The Reply

Abstract

The primary purpose of our review is to provide a broad conceptual framework to highlight the complexity and ambiguity of diabetic cardiomyopathy in humans, and the evolving understanding with the availability of newer technologies and clinical tools. We have emphasized that a clear understanding of the precise pathophysiologic mechanisms of diabetic cardiomyopathy is still lacking, although the available evidence has suggested the potential for hyperglycemia to be a central driver. We thank Ashrith et al for highlighting the potential role of insulin resistance in the pathogenesis of diabetic cardiomyopathy. Indeed, the role of myocardial insulin resistance has been studied in several animal models, and the potential contribution to the development of cardiomyopathy has been examined in a recent review.1Witteles R.M. Fowler M.B. Insulin-resistant cardiomyopathy: Clinical evidence, mechanisms, and treatment options.J Am Coll Cardiol. 2008; 51: 93-102Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar It is important to acknowledge the association between insulin resistance and cardiomyopathy, but it is equally important to recognize that not all patients with diabetes mellitus and cardiomyopathy have demonstrable insulin resistance. Arguably, few epidemiologic or mechanistic studies have carefully defined the presence of “diabetic cardiomyopathy” because a unified definition is not available. Also, many of the precipitating factors responsible for the development of insulin resistance, such as activation of the sympathetic nervous system or the renin-angiotensin-aldosterone system might directly contribute to the development of cardiomyopathy, independent of the glycemic consequences of insulin resistance. Nevertheless, we are in full agreement with Ashrith et al that the association of insulin resistance as a marker of contractile dysfunction is evident, and the presence of insulin resistance is likely synergistic to other pathogenic mechanisms in the development of diabetic cardiomyopathy. However, we have yet to identify any direct evidence that improving insulin resistance itself can reverse or halt the progression of diabetic cardiomyopathy independent of glycemic control in humans, which should be a clear objective for future investigations. Insulin Resistance: Marker or Mediator?The American Journal of MedicineVol. 122Issue 3PreviewWe read with interest the excellent review by Aneja et al1 on diabetic cardiomyopathy. The authors have stressed the central role of hyperglycemia in the pathogenesis of diabetic cardiomyopathy, but they have almost forgotten the association of hyperinsulinemia or insulin resistance and cardiomyopathy. Although it is still not clear whether insulin resistance is the cause or effect of heart failure, it is associated with heart failure.2 From cohort and observational studies we know the following: insulin resistance is associated with an increase in left ventricular mass; this relation is stronger in women and may be related to obesity3; insulin resistance is associated with an increased risk of heart failure in elderly men, and this increased risk was seen even in nondiabetic elderly men. Full-Text PDF