Adaptation and Maladaptation of the Heart in Diabetes: Part I

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Abstract
Diabetes mellitus (type 2 diabetes) is as much a disease of modern lifestyle as it is a disease of genetic predisposition. Worldwide, there are about 143 million patients with diabetes, almost 5 times more than estimates of 10 years ago.1,2⇓ Heart disease, often presenting as cardiomyopathy, is the leading cause of death among patients with diabetes mellitus (Figure 1).3 Like diabetes, the prevalence of heart failure also continues to rise in Western countries.4 Diabetes, in turn, is the largest comorbidity of patients with heart failure and adversely affects outcomes of cardiovascular disease.5 The trend is unmistakable; both insulin resistance and heart failure have emerged as major worldwide epidemics. It is therefore timely to take a fresh look at the effects of diabetes on the heart. Figure 1. Multiple Risk Factor Intervention Trial (MRFIT). Age-adjusted cardiovascular disease death rates (per 10 000 person-years) by presence of number of risk factors in men with and without diabetes. Reproduced with permission from Stamler et al.3 Copyright 1993 American Diabetes Association ( Diabetes Care . 1993;16:434–444). Reprinted with permission from the American Diabetes Association. The difficulties in making a causal connection between diabetes and heart failure are formidable. Some simple definitions remain elusive. For example, the distinction between the insulin-deficient (type 1) and insulin-resistant (type 2) forms of diabetes on the one hand, and the distinction between systolic and diastolic dysfunction as causes of heart failure, on the other hand, are hard to define. The known trophic and hemodynamic effects of insulin in healthy individuals,6 the well-described endothelial dysfunction, the deposition of advanced glycation end products, and an accelerated progression of atherosclerosis in patients with diabetes add further complexities to the clinical picture of heart failure in diabetes. Nonetheless, diabetes as a primary cause for heart failure …