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Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis

Abstract

NAFLD is a spectrum of progressive liver disease that encompasses simple steatosis, NASH, fibrosis and, ultimately, cirrhosis. NAFLD is recognized as the hepatic component of the metabolic syndrome, as these conditions have insulin resistance as a common pathophysiological mechanism. Therefore, NAFLD is strongly associated with type 2 diabetes mellitus and abdominal obesity. As lifestyles have become increasingly sedentary and dietary patterns have changed, the worldwide prevalence of NAFLD has increased dramatically and is projected to be the principal aetiology for liver transplantation within the next decade. Importantly, a growing body of clinical and epidemiological evidence suggests that NAFLD is associated not only with liver-related morbidity and mortality, but also with an increased risk of developing both cardiovascular disease and type 2 diabetes mellitus. This article reviews the evidence that suggests NAFLD is a multisystem disease and the factors that might determine interindividual variation in the development and progression of its major hepatic and extrahepatic manifestations (principally type 2 diabetes mellitus and cardiovascular disease).

Key Points

  • NAFLD is a spectrum of progressive liver disease that includes steatosis, NASH, fibrosis, cirrhosis and hepatocellular carcinoma

  • NAFLD is a common and underdiagnosed condition that is strongly associated with features of the metabolic syndrome, particularly abdominal obesity and type 2 diabetes mellitus

  • NAFLD, and especially NASH, are associated with an increased risk of morbidity and mortality related to the liver and cardiovascular system

  • NAFLD is also associated with an increased risk of developing type 2 diabetes mellitus

  • Considerable interindividual variation exists in the severity of NAFLD and the risk of morbidity and mortality that might be influenced by a combination of genetic and environmental factors

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Figure 1: Patients with NAFLD have a myriad of traditional and nontraditional risk factors for CVD.
Figure 2: The putative mechanisms underlying the contribution of NAFLD to the increased risk of developing CVD and T2DM.

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Acknowledgements

Q. M. Anstee would like to acknowledge the support of a Clinical Senior Lectureship Award from the Higher Education Funding Council for England (HEFCE). Q. M. Anstee and C. P. Day are members of the European Union FP7-funded Fatty Liver Inhibition of Progression (FLIP) Consortium.

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Anstee, Q., Targher, G. & Day, C. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 10, 330–344 (2013). https://doi.org/10.1038/nrgastro.2013.41

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