NAFLD improves risk prediction of type 2 diabetes: with effect modification by sex and menopausal status
NAFLD improves risk prediction of type 2 diabetes: with effect modification by sex and menopausal status
Background and Aims: The effects of sex and menopausal status on the association between NAFLD and incident type 2 diabetes (T2D) remain unclear. We investigated the effect modification by sex and menopause in the association between NAFLD and T2D; also, the added predictive ability of NAFLD for the risk of T2D was assessed. Approach and Results: This cohort study comprised 245,054 adults without diabetes (109,810 premenopausal women; 4958 postmenopausal women; 130,286 men). Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident T2D according to NAFLD status. The incremental predictive role of NAFLD for incident T2D was assessed using the area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. A total of 8381 participants developed T2D (crude incidence rate/10
3 person-years: 2.9 premenopausal women; 12.2 postmenopausal women; 9.3 men) during median follow-up of 5.3 years. NAFLD was positively associated with incident T2D in all groups. After adjustment for potential confounders, the multivariable-adjusted HRs (95% CIs) for incident T2D comparing NAFLD to no NAFLD were 4.63 (4.17–5.14), 2.65 (2.02–3.48), and 2.16 (2.04–2.29) in premenopausal women, postmenopausal women, and men, respectively. The risks of T2D increased with NAFLD severity as assessed by serum fibrosis markers, and the highest relative excess risks were observed in premenopausal women. The addition of NAFLD to conventional risk factors improved risk prediction for incident T2D in both sexes, with a greater improvement in women than men. Conclusions: NAFLD, including more severe NAFLD, is a stronger risk factor for incident T2D in premenopausal women than in postmenopausal women or men; protection against T2D is lost in premenopausal women with NAFLD.
1755-1765
Kim, Yejin
3b16bf66-f267-4b35-ba24-28915018c58d
Chang, Yoosoo
b81cdc89-eb02-4e38-b907-b4d10efbee5c
Ryu, Seungho
81f50c62-0552-4e67-8a03-e7d02c37b4e2
Wild, Sarah H.
48559e0e-667c-4f90-9ada-91be5918a515
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
1 December 2022
Kim, Yejin
3b16bf66-f267-4b35-ba24-28915018c58d
Chang, Yoosoo
b81cdc89-eb02-4e38-b907-b4d10efbee5c
Ryu, Seungho
81f50c62-0552-4e67-8a03-e7d02c37b4e2
Wild, Sarah H.
48559e0e-667c-4f90-9ada-91be5918a515
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Kim, Yejin, Chang, Yoosoo, Ryu, Seungho, Wild, Sarah H. and Byrne, Christopher
(2022)
NAFLD improves risk prediction of type 2 diabetes: with effect modification by sex and menopausal status.
Hepatology, 76: (6), .
(doi:10.1002/hep.32560).
Abstract
Background and Aims: The effects of sex and menopausal status on the association between NAFLD and incident type 2 diabetes (T2D) remain unclear. We investigated the effect modification by sex and menopause in the association between NAFLD and T2D; also, the added predictive ability of NAFLD for the risk of T2D was assessed. Approach and Results: This cohort study comprised 245,054 adults without diabetes (109,810 premenopausal women; 4958 postmenopausal women; 130,286 men). Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident T2D according to NAFLD status. The incremental predictive role of NAFLD for incident T2D was assessed using the area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. A total of 8381 participants developed T2D (crude incidence rate/10
3 person-years: 2.9 premenopausal women; 12.2 postmenopausal women; 9.3 men) during median follow-up of 5.3 years. NAFLD was positively associated with incident T2D in all groups. After adjustment for potential confounders, the multivariable-adjusted HRs (95% CIs) for incident T2D comparing NAFLD to no NAFLD were 4.63 (4.17–5.14), 2.65 (2.02–3.48), and 2.16 (2.04–2.29) in premenopausal women, postmenopausal women, and men, respectively. The risks of T2D increased with NAFLD severity as assessed by serum fibrosis markers, and the highest relative excess risks were observed in premenopausal women. The addition of NAFLD to conventional risk factors improved risk prediction for incident T2D in both sexes, with a greater improvement in women than men. Conclusions: NAFLD, including more severe NAFLD, is a stronger risk factor for incident T2D in premenopausal women than in postmenopausal women or men; protection against T2D is lost in premenopausal women with NAFLD.
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More information
Accepted/In Press date: 30 April 2022
e-pub ahead of print date: 5 May 2022
Published date: 1 December 2022
Additional Information:
Funding Information:
This study was supported by the SKKU Excellence in Research Award Research Fund, Sungkyunkwan University, 2020. Christopher D. Byrne is supported in part by the Southampton National Institute for Health and Care research Biomedical Research Centre (IS‐BRC‐20004), UK.
Publisher Copyright:
© 2022 American Association for the Study of Liver Diseases.
Identifiers
Local EPrints ID: 457196
URI: http://eprints.soton.ac.uk/id/eprint/457196
ISSN: 0270-9139
PURE UUID: db8fd72a-bc21-4e81-9238-438991267f2c
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Date deposited: 26 May 2022 16:36
Last modified: 17 Mar 2024 07:17
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Author:
Yejin Kim
Author:
Yoosoo Chang
Author:
Seungho Ryu
Author:
Sarah H. Wild
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