Sex and age influence the association between insulin resistance and all-cause mortality in rheumatoid arthritis patients
6 affiliations
- 1Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 3Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 4Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 5Department of Rheumatology, Jingmen People’s Hospital, Jingmen, Hubei China
- 6Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Abstract
Objectives: To investigate the association between insulin resistance (IR) and all-cause mortality among adults with rheumatoid arthritis (RA).
Methods: In this cohort study, we included 1,427 adults with self-reported RA from the National Health and Nutrition Examination Survey (NHANES) 1999–2010 and 2015–2018. IR was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR). Survey-weighted multivariable Cox proportional hazards models were used to evaluate the association between HOMA-IR and all-cause mortality.
Results: During a mean follow-up of 9.7 years, 491 deaths occurred. Compared with participants in the lowest tertile of HOMA-IR, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were 0.633 (0.466–0.860) and 0.626 (0.463–0.847) for the second and third tertiles, respectively. Each 1-standard deviation increase in HOMA-IR was associated with a 14.5% lower risk of all-cause mortality (HR 0.855, 95% CI 0.734–0.995). The association varied by age and sex. Stratified analyses suggested that higher HOMA-IR was associated with increased mortality risk in men aged < 70 years and women aged < 50 years, whereas inverse associations were observed in men aged ≥ 70 years and women aged ≥ 50 years.
Conclusions: The association between HOMA-IR and all-cause mortality among adults with RA differed according to age and sex. Although higher HOMA-IR was inversely associated with mortality overall, subgroup-specific associations were heterogeneous and should not be interpreted as evidence of a protective effect of IR. Further studies are needed to clarify the mechanisms underlying these age- and sex-related differences. Keypoints
• This study provides the first nationally representative evidence on the association between HOMA-IR and all-cause mortality among U.S. adults reporting rheumatoid arthritis.
• HOMA-IR showed an approximately L-shaped association with all-cause mortality.
• The association differed by age and sex, with higher mortality risk in younger subgroups and inverse associations in older subgroups.
• The findings remained consistent across multiple sensitivity analyses addressing medication use, C-reactive protein (CRP) assessment, missing data, and potential reverse causation.
Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s10067-026-08376-5.
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BibTeX
@article{yan2026influence,
title = {{Sex and age influence the association between insulin resistance and all-cause mortality in rheumatoid arthritis patients}},
author = {Jiahui Yan and Yifei Li and Youpeng Su and Xin Ba and Weiji Lin and Tingting Li and Ruiyuan Zhang and Pan Shen and Yao Huang and Ying Huang and Kai Qin and Hua Huang and Liang Zou and Yafei Liu and Yu Wang and Zhe Chen and Liang Han and Shenghao Tu},
journal = {Clinical Rheumatology},
year = {2026},
month = sep,
doi = {10.1007/s10067-026-08376-5},
url = {https://doi.org/10.1007/s10067-026-08376-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Sex and age influence the association between insulin resistance and all-cause mortality in rheumatoid arthritis patients
AU - Jiahui Yan
AU - Yifei Li
AU - Youpeng Su
AU - Xin Ba
AU - Weiji Lin
AU - Tingting Li
AU - Ruiyuan Zhang
AU - Pan Shen
AU - Yao Huang
AU - Ying Huang
AU - Kai Qin
AU - Hua Huang
AU - Liang Zou
AU - Yafei Liu
AU - Yu Wang
AU - Zhe Chen
AU - Liang Han
AU - Shenghao Tu
PY - 2026
DA - 2026/09/08
JO - Clinical Rheumatology
DO - 10.1007/s10067-026-08376-5
UR - https://doi.org/10.1007/s10067-026-08376-5
AB - Objectives: To investigate the association between insulin resistance (IR) and all-cause mortality among adults with rheumatoid arthritis (RA). Methods: In this cohort study, we included 1,427 adults with self-reported RA from the National Health and Nutrition Examination Survey (NHANES) 1999–2010 and 2015–2018. IR was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR). Survey-weighted multivariable Cox proportional hazards models were used to evaluate the association between HOMA-IR and all-cause mortality. Results: During a mean follow-up of 9.7 years, 491 deaths occurred. Compared with participants in the lowest tertile of HOMA-IR, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were 0.633 (0.466–0.860) and 0.626 (0.463–0.847) for the second and third tertiles, respectively. Each 1-standard deviation increase in HOMA-IR was associated with a 14.5% lower risk of all-cause mortality (HR 0.855, 95% CI 0.734–0.995). The association varied by age and sex. Stratified analyses suggested that higher HOMA-IR was associated with increased mortality risk in men aged < 70 years and women aged < 50 years, whereas inverse associations were observed in men aged ≥ 70 years and women aged ≥ 50 years. Conclusions: The association between HOMA-IR and all-cause mortality among adults with RA differed according to age and sex. Although higher HOMA-IR was inversely associated with mortality overall, subgroup-specific associations were heterogeneous and should not be interpreted as evidence of a protective effect of IR. Further studies are needed to clarify the mechanisms underlying these age- and sex-related differences. Keypoints • This study provides the first nationally representative evidence on the association between HOMA-IR and all-cause mortality among U.S. adults reporting rheumatoid arthritis. • HOMA-IR showed an approximately L-shaped association with all-cause mortality. • The association differed by age and sex, with higher mortality risk in younger subgroups and inverse associations in older subgroups. • The findings remained consistent across multiple sensitivity analyses addressing medication use, C-reactive protein (CRP) assessment, missing data, and potential reverse causation. Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s10067-026-08376-5.
SN - 0770-3198
SN - 1434-9949
ER -