MECHANISMS IN ENDOCRINOLOGY: Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review

Eylem Levelt, Gaurav Gulsin, Stefan Neubauer, Gerry P McCann, Eylem Levelt, Gaurav Gulsin, Stefan Neubauer, Gerry P McCann

Abstract

Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease-specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non-invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies and cardiovascular outcomes with new classes of glucose-lowering therapies.

© 2018 The authors.

Figures

Figure 1
Figure 1
Cardiac energy metabolism and the sites of action of the different metabolic modulators. These range from (A) mitochondrial carnitine shuttle (CPT inhibitors) and (B) β-fatty acid oxidation inhibitors (C) pyruvate dehydrogenase (PDH) activators. In practice, the latter two represent the clinically pertinent therapeutic targets. Group (A) includes perhexiline, etomoxir, oxfenicine and to a lesser extent amiodarone. Group (B) includes trimetazidine and ranolazine. Group (C) includes dichloroacetate. GLUT denotes glucose transporter, PCr phosphocreatine, Cr free creatine.
Figure 2
Figure 2
Differences in cardiac function, hepatic steatosis, and hepatic cT1 among the study cohorts. (A) Peak circumferential systolic strain; (B) diastolic strain rate; (C) hepatic triglyceride content (%) and (D) hepatic corrected T1 map (ms). The dots indicate values outside the interquartile range. Reproduced with permission from Levelt et al. (83). Copyright© The American College of Cardiology.

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