title: Significant effects of biologic therapy on lipid profiles and insulin resistance in patients with rheumatoid arthritis.
abstract: BACKGROUND
  The goal of this study was to investigate (1) the associations of rheumatoid arthritis (RA)-related inflammation or rheumatoid factor/anti-cyclic citrullinated peptide (anti-CCP) positivity with lipid profiles and insulin resistance (IR), (2) the effects of biologic therapy on lipid profiles and IR, and (3) potential predictors for the presence of subclinical atherosclerosis.
  
  
  METHODS
  Serum levels of lipid profiles were determined by enzymatic methods in 32 adalimumab-treated patients, 16 etanercept-treated patients, 24 tocilizumab-treated patients, and 20 biologic-naïve patients. Atherogenic index, which corresponds to the ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C), was calculated. IR was measured by homeostasis model assessment. Pro-inflammatory cytokine levels were examined by enzyme-linked immunosorbent assay. Common carotid artery intima-media thickness was determined by using sonography.
  
  
  RESULTS
  There was an inverse correlation between disease activity (disease activity score for 28 joints, or DAS28) and low-density lipoprotein cholesterol (LDL-C) levels (r=-0.226, P<0.05) and a positive correlation between DAS28 and IR (r=0.361, P<0.005). Anti-CCP-positive patients had significantly higher DAS28 and IR compared with anti-CCP-negative patients. There was also a positive correlation between IR and levels of interleukin-6 or tumor necrosis factor-alpha (TNF-α). HDL-C levels significantly increased in patients receiving 6-month anti-TNF-α therapy, and levels of total cholesterol, LDL-C, and triglyceride increased in tocilizumab-treated patients. IR significantly decreased in patients under biologic therapy but was unchanged in biologic-naïve patients. Age, IR, and DAS28 were significant predictors of severe subclinical atherosclerosis (odds ratios of 1.08, 2.77, and 2.52, respectively).
  
  
  CONCLUSIONS
  Significant associations of RA-related inflammation with lipid profiles and IR indicate the involvement of RA in atherosclerosis pathogenesis. Biologic therapies were associated with IR reduction without change in atherogenic index, but their beneficial effects on atherosclerosis reduction need to be verified in the future.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taiwan Boulevard, Taichung, 40705, Taiwan. dychen@vghtc.gov.tw.|Institute of Biomedical Science, National Chung Hsing University, No.250, Guoguang Rd., South Dist., Taichung, 40227, Taiwan. dychen@vghtc.gov.tw.|Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, No.250, Guoguang Rd., South Dist., Taichung, 40227, Taiwan. dychen@vghtc.gov.tw.|Institute of Microbiology and Immunology, Chung Shan Medical University, No.110, Sec.1, Jianguo N.Rd., Taichung, 40201, Taiwan. dychen@vghtc.gov.tw.
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taiwan Boulevard, Taichung, 40705, Taiwan. ymchen1@vghtc.gov.tw.|Institute of Biomedical Science, National Chung Hsing University, No.250, Guoguang Rd., South Dist., Taichung, 40227, Taiwan. ymchen1@vghtc.gov.tw.|Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, No.250, Guoguang Rd., South Dist., Taichung, 40227, Taiwan. ymchen1@vghtc.gov.tw.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taiwan Boulevard, Taichung, 40705, Taiwan. zuyihsieh@gmail.com.
authors.forename: Tsu-Yi
authors.initials: TY
authors.lastname: Hsieh
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taiwan Boulevard, Taichung, 40705, Taiwan. chiaweih@gmail.com.|Institute of Biomedical Science, National Chung Hsing University, No.250, Guoguang Rd., South Dist., Taichung, 40227, Taiwan. chiaweih@gmail.com.|Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, No.250, Guoguang Rd., South Dist., Taichung, 40227, Taiwan. chiaweih@gmail.com.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Hsieh
authors.affiliation: Institute of Biomedical Science, National Chung Hsing University, No.250, Guoguang Rd., South Dist., Taichung, 40227, Taiwan. lincc@dragon.nchu.edu.tw.|Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, No.250, Guoguang Rd., South Dist., Taichung, 40227, Taiwan. lincc@dragon.nchu.edu.tw.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Immunology and Rheumatology, China Medical University Hospital, No. 2, Yude Rd., North Dist., Taichung, 40404, Taiwan. jounglan2003@yahoo.com.tw.|College of Medicine, China Medical University, No. 2, Yude Rd., North Dist., Taichung, 40404, Taiwan. jounglan2003@yahoo.com.tw.
authors.forename: Joung-Liang
authors.initials: JL
authors.lastname: Lan
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001685:Biological Factors / Q000627:therapeutic use*; D001691:Biological Therapy / Q000379:methods*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001685:Biological Factors; D016207:Cytokines; D008055:Lipids