New Biomarker Links Inflammation, Metabolism to Increased Rheumatoid Arthritis Risk
A novel biomarker combining measures of inflammation adn metabolic dysfunction demonstrates a strong, nonlinear association wiht rheumatoid arthritis (RA) risk, with body mass index (BMI) accounting for nearly one-third of this relationship, according to research published in Mediators of Inflammation in January 2025.
Researchers evaluated data from 4,292 US adults participating in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2010 to investigate the connection between the C-reactive protein-triglyceride-glucose index (CTI) and RA risk within a broad population sample. The study builds on emerging evidence suggesting that systemic low-grade inflammation and metabolic disturbances, alongside genetic and autoimmune factors, play a meaningful role in the development of RA.
The team found that higher CTI values were independently correlated with increased odds of RA across multiple analytical models. Even after accounting for demographic, socioeconomic, lifestyle, and clinical factors – including sex, age, race, education, smoking status, alcohol consumption, diabetes, and hypertension – each one-unit increase in CTI corresponded to a 45% increase in RA odds (OR, 1.45; 95% CI,1.22-1.73; P < .001).
“Unlike earlier studies that assessed CRP or TyG in isolation, our analysis offers novel insights by evaluating CTI as a unified marker and examining its underlying mechanism of action,” one researcher noted. “Importantly, our mediation analysis adds a new dimension to existing knowlege by identifying BMI as a significant mediator in the CTI-RA association.”
Analysis revealed a clear trend: RA prevalence progressively increas
by BMI – likely reflects the convergence of interconnected biological pathways involving systemic inflammation, insulin resistance, and adiposity-driven immune dysregulation.
Subgroup Analysis Reveals Nuances
Subgroup analyses revealed consistent CTI-RA associations across various demographic and clinical groups. The association remained significant for both men and women, and sex did not influence the relationship (interaction P = .760). similarly, race, smoking status, alcohol use, and hypertension did not significantly alter the CTI-RA relationship (interaction P = .353, .710, .543, and .695, respectively).
However, a significant interaction emerged regarding diabetes status. While CTI remained strongly associated with RA risk among non-diabetic individuals, this association weakened and became statistically insignificant among those with diabetes (P = .036). Researchers theorize that advanced metabolic dysregulation in individuals with existing diabetes may obscure the relationship between CTI and RA.
Study Limitations and Future Directions
The investigators acknowledged limitations, including reliance on self-reported RA diagnoses, potential for residual confounding, and the observational, cross-sectional nature of the data, which prevents definitive conclusions about causality. Despite these limitations, the authors concluded that CTI shows promise as a biomarker for RA.
“This study highlights CTI as a promising biomarker reflecting the interplay between metabolic dysfunction and systemic inflammation in relation to RA risk,” the authors wrote. “these findings suggest CTI may help identify individuals with elevated metabolic-inflammatory burden who could be at heightened risk of developing RA.”
The research team believes further investigation into CTI could lead to improved risk stratification and potentially, novel preventative strategies for rheumatoid arthritis.
References:
Xie H, Liu Q, Xu X, et al. Nonlinear association between the C-reactive protein-triglyceride-glucose index and rheumatoid arthritis risk: the mediating role of body mass index. Mediators Inflamm. 2025;2025:8729780. doi:10.1155/mi/8729780
Jutley GS, Sahota K, Sahbudin I, et al. Relationship between inflammation and metabolism in patients with newly presenting rheumatoid arthritis. Front Immunol. 2021;12:676105. doi:10.3389/fimmu.2021.676105
