title: The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  The serum cytokeratin-18 fragment (CK-18) concentration has been suggested to be a biomarker of nonalcoholic fatty liver disease (NAFLD), although its usefulness in patients with type 2 diabetes mellitus (T2DM) is unknown.
  
  
  METHODS
  The study was divided into two parts. In the first cross-sectional study, a total of 200 patients with T2DM and 58 healthy control subjects were recruited. NAFLD was diagnosed using ultrasonography. In the subsequent longitudinal study, we evaluated the three-month change (Δ) in the CK-18 concentration and other parameters in 40 T2DM patients with NAFLD.
  
  
  RESULTS
  The serum CK-18 values were significantly higher in the NAFLD group than in the nonNAFLD group among both diabetic and nondiabetic subjects. The CK-18 concentration was found to be an independent determinant of NAFLD and was positively correlated with the ultrasonography score and AST and ALT concentrations in the T2DM patients. Positive correlations were also identified between the CK-18 and transaminase concentrations in the T2DM and NAFLD cohorts. ΔCK-18 was found to be significantly associated with ΔBMI in the T2DM patients with NAFLD.
  
  
  CONCLUSIONS
  A dose effect between the CK-18 concentration and the severity of NAFLD was found in the T2DM patients; thus, the CK-18 concentration is a potentially useful biomarker for assessing the efficacy of treatment and the improvement in NAFLD in patients with T2DM.
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Miyasato
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan. Electronic address: in1254@poh.osaka-med.ac.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Murase-Mishiba
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Bessho
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Miyawaki
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Imbe
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tsutsumi
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
authors.forename: Jungo
authors.initials: J
authors.lastname: Terasaki
authors.affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood / Q000737:chemistry*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications*; D010446:Peptide Fragments / Q000097:blood*
chemical_list: D015415:Biomarkers; D053538:Keratin-18; D010446:Peptide Fragments
keywords: Apoptosis; Noninvasive biomarker; Ultrasonography scoring system