title: Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis.
abstract: BACKGROUND
  Free fatty acids (FFAs) affect insulin signaling and are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines such as interleukin-6 (IL-6) increase lipolysis and thus levels of FFAs. We hypothesized that increased IL-6 concentrations are associated with increased FFAs resulting in insulin resistance and atherosclerosis in rheumatoid arthritis (RA).
  
  
  METHODS
  Clinical variables, serum FFAs and inflammatory cytokines, homeostasis model assessment for insulin resistance (HOMA-IR), and coronary artery calcium were measured in 166 patients with RA and 92 controls. We compared serum FFAs in RA and controls using Wilcoxon rank sum tests and further tested for multivariable association by adjusting for age, race, sex and BMI. Among patients with RA, we assessed the relationship between serum FFAs and inflammatory cytokines, HOMA-IR, and coronary artery calcium scores using Spearman correlation and multivariable regression analyses.
  
  
  RESULTS
  Serum FFAs did not differ significantly in patients with RA and controls (0.56mmol/L [0.38-0.75] and 0.56mmol/L [0.45-0.70] respectively, p=0.75). Presence of metabolic syndrome was associated with significantly increased serum FFAs in both RA and controls (p=0.035 and p=0.025). In multivariable regression analysis that adjusted for age, race, sex and BMI, serum FFAs were associated with HOMA-IR (p=0.011), CRP (p=0.01), triglycerides (p=0.005) and Framingham risk score (p=0.048) in RA, but not with IL-6 (p=0.48) or coronary artery calcium score (p=0.62).
  
  
  CONCLUSIONS
  Serum FFAs do not differ significantly in patients with RA and controls. FFAs may contribute to insulin resistance, but are not associated with IL-6 and coronary atherosclerosis in RA.
authors.affiliation: Division of Rheumatology, Department of Medicine and Pharmacology, Vanderbilt University, Nashville, TN, USA. michelle.ormseth@vanderbilt.edu
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Ormseth
authors.forename: Larry L
authors.initials: LL
authors.lastname: Swift
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.forename: Macrae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Chung
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Rho
authors.forename: Joseph
authors.initials: J
authors.lastname: Solus
authors.forename: Annette
authors.initials: A
authors.lastname: Oeser
authors.forename: Aihua
authors.initials: A
authors.lastname: Bian
authors.forename: Tebeb
authors.initials: T
authors.lastname: Gebretsadik
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shintani
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology*; D003430:Cross-Sectional Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D061205:Vascular Calcification / Q000097:blood / Q000209:etiology*
chemical_list: D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6