Identification of Peripheral Blood Endotypes Associated With Age in Pediatric Type 1 Diabetes

Aims: This study aimed to identify age-related peripheral immune endotypes in pediatric patients with type 1 diabetes (T1D) at disease onset and assess their metabolic control 1 year post-diagnosis. Methods: Immune cell subpopulations (T and B lymphocytes, myeloid cells, and natural killer [NK] cells) were analyzed via multicolor flow cytometry in pediatric T1D patients and age- and sex-matched controls, grouped as <7 years, 7-12 years, and >12 years. Sociodemographic, clinical, and metabolic data were collected, including autoantibodies, bicarbonate (HCO₃), C-peptide, HbA1c, and time in range (TIR), with follow-up for 1 year to evaluate partial remission (PR) likelihood and metabolic control. Results: Patients <7 years showed reduced regulatory immune cells (memory/activated regulatory T lymphocytes (Tregs), regulatory B cells, and Th17) and more severe disease onset (shorter symptoms, greater acidosis, and lower C-peptide). Ages 7-12 exhibited increased memory B cells, particularly the unswitched ones. Myeloid cells showed no significant variation in T1D, despite age trends in controls. Anti-insulinoma-antigen 2 (IA2) titers were lower in patients >12 years, while anti-glutamic acid decarboxylase 65 (GAD65) positivity remained constant. Younger patients had lower PR rates and poorer glycemic control at 1 year. Conclusions: Younger patients face greater immune dysregulation and β-cell loss, while older patients show better immune maturity and metabolic outcomes. These differences underline the need for age-specific T1D therapies.