Original Contribution
The American Journal of Gastroenterology (2005) 100, 2438–2446; doi:10.1111/j.1572-0241.2005.00297.x
Hypoadiponectinemia Predicts the Severity of Hepatic Fibrosis and Pancreatic Beta-Cell Dysfunction in Nondiabetic Nonobese Patients with Nonalcoholic Steatohepatitis
Giovanni Musso MD1, Roberto Gambino MD1, Giampaolo Biroli MD1, Monica Carello MD1, Emanuela Fagà MD1, Giovanni Pacini DSC3, Franco De Michieli MD1, Maurizio Cassader MD1, Marilena Durazzo MD1, Mario Rizzetto MD2 and Gianfranco Pagano MD1
- 1Department of Internal Medicine, University of Turin, Italy
- 2Gastroenterology, Department of Internal Medicine, University of Turin, Padova, Italy
- 3Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy
Correspondence: Giovanni Musso, Dipartimento di Medicina Interna, Corso A.M. Dogliotti 14, 10126 Torino, Italy
Received 30 December 2004; Revised 0000; Accepted 12 May 2005.
Abstract
OBJECTIVES:
The relationships between the adipokines tumor necrosis factor (TNF)-
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 
-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:
-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 -cell dysfunction and in hepatic necroinflammation and fibrosis, independently of insulin resistance, visceral fat accumulation, TNF-
axis activity, and dietary habits. Our findings provide further rationale for therapeutic approaches aimed at increasing adiponectin levels together with restoring -cell function and insulin sensitivity.
