<p>Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic β-cells, leading to chronic hyperglycemia and lifelong dependence on exogenous insulin. Increasing evidence indicates that T1DM is a highly heterogeneous condition driven by complex interactions among genetic, immune, environmental, and metabolic factors, which collectively influence disease prediction, diagnosis, prevention, and treatment. To date, no curative or durable remission-inducing therapy for T1DM is available. Current therapeutic approaches, acknowledging both the central role of the immune system and the emerging contribution of β-cell stress to disease pathogenesis, include targeted immunotherapies, cytokine inhibitors, tolerance-inducing strategies, and β-cell–protective agents. Despite promising advances, highlighted by the approval of teplizumab, achieving the ultimate therapeutic goal in T1DM, namely preventing or halting disease progression, will require closing critical gaps in our understanding of disease etiopathogenesis and heterogeneity to enable individualized, stage-specific interventions. Consequently, the development, implementation, and clinical validation of novel, easily accessible, and measurable biomarkers, capable of stratifying individuals with T1DM and predicting therapeutic responses, represent a high priority. In this context, circulating microRNAs emerge as an attractive class of candidate biomarkers. In parallel, it is essential to integrate autoantibody screening into routine clinical care through structured, population-based programs.</p>