title: Increased Plasma Levels of Asymmetric Dimethylarginine in Nonalcoholic Fatty Liver Disease: Relation With Insulin Resistance, Inflammation, and Liver Histology.
abstract: OBJECTIVE
  Cardiovascular disease (CVD) is the most frequent cause of death in nonalcoholic fatty liver disease (NAFLD). Insulin resistance, hepatic dysfunction, and chronic inflammation are factors interacting in explaining the increased CVD incidence in NAFLD. We aimed to evaluate the effects of insulin resistance and inflammatory biomarkers on asymmetric dimethylarginine (ADMA) levels, a predictor of CVD. We also investigated relationship between these markers and histological findings in patients with NAFLD.
  
  
  METHODS
  Plasma ADMA, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured in 70 patients with histologically verified NAFLD (53 with nonalcoholic steatohepatitis [NASH], 17 with non-NASH) and 12 controls.
  
  
  RESULTS
  The HOMA-IR (5.3 [3.9] vs 1.9 [1], P < 0.001), hs-CRP (5.6 [4.2] vs 2.2 [2.3] mg/L, P < 0.001), ADMA (0.81 [0.25] vs 0.48 [0.24] μmol/L, P = 0.005), and IL-6 (4.1 [1.2] vs 1.0 [0.4] pg/mL, P < 0.001) levels were all found higher in the NAFLD group than the control group. The ADMA levels were significantly higher in patients with NAFLD independent from HOMA-IR and body composition (P = 0.02). The IL-6 and HOMA-IR levels of the NASH group were found significantly higher than those of the non-NASH group. The only determinant significantly correlated to ADMA was HOMA-IR.
  
  
  CONCLUSIONS
  Our data suggested that although ADMA levels are independently higher in NAFLD, the only determinant correlated to ADMA is HOMA-IR and not inflammatory biomarkers (hs-CRP, IL-6) or presence/absence of NASH.
authors.affiliation: From the Departments of *Gastroenterology and †Pathology, Sisli Hamidiye Etfal Education and Research Hospital; ‡Department of Biochemistry, Bakirkoy Dr. Sadi Konuk Education and Research Hospital; and §Nesiller Genetics Diagnostic Lab, Istanbul, Turkey.
authors.forename: Salih
authors.initials: S
authors.lastname: Boga
authors.forename: Huseyin
authors.initials: H
authors.lastname: Alkim
authors.forename: Ali Riza
authors.initials: AR
authors.lastname: Koksal
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bayram
authors.forename: Muveddet Banu Yilmaz
authors.initials: MB
authors.lastname: Ozguven
authors.forename: Meltem
authors.initials: M
authors.lastname: Ergun
authors.forename: Sebnem Tekin
authors.initials: ST
authors.lastname: Neijmann
authors.forename: Gulay
authors.initials: G
authors.lastname: Ozgon
authors.forename: Canan
authors.initials: C
authors.lastname: Alkim
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood*
chemical_list: C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine