The natural history of type 1 diabetes (T1D) progresses through well-characterized stages, from genetic susceptibility through autoantibody positivity to metabolic dysregulation and eventual clinical diagnosis.1,2 This predictable trajectory has historically been viewed as largely inevitable, with screening prompted by the presence of clinical symptoms and therapeutic intervention limited to insulin replacement after substantial β-cell loss.1,2 Recent evidence demonstrates that immune-directed therapies can delay progression when implemented during early disease stages, creating actionable intervention windows before irreversible β-cell depletion occurs.1,2
Autoimmune-mediated β-cell destruction is mediated primarily through T-cell dependent mechanisms, with CD8+ cytotoxic T-cells and autoreactive CD4+ helper T-cells infiltrating pancreatic islets and targeting β-cell specific antigens.2 This mechanistic understanding has enabled development of targeted immunomodulatory approaches that address pathogenic immune responses while preserving broader immune competence.2
One example is teplizumab, an Fc receptor-nonbinding anti-CD3 monoclonal antibody, that modulates T lymphocyte activity to delay beta cell destruction.2 Clinical trials in patients with Stage 2 T1D, characterized by the presence of at least two autoantibodies and dysglycemia without diagnostic hyperglycemia, have demonstrated that teplizumab can preserve β-cell function and delay progression to Stage 3 disease. The largest reported effect was in the first year following treatment, and reported adverse events include spontaneously resolving rash and lymphopenia.2
Studies show that individuals receiving immunomodulatory therapy maintain higher C-peptide levels indicating preservation of beta cells, however effects are thought to fade over time.3 Additionally, coordinate improvements in HbA1c were not found, creating a disconnect in outcome data that warrants further exploration.3 Studies should also include longer follow-up windows, combination therapies, and the effects of maintenance therapy on glycemic control.3
Practical implementation of early-stage intervention requires systematic screening protocols to identify appropriate candidates. Family history, genetic risk assessment, and autoantibody screening enable identification of at-risk individuals during presymptomatic phases.2 The therapeutic implications extend beyond individual patient management to broader public health considerations. Universal screening programs, cascade testing in families with affected members, and integration of T1D risk assessment into routine pediatric care represent potential strategies to operationalize early detection.4 These approaches require careful consideration of psychological impact, cost-effectiveness, and healthcare system capacity, balanced against potential short- and long-term benefits of disease modification.
Take our type 1 diabetes quiz to see how your knowledge compares to your peers.
