AUTHOR=Fyvie Maxwell J. , Gillespie Kathleen M. 

TITLE=The importance of biomarker development for monitoring type 1 diabetes progression rate and therapeutic responsiveness

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1158278

DOI=10.3389/fimmu.2023.1158278

ISSN=1664-3224

ABSTRACT=Type 1 diabetes (T1D) is an autoimmune disease of children and adults in which immune cells target insulin-producing pancreatic β cells for destruction, resulting in a chronic inability to regulate blood glucose levels. The natural history of the T1D is well characterized in childhood. Evidence of two or more autoantibodies to the islet antigens insulin, GAD, IA-2 or ZnT8A in early childhood is associated with high risk of developing T1D. Prediction of risk is less clear in adults and overall, factors controlling progression rate from multiple islet autoantibody positivity to onset of symptoms are not fully understood. An anti-CD3 antibody, teplizumab, was recently shown to delay clinical progression to T1D in high-risk individuals including adults and older children. This represents an important transition in T1D research and therapeutic interventions will require the most accurate assessments of risk and progression rate, as well as robust strategies to accurately monitor the effects of interventions. 
Given their role in risk assessment, islet autoantibodies might appear the most obvious biomarkers to monitor efficacy but clinical trials have shown limited effects although antibodies to Tetraspanin 7 have not been studied in this context. Measurements of beta cell function remain fundamental to assessing efficacy and different models have been proposed. Improved biomarkers are required. While monitoring immune cell subsets is crucially important in monitoring therapies in T1D, in this mini-review, we consider existing established biomarkers including markers of pancreatic function that could be integrated with metabolic markers towards improved strategies to measure outcomes of therapeutic intervention.