IL-1β/IL-1Ra ratio dysregulation in islet autoantibody–positive adult-onset diabetes

Background: The IL-1 pathway plays a central role in β-cell dysfunction; however, the relationship between IL-1β/IL-1Ra imbalance and islet autoimmunity in newly diagnosed adult-onset diabetes remains insufficiently defined. This study aimed to evaluate whether dysregulation of the IL-1β/IL-1Ra ratio differs according to islet autoantibody status. Methods: This cross-sectional study included 240 adults with newly diagnosed adult-onset diabetes recruited from primary healthcare facilities. Serum IL-1β and IL-1Ra concentrations were measured using enzyme-linked immunosorbent assays, and the IL-1β/IL-1Ra ratio was calculated as an index of inflammatory regulation. Islet autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein-2 (IA-2A), zinc transporter 8 (ZnT8A), and islet cells (ICA) were determined using standardized ELISA assays. Associations were evaluated using nonparametric tests, multivariate logistic regression, and receiver operating characteristic (ROC) analysis. Results: Circulating IL-1β concentrations did not differ between autoantibody-positive and autoantibody-negative individuals. In contrast, IL-1Ra levels were significantly lower in autoantibody-positive patients (p = 0.029). Consequently, the IL-1β/IL-1Ra ratio was significantly higher in autoantibody-positive individuals compared with autoantibody-negative patients (p = 0.030). Among autoantibody-positive participants, the IL-1β/IL-1Ra ratio was significantly higher in individuals with single autoantibody positivity compared to those with multiple autoantibodies (p = 0.018), indicating a non-linear relationship between autoimmune burden and inflammatory imbalance. In multivariate analysis, a higher IL-1β/IL-1Ra ratio (OR 1.94, 95% CI 1.10-3.44; p = 0.024) and lower basal C-peptide levels (OR 0.50, 95% CI 0.33-0.76; p = 0.001) were independently associated with autoantibody positivity. ROC analysis demonstrated modest but statistically significant discriminative performance of the IL-1β/IL-1Ra ratio (AUC = 0.59, p = 0.030). Conclusion: Dysregulation of the IL-1β/IL-1Ra ratio is evident at the time of diabetes diagnosis and varies according to islet autoantibody status. The observed non-linear pattern, with a higher ratio in single autoantibody positivity, suggests stage-dependent inflammatory regulation and supports the concept of immunometabolic heterogeneity in adult-onset diabetes. While the IL-1β/IL-1Ra ratio reflects early inflammatory imbalance, its clinical utility as a standalone biomarker appears limited.