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Original research
Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals
  1. Alessandro Mantovani1,
  2. Graziana Petracca1,
  3. Giorgia Beatrice1,
  4. Herbert Tilg2,
  5. Christopher D Byrne3,
  6. Giovanni Targher1
  1. 1 Endocrinology and Metabolism, University of Verona Department of Medicine, Verona, Italy
  2. 2 Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, University of Innsbruck, Innsbruck, Austria
  3. 3 Faculty of Medicine, University of Southampton, Southampton, UK
  1. Correspondence to Professor Giovanni Targher, Endocrinology and Metabolism, University of Verona Department of Medicine, Verona 37126, Italy; giovanni.targher{at}


Objective Follow-up studies have shown that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident diabetes, but currently, it is uncertain whether this risk changes with increasing severity of NAFLD. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.

Design We systematically searched PubMed, Scopus and Web of Science databases from January 2000 to June 2020 using predefined keywords to identify observational studies with a follow-up duration of at least 1 year, in which NAFLD was diagnosed by imaging techniques or biopsy. Meta-analysis was performed using random-effects modelling.

Results 33 studies with 501 022 individuals (30.8% with NAFLD) and 27 953 cases of incident diabetes over a median of 5 years (IQR: 4.0–19 years) were included. Patients with NAFLD had a higher risk of incident diabetes than those without NAFLD (n=26 studies; random-effects HR 2.19, 95% CI 1.93 to 2.48; I 2=91.2%). Patients with more ‘severe’ NAFLD were also more likely to develop incident diabetes (n=9 studies; random-effects HR 2.69, 95% CI 2.08 to 3.49; I 2=69%). This risk markedly increased across the severity of liver fibrosis (n=5 studies; random-effects HR 3.42, 95% CI 2.29 to 5.11; I 2=44.6%). All risks were independent of age, sex, adiposity measures and other common metabolic risk factors. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias.

Conclusion This updated meta-analysis shows that NAFLD is associated with a ~2.2-fold increased risk of incident diabetes. This risk parallels the underlying severity of NAFLD.

  • liver
  • nonalcoholic steatohepatitis
  • diabetes mellitus
  • meta-analysis

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplementary information.

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  • Contributors Study concept and design: AM and GT; acquisition of data: AM, GP, GB and GT; statistical analysis of data: AM, GT; analysis and interpretation of data: AM, GT; drafting of the manuscript: GT; critical revision of the manuscript for important intellectual content: HT and CDB. All authors revised and approved the final version of the manuscript. GT and AM are the guarantors who take full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

  • Funding GT is supported in part by grants from the University School of Medicine of Verona, Verona, Italy. CDB is supported in part by the Southampton National Institute for Health Research (NIHR) Biomedical Research Centre.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.