title: Aminotransferases are associated with insulin resistance and atherosclerosis in rheumatoid arthritis.
abstract: BACKGROUND
  Serum aminotransferase concentrations are reportedly strongly associated with insulin resistance, an established cardiovascular risk factor that is not routinely assessed in clinical practice. We therefore explored the possibility that serum aminotransferase concentrations are as closely related to large artery disease as insulin resistance in rheumatoid arthritis (RA).
  
  
  METHODS
  Carotid artery plaque (ultrasonography), insulin resistance and liver enzymes (prior to methotrexate (MTX) were determined in 77 consecutive patients with RA (43 with and 34 without MTX).
  
  
  RESULTS
  Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were associated with insulin resistance in univariate analysis (R = 0.54, p < 0.0001 and R = 0.36, p = 0.001, respectively) and after adjustment for age, gender and waist circumference (partial R = 0.43, p = 0.0001 and partial R = 0.37, p = 0.001, respectively). ALT and AST concentrations were higher in patients with plaque as compared to in those without plaque (ALT (u/l): 27 2223242526272829303132 versus 20 181920212223, p = 0.02; AST (u/l): 25 2122232425262728 versus 20 19202122, p = 0.02). The odds ratios [95% CI] for plaque were 1.92 [1.14-3.24] (p = 0.01), 1.93 [1.17-3.16] (p = 0.009) and 1.82 [1.13-2.93] (p = 0.01) for 1 SD increase in ALT (~10 u/l) and AST (approximately 6 u/l) concentrations and in logarithmically transformed homeostasis model assessment of insulin resistance (HOMA-IR) (~0.2 uU.mmol/ml.l), respectively. After adjustment for the potentially confounding characteristics of age, sex, hypertension and hypothyroidism in logistic regression models, ALT (p = 0.049) and AST concentrations (p = 0.027) remained associated with plaque whereas the HOMA-IR did not (p = 0.08). AST concentrations (p = 0.049) were associated with plaque independent of insulin resistance whereas the HOMA-IR (p = 0.1) was not associated with plaque independent of AST concentrations.
  
  
  CONCLUSIONS
  Within currently recommended reference ranges, serum aminotransferase concentrations may be strongly associated with insulin resistance and atherosclerosis in patients with RA. The measurement of aminotransferase concentrations could be a useful tool in cardiovascular risk stratification in patients with RA.
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. dessein@telkomsa.net
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Dessein
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Woodiwiss
authors.forename: Barry I
authors.initials: BI
authors.lastname: Joffe
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Norton
mesh_terms: D050153:Abdominal Fat / Q000503:physiopathology; D000410:Alanine Transaminase / Q000097:blood*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D001219:Aspartate Aminotransferases / Q000097:blood*; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D008954:Models, Biological; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D014463:Ultrasonography; D015854:Up-Regulation
chemical_list: D018501:Antirheumatic Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008727:Methotrexate