Cardiometabolic Remodeling in Type 2 Diabetes Mellitus: the Role of Insulin Resistance and Myocardial Fibrosis

Abstract

Type 2 diabetes mellitus (T2DM) is increasingly recognized as a systemic disorder with profound effects on cardiovascular structure and function, extending beyond traditional atherosclerotic complications. Cardiometabolic remodeling has emerged as a central concept linking metabolic dysregulation to progressive myocardial injury. In this context, insulin resistance represents a key pathophysiological driver, promoting alterations in substrate utilization, mitochondrial dysfunction, low-grade inflammation, and endothelial impairment. These processes collectively contribute to structural and functional changes within the myocardium, even in the absence of overt coronary artery disease.      Growing evidence indicates that myocardial fibrosis plays a pivotal role in the development of diabetic cardiomyopathy. The accumulation of extracellular matrix components, mediated by chronic hyperglycemia, advanced glycation end products, and activation of profibrotic signaling pathways, leads to increased myocardial stiffness and impaired diastolic function. Importantly, these changes may occur at subclinical stages, preceding detectable systolic dysfunction and highlighting the need for early identification of at-risk individuals. Recent advances in cardiac imaging and biomarker research have improved the detection of diffuse myocardial fibrosis and its association with adverse cardiovascular outcomes in patients with T2DM. At the same time, the interplay between insulin resistance and fibrotic remodeling remains an area of active investigation, with implications for targeted therapeutic strategies. Understanding the mechanisms underlying cardiometabolic remodeling in T2DM is essential for refining risk stratification and developing interventions aimed at preventing the progression to heart failure. Further studies are warranted to clarify the temporal relationship between metabolic disturbances and myocardial structural changes, as well as to evaluate the impact of emerging treatments on reversing or attenuating fibrotic remodeling.