Type 1 diabetes (T1D) is the most common chronic metabolic disease in childhood, yet it can occur at any age. Epidemiological data indicate that more than half of the new T1D cases are adults. While there are clear differences in the clinical course of young- compared to adult-onset T1D with a shorter pre-symptomatic period, higher frequencies of autoantibodies, a more aggressive presentation, and faster progression to exogenous insulin, our knowledge on the underlying determinants is limited.
In this project, we aim to identify, in young- and adult-onset T1D, distinct biomarkers that would be predictive and prognostic of promising disease-modifying therapies to halt beta cell destruction. We propose a translational approach in which we first will take advantage of the non-obese diabetic (NOD) mouse model and use state-of-the-art multi-omics technologies (i.e., multiparameter flow cytometry, single-cell CITE-sequencing, and spatial transcriptomics and proteomics) to discover key age-related pathogenic processes that will be validated in a human dataset and bio-samples available via large consortia. Next, we hope to find predictive and prognostic biomarkers of anti-CD3 and low-dose ATG therapies in young- and adult-onset T1D by translating preclinical observations from mice to humans. These findings could revolutionize clinical trial design, paving the way to tailor interventions to specific age groups and guide combination therapies and adaptive trial designs.
Discover the project here.