Insulin-Resistant Pathways Are Associated With Disease Activity in Rheumatoid Arthritis and Are Subject to Disease...

Area of Science:

• Rheumatology
• Metabolic Syndrome
• Immunology

Background:

• Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with significant morbidity and mortality.
• Insulin resistance and associated metabolic dysfunctions are increasingly recognized as contributing factors to RA pathogenesis and severity.
• Understanding the interplay between insulin resistance and inflammation is crucial for developing novel therapeutic strategies in RA.

Purpose of the Study:

• To investigate the role of insulin-resistant pathways in RA inflammation.
• To explore the potential of targeting these pathways for disease modification in RA.
• To assess the association between insulin resistance, disease activity, and cardiovascular risk factors in an Irish RA cohort.

Main Methods:

• Assessed RA disease activity and cardiovascular risk factors, including insulin resistance and BMI, in an Irish RA cohort.
• Examined glucose transporter 1 (GLUT-1) and GLUT-4 activity in RA and osteoarthritis (OA) synovial tissue using immunohistochemistry.
• Quantified spontaneous release of proinflammatory mediators from RA synovial explants and SFs, and analyzed protein expression and cellular metabolism.

Main Results:

• Insulin resistance was independently associated with BMI and swollen joint count in RA patients.
• Increased GLUT-1 expression and decreased GLUT-4 expression were observed in RA synovium compared to OA.
• Metformin treatment reduced pro-inflammatory mediator production and modulated cellular metabolism in RA synovial cells.

Conclusions:

• Insulin resistance is significantly associated with BMI and synovitis in RA, indicating a link between glucose metabolism and inflammation.
• The findings suggest a distinct interplay between glucose availability and inflammation in RA pathogenesis.
• AMPK-modifying compounds like metformin may represent a promising therapeutic approach for RA treatment by targeting inflammatory mechanisms.