Abstract

Rheumatoid factor (RF), traditionally regarded as a serological marker of rheumatoid arthritis (RA), is 
increasingly recognized for its broader relevance in systemic inflammatory states. Accumulating evidence suggests 
that RF positivity may reflect underlying metabolic inflammation, oxidative stress, and immune 
dysregulation—core mechanisms also implicated in insulin resistance and type 2 diabetes mellitus (T2DM). This 
review synthesizes current knowledge on the emerging role of RF as a potential metabolic biomarker. It examines 
biochemical mechanisms through which chronic inflammation, redox imbalance, altered B-cell tolerance, adipokine 
signaling, and post-translational protein modifications may promote RF generation outside autoimmune disease. 
Furthermore, we discuss epidemiological observations linking RF positivity with obesity, dyslipidemia, hepatic 
steatosis, and increased risk of T2DM. We also evaluate how RF-associated immune activation may exacerbate 
metabolic dysfunction through pathways involving TNF-α, IL-6, NF-κB, and oxidative damage. Lastly, the review 
outlines clinical implications for screening, risk stratification, and personalized therapeutic strategies targeting 
inflammation-driven metabolic disease. Understanding RF as a metabolic signal rather than a disease-specific 
autoantibody may expand its utility in the early identification of individuals at risk of insulin resistance and type 2 
diabetes mellitus (T2DM).