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Diabetic vascular complications are common and severe, worsening quality of life and long-term outcomes. In diabetes, chronic hyperglycemia together with dyslipidemia and hypertension reshapes endothelial metabolism and homeostasis. Endothelial cells shift the balance of glucose utilization, fatty acid oxidation, and mitochondrial function, and these metabolic changes bias endothelial behavior toward reduced nitric oxide bioavailability, oxidative stress, and a pro-inflammatory, pro-thrombotic state. Over time, maladaptive stress responses promote senescence, cell loss, and endothelial-to-mesenchymal transition, accelerating the initiation and progression of atherosclerotic plaques. This review summarizes how diabetic cues drive endothelial metabolic reprogramming and how this, in turn, links endothelial dysfunction to plaque formation, growth, and instability. We highlight key metabolic pathways and discuss how local hemodynamic forces at athero-prone regions further shape endothelial phenotypes and inflammatory signaling. Finally, we outline therapeutic opportunities that target endothelial metabolism and stress responses-including modulation of glycolytic flux, mitochondrial and redox-directed strategies, and pathway-level interventions that curb hypoxia and inflammatory programs. We emphasize translational priorities such as endothelium-selective delivery, biomarkers of endothelial metabolic state, and rigorous clinical testing to enable earlier and more effective prevention of diabetes-associated atherosclerotic disease.
Pan et al. (Sun,) studied this question.