Tracking the early-life triggers of type 1 diabetes

Researchers at the University of Adelaide are leading a national collaboration that has been collecting tens of thousands of biological samples from pregnant mothers and their babies in an attempt to discover how genetics and early-life environmental exposures contribute to the development of type 1 diabetes.

Type 1 diabetes develops when the body’s natural immune system starts to attack our insulin-producing cells in the pancreas. Without insulin, which normally tells the body to start breaking down sugar from our food, a person has no way of maintaining their blood sugar levels and can quickly become very sick. To help stabilise their blood sugar levels, people with type 1 diabetes must inject themselves with insulin every day.

While treatment for type 1 diabetes is well-established, we still don’t understand why the immune system suddenly decides to start attacking the pancreas cells in the first place. Understanding this could lead to new treatments that could prevent type 1 diabetes from developing at all.

Importantly, researchers have narrowed down that the elusive triggers of type 1 diabetes are probably events or exposures that occur very early in a person’s life - potentially before they are even born.

Armed with this knowledge, University of Adelaide researchers based at the Robinson Research Institute and the Women’s and Children’s Hospital established the Environmental Determinants of Islet Autoimmunity (ENDIA) study in 2013. The study was expanded to eight other hospitals across five Australian states shortly thereafter.

The study reached its recruitment target of 1,500 participants Australia-wide in 2019, and researchers have so far collected 11,000 faecal samples, 13,000 tongue swabs, and 9,000 tubes of blood. They are also tracking other factors such as food or nutrient exposures and body weight. The study will continue to collect these data until the youngest child turns 10 in 2030.

In 2022 and beyond, the researchers must now begin the monumental task of analysing their thousands of samples and searching for links between their findings and the development of type 1 diabetes in the participating children. All the children enrolled in ENDIA have a family member already diagnosed with type 1 diabetes so their genetic risk of developing the disease is higher.

Excitingly, the ENDIA samples have already been used to make several important discoveries. Women with type 1 diabetes experience different types of viral infections during pregnancy compared to women without type 1 diabetes, and those babies born to mothers with the disease also have different viral infections in their first year of life. On top of this, women with type 1 diabetes also harbour different populations of gut bacteria during pregnancy.

What’s next?

As the team sorts through their samples, they plan to compare factors such as the types of viruses each participant has been exposed to, the kinds of bacteria and fungi living in their gut, and how their white blood cells are functioning. They’ll also study the genes that control how a person responds to all of these environmental exposures.

These studies will reveal new ideas about what causes type 1 diabetes to develop during a person’s early life, leading to new strategies that allow us to prevent the disease developing in the future.

The ENDIA Study is supported by JDRF Australia, the recipient of the Commonwealth of Australia grant for Accelerated Research under the Medical Research Future Fund, and with funding from the Leona M. and Harry B. Helmsley Charitable Trust. In addition, support has been provided by The National Health and Medical Research Council of Australia, JDRF International, and Diabetes SA.