Biomarkers of partial remission in paediatric type 1 diabetes: β-cell stress, immune-metabolic remodelling, and translational priorities-a narrative review.

BACKGROUND AND OBJECTIVE: Partial remission after diagnosis of paediatric type 1 diabetes (T1D) is characterised by improved glycaemic control, lower insulin requirements and residual endogenous insulin secretion, but its onset, depth and duration vary substantially between children. Standard clinical indices such as HbA1c, insulin dose-adjusted HbA1c (IDAA1c), C-peptide and continuous glucose monitoring (CGM) metrics capture functional status but provide limited mechanistic information. This narrative review summarises candidate biomarkers that may explain heterogeneity in partial remission and support remission-focused translational studies.

METHODS: PubMed, Embase, Web of Science and the Cochrane Library were searched for English-language articles published from 1 January 2000 to 31 October 2025. Priority was given to paediatric and adolescent studies, longitudinal cohorts spanning diagnosis and the first year after onset, and studies addressing partial remission, IDAA1c or early C-peptide decline. Mixed-age/adult cohorts and experimental studies were included selectively when they informed biological interpretation.

KEY CONTENT AND FINDINGS: Candidate biomarkers can be organised into two intersecting axes: a β-cell axis reflecting stress, dysfunction and death, and an immune-metabolic axis reflecting immune regulation, inflammatory activity and systemic metabolic adaptation. The proinsulin-to-C-peptide ratio, unmethylated INS-derived cell-free DNA, selected circulating or extracellular vesicle-associated microRNAs, immune-cell phenotypes, soluble mediators and compact omics-derived signatures have varying levels of paediatric evidence. These biomarkers are best interpreted as mechanistic complements to IDAA1c, C-peptide and CGM metrics rather than as replacements for established functional endpoints. Across biomarker classes, associations are modest, assay methods are heterogeneous and external validation remains limited.

CONCLUSIONS: No single biomarker is currently ready for routine clinical staging of partial remission in paediatric T1D. The most realistic translational path is prospective validation of standardised, parsimonious biomarker panels interpreted alongside IDAA1c, C-peptide and CGM endpoints to improve risk stratification, endotype enrichment and pharmacodynamic monitoring in remission-focused trials.