title: Type 2 Diabetes and Hepatocellular Carcinoma: Risk Factors and Pathogenesis.
abstract: This review aims to assess the epidemiological evidence for a link between type 2 diabetes and hepatocellular carcinoma and to investigate possible pathophysiological mechanisms.
  
  
  
  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. 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.
authors.affiliation: Clinical Biochemistry, University Hospital Southampton, Southampton, UK. patrick.wainwright@uhs.nhs.uk.|Chemical Pathology and Metabolic Medicine, Department of Laboratory Medicine, D-Level Pathology Block, University Hospital Southampton, Tremona Road, Southampton, SO16 6YD, UK. patrick.wainwright@uhs.nhs.uk.
authors.forename: P
authors.initials: P
authors.lastname: Wainwright
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.|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.
authors.forename: E
authors.initials: E
authors.lastname: Scorletti
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.|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.
authors.forename: C D
authors.initials: CD
authors.lastname: Byrne
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D024821:Metabolic Syndrome / Q000150:complications; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology; D009765:Obesity / Q000150:complications; D012307:Risk Factors
chemical_list: D048055:Mitogen-Activated Protein Kinase 8
keywords: Diabetes; Hepatocellular carcinoma; Non-alcoholic fatty liver disease; Obesity; Pathogenesis; Risk factors