Research shows that while metformin is beneficial in pregnant animals, it may not have positive effects on their offspring, highlighting the complexity of risk management for gestational diabetes and the importance of pursuing preventive strategies. It is emphasized.
Due to the increase in cases of gestational diabetes and metabolic disorders during pregnancy, metformin prescriptions have become more common. Despite the understanding that this oral antidiabetic drug can cross the placental barrier, its effects on children’s brain development remain largely unknown. However, a multidisciplinary team at the German Institute for Human Nutrition Potsdam-Lebrücke (DIfE) recently found in a mouse study that while metformin is beneficial in pregnant animals, these positive effects do not extend to offspring. It was shown that
The results were published in a specialized journal Molecular metabolism.
Current statistics show that approximately one in six pregnant women worldwide has a special form of diabetes known as gestational diabetes. According to the Robert Koch Institute, 63,000 women in Germany will be affected by the disease in 2021, and the trend is increasing.
These numbers are alarming because excessively high blood sugar levels during pregnancy have a negative impact on mother and baby. This increases the risk that the affected woman will later develop her type 2 diabetes, and increases the risk that her children will develop metabolic disorders or be overweight.
The long-term effects of metformin on offspring are unknown
In recent years, it has become increasingly important as an alternative to the placenta-crossing oral antidiabetic drug metformin. insulin Administered when lifestyle changes are ineffective during treatment of gestational diabetes. However, there are currently few studies on the long-term effects of metformin on offspring health. Metformin is known to affect the AMPK signaling pathway, which regulates neuronal networks during brain development.
Therefore, an interdisciplinary team of DIfE researchers, led by junior research group leader Dr. Rachel Lippert, addressed two central questions. Does metformin treatment benefit only the mother, or does it also benefit the child? Also, does metformin treatment benefit the offspring, particularly in relation to the development of neural circuits in the hypothalamus, an area important in the regulation of energy homeostasis? Do they result in long-term negative physiological changes?
Light hits the mouse model
To answer important questions, researchers used two mouse models to represent the main causes of gestational diabetes.
Severe maternal obesity before pregnancy and excessive weight gain during pregnancy. These metabolic states were achieved through different feeding patterns, with mice fed high-fat or control diets. Antidiabetic treatment of female mice and their offspring was performed during lactation, which corresponds to the third trimester of human pregnancy in terms of brain development.
Treatment included insulin, metformin, or a placebo, with dosages based on standard human care. The research team collected data on the mice’s body weight, analyzed various metabolic parameters and hormones, and investigated molecular signaling pathways in the hypothalamus.
The metabolic status of the mother is very important
“As a result of antidiabetic treatment early in life, we were able to identify changes in offspring weight gain and hormonal status that are highly dependent on the metabolic status of the mother,” Lippert explains. Furthermore, we also observed sex-specific changes in hypothalamic AMPK signaling in response to metformin exposure. Together with the metformin-induced changes in hormone levels investigated, this result indicates that the maternal metabolic status should be considered before initiating treatment of gestational diabetes.
focus on prevention
Rachel Lippert says future treatments for gestational diabetes may require the development of drugs that are universally available and do not cross the placenta. “Given its increasing prevalence, education and prevention measures regarding gestational diabetes are extremely important. The more we can find ways to manage our lifestyle and diet more actively, the more we can take advantage of the potential of gestational diabetes treatment.” It puts us in a position where we can,” Lippert said.
Reference: “Developmental metformin exposure does not rescue physiological deficits derived from early exposure to altered maternal metabolic status in mouse pups” Lídia Cantacorps, Jiajie Zhu, Selma Yagoub, Bethany M. Coull, Joanne Falck, Robert A. Chesters, Katrin Ritter, Miguel Serrano-Lope, Katarina Cherepenchuk, Lee-Sophie Kash, Maya Patterson, Paula Tager, David Baidor-Ansah, Shchita Pandey, Carla Igual-Gil, Annette Brown, Rachel N. Lippert, December 23, 2023, molecular metabolism.
DOI: 10.1016/j.molmet.2023.101860
