Cardiomyopathy in type 2 diabetes: update on pathophysiological mechanisms

Type 2 diabetes mellitus (DM) is associated with increased risk for developing heart failure (HF) and worse outcomes once HF is present. While the exact mechanisms underpinning these observations remain poorly understood, several metabolic perturbations associated with DM have been implicated as contributors to the HF risk, including alterations of cardiomyocyte metabolic substrate switching between free fatty acid (FFA) and glucose metabolism; increased FFA exposure and cellular accumulation; and alterations in peroxisome proliferator-activated receptor-(PPAR-)alpha activity, among others. The commonly coincident conditions of left ventricular hypertrophy and ischemic heart disease likely confound the metabolic derangements further increasing HF risk. Continued investigation into these mechanistic connections is necessary to better understand the pathophysiology and ideally inform the pursuit of novel therapeutic targets and strategies to intervene on the HF associated with DM.