Obesity in pregnancy: risk of gestational diabetes

Background: Maternal obesity is a risk factor for gestational diabetes and other adverse pregnancy outcomes, but the body fat distribution may be a more important risk factor than body mass index. Pregnancy is an insulin resistant state and more so, in obese women. Metformin could be beneficial in obese pregnant women due to its insulin sensitizing action. The aims of this study are to investigate visceral fat mass as a risk factor for gestational diabetes (VFM study), to develop a mathematical model for the prediction of gestational diabetes in obese women (VFM study) and to examine the effect of metformin on pregnancy outcomes in obese non-diabetic women (MOP Trial). Methods and Results: VFM study: The body composition of 302 obese pregnant women was assessed using bioelectrical impedance. A mathematical model to predict gestational diabetes using machine learning was developed using visceral fat mass which is a novel risk factor in addition to conventional risk factors. 72 of the women developed gestational diabetes (GDM). These women had higher visceral fat mass. Women with a baseline visceral fat mass ≥ 75th percentile, had a 3-fold risk of subsequent gestational diabetes. The mathematical model predicted gestational diabetes with an average overall accuracy of 77.5% and predicted birth centile classes with an average accuracy of 68%. According to the decision tree developed, VFM emerged as the most important variable in determining the risk of GDM and a VFM < 210 was used as the first split in the decision tree. MOP Trial: 133 obese pregnant women were randomised to either metformin or placebo. The pregnancy outcomes were compared in both groups. Insulin resistance was measured in all women. 118 women completed the trial. Metformin did not reduce the neonatal birth weight z-score, which was the primary outcome of the trial or the incidence of large for gestational age babies. However, metformin therapy significantly reduced gestational weight gain, reduced the pregnancy rise in visceral fat mass, and attenuated the expected physiological rise in insulin resistance at 28 weeks gestation. However, this did not result in an overall significant reduction in the incidence of gestational diabetes. There was a trend towards a reduced incidence of gestational diabetes in women with high baseline insulin resistance randomised to metformin. Conclusions: Visceral fat mass is a novel risk factor for gestational diabetes. The mathematical model successfully predicted gestational diabetes. Metformin reduced gestational weight gain and insulin resistance but did not lower the median neonatal birth weight or reduce the incidence of GDM.