Evaluation of pro-inflammatory cytokines IL-15, IL-18, and IFN-γ as diagnostic biomarkers and their relationship with glycemic control in type 1 diabetes mellitus

Abstract

Background. Type 1 diabetes mellitus (T1DM) is a persistent autoimmune condition marked by the T-cell-mediated obliteration of insulin-secreting pancreatic beta cells. This mechanism is governed by a complex network of pro-inflammatory cytokines that facilitate chronic inflammation and immune-mediated cell death. Comprehending the interaction between these cytokines and glycemic regulation is crucial for enhancing diagnosis and disease management. The study purposed to evaluate the levels of pro-inflammatory cytokines (IL-15, IL-18, and IFN-γ) in patients with type 1 diabetes mellitus to determine their potential as biomarkers for disease prediction and their correlation with glycated hemoglobin (HbA1c). Materials and methods. Case-control research was performed with 100 T1DM patients from southern Iraq and 100 healthy controls between January and March 2026. Serum cytokine concentrations were quantified with the enzyme-linked immunosorbent assay. Statistical methods, comprising Pearson correlation and receiver operating characteristic (ROC) curve analysis, were employed to evaluate the correlations between parameters and diagnostic accuracy. Results. The study showed the patients with T1DM demonstrated markedly elevated levels of IL-15, IL-18, and IFN-γ compared to the control group (p < 0.01). A notable positive correlation exists between HbA1c and all three cytokines, with the most robust association identified for IFN-γ (r = 0.478, p = 0.000). Furthermore, IFN-γ levels were significantly elevated in male patients and among younger age groups (≤ 10 years). ROC analysis demonstrated that all three cytokines serve as strong predictors for T1DM, exhibiting area under the curve values between 0.903 and 1.00. Conclusions. The results demonstrate that IL-15, IL-18, and IFN-γ contribute synergistically to the pathogenesis of T1DM and are significantly associated with chronic hyperglycemia. Cytokines function as sensitive and specific biomarkers indicate that their integration into clinical screening protocols may improve early detection and monitoring of autoimmune inflammation in T1DM patients.