Pentraxin-3 and Interleukin-18: Potential Biomarkers for the Early Diagnosis and Severity Prediction of Diabetic Foot Ulcer

Abstract

Background/Aim: As the global incidence of diabetes mellitus (DM) rises, diabetic foot ulcers (DFUs) have emerged as a critical complication associated with increased lower-limb amputations, reduced quality of life, and higher mortality rates. Early detection of DFUs is crucial, sparking interest in potential biomarkers. Interleukin-18 (IL-18) and Pentraxin-3 (PTX-3) are known contributors to inflammation, and recent studies suggest their involvement in diabetic foot events. This study aims to compare IL-18 and PTX-3 levels in type 2 DM (T2DM) patients, with or without foot ulcers (FUs), and healthy controls while exploring their association with DFU diagnosis and severity. Methods: Eighty-four males participated in the study, including 28 patients with T2DM with FUs, 28 T2DM patients without FUs, and 28 healthy controls. Individuals with type 1 DM (T1DM) or any other types of diabetes, those with infectious or other chronic diseases, and inflammation (such as chronic inflammation and autoimmune diseases), were excluded from participation. Serum IL-18 and PTX-3 were examined using the ELISA method. Enzymatic and colorimetric techniques were used to investigate fasting blood glucose (FBG), hemoglobin A1c (HbA1c), creatinine, urea, alanine transaminase (ALT), and the lipid profile. Results: The average serum levels of IL-18 and PTX-3 were higher in cases of DFU compared to both T2DM cases and controls (P < 0.0001), with the highest levels observed in the DFU group. There was a statistically significant difference in FBG, HbA1c, urea, and creatinine between the different studied groups. ROC curve results showed that the IL-18 cut-off value for predicting severity in patients with DFU compared to T2DM without DFU is > 124.0 pg/ml (P < 0.0001). Meanwhile, the PTX-3 cut-off value for predicting DFU in patients with T2DM is > 8.67 ng/ml. The level of IL-18 differed significantly across the different groups based on perfusion, extent, sensation, infection, depth, and nephropathy conditions. Conclusion: The results indicate that PTX-3 is a promising biomarker for predicting DFU, while IL-18 is a valuable biomarker for predicting severity.