title: Hypoadiponectinemia predicts the severity of hepatic fibrosis and pancreatic Beta-cell dysfunction in nondiabetic nonobese patients with nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  The relationships between the adipokines tumor necrosis factor (TNF)-alpha and adiponectin and the parameters of glucose homeostasis and severity of liver disease were assessed in nonobese nondiabetic subjects with nonalcoholic steatohepatitis (NASH).
  
  
  METHODS
  A frequently sampled intravenous glucose tolerance test, serum cytokine measurement, and 7-day alimentary record were performed in 20 biopsy-proven NASH patients and 45 age-, sex-, and BMI-matched controls (30 insulin sensitive and 15 insulin resistant).
  
  
  RESULTS
  Patients with NASH had impaired pancreatic beta-cell function compared with both insulin-sensitive (adaptation index, AI: 97.7 +/- 17.7 vs 307.4 +/- 24.1 min(-2) mmol(-1) L; p= 0.00001) and insulin-resistant (adaptation index, AI: 97.7 +/- 17.7 vs 201.4 +/- 41.1 min(-2) mmol(-1) L; p= 0.001) controls. Serum adiponectin levels were also significantly lower in the NASH group than in the two control groups and correlated with adaptation index and with the severity of hepatic steatosis, necroinflammation, and fibrosis. When NASH patients were grouped according to the severity of histological liver damage, adiponectin was the only variable discriminating patients with higher necroinflammatory grade and fibrosis score from those with milder lesions.
  
  
  CONCLUSIONS
  Beta-cell secretory impairment is present in nonobese patients with NASH before glucose intolerance appears and may contribute to their increased risk for developing diabetes. Hypoadiponectinemia is a feature of NASH and may have a pathogenetic role in beta-cell dysfunction and in hepatic necroinflammation and fibrosis, independently of insulin resistance, visceral fat accumulation, TNF-alpha axis activity, and dietary habits. Our findings provide further rationale for therapeutic approaches aimed at increasing adiponectin levels together with restoring beta-cell function and insulin sensitivity.
authors.affiliation: Department of Internal Medicine, University of Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Musso
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambino
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Biroli
authors.forename: Monica
authors.initials: M
authors.lastname: Carello
authors.forename: Emanuela
authors.initials: E
authors.lastname: Fagà
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Franco
authors.initials: F
authors.lastname: De Michieli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cassader
authors.forename: Marilena
authors.initials: M
authors.lastname: Durazzo
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pagano
mesh_terms: D000222:Adaptation, Physiological; D052242:Adiponectin / Q000097:blood*; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D005234:Fatty Liver / Q000097:blood / Q000503:physiopathology*; D005247:Feeding Behavior; D005260:Female; D005544:Forecasting; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008103:Liver Cirrhosis / Q000145:classification* / Q000473:pathology; D008297:Male; D008499:Medical Records; D009336:Necrosis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D052242:Adiponectin; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose