Abstract

Peripheral artery disease (PAD) is a progressive atherosclerotic disorder with reduced blood flow and endothelial dysfunction. Diabetes further impairs vascular function in PAD. This systematic review and meta-analysis compared blood flow and endothelial function in PAD patients with and without diabetes. This review was conducted across different databases, i.e., PubMed, Embase, Cochrane Library, Scopus, Web of Science, CINAHL, and ClinicalTrials. gov. Studies evaluated blood flow velocity, endothelial function, and walking distance in diabetic and non-diabetic PAD patients. Risk of bias was assessed using ROBINS-I for observational studies and the Cochrane RoB 2.0 for randomized trials. Meta-analyses used random-effects models for flow-mediated dilation and fixed-effects models for walking distance, with heterogeneity assessed using I² and Chi². Eleven studies met the inclusion criteria. The meta-analysis showed significantly reduced endothelial function in diabetic PAD patients, with a pooled flow-mediated dilation mean difference of −1.20% (95% CI: −1.56 to −0.84; P < 0.00001) and moderate-to-high heterogeneity (I² = 63%) owing to heterogeneity in study designs. Walking distance was significantly decreased in diabetic PAD patients, with a pooled mean difference of -45.44 meters (95% CI: -60.00 to -30.88, P < 0.00001). Heterogeneity was low (I² = 0%) hence acceptable to use a fixed-effects model. Exercise consistently improved walking capacity, whereas pharmacologic and dietary interventions had variable effects, underscoring the need for targeted therapies and standardized assessments. Overall, diabetes markedly impairs endothelial function and walking ability in PAD, emphasizing the importance of tailored interventions to improve vascular outcomes in this high-risk population.

Key words: PAD, Diabetes mellitus, Endothelial dysfunction, FMD, Exercise therapy