Analysing pancreas biology to enable early detection of type 1 diabetes

Breakthrough T1D UK-funded researcher Professor Kourosh Saeb-Parsy is hunting for the very first signs that type 1 is developing. He thinks subtle changes in pancreas biology hold the key to detecting type 1 earlier than ever before.

The pancreas may reveal the first signs of type 1

Type 1 diabetes develops gradually, with the immune system launching an attack on insulin-producing beta cells long before someone starts experiencing symptoms of type 1. Currently, we can screen people’s blood to look for proteins called autoantibodies, which show type 1 has begun to develop.

Breakthrough T1D UK-funded researcher Kourosh thinks we may be able to see changes in the pancreas of people developing type 1 even before autoantibodies appear in the blood. At the University of Cambridge, he will study pancreas samples in depth to identify features to help diagnose type 1 earlier and track its progression in clinical and research settings.

Why is Breakthrough T1D UK funding this research?

We know that detecting type 1 early reduces the risk of a diagnosis in the emergency condition diabetic ketoacidosis and lowers the long-term risks of diabetes complications. It also gives us time to protect the remaining beta cells that have yet to be destroyed by the immune system.

Immune therapies or immunotherapies are drugs that target the immune system and can interfere with the immune attack in type 1. New immune therapies are emerging from clinical trials, and we hope they will one day be a part of routine diabetes care. For these drugs to be successful, we need to detect type 1 as early as possible, before many beta cells have been lost.

Unique collection of pancreas samples

Kourosh and his research team have a collection of pancreas samples that are representative of the general population, from completely healthy to advanced diabetes. These pancreases are from organ donors whose pancreas wasn’t in good enough condition to give to someone needing a transplant. For example, some were damaged by surgery, while others were donated by someone who had diabetes or an unrelated disease, such as cancer, elsewhere in their body. But these safety issues for transplantation make the samples perfect for teaching us about pancreas biology under different circumstances.

What will the researchers do?

The researchers will look at the biology of their pancreas samples from the genes to the proteins and other molecules they code for. Kourosh also has clinical data for every person who donated their pancreas, which includes their medical history, sex, age, weight, height, smoking, alcohol use and medications. They also have blood samples from some of the donors. The team will use advanced data analysis tools including artificial intelligence and machine learning to study and compare 40 donors without diabetes, 20 donors with type 1 and 20 with type 1.

Comparing features in the pancreas sample with features in the blood sample of the same donor, we can understand what markers we can see in the blood that reflect changes in the pancreas, which we can’t access in living patients. Then, to validate the conclusions the researchers make from this initial comparison, they will analyse a further 50 samples: 10 without diabetes and 20 each with type 1 and type 2.

How will this help people with type 1 diabetes?

This detailed study will give us new insights on how diabetes arises and progresses and help us develop methods to diagnose type 1 earlier. The research will also help identify potential new treatments that may slow or reverse the immune attack behind type 1. Kourosh aims to discover at least one new marker in the pancreas that shows type 1 is developing and that researchers can develop drugs to target.

Therefore, Kourosh’s research will help people at multiple stages of life with type 1. The project will contribute to the design of new treatments for people who already have diabetes that can be used to protect remaining beta cells and transplanted beta cells from donors or grown in a lab. It will also help people who at yet to be diagnosed with type 1 catch the condition an earlier, less dangerous and more treatable stage.

Free access for other researchers

At the end of his Breakthrough T1D UK-funded project, Kourosh will make all the data he has gathered and analysed, as well as any unused pancreas samples in their collection, freely available to other researchers worldwide. This will allow the Breakthrough T1D UK funding to go further because other researchers will be able to study the data and make their own discoveries about the diagnosis and treatment of type 1 diabetes. Such a collaborative approach to research is vital for us to find treatments for type 1 quicker and improve the lives of everyone living with type 1.