Sites and Mechanisms of Insulin Resistance in Nonobese, Nondiabetic Patients with Chronic Hepatitis C

Vanni, E, Abate, ML, Gentilcore, E, Hickman, I, Gambino, R, Cassader, M, Smedile, A, Ferrannini, E, Rizzetto, M, Marchesini, G, Gastaldelli, A and Bugianesi, E (2009) Sites and Mechanisms of Insulin Resistance in Nonobese, Nondiabetic Patients with Chronic Hepatitis C. HEPATOLOGY, 50 3: 697-706. doi:10.1002/hep.23031

Author Vanni, E
Abate, ML
Gentilcore, E
Hickman, I
Gambino, R
Cassader, M
Smedile, A
Ferrannini, E
Rizzetto, M
Marchesini, G
Gastaldelli, A
Bugianesi, E
Title Sites and Mechanisms of Insulin Resistance in Nonobese, Nondiabetic Patients with Chronic Hepatitis C
Journal name HEPATOLOGY   Check publisher's open access policy
ISSN 0270-9139
Publication date 2009-09
Year available 2009
Sub-type Article (original research)
DOI 10.1002/hep.23031
Volume 50
Issue 3
Start page 697
End page 706
Total pages 10
Editor Blei, A. T.
Place of publication United State of America
Publisher John Wiley & Sons
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
920104 Diabetes
920106 Endocrine Organs and Diseases (excl. Diabetes)
920109 Infectious Diseases
111201 Cancer Cell Biology
110306 Endocrinology
Abstract Chronic hepatitis C (CHC) has been associated with type 2 diabetes and insulin resistance, but the extent of impairment in insulin action, the target pathways involved, and the role of the virus per se have not been defined. In this study, we performed a euglycemic hyperinsulinemic clamp (1 mU . minute(-1) . kg(-1)) coupled with infusion of tracers ([6,6-H-2(2)] glucose, [2 H-5]glycerol) and indirect calorimetry in 14 patients with biopsy-proven CHC, who were selected not to have any features of the metabolic syndrome, and in seven healthy controls. We also measured liver expression of inflammatory cytokines/mediators and tested their association with the metabolic parameters. Compared to controls, in patients with CHC: (1) total glucose disposal (TGD) during the clamp was 25% lower (P = 0.003) due to impaired glucose oxidation (P = 0.0002), (2) basal endogenous glucose production (EGP) was 20% higher (P = 0.011) and its suppression during the clamp was markedly reduced (P = 0.007), and (3) glycerol appearance was not different in the basal state or during the clamp, but lipid oxidation was less suppressed by insulin (P = 0.004). Lipid oxidation was higher in patients with CHC who had more steatosis and was directly related to EGP, TGD, and glucose oxidation. The decreased insulin-stimulated suppression of EGP was associated with increased hepatic suppressor of cytokine signaling 3 (SOCS3; P < 0.05) and interleukin-18 (P < 0.05) expression. Conclusion: Hepatitis C infection per se is associated with peripheral and hepatic insulin resistance. Substrate competition by increased lipid oxidation and possibly enhanced hepatic expression of inflammatory cytokines/mediators could be involved in the defective glucose regulation. (HEPATOLOGY 2009;50:697-706.)
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
UQ Diamantina Institute Publications
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Created: Wed, 24 Mar 2010, 13:44:04 EST by Kylie Hengst on behalf of UQ Diamantina Institute