Gestational diabetes mellitus (GDM), a form of diabetes that occurs during pregnancy, impacts the mother and her baby perinatally and poses an increased risk of lifelong chronic disease for both[1]. The rate of GDM in Australia has tripled from 5.4% to 16.1% over the past decade[2].
Etiology of GDM is mostly related to obesity, maternal age and ethnicity[3], yet the rise in GDM is seen across all groups and the current trajectory began before the 2014 change in World Health Organisation diagnostic criteria. Recent evidence shows an association of folic acid (FA) with insulin resistance and GDM[4-6]. Interestingly, the Australian government implemented FA food fortification in September 2009; the rise in GDM incidence soon followed. Despite shared etiology, type 2 diabetes has not significantly changed in the past decade. We have therefore turned to the placenta, an organ unique to pregnancy and an essential regulator of maternal glucose tolerance, insulin sensitivity and glucose transport to the fetus. Placenta starts to secrete hormones early in normal gestation into maternal circulation to stimulate maternal beta cell expansion and insulin resistance and ensure adequate glucose transport to the fetus[7]. Our preliminary data from two pregnancy cohorts that recruited women prior to and post FA fortification mandate (SCOPE n=1164, 4.2% GDM; STOP n=1300, 15.2% GDM) shows circulating placental hormones at 12-16 weeks’ gestation are substantially different between the cohorts. Mean maternal red cell folate post fortification is also elevated (SCOPE 619.0±15.6 nmol/L; STOP 1442.8±321.1nmol/L), levels exceeding normal RCPA reference range.
These data suggest altered placental endocrine responses to elevated folate should be investigated as a potential mechanism driving the GDM rise. In order to improve short and long-term health of more than 500,000 mothers and babies who are predicted to be diagnosed with GDM over the next decade, further research is urgently required.