettitt, 2001; Fadl et al, 2014). GDM results in preferential development of adipose tissue over lean tissue in the fetus, resulting in a “thin–fat” phenotype, in which the baby is the same size as a non-GDM baby but has more fat.

Supporting the thin–fat hypothesis is a new study from Venkataraman and colleagues (summarised alongside). The authors conducted a retrospective analysis of the pregnancies of 153 women with GDM and 178 controls in India. At 12 weeks’ gestation, fetal measurements were similar in both groups. At 20 weeks’ gestation, however, fetuses in the GDM group had higher anterior abdominal wall thickness (a measure of excess adiposity) but smaller head circumference, abdominal circumference, femur length and biparietal diameter, indicating the thin–fat phenotype. Higher anterior abdominal wall thickness persisted at 32 weeks’ gestation. There was an independent relationship between the mothers’ blood glucose levels and abdominal adiposity in the fetus. At birth, baby size did not differ between the groups, but the babies born to mothers with GDM had greater adiposity. There was a higher prevalence of caesarean deliveries in the GDM group.

These findings support the view that key deleterious fetal metabolic changes can occur in early pregnancy, prior to screening tests for GDM that are conducted in the second trimester. Preventing GDM is a key priority for reducing obesity and type 2 diabetes, but more research is needed to identify the best approaches. It is also important to diagnose GDM as early as possible, preferably in the first trimester. The challenge is to develop effective screening tools to achieve this.

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