Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals
Open accessAbstract
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.
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The presence of MASLD is associated with a more than two-fold increased risk of an incident diagnosis of T2D, and this risk is increased with more advanced stages of MASLD.
“The presence of MASLD is associated with a more than two-fold increased risk of an incident diagnosis of T2D, and this risk is increased with more advanced stages of MASLD. 218”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [218]
The Discussion (page not available in our copy) reports a 2.19 hazard ratio for incident diabetes with NAFLD and says the risk increases with disease severity, especially fibrosis. The cited analysis studied NAFLD, not MASLD; our copy does not establish that the same estimates apply specifically to MASLD. (LLM, conf=0.86)
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- Authors
- Mantovani, A., Petracca, G., Beatrice, G., Tilg, H., Byrne, C. D., & Targher, G.
- Affiliations
- University of Verona (IT)
- Innsbruck Medical University (AT)
- University of Southampton (GB)
- Corresponding author
- Targher, Giovanni
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2020-09-16
- Volume
- 70
- Issue
- 5
- Pages
- 962-969
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W3084528742
- Cited by
- 481
- References
- 44
- Citations by year
- 2026: 56 · 2025: 89 · 2024: 95 · 2023: 90 · 2022: 72 · 2021: 74 · 2020: 5
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- green
- eprints.soton.ac.uk
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- National Institute for Health and Care Research
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, new-onset diabetes, NAFLD severity, liver fibrosis, diabetes risk, metabolic risk factors, adiposity
- MeSH terms
- Diabetes Mellitus, Type 2, Humans, Risk Factors, Severity of Illness Index, Non-alcoholic Fatty Liver Disease
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