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  • Review Article
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Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus

Key Points

  • Convincing epidemiological evidence substantiates a strong association between the presence and severity of nonalcoholic fatty liver disease (NAFLD) and the risk of chronic macrovascular (mainly cardiovascular disease) and microvascular (mainly chronic kidney disease) complications of diabetes mellitus

  • NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and causes the release of pro-inflammatory, procoagulant and proatherogenic factors that have a role in the development of chronic vascular complications of diabetes mellitus

  • Despite the evidence linking NAFLD to these chronic vascular complications, it has not been definitively established whether a causal association also exists

  • These findings call for a more active and systematic search for NAFLD in adult patients with diabetes mellitus with a view to implementing an earlier and more aggressive treatment whenever indicated

  • Whether a more liberal screening policy and more aggressive treatment will cost-effectively prevent the development of chronic vascular complications of diabetes mellitus will be the target of future larger studies

  • Although further research is needed, correction of intestinal dysbiosis might be a novel therapeutic target to ameliorate the risk of NAFLD and chronic vascular complications of diabetes mellitus

Abstract

Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70–80% of patients with type 2 diabetes mellitus and up to 30–40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.

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Figure 1: Proposed pragmatic algorithm for the management of suspected nonalcoholic fatty liver disease in patients with established diabetes mellitus.
Figure 2: Prevalence of clinically manifest cardiovascular disease in patients with type 2 diabetes mellitus.
Figure 3: Prevalence of diabetic nephropathy and retinopathy in patients with type 2 diabetes mellitus.
Figure 4: Potential pathways, factors and processes that link dysbiosis, mediators of the gut microbiota and alterations in hepatic structure and function to cardiovascular risk factors and vascular and renal diseases.
Figure 5: Potential pathways linking dysbiosis to cardiovascular disease, type 2 diabetes mellitus and chronic kidney disease.
Figure 6: Liver-specific pathways linking nonalcoholic fatty liver disease to cardiovascular and chronic kidney disease.

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Acknowledgements

G.T. is supported in part by grants from the University School of Medicine of Verona, Italy. C.D.B. is supported in part by the Southampton National Institute for Health Research Biomedical Research Centre.

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G.T. and C.D.B. declare no competing interests. A.L. is a researcher of a phase III, double-blind, randomized, placebo-controlled, multicentre study evaluating the safety and efficacy of obeticholic acid in patients with nonalcoholic steatohepatitis (EudraCT 2015-002560-16).

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Targher, G., Lonardo, A. & Byrne, C. Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol 14, 99–114 (2018). https://doi.org/10.1038/nrendo.2017.173

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