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Diabetes research: can foetuses develop susceptibility to diabetes in uteri?

The measurement of blood glucose levels reveals changes in foetal brain response after a pregnant woman has consumed glucose. The postprandial brain response generated by the unborn children of women with gestational diabetes differs from that of children of women without gestational diabetes. Researchers from Tübingen have been using magnetic encephalography to examine the effect of insulin on the brain and the relationships between gestational diabetes and foetal brain responses.

Schematic representation of the fMEG measurement principle. Left: cross section through the abdomen of a pregnant woman, showing the foetus; right: measurement unit with the sensors of the fMEG shell. The fMEG shell contains 156 sensors and a pregnant woman’s belly fits perfectly into this shell. Ultrasound examination prior to MEG to determine the location of the child and arrange the stimulus sender for sound and light signals. © Tübingen University Hospital

Gestational diabetes is a special type of diabetes that can occur during pregnancy and usually disappears after birth. The disease is characterised by increased insulin resistance. This means that although the hormone insulin is produced following sugar consumption, it cannot control the sugar metabolism effectively. Children born to mothers with untreated gestational diabetes are at risk of becoming overweight and developing metabolic diseases such as diabetes in later life. A research group from Tübingen led by Prof. Dr. Hubert Preißl is investigating these relationships using a method known as foetal magnetic encephalography (fMEG) to measure the brain's magnetic signals.

Preißl, a physicist by training, has been using MEG for a long time to investigate the effect of insulin on the brain. He explains the advantages of the method for investigating foetuses: "fMEG is ideal for measuring the brain activity of foetuses because it is a non-invasive method that detects the signals from the outside through the belly of pregnant women. Foetal brain development can also be investigated using magnetic resonance tomography, although this has the drawback that both foetus and mother are exposed to magnetic fields." The fMEG used in Tübingen has 156 sensors distributed over a concave shell shaped like the abdomen of a pregnant woman. "We have 156 channels to record the biomagnetic signals created in the maternal abdomen. These signals contain information from the foetal and maternal hearts, foetal brain, uterine muscles etc. The different signal types can be separated and we are thus able to partial out the signals of the maternal and the foetal heart," explains Preißl.

fMEG enables the non-invasive measurement of foetal brain activity

Prof. Dr. Hubert Preißl became professor for central nervous causes of type 2 diabetes in the Faculty of Pharmacy and Biochemistry at the University of Tübingen in the 2015 summer semester. © University of Tübingen/Friedhelm Albrecht

Together with Prof. Dr. Andreas Fritsche from the Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry at Tübingen University Hospital and the University Women's Hospital in Tübingen, Preißl carried out a study using fMEG that showed that foetal brain responses to auditory stimuli were slower in the children of women with gestational diabetes than in the children of women in a control group after all the women had drunk a glucose solution. This possibly indicates that foetal brain function is affected by maternal metabolism. Preißl assumes that increased glucose concentration in the women also leads to an elevated insulin concentration in the foetuses. In previous studies, Preißl and his colleagues used MEG to show that insulin has an effect on brain activity, especially in the areas that influence eating behaviour. "It has been known since the 1970s that the brain contains insulin receptors. Insulin affects several brain regions, including the hypothalamus which controls eating behaviour as well as areas in the frontal cortex where cognitive control and the reward system are located," says Preißl.

Preißl's theory is that the maternal and foetal sugar and insulin levels are elevated in pregnant women with gestational diabetes mellitus, and that these children develop resistance to insulin in uteri. After birth, the children of mothers with gestational diabetes mellitus are at greater risk of becoming overweight and developing diabetes and other metabolic disorders such as metabolic syndrome. Preißl says that it is still too early to establish causal relationships, but he believes that this will be possible. "Our research is still in its infancy, especially as far as the long-term effects of gestational diabetes on children is concerned. In addition, fMEG is currently not suitable for diagnostic examinations. In our study, which involved pregnant women with gestational diabetes mellitus and pregnant women with normal glucose tolerance, we were able to show for the first time that maternal postprandial glucose metabolism influences foetal postprandial brain activity. We will continue to investigate this in greater detail," noted the researcher.

Predisposition for metabolic diseases might already develop in foetuses

In summer 2009, the first foetal magnetic encephalography (fMEG) centre for the investigation of functional brain development in foetuses was opened at Tübingen University Hospital. The device allows the pregnant women to assume a relaxed position. © Tübingen University Hospital

Preißl is well placed to carry out his research. In April 2015, he was appointed professor for central nervous causes of type diabetes, which is part of the Faculties of Pharmacy and Biochemistry. He is also head of the Metabolic Neuroimaging research group at the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen. Since 2011, he has been a member of the CIN (Centre for Integrative Neuroscience) excellence cluster and since 2007, scientific director of the Centre for Foetal Magnetic Encephalography in Tübingen. However, crucially important for his work is his affiliation to the BMBF-funded German Centre for Diabetes Research (DZD). The DZD pursues translational research focused on finding new strategies for diabetes prevention and therapy. "Our work is so successful because different disciplines and research institutions work together on an equal footing. In Tübingen, this is reflected in cooperative projects involving Prof. Fritsche and Prof. Häring from the Department of Internal Medicine at Tübingen University Hospital, Prof. Wallwiener and Dr. Kiefer-Schmidt from the University Women's Hospital in Tübingen, and Prof. Brüning from the Max Planck Institute for Metabolic Research in Cologne," says Preißl.

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/diabetes-research-can-foetuses-develop-susceptibility-to-diabetes-in-uteri