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Type 2 Diabetes and Hepatocellular Carcinoma: Risk Factors and Pathogenesis

  • Other Forms of Diabetes and Its Complications (JJ Nolan, Section Editor)
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Abstract

Purpose of Review

This review aims to assess the epidemiological evidence for a link between type 2 diabetes and hepatocellular carcinoma and to investigate possible pathophysiological mechanisms.

Recent Findings

The presence of type 2 diabetes significantly increases the risk of developing hepatocellular carcinoma, and treatment with metformin may be associated with a lower risk. Treatment with insulin and sulphonylureas may be associated with increased risk. The pathophysiology underlying development of hepatocellular carcinoma in this context is complex and is likely to involve increased proinflammatory mediators, oxidative stress, JNK-1 activation, increased IGF-1 activity, altered gut microbiota and immunomodulation.

Summary

Hepatocellular carcinoma incidence is increasing and this is likely to be linked to the increasing incidence of type 2 diabetes, obesity and the metabolic syndrome. These conditions increase the risk of developing hepatocellular carcinoma, and a greater understanding of the underlying pathophysiology may help with the development of novel treatments.

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Acknowledgements

C. D. Byrne is supported in part by the Southampton National Institute for Health Research Biomedical Research Centre.

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Authors and Affiliations

  1. Clinical Biochemistry, University Hospital Southampton, Southampton, UK

    P. Wainwright

  2. Chemical Pathology and Metabolic Medicine, Department of Laboratory Medicine, D-Level Pathology Block, University Hospital Southampton, Tremona Road, Southampton, SO16 6YD, UK

    P. Wainwright

  3. Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK

    E. Scorletti & C. D. Byrne

  4. National Institute for Health Research Southampton Biomedical Research Center (in Nutrition) and Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK

    E. Scorletti & C. D. Byrne

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P. Wainwright and E. Scorletti declare that they have no conflict of interest.

C. D. Byrne is principal investigator for the INvestigation of SYnbiotic TreatmEnt in NAFLD (INSYTE) trial. The INSYTE randomised placebo-controlled double blind trial is testing the effects of a synbiotic on liver fat, disease biomarkers and intestinal microbiota in non-alcoholic fatty liver disease and is currently in recruitment phase (www.clinicaltrials.gov NCT01680640). The INSYTE trial is completely independent of industry, but Christian Hansen (Denmark) are providing the synbiotic intervention and placebo at no cost to the investigators.

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This article is part of the Topical Collection on Other Forms of Diabetes and Its Complications

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Wainwright, P., Scorletti, E. & Byrne, C.D. Type 2 Diabetes and Hepatocellular Carcinoma: Risk Factors and Pathogenesis. Curr Diab Rep 17, 20 (2017). https://doi.org/10.1007/s11892-017-0851-x

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