High leptin levels in blood are associated with chronic widespread pain in rheumatoid arthritis

High body mass index (BMI) has been shown to have an association with chronic widespread pain (CWP), both in Rheumatoid arthritis (RA) and in other pain conditions such as fibromyalgia. Research on the adipose tissue and it’s adipokines, for example the well described leptin, is emerging. The objective of this study was to determine if there is an association between leptin levels in blood and CWP in patients with RA. In this cross-sectional study 334 patients with RA filled in a questionnaire including a pain mannequin and questions on weight, length and waist circumference. Data from the pain mannequin was used to calculate CWP. The subjects also submitted blood samples to a biobank that were used for this study to determine leptin levels using an ELISA-method. Patients fulfilling the 2019 criteria for CWP in this study had significantly higher leptin levels, waist circumferences and BMI. There was a significant association between leptin levels and CWP, odds ratio (OR) 1.014 (95% confidence interval (CI) 1.007–1.020), p < 0.001. The association remained after adjusting for BMI, gender and age OR 1.008 (95% CI 1.000-1.017), p 0.046. When leptin was divided into quartile groups a trend could be observed where higher leptin values gave higher OR for CWP. This study showed an increased occurrence of CWP in RA-patients with high leptin levels. The association between leptin and CWP remained after adjusting for gender, age and BMI or waist circumference. This suggests that not just production of leptin in the adipose tissue, but also other factors such as leptin resistance may play a role. The association between leptin and CWP was strongest in the patients with the highest leptin levels. This study is a cross-sectional study without intervention and the cohort used was initiated prior to the implementation of mandatory registration requirements, therefore it is not registered.