Predictors and prevention of diabetic cardiomyopathy

Abstract

Despite our cognizance that diabetes can enhance the chances of heart failure, causes multiorgan failure,and contributes to morbidity and mortality, it is rapidly increasing menace worldwide. Less attention has been paid to alert prediabetics through determining the comprehensive predictors of diabetic cardiomyopathy (DCM) and ameliorating DCM using novel approaches. DCM is recognized as asymptomatic progressing structural and functional remodeling in the heart of diabetics, in the absence of coronary atherosclerosis and hypertension. The three major stages of DCM are: (1) early stage, where cellular and metabolic changes occur without obvious systolic dysfunction; (2) middle stage, which is characterized by increased apoptosis, a slight increase in left ventricular size, and diastolic dysfunction and where ejection fraction (EF) is <50%; and (3) late stage, which is characterized by alteration in microvasculature compliance, an increase in left ventricular size, and a decrease in cardiac performance leading to heart failure. Recent investigations have revealed that DCM is multifactorial in nature and cellular, molecular, and metabolic perturbations predisposed and contributed to DCM. Differential expression of microRNA (miRNA), signaling molecules involved in glucose metabolism, hyperlipidemia, advanced glycogen end products, cardiac extracellular matrix remodeling, and alteration in survival and differentiation of resident cardiac stem cells are manifested in DCM. A sedentary lifestyle and high fat diet causes obesity and this leads to type 2 diabetes and DCM. However, exercise training improves insulin sensitivity, contractility of cardiomyocytes, and cardiac performance in type 2 diabetes. These findings provide new clues to diagnose and mitigate DCM. This review embodies developments in the field of DCM with the aim of elucidating the future perspectives of predictors and prevention of DCM.

Keywords: diabetes; exercise; heart failure; miRNA; obesity; oxidative stress.

Figure 1

Different risk factors associated with diabetic cardiomyopathy. Note: “↑” indicates increased levels. Abbreviations: AGE, advanced glycation end product; DCM, diabetic cardiomyopathy; FFA, free fatty acid; miRNA, micro-RNA; RAGE, receptor for AGE; ROS, reactive oxygen species.

Figure 2

(A) Different pathways associated with increased free fatty acid mediated diabetic cardiomyopathy and (B) different pathways associated with hyperglycemia mediated diabetic cardiomyopathy. Notes: “↑” indicates increased levels and “↓” indicates decreased levels. Abbreviations: AGE, advanced glycation end product; AKT-1, serine/threonine kinase; DCM, diabetic cardiomyopathy; ECM, extracellular matrix; FFA, free fatty acid; GAPDH, glyceraldehyde phosphate dehydrogenase; GLUT, glucose transporter; GSK-3β, glycogen synthase kinase-3β; K-ATP, ATP sensitive potassium channel; miRNA, micro-RNA; MMP9, matrix metalloprotinease 9; mTOR, mammalian target of rapamycin; PARP, poly(ADP ribose) polymerase; PKC, protein kinase C; PPAR, peroxisome proliferator-activated receptor; ROS, reactive oxygen species; RyR, ryanodine receptor; SERCA2, sarco-endoplasmic reticulum-calcium ATPase 2; TNF-α, tumor necrosis factor-α.

Figure 3

Effect of high fat diet, type 1 diabetes, and type 2 diabetes on cardiac remodeling leading to diabetic cardiomyopathy. Abbreviations: DCM, diabetic cardiomyopathy; E-M, endothelial-myocytes; T1D, type 1 diabetes; T2D, type 2 diabetes.