ABSTRACT
Diabetes is a common modiable risk factor and a signicant contributor to mortality worldwide. Its etiology is complex and multifactorial, with an inherited component that involves the interactions between environmental factors and multiple genetic susceptibility alleles. Diabetes is the most common cause of cardiovascular disease and heart failure. Nearly 80% of diabetics die of cardiovascular disease or complications. Diabetic cardiomyopathy has been dened as ventricular dysfunction that occurs in diabetic patients independent of a recognized cause such as coronary artery disease (CAD) or hypertension. This review discusses the etiology of the condition, the mechanisms causing it, the factors affecting various aspects of the disease, and the treatment modalities that are available today and those currently under development. Diabetic cardiomyopathy, a complication of diabetes mellitus, is a condition characterized by left ventricular hypertrophy and diastolic dysfunction progressing to heart failure and systolic dysfunction, independent of hypertension or CAD. Hyperglycemia, insulin resistance, and hyperinsulinemia lead to an increase in serum fatty acids, oxidative stress, abnormal calcium handling, and hypertrophy. The changes in substrate oxidation prole and glucose availability, mitochondrial dysfunction, and microvascular dysfunction cause an energy shortage and
12.1 Introduction .......................................................................................................................... 212 12.2 Pathogenetic Mechanisms .................................................................................................... 213 12.3 Role of Hyperglycemia ......................................................................................................... 215 12.4 Nonesteried Fatty Acids ..................................................................................................... 215 12.5 Mitochondrial Dysfunction and Oxidative Stress ................................................................ 216
12.5.1 Impaired Mitochondrial Function ............................................................................ 216 12.5.2 ROS Production ........................................................................................................ 217 12.5.3 ATP Production ........................................................................................................ 217
12.6 High-Fat Diet as a Risk Factor for Diabetic Cardiomyopathy ............................................. 217 12.7 Animal Models of Diabetes and Diabetic Cardiomyopathy ................................................ 219 12.8 Treatment of Diabetic Cardiomyopathy ............................................................................... 221
12.8.1 Caloric Restriction .................................................................................................... 221 12.8.2 Pharmacotherapy ...................................................................................................... 221 12.8.3 Experimental Studies Point to Additional Therapies ............................................... 222 12.8.4 Mesenchymal Stem Cells .........................................................................................224
12.9 Conclusions ...........................................................................................................................225 Abbreviations .................................................................................................................................225 References ......................................................................................................................................226
