Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort

Author:

Chew Christine1ORCID,Reynolds John A23ORCID,Lertratanakul Apinya4ORCID,Wu Peggy4,Urowitz Murray5,Gladman Dafna D5,Fortin Paul R6,Bae Sang-Cheol7,Gordon Caroline3,Clarke Ann E8,Bernatsky Sasha9ORCID,Hanly John G10,Isenberg David11ORCID,Rahman Anisur11ORCID,Sanchez-Guerrero Jorge5,Romero-Diaz Juanita12,Merrill Joan13,Wallace Daniel14,Ginzler Ellen15,Khamashta Munther16,Nived Ola17,Jönsen Andreas17,Steinsson Kristjan18,Manzi Susan19,Kalunian Ken20,Dooley Mary Anne21,Petri Michelle22,Aranow Cynthia23,van Vollenhoven Ronald24,Stoll Thomas25,Alarcón Graciela S26,Lim S Sam27,Ruiz-Irastorza Guillermo28ORCID,Peschken Christine A29,Askanase Anca D30,Kamen Diane L31,İnanç Murat32,Ramsey-Goldman Rosalind4,Bruce Ian N3334

Affiliation:

1. Lydia Becker Institute of Immunology and Inflammation, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester

2. Department of Rheumatology, Sandwell and West Birmingham NHS Trust

3. Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK

4. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

5. Toronto Western Hospital Centre for Prognosis Studies in the Rheumatic Diseases Toronto, ON

6. Department of Rheumatology, Université Laval Faculté de médecine, Quebec, QC, Canada

7. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea

8. Divisions of Clinical Immunology/Allergy and Clinical Epidemiology, University of Calgary Cumming School of Medicine, Calgary, AB

9. Faculty of Medicine, Division of Rheumatology, McGill University, Montreal, QC

10. Division of Rheumatology, Department of Medicine and Department of Pathology Halifax, Queen Elizabeth II Health Sciences Centre, NS, Canada

11. Faculty of Medical Sciences, Division of Medicine, University College London, London, UK

12. Immunology and Rheumatology Tlalpan, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, DF, Mexico

13. Department of Clinical Pharmacology, Oklahoma Medical Research Foundation Arthritis and Clinical Immunology Research Program, Oklahoma City, OK

14. Cedars-Sinai/David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, Los Angeles, CA

15. Department of Medicine, SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, USA

16. Rayne Institute, St Thomas' Hospital, King’s College London School of Medicine, London, UK

17. Faculty of Medicine, Department of Clinical Sciences Lund, Section of Rheumatology, Lunds University, Lund, Sweden

18. Department of Rheumatology, National University Hospital of Iceland, Reykjavik, Iceland

19. Allegheny Health Network, Lupus Center of Excellence, Pittsburgh, PA

20. University of California San Diego School of Medicine, La Jolla, CA

21. Division of Rheumatology and Immunology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC

22. Department of Rheumatology, Johns Hopkins University School of Medicine Center for Musculoskeletal Research, Baltimore, MD

23. Northwell Health Feinstein Institutes for Medical Research, Manhasset, NY, USA

24. Amsterdam University Medical Centres, Duivendrecht, Noord-Holland, Netherlands

25. Department of Rheumatology, Kantonsspital Schaffhausen, Schaffhausen, Schaffhausen, Switzerland

26. Department of Medicine, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham School of Medicine, Birmingham, AL

27. Division of Rheumatology, Emory University School of Medicine, Atlanta, GA, USA

28. Hospital Universitario Cruces, Autoimmune Diseases Units, Biocruces Bizkaia Health Research Institute, Barakaldo, País Vasco, Spain

29. University of Manitoba, Winnipeg, MB, Canada

30. Columbia University Irving Medical Center, New York, NY

31. Medical University of South Carolina, Charleston, SC, USA

32. Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul University Istanbul, Istanbul, Istanbul, Turkey

33. Kellgren Centre for Rheumatology, Manchester University NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, Greater Manchester

34. Versus Arthritis Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

Abstract

Abstract Objectives Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance. Methods The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10–36 nmol/l), T2 (37–60 nmol/l) and T3 (61–174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels. Results Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased high-density lipoprotein (HDL) were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance. Conclusions MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.

Funder

Canadian Institutes of Health Research

Versus Arthritis (Versus Arthritis Research UK Epidemiology Unit Core Support Programme Grant

National Institute for Health Research (NIHR) Manchester Biomedical Research Centre

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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