Diabetes-related cardiomyopathy: The sweet story of glucose overload from epidemiology to cellular pathways

Diabetes Metab. 2019 Jun;45(3):238-247. doi: 10.1016/j.diabet.2018.07.003. Epub 2018 Jul 23.


Type 2 diabetes (T2D) is a major risk factor for heart failure (HF). Although the number of cases of myocardial infarction in the T2D population has been reduced by 25% over the last 10 years, the incidence of HF is continuously increasing, making it the most worrying diabetes complication. This strongly reinforces the urgent need for innovative therapeutic interventions to prevent cardiac dysfunction in T2D patients. To this end, epidemiological, imaging and animal studies have aimed to highlight the mechanisms involved in the development of diabetic cardiomyopathy. Epidemiological observations clearly show that hyperglycaemia correlates with severity of cardiac dysfunction and mortality in T2D patients. Both animal and cellular studies have demonstrated that, in the context of diabetes, the heart loses its ability to utilize glucose, therefore leading to glucose overload in cardiomyocytes that, in turn, promotes oxidative stress, accumulation of advanced glycation end-products (AGEs) and chronic activation of the hexosamine pathway. These have all been found to activate apoptosis and to alter heart contractility, calcium signalling and mitochondrial function. Although, in the past, tight glycaemic control has failed to improve cardiac function in T2D patients, recent clinical trials have reported cardiovascular benefit with hypoglycaemic antidiabetic drugs of the SGLT2-inhibitor family. This review, based on clinical evidence from mechanistic studies as well as several large clinical trials, covers 15 years of research, and strongly supports the idea that hyperglycaemia and glucose overload play a central role in the pathophysiology of diabetic cardiomyopathy.

Keywords: Diabetic cardiomyopathy; Glucotoxicity; Hexosamine pathway; Oral hypoglycaemic agents; SGLT2 inhibitors; Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Cardiomyopathies / epidemiology*
  • Diabetic Cardiomyopathies / metabolism
  • Humans
  • Hyperglycemia / epidemiology*
  • Hyperglycemia / metabolism
  • Oxidative Stress / physiology*
  • Prevalence
  • Risk Factors


  • Blood Glucose