ArticleFrontiers in endocrinology2026
Association of novel inflammatory biomarkers with major amputation level in diabetic foot ulcer patients undergoing amputation: a retrospective comparative study.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: This study aimed to comprehensively evaluate the association of twelve inflammation-related biomarkers with amputation level (major vs. minor) in diabetic foot ulcer (DFU) patients undergoing amputation, with particular focus on identifying the strongest associated factor and exploring differences between above-knee amputation (AKA) and below-knee amputation (BKA). Methods: We retrospectively enrolled DFU patients who underwent amputation between January 2020 and June 2025. Twelve indices were calculated: SIRI, SII, AISI, NAR, MAR, RAR, HALP, PNI, ALI, CALLY, IBI, and CLR. LASSO regression and multivariate logistic regression were used for variable selection. AUC comparisons and Bootstrap internal validation assessed model performance. Subgroup analysis compared AKA vs. BKA. Results: A total of 538 patients were included (271 major, 267 minor). In univariate analysis, higher levels of NAR, MAR, RAR, SIRI, SII, AISI, IBI, and CLR were associated with major amputation, whereas lower levels of HALP, PNI, ALI, and CALLY were associated with major amputation. RAR exhibited the highest odds ratio (OR = 3.25, 95% CI: 2.54-4.16, p < 0.001) for major versus minor amputation. LASSO regression selected eight indices; multivariate analysis confirmed RAR, HALP, PNI, and ALI as independently associated with amputation level. The combined model incorporating RAR, HALP, PNI, and ALI demonstrated superior predictive performance compared to RAR alone (AUC: 0.816 vs. 0.773, p = 0.001). Bootstrap validation confirmed the stability of the combined model (optimism-corrected AUC: 0.811; optimism: 0.005). In the exploratory subgroup analysis, AKA patients had significantly higher RAR levels and lower PNI and ALI levels compared to BKA patients (all p < 0.05); however, only RAR remained significantly associated with AKA after multivariable adjustment. Conclusion: The combined model may provide modest incremental predictive value over RAR alone, but the clinical gain is limited. RAR alone remains a practical and sufficient tool for risk stratification, particularly in resource-limited settings. However, these findings are retrospective, and external validation is warranted before clinical application.
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