As the prevalence of gestational diabetes and metabolic disorders rises among pregnant women, the use of metformin, an oral antidiabetic medication, has become increasingly common. However, while metformin offers benefits for pregnant individuals, a recent study conducted by a cross-disciplinary team from the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) suggests that its positive effects may not extend to offspring brain development.
Published in Molecular Metabolism, the study addresses concerns regarding the long-term impact of metformin on children’s health, particularly in the context of gestational diabetes.
Gestational diabetes affects approximately one in six pregnant women worldwide, with figures on the rise. Excessively high blood sugar levels during pregnancy pose risks for both mother and child, increasing the likelihood of type 2 diabetes in mothers and metabolic disorders and obesity in children.
Despite metformin’s growing use as an alternative to insulin in gestational diabetes treatment, limited research exists on its long-term effects on offspring health. The medication’s influence on the AMPK signaling pathway, crucial for nerve cell networking during brain development, adds complexity to the discussion.
Led by Dr. Rachel Lippert, the DIfE research team explored whether metformin benefits only the mother or extends to the child, and whether it leads to adverse physiological changes in offspring, particularly in hypothalamic neuronal circuits crucial for energy regulation.
Using mouse models representing the primary causes of gestational diabetes—maternal obesity and excessive weight gain during pregnancy—the researchers administered antidiabetic treatment during lactation, corresponding to the third trimester of human pregnancy in terms of brain development.
Treatment options included insulin, metformin, or a placebo, with dosage based on standard human regimens. The team assessed various parameters including body weight, metabolic indicators, hormone levels, and molecular signaling pathways in the hypothalamus.
Results indicated that maternal metabolic state significantly influenced offspring outcomes following early postnatal antidiabetic treatment. Sex-specific changes in hypothalamic AMPK signaling and alterations in hormone levels were observed in response to metformin exposure, highlighting the need to consider maternal metabolic status before initiating gestational diabetes treatment.
Dr. Lippert emphasizes the importance of developing medications that do not cross the placenta to ensure the safety of fetal brain development. She underscores the significance of education and preventive measures in managing gestational diabetes, advocating for proactive lifestyle and dietary interventions to optimize treatment outcomes.
The study underscores the need for further research to refine gestational diabetes management strategies and minimize potential risks to maternal and child health.
