{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:07:43Z","timestamp":1775797663854,"version":"3.50.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The IL-1 pathway plays a central role in \u03b2-cell dysfunction; however, the relationship between IL-1\u03b2\/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-1\u03b2\/IL-1Ra ratio differs according to islet autoantibody status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This cross-sectional study included 240 adults with newly diagnosed adult-onset diabetes recruited from primary healthcare facilities. Serum IL-1\u03b2 and IL-1Ra concentrations were measured using enzyme-linked immunosorbent assays, and the IL-1\u03b2\/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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Circulating IL-1\u03b2 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-1\u03b2\/IL-1Ra ratio was significantly higher in autoantibody-positive individuals compared with autoantibody-negative patients (p = 0.030). Among autoantibody-positive participants, the IL-1\u03b2\/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-1\u03b2\/IL-1Ra ratio (OR 1.94, 95% CI 1.10\u20133.44; p = 0.024) and lower basal C-peptide levels (OR 0.50, 95% CI 0.33\u20130.76; p = 0.001) were independently associated with autoantibody positivity. ROC analysis demonstrated modest but statistically significant discriminative performance of the IL-1\u03b2\/IL-1Ra ratio (AUC\u00a0=\u00a00.59, p = 0.030).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dysregulation of the IL-1\u03b2\/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-1\u03b2\/IL-1Ra ratio reflects early inflammatory imbalance, its clinical utility as a standalone biomarker appears limited.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1784582","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T04:26:28Z","timestamp":1775795188000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-1\u03b2\/IL-1Ra ratio dysregulation in islet autoantibody\u2013positive adult-onset diabetes"],"prefix":"10.3389","volume":"17","author":[{"given":"Bibigul","family":"Tleumagambetova","sequence":"first","affiliation":[{"name":"Department of Internal Diseases \u2116 1, West Kazakhstan Marat Ospanov Medical University","place":["Aktobe, Kazakhstan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khatimya","family":"Kudabayeva","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases \u2116 1, West Kazakhstan Marat Ospanov Medical University","place":["Aktobe, Kazakhstan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yerlan","family":"Bazargaliyev","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases \u2116 1, West Kazakhstan Marat Ospanov Medical University","place":["Aktobe, Kazakhstan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorina","family":"Vudu","sequence":"additional","affiliation":[{"name":"The Department of Endocrinology and the Endocrinology Laboratory Nicolae Testemitanu State University of Medicine and Pharmacy","place":["Chisinau, Moldova"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/s41392-024-01951-9","article-title":"Type 2 diabetes mellitus in adults: pathogenesis, prevention and 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