Association Between Three Systemic Inflammatory Biomarkers and Diabetic Foot Ulcer: A Cross-Sectional Study and a Clinical Retrospective Study.

Background: This study aimed to investigate the association between systemic inflammatory biomarkers-specifically the systemic inflammatory response index (SIRI), systemic immune inflammation index (SII), and aggregate index of systemic inflammation (AISI)-and the prevalence of diabetic foot ulcer (DFU). Method: We conducted a cross-sectional analysis using data from three cycles of the National Health and Nutrition Examination Survey (NHANES), supplemented by a single-center retrospective clinical study. Initially, 31,126 participants were screened from NHANES. Binary logistic regression models (both unadjusted and adjusted for covariates) were employed to evaluate the associations between ln SIRI, ln SII, and ln AISI and DFU prevalence. Restricted cubic spline (RCS) analysis was applied to assess nonlinear relationships, and subgroup analyses were performed to examine the stability of associations across strata defined by age, gender, race, body mass index (BMI), smoking status, and hypertension. Additionally, a clinical validation study was conducted from January to December 2023, comprising 34 DFU patients and 68 diabetic controls. We performed multivariable binary logistic regression analyses to assess the independent associations between systemic inflammatory indices and the presence of DFU, adjusting for age, sex, diabetes duration, BMI, and albumin levels. Receiver operating characteristic (ROC) curve analysis was used to preliminarily assess the discriminatory ability of SII, SIRI, and AISI for DFU status. Results: The cross-sectional analysis included 135 participants with DFU and 1560 without DFU. Logistic regression revealed consistent positive associations between ln SIRI, ln SII, and ln AISI and DFU prevalence in both unadjusted and adjusted models. RCS analysis indicated linear dose-response relationships for all three biomarkers. Subgroup analyses confirmed that these associations remained stable across demographic and clinical subgroups. In the retrospective clinical study, ln SIRI, ln SII, and ln AISI were significantly associated with DFU prevalence, with odds ratios (ORs) as follows: ln SIRI: OR = 2.51 (95% CI: 1.39-4.54), ln SII: OR = 5.44 (95% CI: 2.48-11.91), and ln AISI: OR = 2.75 (95% CI: 1.59-4.74). After adjusting for key confounders, the associations between these biomarkers and DFU remained consistent in both direction and statistical significance. ROC analysis showed that SII was more reliable than the other two for predicting DFU. Conclusion: By integrating a cross-sectional NHANES-based analysis with a clinical retrospective study, this research demonstrates that elevated levels of SIRI, SII, and AISI are significantly associated with an increased prevalence of DFU. These systemic inflammatory biomarkers may serve as valuable tools for risk assessment in patients with DFU.