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Aim Insulin resistance ( IR) plays an important role in the development of cardiovascular events in rheumatoid arthritis ( RA) patients. Adiponectin influences insulin sensitivity but its impact on IR in RA patients remains unclear. The present study aims to investigate the role of methotrexate ( MTX) and low doses of prednisolone ( LDP) on IR and adiponectin levels in RA patients who are naïve to disease-modifying antirheumatic drugs ( DMARDs), as well as determining the relationship between disease activity, acute phase response, IR and adiponectin levels in patients with RA. Methods Sixty-five RA patients naïve to DMARDs and prednisolone were involved in this study. The medication for RA patients was standardized for MTX and prednisolone. Body mass index, acute phase response reactants, 28-joint-count disease activity score, fasting blood glucose, serum cholesterol levels, insulin levels and adiponectin levels were measured in all RA patients both at the baseline and 3 months after the onset of the study. Results Adiponectin levels in the third month of the therapy with MTX and LDP were significantly increased in patients with RA ( P = 0.03). Insulin resistance tended to decrease in the third month of the treatment, which achieved no statistical significance. Conclusion Increased levels of adiponectin due to MTX and LDP could be related to the decrease in homeostasis model assessment insulin resistance ( HOMA- IR) in RA patients. This, in turn, could prove advantageous for cardiovascular conditions in RA. [ABSTRACT FROM AUTHOR]