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Increased Plasma Levels of Asymmetric Dimethylarginine in Nonalcoholic Fatty Liver Disease
  1. Salih Boga, MD*,
  2. Huseyin Alkim, MD*,
  3. Ali Riza Koksal, MD*,
  4. Mehmet Bayram, MD*,
  5. Muveddet Banu Yilmaz Ozguven, MD,
  6. Meltem Ergun, MD*,
  7. Sebnem Tekin Neijmann, MD,
  8. Gulay Ozgon, MD§,
  9. Canan Alkim, MD*
  1. 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.
  1. Received February 22, 2015, and in revised form June 16, 2015.
  2. Accepted for publication July 4, 2015.
  3. Reprints: Salih Boga, MD, Department of Hepatology, Yale University Medical Center, 333 Cedar St, LMP 1080, New Haven, CT 06520. E-mail: salihboga{at}
  4. None of the authors has any conflicts of interest.
  5. We confirm that there are no financial or other relations that could lead to a conflict to interest. We also verify that all authors had access to the data and a role in writing the manuscript.

Relation With Insulin Resistance, Inflammation, and Liver Histology


Background and Aim 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.

Patients and 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.

Key Words
  • asymmetric dimethylarginine
  • hs-CRP
  • IL-6

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