Clin Rheumatol. 2026 Jan 13. doi: 10.1007/s10067-026-07929-y. Online ahead of print.
ABSTRACT
BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation. Growing evidence suggests a link between insulin resistance (IR) and RA. However, the association of specific lipid-based IR indices, such as the Mffm/I index (Metabolic Score for Insulin Sensitivity), with RA prevalence remains underexplored. This study aimed to investigate the associations of the Mffm/I index and the Quantitative Insulin Sensitivity Check Index (QUICKI) with the prevalence of RA in a large, nationally representative population.
METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018. A total of 8,477 adult participants were included and categorized based on their RA status. The associations between Mffm/I, QUICKI (as both continuous variables and quartiles), and RA were evaluated using multivariable logistic regression models, adjusting for a comprehensive set of sociodemographic and clinical covariates. Results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses, interaction tests, and mediation analyses were conducted to explore the consistency of these associations and the potential mediating role of obesity.
RESULTS: Of the 8,477 participants, 549 (6.5%) reported a diagnosis of RA. After full adjustment for potential confounders, both the Mffm/I index and QUICKI demonstrated a significant inverse association with RA. In the fully adjusted model (Model 3), participants in the highest quartile (Q4) of Mffm/I had a 40% lower odds of RA (OR = 0.60, 95% CI: 0.45-0.79) compared to the lowest quartile (Q1). Similarly, the highest quartile of QUICKI was associated with a 28% lower odds of RA (OR = 0.72, 95% CI: 0.55-0.94). These negative associations were consistent across most predefined subgroups. Mediation analysis revealed that obesity significantly mediated the relationships, accounting for 43.87% of the total effect for Mffm/I and 51.04% for QUICKI.
CONCLUSION: This study establishes a stable and robust inverse association between both the Mffm/I index and QUICKI and the prevalence of rheumatoid arthritis in the U.S. adult population. These findings highlight the potential role of insulin sensitivity in the pathophysiology of RA and suggest that obesity is a critical mediator in this relationship. These easily accessible indices may serve as valuable tools for risk assessment in clinical practice. Key Points • High insulin sensitivity is strongly associated with lower rheumatoid arthritis prevalence. • The novel lipid-based Mffm/I index is a robust indicator of RA prevalence. • Obesity mediates over 40% of the link between insulin resistance and RA. • Accessible insulin sensitivity indices may aid in clinical RA risk assessment.
PMID:41528638 | DOI:10.1007/s10067-026-07929-y
