OBJECTIVE: In women with gestational diabetes mellitus, who were randomized to metformin or insulin treatment, pregnancy outcomes were similar (Metformin in Gestational diabetes [MiG] trial). Metformin crosses the placenta, so it is important to assess potential effects on growth of the children. RESEARCH DESIGN AND METHODS: In Auckland, New Zealand, and Adelaide, Australia, women who had participated in the MiG trial were reviewed when their children were 2 years old. Body composition was measured in 154 and 164 children whose mothers had been randomized to metformin and insulin, respectively. Children were assessed with anthropometry, bioimpedance, and dual energy X-ray absorptiometry (DEXA), using standard methods. RESULTS: The children were similar for baseline maternal characteristics and pregnancy outcomes. In the metformin group, compared with the insulin group, children had larger mid-upper arm circumferences (17.2 ± 1.5 vs. 16.7 ± 1.5 cm; P = 0.002) and subscapular (6.3 ± 1.9 vs. 6.0 ± 1.7 mm; P = 0.02) and biceps skinfolds (6.03 ± 1.9 vs. 5.6 ± 1.7 mm; P = 0.04). Total fat mass and percentage body fat assessed by bioimpedance (n = 221) and DEXA (n = 114) were not different. CONCLUSIONS: Children exposed to metformin had larger measures of subcutaneous fat, but overall body fat was the same as in children whose mothers were treated with insulin alone. Further follow-up is required to examine whether these findings persist into later life and whether children exposed to metformin will develop less visceral fat and be more insulin sensitive. If so, this would have significant implications for the current pandemic of diabetes.

Objective To compare body composition and metabolic outcomes at 7–9 years in offspring of women with gestational diabetes (GDM) randomized to metformin (±insulin) or insulin treatment during pregnancy. Research design and methods Children were assessed at 7 years in Adelaide (n=109/181) and 9 years in Auckland (n=99/396) by anthropometry, bioimpedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) (n=92/99) and fasting bloods (n=82/99). Results In the Adelaide subgroup, mothers were similar at enrollment. Women randomized to metformin versus insulin had higher treatment glycemia (p=0.002) and more infants with birth weight >90th percentile (20.7% vs 5.9%; p=0.029). At 7 years, there were no differences in offspring measures. In Auckland, at enrollment, women randomized to metformin had a higher body mass index (BMI) (p=0.08) but gained less weight during treatment (p=0.07). Offspring birth measures were similar. At 9 years, metformin offspring were larger by measures of weight, arm and waist circumferences, waist:height (p<0.05); BMI, triceps skinfold (p=0.05); DXA fat mass and lean mass (p=0.07); MRI abdominal fat volume (p=0.051). Body fat percent was similar between treatment groups by DXA and BIA. Abdominal fat percentages (visceral adipose tissue, subcutaneous adipose tissue and liver) were similar by MRI. Fasting glucose, triglyceride, insulin, insulin resistance, glycosylated hemoglobin (HbA1c), cholesterol, liver transaminases, leptin and adiponectin were similar. Conclusions Metformin or insulin for GDM was associated with similar offspring total and abdominal body fat percent and metabolic measures at 7–9 years. Metformin-exposed children were larger at 9 years. Metformin may interact with fetal environmental factors to influence offspring outcomes.

Offspring born following maternal gestational diabetes are at risk of excessive childhood weight gain and Type 2 diabetes in childhood, which in turn is associated with an increased rate of hypertension. We aimed to determine the systolic and diastolic blood pressure at two years of age in a cohort of children exposed to gestational diabetes mellitus using data from the MiG trial of metformin use in gestational diabetes. The secondary aim was to analyze these data by randomization of treatment to insulin or metformin. The offspring of women who had gestational diabetes and had been assigned to either open treatment with metformin (with supplemental insulin if required) or insulin in the MiG trial were followed up at 2 years of age. Oscillometric measurement of BP in the right arm was performed by a researcher using an appropriately sized cuff. A total of 489 measurement blood pressure measurements were obtained in 170 of the 222 children who were seen at a median (range) age of 29 (22–38) months corrected gestational age. At the time of assessment the mean (SD) weight and height was 13.8(2) kg and 90 (4.2) cm respectively. For the whole group the mean (SD) systolic pressure was 90.9 (9.9) mmHg and mean (SD) diastolic pressure was 55.7 (8.1) mmHg. No difference was found between the metformin and insulin treatment arms. In a regression model, height and weight were only two factors associated with the levels of systolic blood pressure. For each additional kg the systolic blood pressure increased by 1.0 mmHg. For each additional cm of height the systolic blood pressure increased by 0.42 mmHg. Blood pressure data was obtained at approximately two years of age in a substantial cohort of children whose mothers received treatment for GDM. These novel data compare favorably with published norms. This study was registered under the Australian New Zealand Clinical Trials Registry ( ACTRN12605000311651 ).