Jiahui Yan, Yifei Li, Youpeng Su, Xin Ba, Weiji Lin, Tingting Li, Ruiyuan Zhang, Pan Shen, Yao Huang, Ying Huang, Kai Qin, Hua Huang, Liang Zou, Yafei Liu, Yu Wang, Zhe Chen, Liang Han, Shenghao Tu
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.
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.