Associations of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with amputation risk in patients with diabetic foot disease: a systematic review and meta-analysis

Background Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inexpensive inflammatory markers derived from routine blood counts. However, their value for assessing amputation risk in patients with diabetic foot ulcers (DFUs) remains uncertain. This meta-analysis aims to evaluate the associations and discriminatory performance of baseline NLR and PLR for DFU-related amputation. Material and methods PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 2026 for English-language observational studies. Eligible studies reported baseline NLR or PLR according to amputation status or their area under the receiver operating characteristic curve (AUC) for amputation. Random-effects models were used to pool standardized mean differences (SMD) and AUC with 95% confidence intervals (CI). Risk of bias and certainty of evidence were assessed using the QUIPS tool and GRADE framework, respectively. Results Thirteen studies involving 3,667 patients were included. Baseline NLR was higher in patients who underwent any amputation than in those managed with limb salvage (SMD 0.69, 95% CI 0.42–0.97; I 2 = 85.5%) and showed moderate discriminatory performance (AUC 0.713, 95% CI 0.665–0.757; I 2 = 0%). NLR was also higher in patients undergoing major amputation (SMD 0.97, 95% CI 0.18–1.77), whereas the minor-amputation comparison was not statistically significant (SMD 0.24, 95% CI −0.04 to 0.51). PLR was higher in patients undergoing any amputation (SMD 0.55, 95% CI 0.17–0.93) and showed a pooled AUC of 0.664 (95% CI 0.631–0.697; I 2 = 0%). The certainty of evidence was moderate for both the associations of NLR and PLR with any amputation and their discriminatory performance assessed by AUC. Higher PLR was observed in the minor- and major-amputation groups, but both analyses were exploratory and included only two studies. Evidence certainty was moderate for minor amputation and low for major amputation. Conclusions Higher baseline NLR and PLR were associated with DFU-related amputation, with more consistent evidence for NLR. These markers may complement clinical risk assessment but are insufficient for stand-alone decision-making. Prospective multicenter studies are needed to validate standardized thresholds and determine their added value within established classification systems. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261461714 , PROSPERO CRD420261461714.