A research project that aims to answer key questions about how adult-onset type 1 diabetes (T1D) develops has opened for recruitment.
The Type 1 Diabetes Risk in Adults (T1DRA) study, launched to coincide with World Diabetes Day, aims to screen 20,000 UK adults aged between 18 and 70 years, recruited from the general population.
The T1DRA study mirrors the launch of a parallel study of children initiated to mark World Diabetes Day last year, and according to the research team, led by the University of Bristol, it will help put the UK at the forefront of research into T1D.
The researchers explained that although a family history of T1D increases the risk of developing the disease, more than 90% of people with T1D do not have a close relative with the condition.
Autoantibodies May Be Detected Decades Before Symptoms Occur
The T1DRA programme draws on the UK's longest running study of T1D, namely the Bart's Oxford Family study (BOX), funded by Diabetes UK. BOX has been recruiting children with T1D and their close relatives since 1985, and has greatly improved our understanding of the role of autoantibodies in T1D, which can appear in the blood years, or sometimes decades, before any symptoms occur.
A new test to detect autoantibodies to glutamic acid decarboxylase (GAD), the major autoantigen in T1D, is better than previous tests at predicting the risk of T1D, the T1DRA team said. Participants will also be tested for autoantibodies to insulin, islet antigen 2 (IA-2), and zinc transporter 8 (ZnT8).
Early Diagnosis Can Avert Diabetic Ketoacidosis
The rollout of T1DRA follows the launch of the EarLy Surveillance for Autoimmune (ELSA) T1D screening trial for children last year.
A feasibility study of childhood screening noted that autoantibody testing could enable early treatment and avert the development of diabetic ketoacidosis, which otherwise occurs in around a quarter of children with T1D before they have been diagnosed.
The launch of T1DRA means that the UK is now the first country in the world to offer general-population T1D screening in a research setting to both children and adults. ELSA, funded by Diabetes UK and the Juvenile Diabetes Research Foundation, and led by the University of Birmingham, also aims to screen 20,000 participants. According to Diabetes UK, 11,000 children aged 3-13 years have so far enrolled in ELSA, and 1.5% of them have screened antibody-positive for T1D.
Children with one T1D autoantibody have been shown to have a 22% risk of progressing to developing at least two autoantibodies within the next 5 years. For children with two or more autoantibodies, the likelihood of being diagnosed with T1D within the next 5 years is 44%, rising to 85% within the next 15 years, and with an almost 100% lifetime risk of a T1D diagnosis at some point.
New Trial Important for Understanding Autoantibodies in Adult T1D
A spokesperson for Diabetes UK told Medscape News UK: "We don't know yet exactly what these risks look like for adults who have T1D autoantibodies, and T1DRA will be important to help us find answers."
The research team pointed out that over half of new T1D diagnoses are in adults, but its development has mostly been studied in children, so adult-onset type 1 diabetes is "not well understood".
Kathleen Gillespie, professor of molecular medicine at the University of Bristol and lead researcher on T1DRA, said: "This research will help us get a much clearer idea of how many adults in the UK are at risk of T1D." Participants who are found to have islet autoantibodies will be followed up to see how many develop T1D, how quickly they progress to a clinical diagnosis, and whether any genetic, biological, or environmental factors can be identified that are linked with rapid symptom onset.
Innovative Preventive Treatments Imminent
Participants who are found to be at high risk will be offered education and monitoring, and invited to participate in trials of innovative treatments that could prevent or delay the condition. For example, teplizumab, a humanised recombinant monoclonal antibody, has been found to delay T1D diagnosis by an average of 3 years. It was approved by the Food and Drug Administration for use in the United States in 2022, and it is currently being reviewed for approval in the UK.
Several other immunotherapies for people at high risk are currently being tested in clinical trials, the researchers said.
Dr Elizabeth Robertson, director of research at Diabetes UK, said: "We're delighted that the pioneering T1DRA programme is now recruiting, and hope it will offer a better future for adults at high risk of developing T1D. With the ELSA T1D screening study actively recruiting children, the UK is at the forefront of research that will bring us closer to the day when risk of T1D can be spotted early, and a diagnosis prevented."