Diabetic cardiomyopathy: bench to bedside

Abstract

The study of diabetic cardiomyopathy is an area of significant interest given the strong association between diabetes and the risk of heart failure. Many unanswered questions remain regarding the clinical definition and pathogenesis of this metabolic cardiomyopathy. This article reviews the current understanding of diabetic cardiomyopathy with a particular emphasis on the unresolved issues that have limited translation of scientific discovery to patient bedside.

Figure 1. The multifaceted effects of diabetes on cardiomyocyte biology

In the diabetic state, excess fatty acids are present inside the cell leading to excessive mitochondrial FAO, PPARα activation, and the generation of lipid signaling molecules such as ceramide and DAG. This metabolic reprogramming leads to mitochondrial dysfunction manifested by excess ROS production, less efficient ATP generation, metabolic inflexibility. Stressed mitochondria also amplify inflammatory and cell death responses. Hyperglycemia can further augment cardiac myocyte toxicity via the formation of AGEs as well as promoting excess ROS and DAG generation.

Figure 2. Diabetes amplifies cardiac injury response to a variety of stimuli

Diabetes augments the risk of adverse cardiovascular outcomes in patients with ischemic heart disease, HTN, AS, and heart failure (blue boxes). The dashed arrows connecting to the text boxes indicate how diabetes influences the outcomes of the above-mentioned cardiovascular diseases.