Obesity is increasingly prevalent and related to increased risk of several autoimmune diseases, likely via generation of inflammatory adipokines. Prior studies have not evaluated obesity in relation to systemic lupus erythematosus (SLE) risk. We prospectively evaluated whether obesity was associated with increased SLE risk among women in the U.S. Nurses' Health Study cohorts.
We conducted a prospective cohort study among 238,130 women in the Nurses' Health Studies (NHS, 1976-2012; NHSII, 1989-2013). Incident SLE was confirmed by American College of Rheumatology 1997 criteria and validated through medical record review. Body mass index (BMI, kg/m
We identified 153 NHS incident SLE cases and 115 incident NHSII cases during 5,602,653 person-years of follow-up. At baseline, 8.4% of women in NHS and 11.8% in NHSII were obese. Mean age at enrollment was 42.5 (SD 7.2) years in NHS and 34.4 (SD 4.7) years in NHSII. Cumulative average obesity was significantly associated with SLE risk in NHSII [HR = 1.85 (1.17-2.91)], but not in NHS [HR = 1.11 (0.65-1.87)] compared to normal BMI. In the meta-analysis of both cohorts, obesity was not significantly associated with increased risk of SLE [HR = 1.46 (0.88-2.40)]. Simple time-varying BMI and lagging the exposure window by 4 years produced similar findings to the primary analysis. In NHSII, a 4.54 kg gain between age 18 and enrollment slightly increased SLE risk [HR = 1.09 (1.02-1.18)]. In the secondary analysis starting follow-up of both cohorts at similar calendar years, the point estimate for obesity in NHS was higher than the primary analysis [HR = 1.67 (0.81-3.45)].
We observed an 85% significantly increased risk of SLE among obese compared to normal BMI women in the more recent NHSII cohort, but no association was observed in the earlier NHS cohort. Secular trends in obesity may account for the differences between the two birth cohorts.