Maternal and neonatal circulating markers of metabolic and cardiovascular risk in the metformin in gestational diabetes (MiG) trial: responses to maternal metformin versus insulin treatment

Abstract

Objective: This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth.

Research design and methods: Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks' gestation, and 6-8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included.

Results: Maternal plasma triglycerides increased more from randomization to 36 weeks' gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks.

Conclusions: There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.

Figure 1

Correlations between maternal variables and between cord plasma variables and birth weight. Graphs represent correlations between birth weight and maternal BMI at baseline (kg/m²) (A), maternal HbA_1c (%) at baseline (B), maternal fasting glucose at 36 weeks' gestation (mmol/L) (C), maternal fasting C-peptide at 36 weeks' gestation (D), maternal HDL cholesterol at 36 weeks' gestation (mmol/L) (E), cord leptin (μg/L) (F), cord C-peptide (μg/L) (G), cord glucose (mmol/L) (H), and cord triglyceride (mmol/L) (I). Subjects with gestational diabetes mellitus were randomized to either insulin or metformin therapy. Relationships between variables were tested using two-sided Spearman rank correlation. Regression lines are shown only where significance was P < 0.1. □, data for insulin-treated women; •, data for metformin-treated women. Regressions are shown with solid lines for overall relationships, with dashed lines for the insulin-treated group, and with dotted lines for the metformin-treated group.