Review
Diabetic Cardiomyopathy: Insights into Pathogenesis, Diagnostic Challenges, and Therapeutic Options

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Abstract

Diabetic cardiomyopathy is the presence of myocardial dysfunction in the absence of coronary artery disease and hypertension. Hyperglycemia seems to be central to the pathogenesis of diabetic cardiomyopathy and to trigger a series of maladaptive stimuli that result in myocardial fibrosis and collagen deposition. These processes are thought to be responsible for altered myocardial relaxation characteristics and manifest as diastolic dysfunction on imaging. Sophisticated imaging technologies also have permitted the detection of subtle systolic dysfunction in the diabetic myocardium. In the early stages, these changes appear reversible with tight metabolic control, but as the pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients independently of common comorbidities, such as coronary artery disease and hypertension. Therapeutic agents specifically targeting processes that lead to these pathophysiologic changes are in the early stages of development. Although glycemic control and early administration of neurohormonal antagonists remain the cornerstones of therapeutic approaches, newer treatment targets are currently being explored.

Section snippets

Pathophysiologic Mechanisms of Diabetic Cardiomyopathy

A clear understanding of the precise pathophysiologic mechanisms of diabetic cardiomyopathy is still lacking. However, several pathophysiologic mechanisms have been proposed to explain the structural and functional changes associated with diabetic cardiomyopathy (Figure 1). These processes are not mutually exclusive and likely act synergistically to develop diabetic cardiomyopathy. Hyperglycemia is considered to be a central driver in the pathophysiology of diabetic cardiomyopathy because it

Diagnosing Diabetic Cardiomyopathy

There are 2 important components in the clinical diagnosis of diabetic cardiomyopathy: the detection of myocardial abnormalities and the exclusion of other contributory causes of cardiomyopathy. An important challenge in the clinical diagnosis of diabetic cardiomyopathy has been the lack of any pathognomonic histologic changes or imaging characteristics associated with the diagnosis. Endomyocardial biopsies are not indicated because of their invasiveness, unless circumstances to suspect other

Glycemic Control

The prevention and treatment of diabetic cardiomyopathy are clinically relevant because of its role in the pathogenesis of heart failure. Although the effect of glycemic control on diabetic cardiomyopathy has been studied in only a limited fashion, evidence suggests that good glycemic control is beneficial, at least in the early stages of myocardial dysfunction.61, 62, 63 Evidence also suggests that diabetic cardiomyopathy does not develop in patients with tightly controlled type 1 diabetes,

Conclusions

Diabetic cardiomyopathy has progressed from a nebulous concept to concrete reality during the last 3 decades. Multiple pathophysiologic mechanisms have been proposed to explain this entity, but hyperglycemia seems to be the central mechanism triggering the processes that lead to the ultimate pathologic changes of myocardial hypertrophy, fibrosis, and collagen deposition. From epidemiologic studies, the natural history of diabetic cardiomyopathy seems to start with impaired glucose tolerance and

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