Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies

Abstract

Diabetic cardiomyopathy (DCM), although a distinct clinical entity, is also a part of the diabetic atherosclerosis process. It may be independent of the coexistence of ischemic heart disease, hypertension, or other macrovascular complications. Its pathological substrate is characterized by the presence of myocardial damage, reactive hypertrophy, and intermediary fibrosis, structural and functional changes of the small coronary vessels, disturbance of the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. These alterations make the diabetic heart susceptible to ischemia and less able to recover from an ischemic attack. Arterial hypertension frequently coexists with and exacerbates cardiac functioning, leading to the premature appearance of heart failure. Classical and newer echocardiographic methods are available for early diagnosis. Currently, there is no specific treatment for DCM; targeting its pathophysiological substrate by effective risk management protects the myocardium from further damage and has a recognized primary role in its prevention. Its pathophysiological substrate is also the objective for the new therapies and alternative remedies.

Keywords: atherosclerosis; cardiac autonomic neuropathy; cardiovascular disease; echocardiography; treatment strategies.

Figure 1

The pathophysiological substrate of diabetic cardiomyopathy: in diabetes, hyperglycemia, excess free fatty acid (FFA) release, and insulin resistance, engender adverse metabolic events that affect the cardiac myocytes. Hyperglycemia is associated with decreased glucose transportation (GLUT), uptake, and oxidation, as well as increased formation of advanced glycation end products (AGEs) and increased activation of protein kinase C (PKC). Excess FFA release is followed by cardiac lipotoxicity, ie, increased cardiac lipid accumulation and increased generation of reduced reactive oxygen species (ROS) at the level of the electron transport chain. Together with insulin resistance and impaired insulin action and signaling, these metabolic paths augment vasoconstriction, produce and further aggravate arterial hypertension, increase inflammation with liberation of leukocyte-attracting chemokines, increase production of inflammatory cytokines, and augment expression of cellular adhesion molecules. Thrombosis is further promoted, together with platelet activation.