Type 1 diabetes (T1D) results from destruction of insulin-producing beta cells in the pancreas by the body's own immune system (autoimmunity). It is not fully understood what causes this type of diabetes and why there is variation in age of onset and severity between people who develop the disease. The aim of this work is to study very unusual people who develop T1D extremely young, as babies under 2 years of age (EET1D). The investigators think that, for the condition to have developed that early, they must have an unusual or extreme form of autoimmunity.

Studying people with EET1D will enable us to look at exactly what goes wrong with the immune system because they have one of the most extreme forms of the disease. We may be able to learn a lot about the disease from a small number of rare individuals. We aim to confirm that they have autoimmune type 1 diabetes and then try to understand how they have developed diabetes so young by studying their immune system genes, the function of their immune system, and environmental factors (such as maternal genetics) that may play a role in their development of the disease.

People with diabetes diagnosed under 12 months are very rare, live all over the world. and are usually referred to Exeter for genetic testing. As part of their wider clinical team, we will contact them via their clinician to ask for more information about their diabetes and their family history. We will collect samples to study whether they still make any of their own insulin and whether they make specific antibodies against their beta cells in the pancreas. Separately, we will study their immune system in depth using immune cells isolated from a blood sample. We will then study these cells using cutting edge techniques by Dr Tim Tree at King's College London, by Professor Bart Roep at the Diabetes Metabolism Research Institute Faculty, City of Hope National Medical Center, California (USA), and Dr Cate Speake, Benaroya Research Institute, Seattle (USA). Some of these tests have never been used in people of young ages around the world, so an aim of this project will be to develop methods that can be used to study people even if they live far away.

Additional funding extends the study for a further 3 years (Phase 2) to include recruitment of infants without diabetes, aged 0-6 years, as controls to enable assessment of how the abnormalities found in autoimmune and non-autoimmune diabetes compare to normal early life development of the immune system.