Why is type 1 diabetes more aggressive in young children?

By adopting new histological approaches to examine sections of pancreas tissue, investigators led by Professor Sarah Richardson have gained new insights into how type 1 diabetes develops in individuals of different ages. Their findings have important implications for future screening and treatment strategies.

Type 1 diabetes is an autoimmune disease in which immune cells selectively target pancreatic beta-cells, which produce insulin. In young children, typically under 7 years, the destruction of beta-cells progresses rapidly, increasing the likelihood of DKA at diagnosis and making the condition more difficult to manage.

In a healthy pancreas, beta-cells are classically recognised as being situated within islet structures. However, recent advances in imaging have captured an abundance of small clusters of endocrine cells outside of these islets. These “endocrine objects” (EOs) have not been widely studied.

In its study, Professor Richardson’s team used innovative techniques to analyse sections of pancreas from donors of varying age and diabetes duration, both with and without type 1 diabetes. They confirmed the presence of small, insulin-positive EOs in tissue from donors without diabetes, and that they comprise most of the pancreatic endocrine area in early life. A pronounced shift towards larger EOs was observed with increasing age.

By contrast, in samples from donors with type 1 diabetes, the small EOs were virtually absent. While some retained a few large clusters that could produce small amounts of insulin, this was not the case for those diagnosed at a very young age.

By establishing that insulin-producing clusters play a critical role in healthy pancreas development and explaining why type 1 diabetes in the very young is so aggressive, the potential for new treatment strategies is opened. Protecting these small clusters would provide the opportunity for them to mature into large clusters that are less vulnerable to immune attack, potentially delaying the need for insulin therapy. The findings also strengthen the case for screening individuals at risk of type 1 diabetes.

The full study can be read here.