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Newly defined clinical obesity versus BMI-defined obesity: differential risks of overall death and adverse events in a population-based cohort

Newly defined clinical obesity versus BMI-defined obesity: differential risks of overall death and adverse events in a population-based cohort
Newly defined clinical obesity versus BMI-defined obesity: differential risks of overall death and adverse events in a population-based cohort
Aims: to compare the prognostic implications of the newly proposed clinical obesity classification against traditional body mass index (BMI)-defined obesity in a population-based cohort.

Materials and Methods: using UK Biobank, we compared the impact of newly defined obesity, including clinical obesity (obesity status with obesity-related comorbidities) and pre-clinical obesity (obesity status with preserved organ function), with traditional BMI-defined obesity on death, cardiovascular disease (CVD), chronic kidney disease (CKD), and liver-related events (LREs). To further delineate heterogeneity within the clinical obesity group, we performed stratified analyses based on comorbidity burden (number of comorbidities), severity of adiposity, and presence of diabetes or hypertension.

Results: a total of 502 129 participants were enrolled. About 375 585 (74.8%) had non-obesity, 126 544 (25.2%) had BMI-defined obesity (including 93 410 [73.8%] with clinical obesity and 13 875 [11.0%] with pre-clinical obesity). During a median follow-up of 15.8 years, clinical obesity was associated with significantly higher risks of death (HR = 1.097, 95% CI: 1.071–1.125, p < 0.001), LRE (HR = 1.103, 95% CI: 1.040–1.169, p < 0.001), CVD (HR = 1.118, 95% CI: 1.091–1.146, p < 0.001), and CKD (HR = 1.111, 95% CI: 1.081–1.141, p < 0.001) compared to BMI-based obesity. Conversely, pre-clinical obesity showed significantly lower risks across these outcomes. High-risk clinical obesity subgroups with multiple comorbidities or severe adiposity showed particularly increased risks.

Conclusion: the clinical obesity classification helps to define a high-risk phenotype with substantially increased risks of mortality and major comorbidities, while pre-clinical obesity defines a distinct subgroup with more favourable outcomes.
cardiovascular disease, chronic kidney disease, clinical obesity, liver-related events, obesity
1462-8902
Lian, Li-You
07ebf0ab-ad4c-49fe-b214-4ebde5a5413c
Liu, Chuan
f307e64d-1311-4195-91f9-6ad2030a96fc
Zhou, Xiao-Dong
65011d8c-4237-4dae-b6d4-55ec3f28ae16
Targher, Giovanni
93b7aea7-7f16-4bad-8518-9a45e464583a
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Zhang, Yilin
8b44343d-1dc2-44c8-9367-b44117060a0c
Qi, Xiaolong
889635ea-d477-42b2-85f9-308ca65a629e
Jin, Hui
1b3b1979-a52b-4589-acc9-ed79aa5acac1
Zheng, Ming-Hua
b36e1d46-dd41-4575-b1d0-1f380cecaadc
Liu, Wen-Yue
5d352d80-f01d-4430-8cf4-0340676880ed
Lian, Li-You
07ebf0ab-ad4c-49fe-b214-4ebde5a5413c
Liu, Chuan
f307e64d-1311-4195-91f9-6ad2030a96fc
Zhou, Xiao-Dong
65011d8c-4237-4dae-b6d4-55ec3f28ae16
Targher, Giovanni
93b7aea7-7f16-4bad-8518-9a45e464583a
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Zhang, Yilin
8b44343d-1dc2-44c8-9367-b44117060a0c
Qi, Xiaolong
889635ea-d477-42b2-85f9-308ca65a629e
Jin, Hui
1b3b1979-a52b-4589-acc9-ed79aa5acac1
Zheng, Ming-Hua
b36e1d46-dd41-4575-b1d0-1f380cecaadc
Liu, Wen-Yue
5d352d80-f01d-4430-8cf4-0340676880ed

Lian, Li-You, Liu, Chuan, Zhou, Xiao-Dong, Targher, Giovanni, Byrne, Christopher D., Zhang, Yilin, Qi, Xiaolong, Jin, Hui, Zheng, Ming-Hua and Liu, Wen-Yue (2025) Newly defined clinical obesity versus BMI-defined obesity: differential risks of overall death and adverse events in a population-based cohort. Diabetes, Obesity and Metabolism. (doi:10.1111/dom.70271).

Record type: Article

Abstract

Aims: to compare the prognostic implications of the newly proposed clinical obesity classification against traditional body mass index (BMI)-defined obesity in a population-based cohort.

Materials and Methods: using UK Biobank, we compared the impact of newly defined obesity, including clinical obesity (obesity status with obesity-related comorbidities) and pre-clinical obesity (obesity status with preserved organ function), with traditional BMI-defined obesity on death, cardiovascular disease (CVD), chronic kidney disease (CKD), and liver-related events (LREs). To further delineate heterogeneity within the clinical obesity group, we performed stratified analyses based on comorbidity burden (number of comorbidities), severity of adiposity, and presence of diabetes or hypertension.

Results: a total of 502 129 participants were enrolled. About 375 585 (74.8%) had non-obesity, 126 544 (25.2%) had BMI-defined obesity (including 93 410 [73.8%] with clinical obesity and 13 875 [11.0%] with pre-clinical obesity). During a median follow-up of 15.8 years, clinical obesity was associated with significantly higher risks of death (HR = 1.097, 95% CI: 1.071–1.125, p < 0.001), LRE (HR = 1.103, 95% CI: 1.040–1.169, p < 0.001), CVD (HR = 1.118, 95% CI: 1.091–1.146, p < 0.001), and CKD (HR = 1.111, 95% CI: 1.081–1.141, p < 0.001) compared to BMI-based obesity. Conversely, pre-clinical obesity showed significantly lower risks across these outcomes. High-risk clinical obesity subgroups with multiple comorbidities or severe adiposity showed particularly increased risks.

Conclusion: the clinical obesity classification helps to define a high-risk phenotype with substantially increased risks of mortality and major comorbidities, while pre-clinical obesity defines a distinct subgroup with more favourable outcomes.

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More information

Accepted/In Press date: 27 October 2025
e-pub ahead of print date: 10 November 2025
Keywords: cardiovascular disease, chronic kidney disease, clinical obesity, liver-related events, obesity

Identifiers

Local EPrints ID: 507454
URI: http://eprints.soton.ac.uk/id/eprint/507454
ISSN: 1462-8902
PURE UUID: 3380b9da-8d86-48e4-925b-873a1c96e43d
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

Catalogue record

Date deposited: 09 Dec 2025 17:52
Last modified: 16 Dec 2025 02:36

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Contributors

Author: Li-You Lian
Author: Chuan Liu
Author: Xiao-Dong Zhou
Author: Giovanni Targher
Author: Yilin Zhang
Author: Xiaolong Qi
Author: Hui Jin
Author: Ming-Hua Zheng
Author: Wen-Yue Liu

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