Viral triggers, ticks to tackle the immune system and a smart coat for insulin: Latest type 1 diabetes research

At the Type 1 Diabetes Grand Challenge, we support cutting-edge research aimed at bringing us closer to better treatments, and potentially, a cure. The research teams we fund are leaders in the field and their latest discoveries, highlighted here, are contributing to global efforts to transform the treatment of type 1 diabetes.  

Connection between a common virus and type 1 diabetes

The development of type 1 diabetes is caused by a complex interplay of genetic and environmental factors, which trigger the immune system to turn on and destroy insulin-producing beta cells. The Type 1 Diabetes Grand Challenge is investing in research to learn more about precisely what goes wrong and how this process unfolds.

An international research team, including our Senior Research Fellow Professor Sarah Richardson, has just published the strongest evidence to date that enteroviruses play a role in the development of type 1 diabetes.

They studied pancreas samples from nearly 200 donors to check for signs of enterovirus infections. These included samples from people with and without type 1 diabetes, as well as individuals who had type 1 diabetes autoantibodies – early immune warning signals that indicate a high risk of developing the condition in the future.

They reported that signs of enterovirus infection were most common in people with type 1 diabetes who still had some functioning beta cells. Infections were also present in people with autoantibodies, but much less common in those without diabetes or in people with type 1 whose beta cells had already been completely destroyed.

A key finding was the presence of a protein made by the enterovirus, called VP1. The researchers found VP1 was strongly linked to high levels of HLA class I molecules. These are markers of an early immune system response in the pancreas. This is the first time these viral and immune markers have been found together – including in the early stages of type 1 before a diagnosis.

These findings offer the strongest evidence to date that enteroviruses may trigger or accelerate the onset of beta cell destruction in early type 1 diabetes. A clearer understanding of their role could lead to new approaches that target the immune processes they influence — potentially slowing or even preventing type 1.

‘Ticking’ beta cell protection

One part of a solution to curing type 1 diabetes is to transplant beta cells, either donated or grown in labs, into people with type 1 so they could produce their own insulin again. However, the immune system is primed to attack the new cells too. This happens partly because the transplanted cells release chemokines—chemical signals that attract immune cells. Blocking these signals is difficult, as there are many different types.

Scientists have discovered that ticks produce proteins called evasins that can block several of these signals at once. Professor Shoumo Bhattacharya’s team has studied these evasin proteins and identified the specific peptides that have this powerful blocking ability. They’ve established a new method that allows them to test many versions of these peptides rapidly, and pinpointed those that work best at calming the immune response.

Published in Communications Biology, these innovative findings lay the groundwork for Professors Shoumo Bhattacharya and David Hodson’s Grand Challenge project. They aim to use these peptides to help protect new beta cells from immune attack after being transplanted. This could create a safer alternative to immunosuppressive drugs and improve the success of beta cell therapies for type 1 diabetes.

Giving insulin a smart coat

Professor Zhen Gu’s team at Zhejiang University in China has developed a new insulin delivery system, called i-crystal, as reported in their latest publication in Nature Nanotechnology.

Designed to help people with type 1 diabetes keep blood sugar levels within target range, the system uses specially coated insulin crystals that release insulin slowly and steadily. The coating is a unique membrane that enables the crystals to respond precisely to changes in blood sugar and ketone levels. This means insulin is only released when blood sugar levels rise and stops when it drops,  helping people with type 1 avoid highs (hypers) and lows (hypos).

Early tests show that i-crystal could help regulate blood sugar levels for over a month in mice after just one injection, and for more than three weeks in minipigs after five daily doses. This suggests this delivery system could reduce the need for frequent injections and make daily diabetes management easier.

If successful, i-crystal could offer a safer, longer-lasting, and more adaptable form of insulin therapy for people living with type 1 diabetes.