Nonalcoholic fatty liver disease without overlapping metabolic associated fatty liver disease and the risk of incident type 2 diabetes
Nonalcoholic fatty liver disease without overlapping metabolic associated fatty liver disease and the risk of incident type 2 diabetes
Background and aims: re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex.
Methods: 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups.
Results: a total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63–3.51) and 5.75 (5.17–6.36) (women), and 1.53 (1.25–1.88) and 2.60 (2.44–2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex <0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes).
Conclusions: NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.
2445-2454
Cho, Yoosun
343fc92f-22b1-4b0e-8705-8beb51a3f8c5
Chang, Yoosoo
dea6c8e3-fb05-4204-b18f-16eca7d115f7
Ryu, Seungho
6c43ded0-ab8f-450c-92d3-61abbec648ca
Wild, Sarah H.
77107afb-752d-4c97-b71c-f567a8cdf805
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
November 2023
Cho, Yoosun
343fc92f-22b1-4b0e-8705-8beb51a3f8c5
Chang, Yoosoo
dea6c8e3-fb05-4204-b18f-16eca7d115f7
Ryu, Seungho
6c43ded0-ab8f-450c-92d3-61abbec648ca
Wild, Sarah H.
77107afb-752d-4c97-b71c-f567a8cdf805
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Cho, Yoosun, Chang, Yoosoo, Ryu, Seungho, Wild, Sarah H. and Byrne, Christopher
(2023)
Nonalcoholic fatty liver disease without overlapping metabolic associated fatty liver disease and the risk of incident type 2 diabetes.
Liver International, 43 (11), .
(doi:10.1111/liv.15661).
Abstract
Background and aims: re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex.
Methods: 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups.
Results: a total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63–3.51) and 5.75 (5.17–6.36) (women), and 1.53 (1.25–1.88) and 2.60 (2.44–2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex <0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes).
Conclusions: NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.
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Accepted/In Press date: 15 June 2023
e-pub ahead of print date: 30 June 2023
Published date: November 2023
Additional Information:
Funding Information:
We thank our staff members at the Kangbuk Samsung Health Study for their hard work, dedication and support. This study was supported by the SKKU Excellence in Research Award Research Fund, Sungkyunkwan University (2020), and the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning (NRF‐2021R1A2C1012626). CDB was supported in part by the Southampton National Institute for Health Research Biomedical Research Centre (IS‐BRC‐20004), U.K.
Identifiers
Local EPrints ID: 478065
URI: http://eprints.soton.ac.uk/id/eprint/478065
ISSN: 1478-3223
PURE UUID: c639e724-c5a9-47fd-b979-b6b4bfa90456
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Date deposited: 21 Jun 2023 16:48
Last modified: 12 Jul 2024 04:05
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Author:
Yoosun Cho
Author:
Yoosoo Chang
Author:
Seungho Ryu
Author:
Sarah H. Wild
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