Breakthrough T1D Request for Applications: Beyond Pediatrics: Advancing Early Detection in Adult-Onset Type 1 Diabetes

Funding over a maximum of three years for studies aiming to improve adult diagnosis of type 1 diabetes, with emphasis on advancing understanding of the distinct clinical and immunological features in the early stages of disease.

Breakthrough T1D, based in the United States, is an international organisation that funds innovative research in pursuit of its mission to advance the treatment, prevention and cure of type 1 diabetes (T1D). The Breakthrough T1D research strategy is based on two pillars: curing T1D and improving the lives of individuals with T1D, and focuses on five areas: early detection, disease-modifying therapies, cell therapies, improving lives and growing the T1D research community.

Breakthrough T1D has issued a second 2025 RFA under its Early Detection of T1D research portfolio – ‘Beyond Pediatrics: Advancing Early Detection in Adult-Onset Type 1 Diabetes‘ – to offer funding over a maximum of three years for studies aiming to improve adult diagnosis of type 1 diabetes, with emphasis on advancing understanding of the distinct clinical and immunological features in the early stages of disease.

The Breakthrough T1D Early Detection research portfolio aims to apply understanding of the aetiology, progression, and autoimmune pathogenesis of T1D to improve detection and diagnosis of the disease, especially in historically understudied populations such as those with adult-onset T1D.

While T1D is typically defined as a childhood disease, approximately 62% of new T1D diagnoses worldwide occur in adults at or above 20 years of age. Around 40% of adult diagnoses are misclassified as type 2 diabetes (T2D), leading to delays in appropriate treatment and care. Understanding disease progression requires distinguishing between early stages (Stage 1 and 2), where individuals show the presence of persistent multiple autoantibodies without or with dysglycaemia, and Stage 3 (clinical diagnosis) when symptoms appear due to significant beta cell loss and impaired glycaemic control.

Emerging evidence also indicates that adult-onset T1D may differ in its clinical presentation, rate of progression, and underlying immunological characteristics compared to paediatric T1D, underscoring the need for dedicated research in this area to address knowledge gaps and improve the diagnosis, treatment, and long-term management of adult-onset T1D.

Gaining deeper understanding of disease progression and the distinct clinical and immunological features of T1D in adults may accelerate clinical research and facilitate access to emerging disease-modifying therapies that have the potential to delay or prevent the onset of clinical symptoms. Accordingly, Breakthrough T1D is inviting proposals for research studies with capacity to address and inform the identified knowledge gaps and enhance diagnosis, treatment, and management of the condition with the most appropriate care.

Knowledge generated through this RFA may ultimately inform regulatory decisions and contribute to the development of screening and monitoring guidelines in adults.

Research proposals are encouraged that address one or more of the following areas, including, but not limited to:

• Immune Activation and Autoimmunity: The autoimmune process in adult-onset T1D appears to exhibit distinct patterns of immune activation compared to paediatric cases, including differences in immune cell subsets, cytokine profiles, and the timing and magnitude of the immune response.
  • Proposed studies should aim to characterise these adult-specific immune signatures and investigate their relationship to clinical progression, treatment requirements, and therapeutic responsiveness.
  • Research should leverage established datasets and biobanks with adult-onset T1D cohorts to validate findings across diverse populations.
  • These efforts will be critical to informing the design and timing of disease-modifying therapies targeted at the early stages of T1D in adults.
• Islet Pathology and Beta Cell Function: Adults diagnosed with T1D often retain greater residual beta cell function at onset than children, suggesting slower disease progression and potential differences in islet pathology.
  • Research should explore the mechanisms underlying these differences, including the pace of beta cell destruction and the regenerative capacity of the adult human pancreas, with implications for therapeutic timing and response.
• Autoantibodies and Biomarker Validation: In early-stage T1D, adults are more likely to test positive for GADA, while children more commonly exhibit IAA, IA-2A, or ZnT8A.
  • Proposals are sought that aim to better characterise and validate alternative autoantibodies and other established biomarkers of disease progression through Stages 1 to 3 in adults, with the goal of improving diagnostic accuracy and stratification of progression, including adults with slow disease progression.
• Accuracy in Misdiagnosis and Diagnostic Tools: proposals are sought that aim to address the misdiagnosis of adult-onset T1D, including efforts to distinguish it from T2D through the integration of autoantibodies, C-peptide, and clinical features.
  • Proposals may also include the analysis of existing electronic health record (EHR) data to identify diagnostic patterns and improve classification strategies.
• Epidemiology Studies: Evidence suggests that while a family history of T1D increases risk at all ages, the strength of this association appears to be greater in childhood-onset cases.
  • Studies are sought that aim to advance understanding of the epidemiology of adult-onset T1D using existing databases, as this area remains poorly defined. Projects examining incidence, prevalence, and age-related trends are encouraged to help clarify population-level risk factors.