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Weight-adjusted-waist index, estimated glucose disposal rate, C-reactive protein, and mortality risks among individuals with type 2 diabetes : 2 prospective cohort studies in China and the United Kingdom

Geng, Yang ; Gu, Shujun ; Fan, Yulong ; Lu, Xujia ; Zhou, Zhengyuan ; Zhang, Ning ; Pei, Yalong ; Lu, Xinmei ; Borné, Yan LU and Ke, Chaofu (2025) In The American journal of clinical nutrition
Abstract

BACKGROUND: Weight-adjusted-waist index (WWI) is an anthropometric index reflecting fat mass and muscle mass, both of which are important factors influencing insulin resistance and inflammation.

OBJECTIVES: We aimed to examine the associations of WWI with all-cause, cardiovascular, and noncardiovascular mortality among individuals with type 2 diabetes (T2D) and further investigate whether insulin resistance and inflammation, measured by estimated glucose disposal rate (eGDR) and C-reactive protein (CRP) respectively, can mediate these associations.

METHODS: Participants with T2D from 2 prospective cohorts, the China Changshu Cohort of Type 2 Diabetes (CT2D) (N = 10,157) and UK Biobank (UKB) (N = 25,019), were included. WWI... (More)

BACKGROUND: Weight-adjusted-waist index (WWI) is an anthropometric index reflecting fat mass and muscle mass, both of which are important factors influencing insulin resistance and inflammation.

OBJECTIVES: We aimed to examine the associations of WWI with all-cause, cardiovascular, and noncardiovascular mortality among individuals with type 2 diabetes (T2D) and further investigate whether insulin resistance and inflammation, measured by estimated glucose disposal rate (eGDR) and C-reactive protein (CRP) respectively, can mediate these associations.

METHODS: Participants with T2D from 2 prospective cohorts, the China Changshu Cohort of Type 2 Diabetes (CT2D) (N = 10,157) and UK Biobank (UKB) (N = 25,019), were included. WWI was calculated as waist circumference divided by the square root of body weight.

RESULTS: In CT2D, participants in the highest WWI quartile had higher risks of all-cause mortality (hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.44, 1.86), cardiovascular mortality (HR: 1.51; 95% CI: 1.20, 1.89), and noncardiovascular mortality (HR: 1.71; 95% CI: 1.47, 2.00) compared with those in the lowest quartile. In UKB, the corresponding HRs for all-cause mortality, cardiovascular mortality, and noncardiovascular mortality were 1.55 (95% CI: 1.42, 1.70), 1.80 (95% CI: 1.52, 2.13), and 1.46 (95% CI: 1.31, 1.62), respectively. WWI also showed better predictive ability than many current obesity indicators in both cohorts. Furthermore, eGDR mediated the relation between WWI and all-cause, cardiovascular, and noncardiovascular mortality by 16.20% (95% CI: 6.77, 27.63), 57.92% (95% CI: 33.52, 115.98), and 1.03% (95% CI: -9.96, 11.95) in CT2D and by 23.70% (95% CI: 15.60, 34.57), 38.02% (95% CI: 23.89, 59.19), and 16.06% (95% CI: 5.51, 29.55) in UKB, respectively. In UKB, the mediation proportions of CRP for all-cause, cardiovascular, and noncardiovascular mortality were 8.75% (95% CI: 6.23, 12.18), 7.64% (95% CI: 4.40, 12.73), and 9.38% (95% CI: 6.20, 13.91), respectively.

CONCLUSIONS: High WWI levels are associated with increased risks of all-cause, cardiovascular, and noncardiovascular mortality among individuals with T2D, and eGDR and CRP mediate these associations. Our study highlights the value of WWI in identifying high-risk individuals and the potential of monitoring eGDR and CRP concentration and intervening as needed to prevent mortality in individuals with T2D.

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Contribution to journal
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in
The American journal of clinical nutrition
publisher
Elsevier
external identifiers
  • pmid:40953704
ISSN
1938-3207
DOI
10.1016/j.ajcnut.2025.09.018
language
English
LU publication?
yes
additional info
Copyright © 2025 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.
id
b680ddc3-75b4-4e3a-93e2-5993202c0647
date added to LUP
2025-10-21 12:44:55
date last changed
2025-10-22 08:10:56
@article{b680ddc3-75b4-4e3a-93e2-5993202c0647,
  abstract     = {{<p>BACKGROUND: Weight-adjusted-waist index (WWI) is an anthropometric index reflecting fat mass and muscle mass, both of which are important factors influencing insulin resistance and inflammation.</p><p>OBJECTIVES: We aimed to examine the associations of WWI with all-cause, cardiovascular, and noncardiovascular mortality among individuals with type 2 diabetes (T2D) and further investigate whether insulin resistance and inflammation, measured by estimated glucose disposal rate (eGDR) and C-reactive protein (CRP) respectively, can mediate these associations.</p><p>METHODS: Participants with T2D from 2 prospective cohorts, the China Changshu Cohort of Type 2 Diabetes (CT2D) (N = 10,157) and UK Biobank (UKB) (N = 25,019), were included. WWI was calculated as waist circumference divided by the square root of body weight.</p><p>RESULTS: In CT2D, participants in the highest WWI quartile had higher risks of all-cause mortality (hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.44, 1.86), cardiovascular mortality (HR: 1.51; 95% CI: 1.20, 1.89), and noncardiovascular mortality (HR: 1.71; 95% CI: 1.47, 2.00) compared with those in the lowest quartile. In UKB, the corresponding HRs for all-cause mortality, cardiovascular mortality, and noncardiovascular mortality were 1.55 (95% CI: 1.42, 1.70), 1.80 (95% CI: 1.52, 2.13), and 1.46 (95% CI: 1.31, 1.62), respectively. WWI also showed better predictive ability than many current obesity indicators in both cohorts. Furthermore, eGDR mediated the relation between WWI and all-cause, cardiovascular, and noncardiovascular mortality by 16.20% (95% CI: 6.77, 27.63), 57.92% (95% CI: 33.52, 115.98), and 1.03% (95% CI: -9.96, 11.95) in CT2D and by 23.70% (95% CI: 15.60, 34.57), 38.02% (95% CI: 23.89, 59.19), and 16.06% (95% CI: 5.51, 29.55) in UKB, respectively. In UKB, the mediation proportions of CRP for all-cause, cardiovascular, and noncardiovascular mortality were 8.75% (95% CI: 6.23, 12.18), 7.64% (95% CI: 4.40, 12.73), and 9.38% (95% CI: 6.20, 13.91), respectively.</p><p>CONCLUSIONS: High WWI levels are associated with increased risks of all-cause, cardiovascular, and noncardiovascular mortality among individuals with T2D, and eGDR and CRP mediate these associations. Our study highlights the value of WWI in identifying high-risk individuals and the potential of monitoring eGDR and CRP concentration and intervening as needed to prevent mortality in individuals with T2D.</p>}},
  author       = {{Geng, Yang and Gu, Shujun and Fan, Yulong and Lu, Xujia and Zhou, Zhengyuan and Zhang, Ning and Pei, Yalong and Lu, Xinmei and Borné, Yan and Ke, Chaofu}},
  issn         = {{1938-3207}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{Elsevier}},
  series       = {{The American journal of clinical nutrition}},
  title        = {{Weight-adjusted-waist index, estimated glucose disposal rate, C-reactive protein, and mortality risks among individuals with type 2 diabetes : 2 prospective cohort studies in China and the United Kingdom}},
  url          = {{http://dx.doi.org/10.1016/j.ajcnut.2025.09.018}},
  doi          = {{10.1016/j.ajcnut.2025.09.018}},
  year         = {{2025}},
}