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NAFLD and diabetes mellitus

Nature Reviews Gastroenterology & Hepatology volume 14, pages 32–42 (2017)Cite this article

Subjects

Key Points

  • As a result of increased prevalence, NAFLD and type 2 diabetes mellitus (T2DM) are of increasing clinical relevance worldwide

  • The liver has a key role in the pathophysiology of T2DM, as this organ contributes substantially to the development of insulin resistance

  • Rates of NAFLD, NASH, liver cirrhosis and hepatocellular carcinoma in patients with T2DM are rapidly rising

  • Medications used in the treatment of T2DM are also effective in the therapy of NASH

Abstract

The liver constitutes a key organ in systemic metabolism, contributing substantially to the development of insulin resistance and type 2 diabetes mellitus (T2DM). The mechanisms underlying these processes are not entirely understood, but involve hepatic fat accumulation, alterations of energy metabolism and inflammatory signals derived from various cell types including immune cells. Lipotoxins, mitochondrial function, cytokines and adipocytokines have been proposed to play a major part in both NAFLD and T2DM. Patients with NAFLD are commonly insulin resistant. On the other hand, a large number of patients with T2DM develop NAFLD with its inflammatory complication, NASH. The high incidence of NASH in patients with T2DM leads to further complications, such as liver cirrhosis and hepatocellular carcinoma, which are increasingly recognized. Therapeutic concepts such as thiazolidinediones (glitazones) for treating T2DM also show some efficacy in the treatment of NASH. This Review will describe the multifaceted and complex interactions between the liver and T2DM.

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Figure 1: Pathophysiological aspects of insulin resistance in NAFLD: role of lipids and energy metabolism.
Figure 2: Inflammatory pathways affecting hepatic insulin resistance.
Figure 3: Clinical algorithms in the management of NASH and diabetes mellitus.

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Authors and Affiliations

  1. Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Anichstrasse 35, Innsbruck, 6020, Austria

    Herbert Tilg & Alexander R. Moschen

  2. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, c/o Auf'm Hennekamp 65, Düsseldorf, 40225, Germany

    Michael Roden

  3. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, c/o Auf'm Hennekamp 65, Düsseldorf, 40225, Germany

    Michael Roden

  4. German Center of Diabetes Research, Ingolstädter Landstraße 1, München-Neuherberg, 85764, Germany

    Michael Roden

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H.T. and M.R. researched data for the article. A.R.M., H.T. and M.R. contributed to discussion of content, and wrote, reviewed and edited the manuscript before submission.

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Correspondence to Herbert Tilg or Michael Roden.

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Tilg, H., Moschen, A. & Roden, M. NAFLD and diabetes mellitus. Nat Rev Gastroenterol Hepatol 14, 32–42 (2017). https://doi.org/10.1038/nrgastro.2016.147

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