Metformin Usage During Pregnancy: Effects on Offspring’s Brain Development and Gestational Diabetes Risk

Introduction

The prescription of metformin, an oral antidiabetic medication, has seen a rise in cases of gestational diabetes and metabolic disorders during pregnancy. Despite its ability to pass through the placental barrier, the impacts of metformin on a child’s brain development are still not well understood. A recent study conducted by the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) sheds light on this issue, revealing that while metformin may benefit pregnant animals, such positive effects do not extend to their offspring. These findings, published in the specialist journal Molecular Metabolism, highlight the complexity of managing gestational diabetes risks and the importance of pursuing preventive strategies.

The Prevalence of Gestational Diabetes

Gestational diabetes, a special form of diabetes that occurs specifically during pregnancy, affects approximately one in six pregnant women worldwide. In Germany alone, the Robert Koch Institute reported that 63,000 women were affected by the disease in 2021, with the numbers continuing to rise. High blood sugar levels during pregnancy have negative consequences for both the mother and the child, increasing the risk of affected women developing type 2 diabetes later in life and their children developing metabolic disorders and being overweight.

Uncertainty Surrounding Long-Term Effects of Metformin

Metformin has become an alternative to insulin administration for the treatment of gestational diabetes when lifestyle changes prove ineffective. However, there is limited research on its long-term effects on the health of offspring. Metformin is known to affect the AMPK signaling pathway, which regulates the networking of nerve cells during brain development. To address the knowledge gap, a cross-disciplinary team of researchers from DIfE conducted a study using mouse models to investigate whether metformin treatment is beneficial for both the mother and the child and whether it leads to negative physiological changes in the offspring’s brain development, particularly in the hypothalamus, a critical region in the regulation of energy homeostasis.

Insights from Mouse Models

The study used two mouse models that represent the main causes of gestational diabetes: pre-pregnancy severe obesity and excessive weight gain during pregnancy. Different feeding patterns, including a high-fat or control diet, were used to induce these metabolic states. The female mice and their offspring received various treatments, including insulin, metformin, or a placebo, during the lactation period, which corresponds to the third trimester of human pregnancy in terms of brain development. The researchers collected data on the mice’s body weight, analyzed metabolic parameters and hormones, and examined molecular signaling pathways in the hypothalamus.

Impact of Maternal Metabolic State

The study found that the effect of antidiabetic treatment in the early postnatal period on the offspring’s weight gain and hormonal status depended on the metabolic state of the mother. Additionally, sex-specific changes in hypothalamic AMPK signaling were observed in response to metformin exposure. The results, coupled with the metformin-induced shift in examined hormone levels, highlight the importance of considering the maternal metabolic state prior to initiating gestational diabetes treatment.

Focusing on Prevention

Dr. Rachel Lippert, the leader of the interdisciplinary research team, suggests that future treatment of gestational diabetes could involve the development of a medication that is safe for all pregnant women and does not cross the placenta. Furthermore, improving education on gestational diabetes and implementing preventive measures play vital roles in combating the increasing prevalence of the disease. The study emphasizes the necessity of managing lifestyle and diet proactively to harness the full potential of gestational diabetes treatment.

Conclusion

The study conducted by the German Institute of Human Nutrition Potsdam-Rehbrücke provides valuable insights into the effects of metformin on offspring’s brain development and the associated risks of gestational diabetes. It underscores the need for further research and preventive strategies to tackle this complex issue. By understanding the impact of maternal metabolic state on treatment outcomes and exploring safer alternatives, healthcare professionals can enhance the well-being of both mothers and children.

Reference: “Developmental metformin exposure does not rescue physiological impairments derived from early exposure to altered maternal metabolic state in offspring mice” by Lídia Cantacorps, Jiajie Zhu, Selma Yagoub, Bethany M. Coull, Joanne Falck, Robert A. Chesters, Katrin Ritter, Miguel Serrano-Lope, Katharina Tscherepentschuk, Lea-Sophie Kasch, Maya Paterson, Paula Täger, David Baidoe-Ansah, Shuchita Pandey, Carla Igual-Gil, Annett Braune and Rachel N. Lippert, 23 December 2023, Molecular Metabolism. DOI: 10.1016/j.molmet.2023.101860