Article Text
Abstract
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.
- gestational diabetes mellitus
- metformin
- offspring
- insulin
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Footnotes
Contributors JAR was the principal investigator (PI) and developed the study design, contributed to the research and analysis, and wrote the manuscript. ECR was a collaborator, contributed to the study design, research in Auckland, data entry and analysis, and reviewed and edited the manuscript. LDP was a collaborator, performed the DXA measures and analysis, and oversaw the laboratory sampling, testing and analysis, and reviewed and edited the manuscript. JL was a collaborator, contributed to the development of the MRI measures in Auckland, analyzed the MRI and MRS data and reviewed and edited the manuscript. VO was involved with developing the database, performed most of the analysis, and reviewed and edited the manuscript. SC was involved with setting up and performing the research in Adelaide, including data entry and analysis, and reviewed the manuscript. WMH was the PI in Adelaide, contributed to the study design, oversaw the research and data collection, and reviewed and edited the manuscript.
Funding This work was supported by the Auckland Medical Research Foundation (AMRF) in New Zealand, grant number 111013 and National Health and Medical Research Council (NHMRC) in Australia, grant number 508061.
Competing interests None declared.
Patient consent Not required.
Ethics approval The study has local ethics approval (Auckland AKX/04/08/228/AM04, Adelaide REC1892/11/09).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement There are additional unpublished data that have not yet been analyzed, as they were not specifically related to this manuscript. These include additional data around the health of the family and the child’s diet and activity. There are also neurodevelopmental assessments in the 7-year-old cohort and questions about school performance and development in the 9-year-old cohort. These are available to the authors of this manuscript and their research teams at this stage, with a plan to publish further findings. The first author can be emailed with relevant queries.