Research questions to be addressed in this study
More than half of type 1 diabetes cases are diagnosed in adulthood and the majority of these occur in individuals with no family history, yet the natural history of adult-onset type 1 diabetes (T1D) has never been explored. The work described in this application will
• Determine the frequency of islet autoimmunity in UK adults by screening 40,000 members of the adult general population for risk of T1D.
• Invite to long-term monitoring “at risk” individuals (single and multiple autoantibody positive) from the general population. A comparator population of “at risk” adult first degree relatives from the Bart’s Oxford (BOX) study and UK TrialNet will be monitored in parallel. This will prepare the way for the T1D community to learn how to interpret risk in adults, both general population and first-degree relatives.
• Examine islet autoantibody characteristics, genetic susceptibility and pancreatic function to predict Slow Progressors
• In a blinded analysis, test whether the individuals identified have distinct immune profiles (antigen-specific CD8 T cells responses absent, increased Regulatory T cell frequency with decreased suppressive capacity and Increased expression of CD95 on B cells) compared with progressors and age-matched controls)