In young children with type 1 diabetes (T1D), nearly all insulin-producing cells are destroyed before they can mature, helping explain why the progression of T1D is more aggressive in early childhood.
The study, published in Science Advances, ahead of World Diabetes Day, was funded by the UK Type 1 Diabetes Grand Challenge– a partnership between Breakthrough T1D UK, the Steve Morgan Foundation, and Diabetes UK. This important finding provides valuable information into the wide range of T1D progression and highlights the need for universal T1D screening and early-stage immunotherapies in young children at risk of developing T1D.
T1D is an autoimmune condition, where the immune system attacks and destroys the insulin-producing cells in the pancreas. In young children T1D often progresses more rapidly, increasing the likelihood of medical emergencies such as diabetic ketoacidosis at diagnosis and requiring higher doses of insulin than those diagnosed at an older age.
Until now, scientists had limited tools to study the early development of insulin-producing beta cells. Beta cells are found in ‘clusters’ called islets of Langerhans, or islets, in the pancreas. To date, the majority of cell biology research has focused on the medium-large islets, particularly because small islets are often lost during the isolation process to study individual cells. In young children, approximately under the age of 7, the majority of islets are small and still forming and only contain a few insulin-producing beta cells.
The new study, led by Dr. Sarah Richardson, Associate Professor in Cellular Biomedicine at the University of Exeter in the UK, used cutting-edge scientific techniques to study these small clusters in unprecedented detail. The team analysed rare pancreas samples from more than 250 people of varying ages, both with and without T1D. The samples were accessed from numerous global biobanks including the Breakthrough T1D-funded Network for Pancreatic Organ Donors with Diabetes (nPOD). They looked at how these clusters change as we age and how they are affected by the immune system.
The findings confirm most rapid development of islet cells occur in the first few years of life.
For the first time, the researchers showed that in people with type 1 diabetes, these small clusters (pre-cursors to islets) are almost completely absent, having been destroyed by the immune system. While some people with T1D retained a few large clusters, allowing them to produce small amounts of insulin, this was not the case for those diagnosed at a young age.
Together, the results suggest that the abundant small clusters found in young children are especially vulnerable to the type 1 diabetes immune attack. Their rapid destruction prevents them from maturing, leaving very few insulin-producing cells later in life, while more mature islets in adults are somewhat more resistant to the autoimmune attack and the onset of T1D in adulthood may preserve minor insulin-producing capability.
This research underscores the critical role of these small clusters in healthy pancreas development and opens the door for new treatments to protect children’s clusters of insulin-producing cells, giving them the chance to mature into islets that are less vulnerable to the immune attack. It also strengthens the case that type 1 diabetes screening – particularly in young children is essential for identifying those in the early stages of type 1 diabetes before these crucial cells are lost, (when accompanied by early-stage immunotherapy interventions to prevent the loss of immature islet clusters.)
Breakthrough T1D Canada currently has a $12 million grant co-funded through the Breakthrough T1D-CIHR Partnership to Defeat Diabetes that is funding CanScreen T1D – a single nationally coordinated research network that explores key research questions about the feasibility and acceptability of general population T1D screening in Canada.
Results from this research could help to inform immunotherapies for individuals in early-stage T1D to preserve islet mass and insulin-producing capability.
