Ischemia-Modified Albumin in Diabetic Foot Ulcers: A Systematic Review and Bayesian Meta-Analysis

Abstract

Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus, leading to significant morbidity, amputation risk, and healthcare burden. This systematic review and meta-analysis aimed to evaluate the association between circulating ischemia-modified albumin (IMA) levels and DFU. A comprehensive search of PubMed, Scopus, Cochrane Central and Google Scholar databases was conducted to identify eligible observational studies reporting IMA concentrations in DFU patients, diabetics without foot ulcers, and healthy controls. Meta-analyses were performed using both frequentist random-effects models and Bayesian approaches. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to express continuous outcomes. PET-PEESE regression analyses assessed publication bias and small-study effects. A total of six studies were included, with five eligible for meta-analysis. Compared to healthy controls, DFU patients exhibited significantly higher IMA levels [pooled SMD = 3.21 (95% CI: 1.40, 5.03)]. Similarly, DFU patients had higher IMA levels than diabetics without foot ulcers [pooled SMD = 1.21 (95% CI: 0.23, 2.20)]. Both frequentist and Bayesian analyses consistently supported these findings despite notable heterogeneity. Adjusted analyses of IMA for serum albumin further confirmed its discriminative value in DFU. PET-PEESE analyses did not detect significant publication bias. This meta-analysis highlights the potential of IMA as a biomarker for diagnosis, risk stratification, and monitoring in DFU management. Despite significant associations, high inter-study heterogeneity and the limited number of studies restrict generalizability. Future research should focus on standardizing measurement protocols, validating clinical cut-offs, and conducting large-scale prospective studies to confirm its utility.