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  • Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis

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Hepatology
Original research
Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis
  1. Elina En Li Cho1,
  2. Chong Zhe Ang1,
  3. Jingxuan Quek2,
  4. Clarissa Elysia Fu2,
  5. Lincoln Kai En Lim2,
  6. Zane En Qi Heng2,
  7. Darren Jun Hao Tan2,
  8. Wen Hui Lim2,
  9. Jie Ning Yong2,
  10. Rebecca Zeng2,
  11. Douglas Chee1,
  12. Benjamin Nah1,
  13. Cosmas Rinaldi Adithya Lesmana3,
  14. Aung Hlaing Bwa4,
  15. Khin Maung Win4,
  16. Claire Faulkner5,
  17. Majd B Aboona5,
  18. Mei Chin Lim2,6,
  19. Nicholas Syn2,
  20. Anand V. Kulkarni7,
  21. Hiroyuki Suzuki8,
  22. Hirokazu Takahashi9,
  23. Nobuharu Tamaki10,11,
  24. Karn Wijarnpreecha12,
  25. Daniel Q. Huang1,2,13,
  26. Mark Muthiah1,2,13,
  27. Cheng Han Ng2,
  28. Rohit Loomba10
  1. 1 Department of Medicine, National University Hospital, Singapore
  2. 2 Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  3. 3 Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  4. 4 Department of Medical Research, Union of Myanmar, Naypyidaw, Myanmar
  5. 5 Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
  6. 6 Department of Diagnostic Imaging, National University Health System, Singapore
  7. 7 Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
  8. 8 Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  9. 9 Liver Center, Saga University Hospital, Saga, Japan
  10. 10 Department of Medicine, University of California San Diego, La Jolla, California, USA
  11. 11 Department of Medicine, Musashino Red Cross Hospital, Musashino, Japan
  12. 12 Division of Gastroenterology and Hepatology, University of Michigan, Michigan, Michigan, USA
  13. 13 Division of Gastroenterology and Hepatology, National University Health System, Singapore
  1. Correspondence to Dr Cheng Han Ng, National University of Singapore, singapore, Singapore; chenhanng{at}gmail.com

Abstract

Introduction Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with type 2 diabetes mellitus (T2DM) as a major predictor. Insulin resistance and chronic inflammation are key pathways in the pathogenesis of T2DM leading to NAFLD and vice versa, with the synergistic effect of NAFLD and T2DM increasing morbidity and mortality risks. This meta-analysis aims to quantify the prevalence of NAFLD and the prevalence of clinically significant and advanced fibrosis in people with T2DM.

Methods MEDLINE and Embase databases were searched from inception until 13 February 2023. The primary outcomes were the prevalence of NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis in people with T2DM. A generalised linear mixed model with Clopper-Pearson intervals was used for the analysis of proportions with sensitivity analysis conducted to explore heterogeneity between studies.

Results 156 studies met the inclusion criteria, and a pooled analysis of 1 832 125 patients determined that the prevalence rates of NAFLD and NASH in T2DM were 65.04% (95% CI 61.79% to 68.15%, I2=99.90%) and 31.55% (95% CI 17.12% to 50.70%, I2=97.70%), respectively. 35.54% (95% CI 19.56% to 55.56%, I2=100.00%) of individuals with T2DM with NAFLD had clinically significant fibrosis (F2–F4), while 14.95% (95% CI 11.03% to 19.95%, I2=99.00%) had advanced fibrosis (F3–F4).

Conclusion This study determined a high prevalence of NAFLD, NASH and fibrosis in people with T2DM. Increased efforts are required to prevent T2DM to combat the rising burden of NAFLD.

PROSPERO registration number CRD42022360251.

  • META-ANALYSIS
  • DIABETES MELLITUS
  • FATTY LIVER
  • NONALCOHOLIC STEATOHEPATITIS

Data availability statement

All articles included in this manuscript are made publicly available on Medline and Embase. Datarelevant to this study are included in this manuscript or uploaded as supplementary materials. Additional data can be requested from the corresponding author.

https://doi.org/10.1136/gutjnl-2023-330110

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    Data availability statement

    All articles included in this manuscript are made publicly available on Medline and Embase. Datarelevant to this study are included in this manuscript or uploaded as supplementary materials. Additional data can be requested from the corresponding author.

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    Footnotes

    • EELC, CZA and JQ are joint first authors.

    • Twitter @aunghlaingbwa, @AnandVKulkarni2, @KarnJUVE

    • EELC, CZA and JQ contributed equally.

    • Contributors All authors have made substantial contributions to all of the following: (1) the conception and design of the study, acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it critically for important intellectual content; (3) final approval of the version to be submitted. No writing assistance was obtained in the preparation of the manuscript. The manuscript, including related data, figures and tables has not been previously published, and the manuscript is not under consideration elsewhere. All authors approved the final version of the manuscript, including the authorship list, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Overall guarantor: CHN; conceptualisation and design: RL, CHN, MM and DQH; acquisition of data: EELC, CZA, JQ, CEF, LKEL, ZEQH, DJHT, WHL, JNY, RZ, DC, BN, CF, MBA, MCL, NS, AVK, NT and KW; analysis and interpretation of data: EELC, CZA, JQ, DJHT, WHL, AHB, KMW, NS, HS, HT, NT, KW,DQH, MM and CHN; writing of the original draft: EELC, CZA, JQ, CEF, LKEL, ZEQH, DJHT, WHL, JNY, RZ, DC, BN, CRAL, AHB, KMW, CF, MBA, MCL, NS, AVK, HS, HT, NT, KW, DQH, MM, CHN and RL; writing of the review and editing: EELC, CZA, JQ, CEF, LKEL, ZEQH, DJHT, WHL, JNY, RZ, DC, BN, CRAL, AHB, KMW, CF, MBA, MCL, NS, AVK, HS, HT, NT, KW, DQH, MM, CHN and RL.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Map disclaimer The inclusion of any map (including the depiction of any boundaries therein) or of any geographical or locational reference does not imply the expression of any opinion whatsoever on the part of BMJ concerning the legal status of any country, territory, jurisdiction or area or of its authorities. Any such expression remains solely that of the relevant source and is not endorsed by BMJ. Maps are provided without any warranty of any kind, either expressed or implied.

    • Competing interests DQH served as an advisory board member for Gilead and received funding support from the Singapore Ministry of Health’s National Medical Research Council under its NMRC Research Training Fellowship (MOH-000595-01). CHN and MM served as a consultants for Boxer Capital. RL served as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 Bio, Terns Pharmaceuticals and Viking Therapeutics; in addition, his institutions received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes and Terns Pharmaceuticals; cofounder of LipoNexus Inc.

    • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

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

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.