The Inflamed Endothelium in Diabetes Mellitus: Molecular Crosstalk, Vascular Complications, and Therapeutic Perspectives
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Background: Diabetes mellitus causes microvascular and macrovascular complications through interacting metabolic, oxidative, inflammatory, and vascular mechanisms. Increasing evidence identifies the endothelium as an active immunometabolic organ rather than a passive vascular barrier. Objective: To synthesize the mechanisms underlying endothelial inflammation in diabetes, its contribution to organ-specific vascular complications, and the clinical maturity of associated biomarkers and therapies. Methods: A narrative review of experimental, observational, translational, and clinical literature was undertaken. Evidence was organized around endothelial homeostasis, metabolic reprogramming, oxidative stress, inflammatory signalling, immune–endothelial crosstalk, vascular complications, biomarkers, and therapeutic strategies. Results: Hyperglycaemia, insulin resistance, dyslipidaemia, reactive oxygen species, AGE–RAGE, NF-κB, JAK/STAT, and NLRP3 signalling collectively promote endothelial activation, impaired nitric oxide bioavailability, leukocyte recruitment, barrier disruption, thrombogenicity, senescence, and defective repair. Vascular-bed-specific endothelial phenotypes contribute to diabetic kidney disease, retinopathy, cardiomyopathy, atherosclerosis, and peripheral arterial disease. Most biomarkers remain nonspecific or insufficiently validated. SGLT2 inhibitors and GLP-1 receptor agonists have established cardiorenal benefits, whereas direct anti-inflammatory, antioxidant, glycocalyx-targeted, phytochemical, and nanomedicine approaches remain investigational. Conclusion: Endothelial inflammation provides an integrated framework for diabetic vascular injury, but biomarker-guided and endothelial-targeted management requires prospective clinical validation.
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