Progression from early-stage to clinical T1DM varies widely, and accurate risk stratification remains a critical unmet need. This prospective analysis from the Fr1da study, published in Diabetes Care, evaluated tools to predict progression to stage 3 T1DM in children.

A total of 211,464 children aged 1.75 to 10 years were screened for islet autoantibodies. Among those identified with early-stage disease, 485 children underwent metabolic staging using OGTT and hemoglobin A1c (HbA1c) criteria based on current American Diabetes Association definitions. Follow-up assessments occurred every 3 to 6 months.

The PLS incorporated HbA1c, 90-minute OGTT glucose, and islet antigen 2 antibody (IA-2A) titers. Multivariable Cox proportional hazards models were also used to derive a non–OGTT-based score.

Among 360 children with stage 1 disease, progression to stage 3 occurred in 105 cases over a median follow-up of 3.3 years. The PLS stratified 2-year progression risk from 43.7% in high-risk children to 4.7% and 0% in intermediate- and low-risk groups. In children with stage 2 disease and a single dysglycemic abnormality, risk ranged from 42.4% to 5.6%.

The non-OGTT-based score identified children with low (1.7%) and moderate (24.6%) 2-year progression risk using IA-2A categories, HbA1c, obesity status, and autoantibody epitope specificity.

These findings show that PLS-based and non-oral glucose tolerance test-based models stratify near-term progression risk and inform monitoring and trial eligibility.