Distinct associations of life-course body composition with incident Sjögren disease: a prospective cohort study in the UK Biobank.

OBJECTIVES

Existing studies have reported inconsistent associations between body mass index and incident Sjögren disease, with limited evidence on body composition, fat distribution, and underlying mediating mechanisms. This prospective cohort study aimed to investigate the association between life-course obesity indicators and Sjögren disease and potential underlying mechanisms.

METHODS

A total of 326,200 participants from the UK Biobank were included, with a median follow-up of 15.7 years. Cox proportional hazards models evaluated associations between life-course obesity indicators and incident Sjögren disease. Mediation analysis explored the potential mediating effects of inflammatory markers, metabolic indicators, and sex hormones.

RESULTS

A total of 607 incident Sjögren disease cases were observed. Body mass index, arm fat percentage, and leg fat-free mass ratio showed U-shaped associations with Sjögren disease. Muscle mass indicators were inversely associated with Sjögren disease risk: arm fat-free mass index (HR = 0.54, 95% CI: 0.41-0.72) and whole body fat-free mass (HR = 0.79, 95% CI: 0.64-0.97). Adiposity indicators were positively associated with Sjögren disease risk: whole body fat mass index (HR = 1.62, 95% CI: 1.17-2.24) and leg fat mass index (HR = 1.59, 95% CI: 1.11-2.29). Interleukin-6, C-reactive protein, lymphocytes, and sex hormone-binding globulin, among others, partially accounted for these associations.

CONCLUSIONS

Muscle mass is negatively associated with Sjögren disease risk, while adiposity is positively associated, with a U-shaped relationship for body mass index. Sex hormone-binding globulin, interleukin-6, C-reactive protein, and lymphocytes may be key intermediate factors in the association between body composition and Sjögren disease risk, generating hypotheses for future research on precision prevention. Key Points • This is the first prospective study to separately examine the associations of muscle mass and adiposity with incident Sjögren disease (SjD). • BMI showed a U-shaped association with SjD (inflection point 28.73 kg/m2), explaining prior inconsistent findings. • SHBG, IL-6, CRP, and lymphocytes may lie on body composition-SjD pathways, highlighting the muscle-immune-hormone axis for prevention.