Children develop type 1 diabetes differently due to the activation of different genes

In a study co-funded by JDRF and Diabetes UK, researchers identified 13 genes involved in immune responses, which are activated specifically in people who develop type 1 diabetes at a young age. The signalling pathways linked to these genes are potential targets for new therapies to prevent type 1 in young children.

The researchers compared pancreas samples

A team of researchers from the universities of Lincoln, Exeter and Nottingham Trent looked at 36 pancreases donated by people with and without type 1 diabetes. They took a sample from each pancreas and looked for differences in the activity of genes that control immune responses.

Researchers found differences in the genes

Professor Sarah Richardson, a researcher at the University of Exeter who worked on this project, said: “We looked at 750 genes that are associated with autoimmune inflammation, which is a condition where the body’s immune system mistakenly attacks its own cells. We found that some of these genes were changed in people with type 1 diabetes compared to those without the disease.

What was particularly fascinating was that 13 of these genes showed different levels of activity between individuals diagnosed with type 1 below aged 12 compared to those diagnosed during their teenage years or later. This suggests that the process of developing the condition may be different in early childhood compared to later in life.”

What do these results mean?

Lead investigator, Dr Michael Christie at the University of Lincoln, said: “The incidence of type 1 diabetes is increasing fastest in very young children. The findings from our study are important as they identify several signals used by the immune system to activate immune cells that are increased in the pancreas only in people developing type 1 at a young age. In the pancreas, these signals may intensify the immune responses that destroy insulin-producing cells, leading to type 1 developing at a young age.”

Potential new treatments for type 1

Michael said: “Detecting these immune system signals in people already identified from screening programmes as being at risk of diabetes may be indicative of early onset of type 1. The biological pathways these signals use are potential targets for treatments to slow or block the progression of type 1 diabetes.”

Different treatments for different people with type 1

Immune therapies like teplizumab are racing through clinical trials and becoming a reality for people with type 1. By understanding how immune responses differ in different people, we can give people the treatment that will be most effective for them.

Professor Sarah Richardson said: “Understanding disease differences is crucial for choosing the right immunotherapies in the future, ensuring that therapies are targeted correctly to each individual. This research suggests that children may respond to particular immunotherapies differentially according to their age at diagnosis.”

Separate subtypes of type 1

We are learning from projects like this that there are subtypes of type 1 diabetes, referred to scientifically as ‘endotypes’. The pattern of damage caused by the immune system in the pancreas differs between people who develop type 1 at different ages. This latest research shows that these differences are due to different genes being activated in younger people.

Professor Sarah Richardson’s ongoing research

Sarah will continue her exciting research as one of the Senior Research Fellows in the Type 1 Diabetes Grand Challenge, our £50 million research partnership with the Steve Morgan Foundation and Diabetes UK. Part of her multi-million-pound project will investigate how the immune system attack differs between different individuals with type 1.

Head to the Grand Challenge website to read more about Sarah’s Senior Research Fellowship project.

Read the full research paper, published in Diabetic Medicine.