Background: Obesity is a global health epidemic, where 28% of pregnant Australian women are obese. Maternal obesity increases the risk of a complicated pregnancy, including gestational diabetes mellitus (GDM) and cardiovascular dysfunction, highlighting the need for pregnancy interventions to improve maternal and fetal health. The anti-diabetic drug metformin is considered safe to be administrated during pregnancy as a therapeutic for GDM. However, there is limited evidence of the effect metformin has in obese pregnancies.
Methods: Five week old female Wistar-Kyoto rats were allocated to a Control or High-fat (HF) diet. Prior to and during pregnancy rats underwent physiological measurements to determine metabolic and cardiovascular health, with 24h food intake measured. Rats allocated to HFD were allocated to receive metformin (300 mg/kg/day) or vehicle via oral gavage from gestation day 7 (E7-E18). At post-mortem (E20), fetal and placental weights were recorded and maternal tissues collected. Data were analysed by a one-way ANOVA.
Results: Not surprisingly, HFD increased pre-pregnant weight gain (+9%) indicative of increased adiposity, which is likely attributed to increased energy consumption (+44%), with no changes in cardiometabolic health. Although Metformin reduced energy consumption (-30%) and improved adiposity to Control values, pregnancy weight gain was not different across groups. Metformin improved glucose tolerance to Control values with HFD-vehicle being intermediate and no changes in blood pressure. Metformin reduced fetal (female) and placental (male and female) weights compared to Control, however placental efficiency was not affected.
Conclusion: We demonstrated that HFD consumption in rats resulted in glucose intolerance during pregnancy, which was resolved to chow rats with Metformin. These data highlight that Metformin has beneficial actions on maternal metabolic health and adiposity during pregnancy in overweight rats. Future studies are required to determine the impact this has on placental nutrient transportation and fetal development, which may impact long-term offspring health.