IL-1β/IL-1Ra Ratio Dysregulation in Islet Autoantibody–Positive Adult-Onset Diabetes

• Objective: To examine whether dysregulation of the IL-1β/IL-1Ra axis differs by islet autoantibody status in adults newly diagnosed with adult-onset diabetes.
• Design: Cross-sectional evaluation of IL-1 pathway markers in a community-based, primary-care–recruited cohort.

• Sample: 240 adults with newly diagnosed adult-onset diabetes.
• Measurements: Serum IL-1β and IL-1Ra were quantified by enzyme-linked immunosorbent assays; the IL-1β/IL-1Ra ratio was computed as an index of inflammatory regulation.
• Autoimmunity assessment: Islet autoantibodies assessed via standardized ELISAs for GADA, IA-2A, ZnT8A, and ICA.
• Analyses: Associations analyzed with nonparametric tests, multivariate logistic regression, and ROC analysis to evaluate discriminative capability.

• IL-1β levels: No difference between autoantibody-positive and autoantibody-negative groups.
• IL-1Ra levels: Significantly lower in autoantibody-positive individuals.
• Ratio findings: The IL-1β/IL-1Ra ratio was higher in autoantibody-positive participants than in autoantibody-negative participants.
• Autoantibody burden: Among autoantibody-positive participants, the ratio was higher in those with a single autoantibody compared with those with multiple autoantibodies, indicating a non-linear relationship between immune burden and inflammatory imbalance.

Lower basal C-peptide also emerged as an independent correlate (OR 0.50; 95% CI 0.33–0.76; p = 0.001).

• Multivariate context: A higher IL-1β/IL-1Ra ratio independently associated with autoantibody positivity (odds ratio 1.94; 95% CI 1.10–3.44; p = 0.024).
• Predictive performance: ROC analysis showed the ratio had modest discriminative ability for autoantibody positivity (AUC 0.59; p = 0.030).

• Pattern of dysregulation: Dysbalance in the IL-1β/IL-1Ra axis is evident at diagnosis and differs by islet autoantibody status, with a higher ratio particularly in autoantibody-positive individuals.
• Autoimmune burden non-linearity: A single autoantibody presence associates with a higher ratio than multiple autoantibodies, suggesting complex, stage-dependent inflammatory regulation.
• Practical relevance: The IL-1β/IL-1Ra ratio reflects early inflammatory imbalance but shows limited utility as an isolated biomarker for clinical decision-making based on current evidence.

• Not reported: Longitudinal outcomes, dynamic changes in IL-1 pathway markers over time, and how these relationships translate into clinical endpoints.
• The modest AUC indicates limited standalone diagnostic value; whether combining with other biomarkers or clinical features would improve utility remains uncertain.