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  • Review Article
  • Published:

Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy

Nature Reviews Endocrinology volume 12, pages 144–153 (2016)Cite this article

Subjects

Key Points

  • Reported rises in the prevalence of diabetic cardiomyopathy among developed nations have occurred in parallel with increased rates of obesity, insulin resistance and hyperinsulinaemia

  • Insulin resistance and/or hyperinsulinaemia seem to underpin the development of diabetic cardiomyopathy, which is initially characterized by diastolic dysfunction in the absence of coronary artery disease and hypertension

  • Pathophysiological mechanisms include impaired insulin signalling, cardiac mitochondrial dysfunction, endoplasmic reticulum stress, impaired autophagy, impaired myocardial calcium handling, abnormal coronary microcirculation, inappropriate neurohumoral activation and maladaptive immune responses

  • Insulin resistance, or hyperinsulinaemia, independently predisposes to the development of diabetic cardiomyopathy and targeting insulin resistance or hyperinsulinaemia could be a potential therapeutic strategy to prevent the development of diabetic cardiomyopathy

Abstract

Insulin resistance, type 2 diabetes mellitus and associated hyperinsulinaemia can promote the development of a specific form of cardiomyopathy that is independent of coronary artery disease and hypertension. Termed diabetic cardiomyopathy, this form of cardiomyopathy is a major cause of morbidity and mortality in developed nations, and the prevalence of this condition is rising in parallel with increases in the incidence of obesity and type 2 diabetes mellitus. Of note, female patients seem to be particularly susceptible to the development of this complication of metabolic disease. The diabetic cardiomyopathy observed in insulin- resistant or hyperinsulinaemic states is characterized by impaired myocardial insulin signalling, mitochondrial dysfunction, endoplasmic reticulum stress, impaired calcium homeostasis, abnormal coronary microcirculation, activation of the sympathetic nervous system, activation of the renin–angiotensin–aldosterone system and maladaptive immune responses. These pathophysiological changes result in oxidative stress, fibrosis, hypertrophy, cardiac diastolic dysfunction and eventually systolic heart failure. This Review highlights a surge in diabetic cardiomyopathy research, summarizes current understanding of the molecular mechanisms underpinning this condition and explores potential preventive and therapeutic strategies.

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Figure 1: Molecular mechanisms implicated in the development of diabetic cardiomyopathy.
Figure 2: The development and progression of diabetic cardiomyopathy.
Figure 3: Insulin resistance and T2DM leads to system metabolic disorders in the cardiomyocyte.

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Acknowledgements

The authors thank Brenda Hunter (Diabetes and Cardiovascular Center, University of Missouri School of Medicine, USA) for editorial assistance. The authors' research was supported by the NIH (grants R01 HL73101-01A and R01 HL107910-01) for J.R.S and the Veterans Affairs Merit System (grant 0018) for J.R.S.

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  1. Diabetes and Cardiovascular Center, University of Missouri School of Medicine, D109 Diabetes Center HSC, One Hospital Drive, Columbia, 65212, Missouri, USA

    Guanghong Jia, Vincent G. DeMarco & James R. Sowers

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Jia, G., DeMarco, V. & Sowers, J. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nat Rev Endocrinol 12, 144–153 (2016). https://doi.org/10.1038/nrendo.2015.216

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