Causes and characteristics of diabetic cardiomyopathy

Abstract

Type 1 and type 2 diabetic patients are at increased risk of cardiomyopathy and heart failure is a major cause of death for these patients. Cardiomyopathy in diabetes is associated with a cluster of features including decreased diastolic compliance, interstitial fibrosis and myocyte hypertrophy. The mechanisms leading to diabetic cardiomyopathy remain uncertain. Diabetes is associated with most known risk factors for cardiac failure seen in the overall population, including obesity, dyslipidemia, thrombosis, infarction, hypertension, activation of multiple hormone and cytokine systems, autonomic neuropathy, endothelial dysfunction and coronary artery disease. In light of these common contributing pathologies it remains uncertain whether diabetic cardiomyopathy is a distinct disease. It is also uncertain which factors are most important to the overall incidence of heart failure in diabetic patients. This review focuses on factors that can have direct effects on diabetic cardiomyocytes: hyperglycemia, altered fuel use, and changes in the activity of insulin and angiotensin. Particular attention is given to the changes these factors can have on cardiac mitochondria and the role of reactive oxygen species in mediating injury to cardiomyocytes.

Figure 1

Some of the risk factors for heart failure which are associated with diabetes. AGE: advanced glycation end product.

Figure 2. Interacting pathways of ROS production and injury in diabetic cardiomyocytes

ROS: reactive oxygen species. AGE: advanced glycation end products. Ang II: angiotensin II. FFA: free fat acid. Glut: glucose transporter. FATP: free fat acid transport protein. AT1R: angiotensin 2 type 1 receptor. CPT-1: carnitine palmitoyl transferase-1. SR: sarcoplasmic reticulum. SRCA: sarcoplasmic reticulum Ca 2⁺-ATPase.