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Insulin resistance and hyperglycaemia in cardiovascular disease development

Key Points

  • Cardiovascular disease is the leading cause of mortality among individuals with diabetes mellitus—over 50% of patients die from a cardiovascular event

  • High LDL cholesterol levels, elevated blood pressure and smoking are major risk factors for cardiovascular disease in diabetes mellitus; low HDL cholesterol levels, insulin resistance, hyperglycaemia and inflammation also predict adverse cardiovascular events

  • Tissue-specific insulin resistance, such as in adipose tissue, the liver and the endothelium, and cell-type-specific insulin resistance, for example in macrophages, contribute to cardiovascular complications in diabetes mellitus

  • Hyperglycaemia exerts harmful effects on the endothelium, vascular smooth muscle cells and macrophages, and can cause thrombosis and fibrinolysis, which lead to formation of artherosclerotic plaques

  • In hyperglycaemia and insulin resistance, overproduction of reactive oxygen species and advance glycation end products further increases low-grade inflammation, which contributes to an elevated risk of cardiovascular disease

Abstract

The prevalence of diabetes mellitus will likely increase globally from 371 million individuals in 2013 to 552 million individuals in 2030. This epidemic is mainly attributable to type 2 diabetes mellitus (T2DM), which represents about 90–95% of all cases. Cardiovascular disease is the leading cause of mortality among individuals with diabetes mellitus, and >50% of patients will die from a cardiovascular event—especially coronary artery disease, but also stroke and peripheral vascular disease. Classic risk factors such as elevated levels of LDL cholesterol and blood pressure, as well as smoking, are risk factors for adverse cardiovascular events in patients with type 1 diabetes mellitus (T1DM) and T2DM to a similar degree as they are in healthy individuals. Patients with T1DM develop insulin resistance in the months after diabetes mellitus diagnosis, and patients with T2DM typically develop insulin resistance before hyperglycaemia occurs. Insulin resistance and hyperglycaemia, in turn, further increase the risk of adverse cardiovascular events. This Review discusses the mechanisms by which T1DM and T2DM can lead to cardiovascular disease and how these relate to the risk factors for coronary artery disease.

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Figure 1: Hypothetical effects of risk factors on cardiovascular-related mortality in patients with T1DM and T2DM.

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Both authors contributed equally to all aspects of the manuscript.

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Correspondence to Markku Laakso.

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Laakso, M., Kuusisto, J. Insulin resistance and hyperglycaemia in cardiovascular disease development. Nat Rev Endocrinol 10, 293–302 (2014). https://doi.org/10.1038/nrendo.2014.29

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