Effects of metformin treatment of gestational diabetes on offspring glucose tolerance and body composition (#167)
Background: Exposure to diabetes in utero results in an increased risk of insulin resistance, diabetes and obesity in offspring. Determining the long term safety and efficacy of drugs to treat gestational diabetes (GDM) thus has important implications on the metabolic health of our population. There is renewed interest in metformin for the treatment of GDM. In the randomised MiG trial, metformin treatment of GDM resulted in similar outcomes to insulin and decreased maternal weight gain. There are no data on long term effects on the offspring beyond 2 years.
Aims: The effects of metformin treatment of GDM on the long term metabolic phenotype of male offspring were studied in a mouse model.
Methods: We studied β-ARNT mice that have a β-cell specific deletion of ARNT and are a model of mild GDM. β-ARNT females were mated with floxed-control males, and vice versa to obtain diabetic and non diabetic pregnancies respectively. Litters are ~50% β-ARNT and ~50% floxed-control. β-ARNT females were either given drinking water +/- metformin 20mg/kg for the entire pregnancy, floxed control dams were given vehicle. Male offspring were assessed by DEXA, serial weights, dynamic testing of glucose metabolism and indirect calorimetry.
Results: Maternal glucose tolerance was similar in metformin and vehicle treated dams, thus isolating the effects of metformin on offspring. β-ARNT offspring from GDM pregnancies had significantly impaired glucose tolerance at 10 weeks of age compared to β-ARNT offspring from normoglycemic pregnancies. This effect was completely prevented in metformin treated GDM pregnancies. In floxed control offspring, GDM pregnancy was associated with reduced body fat percentage at 12 weeks.
Conclusions: Metformin treatment of GDM in pregnancy has significant beneficial effects on offspring glucose tolerance.