Abstract
AIM: There is an ongoing search for novel biomarkers of diabetes. We conducted a systematic review and meta-analysis of the serum concentrations of ischemia-modified albumin (IMA), a candidate biomarker of oxidative stress, acidosis, and ischemia, in patients with pre-diabetes, different types of diabetes mellitus (type 1, T1DM, type 2, T2DM, and gestational, GDM), and healthy controls. METHODS: We searched for case-control studies published in PubMed, Web of Science, and Scopus from inception to December 31, 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. RESULTS: In 29 studies, T2DM patients had significantly higher IMA concentrations when compared to controls (standard mean difference, SMD = 1.83, 95 % CI 1.46 to 2.21, p˂0.001; I(2) = 95.7 %, p < 0.001; low certainty of evidence). Significant associations were observed between the SMD and glycated hemoglobin (p = 0.007), creatinine (p = 0.003), triglycerides (p = 0.029), and the presence of diabetes complications (p = 0.003). Similar trends, albeit in a smaller number of studies, were observed in T1DM (two studies; SMD = 1.59, 95 % CI -0.09 to 3.26, p˂0.063; I(2) = 95.8 %, p < 0.001), GDM (three studies; SMD = 3.41, 95 % CI 1.14 to 5.67, p = 0.003; I(2) = 97.0 %, p < 0.001) and pre-diabetes (three studies; SMD = 15.25, 95 % CI 9.86 to 20.65, p˂0.001; I(2) = 99.3 %, p < 0.001). CONCLUSION: Our study suggests that IMA is a promising biomarker for determining the presence of oxidative stress, acidosis, and ischemia in pre-diabetes and T1DM, T2DM, and GDM. However, the utility of measuring circulating IMA warrants confirmation in prospective studies investigating clinical endpoints in pre-diabetes and in different types of diabetes (PROSPERO registration number: CRD42024504690).