The Gluco-Vascular Injury Axis in Diabetic Cardiovascular Dysfunction: A Narrative Review

Diabetic cardiovascular dysfunction arises from a progressive metabolic-vascular-myocardial injury pathway rather than from hyperglycemia alone. In this review, the “gluco-vascular injury axis” is used as a proposed conceptual framework describing how diabetes-related metabolic stress promotes endothelial dysfunction, vascular injury, microvascular impairment, myocardial remodeling, and heart failure. Chronic hyperglycemia, insulin resistance, dyslipidemia, oxidative stress, inflammation, AGE-RAGE (advanced glycation end products-receptor for advanced glycation end products) signaling, mitochondrial impairment, arterial stiffness, and coronary microvascular dysfunction contribute to fibrosis, diastolic dysfunction, and heart failure. Because these mechanisms are often discussed separately, the primary clinical message can become obscured. This narrative review synthesizes mechanistic, experimental, and clinical evidence to organize these processes into a clinically interpretable continuum. The novelty of this review lies in integrating diabetic cardiomyopathy, atherosclerosis, endothelial dysfunction, and coronary microvascular disease into one metabolic-vascular-myocardial framework, with endothelial dysfunction positioned as the transition point between glucose-lipid stress and cardiovascular injury. It was not designed as a systematic review and did not use formal search, screening, or meta-analytic methods. The review highlights metabolic triggers, endothelial injury, inflammatory amplification, macrovascular disease, microvascular dysfunction, mitochondrial redox imbalance, and diabetic cardiomyopathy. The key takeaway is that cardiovascular protection in diabetes may need to address the entire gluco-vascular injury process through a combination of metabolic, endothelial, inflammatory, mitochondrial, microvascular, and myocardial protective strategies.