Association of sarcopenia and muscle attenuation with clinical outcomes in patients with diabetic foot: a systematic review and meta-analysis.

Background: Diabetic foot (DF) represents a severe and disabling complication of diabetes, closely linked to ulceration, amputation, functional impairment, and an elevated risk of death. Sarcopenia is a syndrome marked by progressive declines in muscle mass and function. Emerging evidence suggests a possible link between DF and sarcopenia. Nonetheless, a systematic evaluation of the influence of sarcopenia on adverse clinical outcomes in individuals with DF remains unavailable. The present investigation aims to systematically assess and quantitatively synthesize the association of sarcopenia and muscle attenuation with clinical outcomes in those with DF. Methods: A systematic search of Embase, Cochrane, PubMed, Web of Science, SinoMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was conducted from their inception through December 2025. Observational studies enrolling DF individuals aged ≥ 18 years and comparing clinical prognoses between those with and without sarcopenia and muscle attenuation were included. The primary outcomes comprised rates of mortality and amputation. Secondary outcomes encompassed ulcer severity. The NHLBI was adopted for risk-of-bias evaluation. Given substantial between-study heterogeneity, a narrative synthesis was prioritized, with meta-analyses implemented for outcomes amenable to quantitative pooling. Results: Eighteen studies (9 cross-sectional, 4 prospective cohort, 4 retrospective cohort, and 1 retrospective case-control studies) comprising 2,888 individuals were included, of which 9 contributed to the meta-analysis. The meta-analysis revealed that, relative to those without sarcopenia and muscle attenuation, DF individuals with comorbid sarcopenia exhibited an elevated risk of all-cause mortality (HR = 2.38, 95% CI: 1.63-3.48), an association with amputation (OR = 2.11, 95% CI: 1.32-3.38), and a higher proportion of severe ulcers (Wagner grade 4-5) (RR = 1.69, 95% CI: 1.31-2.17). Conclusions: Impaired muscle health was associated with a higher risk of all-cause mortality, higher odds of amputation, and a greater prevalence of severe ulcers in patients with DF. Because the available evidence is observational and heterogeneous, these findings should be considered hypothesis-generating and should not yet be used to support prognostic screening or clinical risk-stratification decisions. Future prospective cohort investigations are necessary to further clarify the temporal relationship and underlying mechanisms. Funding and registration: This study was supported by the Ningxia Natural Science Foundation (Grant Number: 2025AAC030725). This systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD420251247873). Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251247873.