Body and mind

Researchers focus on how diabetes in pregnancy affects the unborn child

A new Danish research project will clarify how a mother developing diabetes during pregnancy affects the genetics of her unborn child.

Previous research suggests that people whose mother had diabetes in pregnancy have a markedly increased risk of developing type 2 diabetes themselves, perhaps because of epigenetic changes before birth that predispose a person to later susceptibility to disease.

Danish researchers will test this hypothesis in a new research project.

In the long term, the research project may result in early intervention to prevent the development of type 2 diabetes, perhaps starting in childhood.

“The children of mothers who develop diabetes during pregnancy are eight times more likely to develop type 2 diabetes later in life, and perhaps already in adolescence. We believe that this may result from epigenetic changes, and in this research project we want to identify epigenetic markers we can use in the future to test children to clarify whether special interventions are required to prevent them from developing a dangerous lifestyle-related disease,” explains the researcher behind the new study, Line Hjort, Postdoctoral Fellow, Center for Pregnant Women with Diabetes, Departments of Obstetrics and Endocrinology, Rigshospitalet, Copenhagen.

Line Hjort and her colleagues recently published an article on this topic in The Lancet Diabetes & Endocrinology.

Gestational diabetes is a serious condition

About 3% of pregnant women in Denmark develop gestational diabetes.

The disease is serious and can have major consequences for mothers and their babies.

Gestational diabetes means that babies can become very large, sometimes weighing more than 5 kg at birth, which can make vaginal birth difficult.

In addition, the high birth weight might cause children to struggle with lifestyle-related diseases associated with overweight for the rest of their lives.

Gestational diabetes is also often linked to pre-eclampsia (a disorder starting with high blood pressure and often substantial protein in the urine) and is a risk factor for the woman developing type 2 diabetes later in life.

“Around half of the women who have gestational diabetes develop type 2 diabetes within 10 years of their pregnancy. Gestational diabetes is also common among overweight women, but then it disappears again after giving birth. Nevertheless, this is an early warning signal that the body is under immense pressure, possibly from an unhealthy lifestyle, and pregnancy then pushes the body beyond its limit during this time,” explains Line Hjort.

Many children develop type 2 diabetes

Researchers led by Peter Damm of the Center for Pregnant Women with Diabetes at Rigshospitalet have focused on mothers with diabetes in pregnancy and the consequences for the children for many years. However, this new research project aims to investigate how diabetes in pregnancy affects their unborn children through epigenetic changes.

More specifically, Line Hjort will investigate how diabetes in pregnancy affects their unborn babies epigenetically, predisposing them to develop type 2 diabetes later in life.

Previous research from Rigshospitalet has shown that the children of mothers who develop diabetes during pregnancy are eight times more likely than average to develop type 2 diabetes later in life. This means that more than 20% of these children will develop diabetes or prediabetes by 20 years of age.

“This is an incredibly large percentage, and we know that epigenetic changes can be associated with developing type 2 diabetes. In addition, we have identified 76 epigenetic changes that predispose children to developing type 2 diabetes. This is the background for the research project we have initiated,” says Line Hjort.

Finding a method for screening children for their risk of diabetes

Line Hjort will draw umbilical cord blood from the children born to women with diabetes in pregnancy. She will then test the children over time to see whether they differ epigenetically from other children and whether this changes throughout childhood in a way that can be used to predict whether they will develop type 2 diabetes.

In addition to samples from the umbilical cord blood and later blood tests from the children, Line Hjort will take biopsies from the placenta.

In all of these, she will assess the degree of DNA methylation, which reflects how the genome is structured epigenetically.

In addition to samples from children in Denmark, Line Hjort also has access to data from children in Tanzania and Australia and data from the Danish National Birth Cohort, which has samples of umbilical cord blood from children who are now 14–20 years old.

Overall, these studies should show whether and how diabetes in pregnancy changes the child’s epigenetics and how these epigenetic changes can affect the child’s health throughout life. The goal is to create knowledge that can be used to help people.

“We hope to find epigenetic markers that can be used in screening. If we can identify children with a specific risk profile, examining all the children of mothers with gestational diabetes to determine their risk of developing type 2 diabetes will be very relevant. If the epigenetic risk is high, extra measures must be taken to ensure a healthy lifestyle from the start to minimize the risk. Conversely, some children may not have an increased risk of developing type 2 diabetes even if the mother had gestational diabetes,” says Line Hjort.

Diabetes in pregnancy and epigenetic mechanisms – how the first 9 months from conception might affect the child’s epigenome and later risk of disease” has been published in The Lancet Diabetes & Endocrinology. In 2016, the Novo Nordisk Foundation awarded a grant to co-author Peter Damm, Center for Pregnant Women with Diabetes, Departments of Obstetrics and Endocrinology, Rigshospitalet, Copenhagen for the project The Long-term Effect of Fetal Exposure to Maternal Hyperglycemia and/or Obesity on Cardiometabolic Health.

Line Hjort
​In The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, care and treatment is provided for women, children and reproduction​. The centre houses the following specialities: gynaecology, gynaecological oncology, infertility, reproduction, childbirth, maternity, paediatrics, neonatology, clinical genetics, surgery for children, and specialised anaesthesiology as well as psychological and social services in relation to these areas. The aim of the Juliane Marie Centre is to ensure the highest possible quality of diagnosis, treatment and health care for the benefit of the patients. The goal is to be among the top leading Women’s and Children’s hospitals in the world.