title: Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study.
abstract: OBJECTIVE
  SLE is associated with increased risk of diabetes mellitus. Treatment for SLE requires high-dose glucocorticoids that may worsen glucose homoeostasis. HCQ can reduce diabetes risk in RA. This study aimed to investigate the association of HCQ use and diabetes mellitus risk in SLE patients.
  
  
  METHODS
  This nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. In the period 2001-10, 8628 newly diagnosed SLE patients were identified after excluding those with a previous diagnosis of RA, psoriasis or diabetes mellitus. Incidence of diabetes mellitus was identified as a new diagnostic code using a diabetes mellitus-specific medication.
  
  
  RESULTS
  Two hundred and twenty-one newly diagnosed diabetes mellitus patients were identified among SLE patients (6795 had taken HCQ and 1833 had never taken HCQ), with an average follow-up period of 5.6 years. Compared with patients without HCQ treatment, the hazard ratio (HR) of diabetes mellitus in patients taking HCQ at a cumulative dose ≥129 g was reduced [HR 0.26 (95% CI 0.18, 0.37), P < 0.001]. Daily glucocorticoid ≥10 mg prednisolone-equivalent dose was associated with increased risk of developing diabetes mellitus [HR 2.47 (95% CI 1.44, 4.23), P = 0.001], which was minimized by concomitant HCQ use at a cumulative dose ≥129 g.
  
  
  CONCLUSIONS
  In SLE patients, the use of HCQ is associated with reduced risk of incident diabetes mellitus in a dose-dependent manner. High-dose glucocorticoids increase the risk of diabetes, which can be decreased by concomitant HCQ use.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Ching-Heng
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Tsuo-Hung
authors.initials: TH
authors.lastname: Lan
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Shih-Ni
authors.initials: SN
authors.lastname: Chang
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Yi-Hsing
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Jun-Sing
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hung
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Joung-Liang
authors.initials: JL
authors.lastname: Lan
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Department of Medical Research, Department of Psychiatry, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Division of Immunology and Rheumatology, College of Medicine, Institute of Biomedical Science, National Chung-Hsing University and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Faculty of Medicine, School of Medicine, Ins
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D015994:Incidence; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D006886:Hydroxychloroquine; D005947:Glucose
keywords: diabetes; glucocorticoid; hydroxychloroquine; systemic lupus erythematosus