Abstract

Rheumatoid factor (RF), a classic autoantibody directed against the Fc portion of immunoglobulin G (IgG), has 
long been recognized as a hallmark of rheumatoid arthritis (RA). However, emerging evidence indicates that RF 
positivity extends far beyond rheumatologic disease and may carry important metabolic and immunologic 
implications, particularly in diabetes mellitus. The rising global burden of diabetes, including both type 1 diabetes 
mellitus (T1DM) and type 2 diabetes mellitus (T2DM), has renewed interest in the role of chronic inflammation 
and autoimmunity in metabolic dysregulation. RF has been detected in a substantial proportion of diabetic 
individuals, especially those with long-standing hyperglycemia, microvascular complications, or coexisting 
autoimmune phenomena. Its presence correlates with oxidative stress, subclinical inflammation, endothelial 
dysfunction, and altered immunometabolic pathways. Recent studies suggest that RF positivity may predict poor 
glycemic control, increased cardiovascular risk, and enhanced susceptibility to diabetic complications, independent 
of traditional risk factors. Moreover, RF may reflect broader immune dysregulation involving B-cell hyperactivity, 
advanced glycation end-products, molecular mimicry, and chronic antigenic stimulation. This review synthesizes 
current evidence on the epidemiology, mechanisms, clinical significance, and potential therapeutic implications of 
RF in diabetes, highlighting its emerging role as a biomarker of systemic immune activation beyond rheumatoid 
arthritis.