Molecular Mechanisms Underlying the Comorbidity of Type 2 Diabetes Mellitus and Coronary Artery Disease: from Insulin Resistance and Inflammation to Endothelial Dysfunction and Therapeutic Implications.

Coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) are among the most prevalent and lethal chronic diseases worldwide. These conditions frequently coexist, forming a vicious “diabetes–coronary artery disease” cycle. Epidemiological evidence indicates that patients with T2DM have a two- to fourfold higher risk of developing CAD than healthy individuals. Moreover, among patients with CAD, the presence of T2DM is associated with significantly increased rates of recurrent myocardial infarction, heart failure, and mortality, posing substantial challenges to clinical management. Traditional studies have largely focused on the detrimental effects of isolated risk factors, such as hyperglycemia and dyslipidemia, on the cardiovascular system. However, recent advances in molecular biology have demonstrated that CAD and T2DM share a complex network of cellular and molecular pathological mechanisms. Moving beyond the conventional framework of individual risk factors, this article systematically summarizes the common pathophysiological basis of these two disorders from key perspectives including insulin resistance, chronic low-grade inflammation, and oxidative stress, with particular emphasis on the interactions among these mechanisms. In addition, in light of current therapeutic advances, it discusses treatment strategies targeting shared molecular pathways to facilitate the development of novel multitargeted interventions and to provide a theoretical basis for improving the prognosis of patients with this comorbidity.