Impact of Diabetes on Outcomes After Lower Limb Revascularization in Patients With Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-Analysis

Background Diabetes mellitus significantly increases the risk of chronic limb-threatening ischemia (CLTI), leading to more severe arterial disease and worse outcomes. Its independent role in mortality and major amputation post-revascularization is still unclear, especially across various follow-up periods. This systematic review and meta-analysis aimed to assess the impact of diabetes on all-cause mortality and major lower-extremity amputation in CLTI patients undergoing revascularization. Methods A systematic search was conducted in MEDLINE, Embase, and Cochrane Library for observational studies comparing outcomes between diabetic and non-diabetic patients with CLTI undergoing lower-extremity revascularization, with a minimum follow-up of one year. The primary outcomes were all-cause mortality and major amputation, reported as hazard ratios (HR) with 95% confidence intervals (CI). Subgroup analyses were stratified by follow-up duration (mid-term: 1–2 years; long-term: ≥3 years). Meta-regression was performed to investigate sources of heterogeneity. Analyses were conducted in R (version 4.4.0) using the ‘meta' package. Results Ten observational studies with 50,242 patients were included. In the pooled analysis, diabetes was associated with significantly higher risks of all-cause mortality (HR 1.23; 95% CI 1.04–1.46; I 2 = 87.6%) and major amputation (HR 1.43; 95% CI 1.23–1.66; I 2 = 62.3%). In temporal subgroup analyses, no significant differences in mortality were observed at mid-term (HR 1.36; 95% CI 0.97–1.90; p=0.075) or long-term follow-up (HR 1.18; 95% CI 0.95–1.46; p=0.10). For amputation, the risk was non-significant in the mid-term (HR 1.24; 95% CI 0.97–1.59; p=0.08) but significantly increased in the long-term (HR 1.56; 95% CI 1.32–1.85; p < 0.001). Meta-regression identified follow-up duration as the only significant moderator of amputation risk (β = 0.0214; p=0.024; R 2 = 35.65%). Substantial heterogeneity persisted across all analyses. Conclusion Diabetes mellitus may be associated with a time-dependent accumulation of major amputation risk following revascularization for CLTI, with a progressive effect emerging beyond three years of follow-up. Mortality differences were not significant at any temporal subgroup. These findings underscore the need for sustained limb surveillance in diabetic patients with CLTI and highlight the importance of integrated revascularization and cardiometabolic management strategies.