New research indicates popular diabetes drug may impact brain development during pregnancy

Posted byadmin Posted onMarch 31, 2024 Comments0
New research indicates popular diabetes drug may impact brain development during pregnancy

Research indicates that metformin, although beneficial for pregnant females, may not have a positive effect on their offspring, highlighting the complexity of managing gestational diabetes risks and the importance of pursuing preventative strategies.

As cases of gestational diabetes and metabolic disorders increase during pregnancy, prescribing metformin has become more common. Although we know that this oral antidiabetic drug can cross the placental barrier, its effects on the child's brain development remain largely unclear. However, an interdisciplinary team from the German Institute for Human Nutrition Potsdam-Rehbrücke (DIfE) recently showed in a study on mice that, although metformin is beneficial for pregnant females, these positive effects do not extend to their offspring.

The results were published in the specialist journal Molecular metabolism.

Current figures show that around one in six pregnant women worldwide suffer from a special form of diabetes called gestational diabetes. According to the Robert Koch Institute, 63,000 women in Germany were affected by the disease in 2021, and the trend is increasing.
These figures are alarming because excessively high blood sugar levels during pregnancy are associated with negative consequences for mother and child. This increases the risk that affected women will later develop type 2 diabetes and that their children are at higher risk of developing metabolic disorders and being overweight.

Long-term effect of metformin on offspring unclear

For several years, metformin, an oral antidiabetic drug that crosses the placenta, has gained increasing importance as an alternative to insulin administration when lifestyle changes do not produce results during the treatment of gestational diabetes. However, there are currently few studies on the long-term effects of metformin on offspring health. Metformin is known to impact the AMPK signaling pathway, which regulates nerve cell networking during brain development.

The interdisciplinary team of DIfE researchers led by Dr. Rachel Lippert, head of the junior research group, therefore addressed two central questions: Is treatment with metformin only beneficial for the mother or also for the child? child ? And does metformin treatment lead to long-term negative physiological changes in offspring, particularly related to the development of neural circuits in the hypothalamus, a critical region in the regulation of energy homeostasis?

Mouse models shed some light

To answer key 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 using different feeding patterns, with mice receiving either a high-fat diet or a control diet. Antidiabetic treatment of female mice and their offspring took place during the lactation period because this corresponds to the third trimester of human pregnancy in terms of brain development.

Treatment involved insulin, metformin, or placebo, with dosing based on standard human treatments. The research team collected data on the mice's body weight, analyzed various metabolic parameters and hormones, and examined molecular signaling pathways in the hypothalamus.

The mother's metabolic state is crucial

“Thanks to antidiabetic treatment in the early postnatal period, we were able to identify changes in weight gain and hormonal status of the offspring, which critically depended on the metabolic state of the mother,” explains Lippert. Furthermore, sex-specific changes in hypothalamic AMPK signaling in response to metformin exposure were also observed. Coupled with the metformin-induced change in the hormone levels examined, the results indicate that the mother's metabolic state should be considered before starting treatment for gestational diabetes.

Focus on prevention

According to Rachel Lippert, the treatment of gestational diabetes could in the future involve the development of a drug accessible to all and which does not cross the placenta. “Given the increasing prevalence, education about gestational diabetes and preventative measures are of vital importance. If we can find a way to manage lifestyle and diet more proactively, we will be better positioned to realize the potential of gestational diabetes treatment,” says Lippert.

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