Molecular Pathways in Diabetic Cardiomyopathy and the Role of Anti-hyperglycemic Drugs Beyond Their Glucose Lowering Effect.

Epidemiological evidence has shown that diabetes is associated with overt heart failure (HF) and worse clinical outcomes. However, the presence of a distinct primary diabetic cardiomyopathy (DCM) has not been easy to prove because the association between diabetes and HF is confounded by hypertension, obesity, microvascular dysfunction, and autonomic neuropathy. In addition, the molecular mechanisms underlying DCM are not yet fully understood, DCM usually remains asymptomatic in the early stage, and no specific biomarkers have been identified. Nonetheless, several mechanistic associations at the systemic, cardiac, and cellular/molecular levels explain different aspects of myocardial dysfunction, including impaired cardiac relaxation, compliance, and contractility. In this review, we focus on recent clinical and preclinical advances in our understanding of the molecular mechanisms of DCM and the role of anti-hyperglycemic agents in preventing DCM beyond their glucose lowering effect.