Are Obesity and Diabetes Pre-programmed in the Womb?

Scientists led by Dr. Hubert Preißl and Prof. Andreas Fritsche of the University Hospital Tübingen and the German Center for Diabetes Research (DZD) have currently published a study in "Diabetologia" (Journal of the European Association for the Study of Diabetes), which provides evidence for the first time of an association between maternal insulin action (= insulin sensitivity) and the brain reaction of the child in the womb after the expectant mother has drunk a sweet beverage. This could indicate that the risk for future obesity and diabetes is pre-programmed in the womb.

It is known that diabetes and obesity of expectant mothers may affect the fetal and postnatal development of their respective child. Children of obese mothers or mothers with gestational diabetes have an increased risk for type 2 diabetes and obesity in adulthood, regardless of their genetic background. Furthermore, the prevalence of overweight and obesity and type 2 diabetes is continuing to rise worldwide. The reasons for these changes are unclear, although it is highly likely that environmental influences and epigenetic mechanisms (when environmental factors influence the genes) are involved.

Fetal programming
An important epigenetic mechanism is fetal programming, in which the expectant mother’s exposure to environmental influences can influence the programming of the genes of her child.
In the current study, Preißl and his colleagues showed that the postprandial metabolism of an expectant mother affects fetal brain activity. For this purpose, healthy pregnant women underwent an oral glucose tolerance test. The maternal insulin sensitivity was determined on the basis of the measured glucose and insulin levels in the blood. During the test, the tone-induced fetal brain reactions were determined several times by means of fetal magnetoencephalography.
The researchers found that after 60 minutes, the fetuses of women with higher insulin resistance levels responded more slowly to the auditory stimuli. When the women were divided into two groups based on insulin sensitivity, the mean response of the fetuses of the expectant mothers with higher insulin resistance occurred 283 milliseconds after the tone in comparison to 178 milliseconds in the group with higher insulin sensitivity.

Is there an association between the maternal and fetal insulin levels?
The results supported the hypothesis established nearly 50 years ago by the researcher Jørgen Pedersenn. The team led by Preißl and Fritsche found that expectant mothers with a higher insulin resistance have higher postprandial glucose and insulin levels. When glucose crosses the placenta, these elevated glucose levels can also cause a surplus of insulin in the fetus (hyperinsulinemia). Accordingly, the mother’s high insulin levels may be related to high insulin levels of the fetuses. The authors add: "While it is true that insulin is necessary for normal brain maturation, chronic hyperinsulinemia (in the case of high maternal insulin resistance) may, however, lead to insulin resistance in the fetal brain.”According to the authors, insulin resistance of the fetal brain may result in metabolic imprinting with important consequences for later life. The subsequent effect of hyperinsulinemia on fetal development has already been shown: Compared with newborns of non-diabetic mothers, newborns of diabetic mothers whose glucose levels are poorly controlled have neurophysiological constraints and a greater risk in later life of developing metabolic syndrome, obesity or diabetes mellitus type 2.The authors conclude that lower maternal insulin sensitivity is associated with slower postprandial fetal brain responses. These results provide the first evidence of a direct effect of maternal metabolism on fetal brain activity. These findings may have an impact on nutritional recommendations during pregnancy.

Original publication
Katarzyna Linder et al. Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity; Diabetologia DOI 10.1007/s00125-014-3217-9
Link to publication