Background Obesity in the U.S. has increased to an alarming extent over the past four decades. Obesity is related to risk of several autoimmune diseases, possibly via generation of adipokines and inflammatory cytokines. Prospective studies of obesity and systemic lupus erythematosus (SLE) risk are lacking however.

Objectives To prospectively evaluate the association between obesity and SLE risk

Methods We conducted a prospective cohort study of women in the U.S. Nurses' Health Studies (NHS, 1976–2012, age 30–55 at baseline; NHSII, 1989–2013, age 25–42 at baseline). Incident SLE was confirmed by American College of Rheumatology 1997 criteria. Body mass index (BMI, kg/m²) was reported at baseline and on biennial questionnaires. Cumulative average BMI (18.5 to <25 [normal (ref)], 25 to <30 [overweight], ≥30 [obese]) was the primary exposure. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for SLE by cumulative average BMI category, adjusting for covariates (Table). Analyses were conducted in each cohort; results were meta-analyzed with a DerSimonian-Laird random effects model. Sensitivity analyses: 1) excluded women with cancer, and 2) started in 1988 (NHS)/1989 (NHSII) when obesity prevalence in the U.S. was most steeply increasing.

Results We identified 154 SLE cases in NHS and 113 cases in NHSII. At baseline, obesity was present in 8.4% (NHS) and 11.8% (NHSII); mean age was 42.7 (SD 7.1) years (NHS) and 34.4 (SD 4.6) years (NHSII); 92% were White in each cohort. Obesity was significantly associated with SLE risk among women in NHSII, but not NHS (Table). In NHSII, a strong dose-dependent relationship between BMI and SLE risk was observed. After meta-analysis, obese women had a non-significantly elevated SLE risk compared to normal weight women (p trend 0.02). Results were similar in sensitivity analyses excluding women with cancer (HR 1.48, 95%CI 0.93–2.37, p trend 0.03). In analyses starting in 1988/1989, obese women had an increased SLE risk (meta-analyzed HR 1.76, 95%CI 1.19–2.58) compared to normal weight women (p trend <0.01).

Conclusions Obesity was associated with a significant 88% increase in SLE risk in the younger cohort, NHSII, but did not significantly elevate SLE risk in NHS subjects. Meta-analysis revealed a non-significant 49% increased risk of SLE in obese women. We observed a stronger obesity-associated SLE risk when analyses started in 1988/1989 in both cohorts. The discrepant results between the cohorts are not fully understood and deserve further study.

Disclosure of Interest None declared