Pos0317 High Levels of Leptin in Blood Are Associated With Chronic Widespread Pain in Rheumatoid Arthritis

Background: Research on the adipose tissue and its involvement in disease has widened from studies on cardiovascular disease and diabetes to encompass its role as an endocrine organ with an important function in metabolism and inflammation. It is known that adipokines produced in the adipose tissue can interact with immune cells. How the adipose tissue interacts with the immune system in autoimmune diseases is under investigation. The adipokine leptin is essential in controlling appetite, insulin production and homeostasis but also plays a role in reproduction, bone mass regulation and chronic inflammatory diseases. Multiple studies have demonstrated that patients with rheumatoid arthritis (RA) and high body mass index (BMI) or metabolic syndrome have increased disease activity and pain, but any contributing role of leptin remains unclear. In patients with osteoarthritis an association between leptin levels and chronic widespread pain has been observed but to our knowledge no similar studies have been conducted on patients with RA [1]. Objectives: To investigate if leptin levels in blood is associated with CWP with the 2019 criteria in a cohort of patients with RA. Methods: 334 patients with RA from the BARFOT-cohort [2] filled out a questionnaire in 2010 including a pain mannequin and questions on length, weight and waist measurement. Blood samples were submitted within one year from finishing the questionnaire. The blood samples were analysed for leptin using an enzyme-linked immunosorbent assay ELISA. CWP was calculated with the new definition from 2019 [3], adapted to the pain mannequin in the questionnaire. Statistical analyses were carried out using nonparametric methods since the leptin levels were not normally distributed. Pearson Chi-Square and Mann-Whitney were used to compare groups and simple and multiple logistic regression analyses to explore associations. For some of the analyses the leptin variable was divided into four quartile groups; one n=83 (range leptin 0.55-6.88), two n=84 (leptin 7.04-17.43), three n=84 (leptin 17.54-39.42) and four n=83 (leptin 40.10-259.72). Results: Patients fulfilling the 2019 criteria for CWP in this study had significantly higher leptin levels, waist measurements and body mass index (BMI), Table 1. CWP was more common among female patients and fewer of them had positive rheumatoid factor (RF) compared to the patients without CWP. The patients with CWP had worse scores on health assessment questionnaire (HAQ) and on visual analogue scales (VAS) for pain and fatigue. There was a significant association between leptin levels and CWP, odds ratio (OR) 1.014 (95% conference interval (CI) 1.007-1.020), p < 0.001. The significant association remained when adjusted for BMI, gender and age OR 1.008 (95% CI 1.000-1.017) p 0.046. The association between leptin and CWP showed a trend where higher leptin levels gave higher OR for CWP, Figure 1. Conclusion: There is an increased risk of CWP in RA-patients with high leptin levels. The association remains after adjusting for BMI, gender and age. This could suggest that not just production of leptin in the adipose tissue, but also other factors such as leptin resistance of leptin receptors may play a role. Patients with the highest leptin levels had the greatest risk of CWP. REFERENCES: [1] Andersson MLE, Thorén E, Sylwander C, Bergman S. Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain. BMC musculoskeletal disorders. 2023;24(1):639. [2] Hafstrom I, Ajeganova S, Andersson ML, Bala SV, Bergman S, Bremander A, et al. A Swedish register-based, long-term inception cohort study of patients with rheumatoid arthritis - results of clinical relevance. Open Access Rheumatol. 2019;11:207-17. [3] Wolfe F, Butler SH, Fitzcharles M, Häuser W, Katz RL, Mease PJ, et al. Revised chronic widespread pain criteria: development from and integration with fibromyalgia criteria. Scandinavian journal of pain. 2019;20(1):77-86. Acknowledgements: We would like to thank the participants of this study for their contribution. We also thank Capio Movement Halmstad, The Swedish Rheumatism Association, The Council of Halland and the BARFOT study group. Disclosure of Interests: None declared.