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Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment

Nature Reviews Endocrinology volume 7, pages 456–465 (2011)Cite this article

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Abstract

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist as they share the pathogenic abnormalities of excess adiposity and insulin resistance. Although type 1 diabetes mellitus (T1DM) is due to a relative lack of insulin, an increased prevalence of obesity and insulin resistance in this population means that NAFLD also commonly coexists with this condition. Both T2DM and NAFLD are associated with adverse outcomes of the other; T2DM is a risk factor for progressive liver disease and liver-related death in patients with NAFLD, whereas NAFLD may be a marker of cardiovascular risk and mortality in individuals with T2DM. Nonalcoholic steatohepatitis—a histological subtype of NAFLD characterized by hepatocyte injury and inflammation—is present in approximately 10% of patients with T2DM and is associated with an increased risk for the development of cirrhosis and liver-related death. Current treatment strategies aim to improve insulin resistance via weight loss and exercise, improve insulin sensitivity by the use of insulin-sensitizing agents (for example, pioglitazone) and reduce oxidative stress by the use of antioxidants, such as vitamin E. Pioglitazone and vitamin E supplementation show the most promise in improving hepatic steatosis and inflammation but have not yet been demonstrated to improve fibrosis, and concern remains regarding the toxicity of long-term use of both of these agents.

Key Points

  • Nonalcoholic fatty liver disease (NAFLD) is present in 50–60% of patients with type 2 diabetes mellitus (T2DM) and up to 45% of individuals with T1DM

  • Insulin resistance and NAFLD are closely related: insulin resistance promotes hepatic lipid accumulation and liver injury and hepatic lipid and cytokine release promote hepatic insulin resistance

  • T2DM increases the risk of cirrhosis and liver-related death in patients with NAFLD, whereas NAFLD may increase the risk of cardiovascular disease and overall mortality in T2DM

  • T2DM is a risk factor for nonalcoholic steatohepatitis, which is associated with a more aggressive course and higher rates of progression to cirrhosis than simple hepatic steatosis

  • NAFLD is an independent risk factor for the development of cardiovascular disease in patients with T1DM and T2DM

  • For patients with T2DM and NAFLD, weight loss and exercise aim to improve insulin resistance; moreover, insulin-sensitizing agents and antioxidants improve some hepatic parameters, but cardiotoxicity remains a concern

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Figure 1: Insulin resistance promotes hepatic triglyceride accumulation by increasing peripheral adipose lipolysis and free fatty acid influx as well as upregulating levels of hepatic lipogenic transcription factors SREBP1c and ChREBP.

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  1. School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Verdun Street, Nedlands, 6009, WA, Australia

    Briohny W. Smith & Leon A. Adams

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Both authors researched data for the article, provided substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Leon A. Adams.

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Smith, B., Adams, L. Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol 7, 456–465 (2011). https://doi.org/10.1038/nrendo.2011.72

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