Global determinants and preventive intervention strategies in pediatric type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) remains one of the most challenging chronic conditions in pediatrics, arising from a complex interplay of genetic vulnerability, immune system dysfunction, and environmental triggers. Early identification of high-risk children and timely intervention hold the potential to delay or even alter the course of the disease. A systematic review of the literature was conducted through PubMed, Scopus, and Web of Science up to July 2025, focusing on studies of islet autoimmunity, genetics, metabolic markers, and preventive strategies in T1DM. Of 115 studies identified, 32 met the inclusion criteria, encompassing large international cohort studies such as The Environmental Determinants of Diabetes in the Young (TEDDY), Bavarian Autoimmunity Study in the Young (BABYDIAB), and Diabetes Prediction and Prevention Study (DIPP), as well as randomized controlled trials testing preventive approaches, collectively following more than 40,000 children with genetic or family risk of T1DM for periods ranging from 5 to 20 years. Study quality was assessed using the Cochrane risk-of-bias tool. The most consistent predictors of progression to diabetes were the presence of multiple islet autoantibodies, high-risk HLA genotypes including DR3/DR4 and DQ8, and younger age at seroconversion. Children showing early metabolic changes such as dysglycemia, rising HbA1c, or falling C-peptide were at particularly high risk, and continuous glucose monitoring (CGM) proved useful in detecting subtle abnormalities before overt diabetes. Immune-modulating therapies, particularly teplizumab, demonstrated that delaying progression is possible, though responses varied, and only a few intervention trials reached the highest quality standards. For practicing pediatricians, these findings emphasize that risk of developing T1DM is best understood through a combination of genetic and immune markers supported by close metabolic monitoring, with CGM offering an added layer of sensitivity in spotting early dysglycemia. While preventive therapies remain limited, they are promising and highlight the importance of moving towards population-based screening, precise risk assessment, and targeted early interventions that may ultimately change the natural course of T1DM in children.