Abstract
<jats:p>Background: Endothelial deregulation (ED) manifests as a major secondary complication in clinical Diabetes mellitus (DM) which is established as the preliminary stage of vascular dysfunction. This study evaluates a broader repertoire of biomarkers that are relevant to diabetic - ED and the inflammatory potential of the high mobility group box-1 (HMGB1) nuclear protein in mitigating type-2 diabetes (T2D) -induced ED. Method: A total of 33 biomarkers were evaluated from retrospective metabolic and sociodemographic data in a forest plot following the PICOS study design. A total of 1830 entries published during the past 10 years ending on mid December 2023 from PUBMED, MEDLINE, SCOPUS, SPRINGER-LINK and WOS databases were screened using a variety of MESH terms. The results were generated using the RevMan and GraphPad Prism software. Modified Cochrane Organisation template for systematic reviews and meta-analyses was followed with data validated in PRISMA. The protocol of this study was registered at https://www.crd.york.ac.uk/Prospero/CRD42023493221. Results: Only 16 single case-control studies qualified for data extraction. 18 biomarkers were identified as having a significantly high risk of ED. IL-6 emerged as the biomarker having the highest effect size (SMD 5.20, 95% CI, 3.21, 7.18, p&lt;0.00001, n=209). HMGB1 comprised the sixth highest standardized mean difference (SMD 2.86, 95% CI, 1.91, 3.81, p&lt;0.00001, n=762) out of the eight highest biomarkers calculated. Conclusion: The biomarkers consisting of a mix of traditional and non-traditional markers carried a high risk in developing T2D-induced cardiovascular disease and it was concluded that HMGB1 provides us with a high-risk inflammatory metabolic target.</jats:p>