Diagnostic Value of Serum Interleukin-9 in Patients with Type 2 Diabetes Mellitus: A Case-Control Study from Basrah, Iraq

Abstract

Background: Type 2 diabetes mellitus (T2DM) is increasingly recognized as a chronic low-grade inflammatory disorder in which immune dysregulation contributes to insulin resistance and disease progression. Interleukin-9 (IL-9), a pleiotropic cytokine of the common γ-chain family, has recently been implicated in metabolic inflammation, but its diagnostic value in T2DM remains inconsistent across studies. Objective: To evaluate serum IL-9 levels in patients with T2DM compared with healthy controls, to examine their correlation with glycemic and clinical parameters, and to determine the diagnostic performance of serum IL-9. Methods: This case-control study enrolled 132 age- and sex-matched participants (49 healthy controls, 83 patients with T2DM) at the Al-Faihaa Specialized Diabetes, Endocrine and Metabolism Center, Basrah, Iraq, between February and September 2025. Serum IL-9 was measured by enzyme-linked immunosorbent assay; glucose, glycated hemoglobin (HbA1c), creatinine, and urinary albumin-to-creatinine ratio (ACR) were also determined. Independent t-test, one-way ANOVA, chi-square test, Pearson correlation, and receiver operating characteristic (ROC) curve analysis were applied, with p<0.05 considered significant. Results: Serum IL-9 was significantly higher in T2DM patients than controls (8.73±6.23 vs 2.22±0.60 ng/mL; p<0.01) but did not differ between patients with and without microalbuminuria (p>0.05). IL-9 correlated positively with HbA1c (r=0.551, p<0.01) and glucose (r=0.389, p<0.01), and negatively with age (r=−0.307, p<0.01) and diabetes duration (r=−0.27, p<0.05). ROC analysis showed good diagnostic accuracy (AUC=0.844; 95% CI 0.767–0.920; p<0.001); at a cut-off of ≥3.706 ng/mL, sensitivity was 80.72% and specificity 100%, with an overall accuracy of 87.88%. Conclusion: Serum IL-9 is significantly elevated in T2DM and closely tracks glycemic burden, with good discriminatory accuracy for distinguishing diabetic patients from healthy controls, supporting its potential as an adjunct diagnostic biomarker pending validation in larger, longitudinal, multi-center studies.