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Obesity and the risk of systemic lupus erythematosus among women in the Nurses' Health Studies.
Semin Arthritis Rheum 2017; 47(3):376-383SA

Abstract

BACKGROUND

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.

METHODS

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/m2) was calculated at baseline and on biennial questionnaires. Cox proportional hazards models estimated HRs (95% CIs) for SLE by cumulative average BMI category {18.5 to <25 [normal (reference)], 25 to <30 (overweight), ≥30 (obese)}, adjusting for potential time-varying confounders. Models were performed separately in each cohort; results were meta-analyzed. Sensitivity analyses used simple time-varying BMI, a 4-year lag between exposure and SLE risk window to address potential reverse causation, and evaluated BMI at age 18 and weight change since age 18. A secondary analysis started follow-up in both cohorts at similar calendar years when the prevalence of obesity in the U.S. increased most dramatically [1988 (NHS)/1989 (NHSII)].

RESULTS

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)].

CONCLUSION

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.

Authors+Show Affiliations

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115. Electronic address: stedeschi1@partners.org.Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115.Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115.Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115.Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115.Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115.Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115.

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28688713

Citation

Tedeschi, Sara K., et al. "Obesity and the Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Studies." Seminars in Arthritis and Rheumatism, vol. 47, no. 3, 2017, pp. 376-383.
Tedeschi SK, Barbhaiya M, Malspeis S, et al. Obesity and the risk of systemic lupus erythematosus among women in the Nurses' Health Studies. Semin Arthritis Rheum. 2017;47(3):376-383.
Tedeschi, S. K., Barbhaiya, M., Malspeis, S., Lu, B., Sparks, J. A., Karlson, E. W., ... Costenbader, K. H. (2017). Obesity and the risk of systemic lupus erythematosus among women in the Nurses' Health Studies. Seminars in Arthritis and Rheumatism, 47(3), pp. 376-383. doi:10.1016/j.semarthrit.2017.05.011.
Tedeschi SK, et al. Obesity and the Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Studies. Semin Arthritis Rheum. 2017;47(3):376-383. PubMed PMID: 28688713.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Obesity and the risk of systemic lupus erythematosus among women in the Nurses' Health Studies. AU - Tedeschi,Sara K, AU - Barbhaiya,Medha, AU - Malspeis,Susan, AU - Lu,Bing, AU - Sparks,Jeffrey A, AU - Karlson,Elizabeth W, AU - Willett,Walter, AU - Costenbader,Karen H, Y1 - 2017/05/25/ PY - 2017/03/01/received PY - 2017/05/11/revised PY - 2017/05/23/accepted PY - 2017/7/10/pubmed PY - 2018/6/28/medline PY - 2017/7/10/entrez KW - Body mass index KW - Obesity KW - Systemic lupus erythematosus SP - 376 EP - 383 JF - Seminars in arthritis and rheumatism JO - Semin. Arthritis Rheum. VL - 47 IS - 3 N2 - BACKGROUND: 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. METHODS: 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/m2) was calculated at baseline and on biennial questionnaires. Cox proportional hazards models estimated HRs (95% CIs) for SLE by cumulative average BMI category {18.5 to <25 [normal (reference)], 25 to <30 (overweight), ≥30 (obese)}, adjusting for potential time-varying confounders. Models were performed separately in each cohort; results were meta-analyzed. Sensitivity analyses used simple time-varying BMI, a 4-year lag between exposure and SLE risk window to address potential reverse causation, and evaluated BMI at age 18 and weight change since age 18. A secondary analysis started follow-up in both cohorts at similar calendar years when the prevalence of obesity in the U.S. increased most dramatically [1988 (NHS)/1989 (NHSII)]. RESULTS: 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)]. CONCLUSION: 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. SN - 1532-866X UR - https://www.unboundmedicine.com/medline/citation/28688713/Obesity_and_the_risk_of_systemic_lupus_erythematosus_among_women_in_the_Nurses'_Health_Studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-0172(17)30086-0 DB - PRIME DP - Unbound Medicine ER -