title: Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection.
abstract: OBJECTIVE
  Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non-cirrhotic and non-diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance.
  
  
  METHODS
  Fifty-six patients diagnosed with HCV-related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)-alpha and HCV-RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA-IR, and the clinical factors responsible for the increase in HOMA-IR in non-diabetic patients was investigated.
  
  
  RESULTS
  Homeostasis model assessment of insulin resistance and IRI levels increased parallel with the progression of fibrosis. Among the non-diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST and TNF-alpha were related with HOMA-IR (BMI: r = 0.395, P = 0.041; AST: r = 0.465, P = 0.014; TNF-alpha: r = 0.396, P = 0.040). In contrast, HOMA-IR related to TNF-alpha (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver fibrosis.
  
  
  CONCLUSIONS
  Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine and Research Center for Infectious Diseases, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Maeno
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okumura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sakakibara
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Ayada
authors.forename: Naoki
authors.initials: N
authors.lastname: Hotta
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Tagaya
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukuzawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kakumu
mesh_terms: D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000473:pathology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D000410:Alanine Transaminase; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin