Hepatitis C virus infection is associated with hepatic and adipose tissue insulin resistance that improves after viral cure

Research output: Contribution to journalArticle

Authors

  • Andrei I Oprescu
  • Nigel P. Davies
  • Robert Flintham
  • David Mutimer
  • Jane A. McKeating
  • Jeremy W. Tomlinson

External organisations

  • Centre for Liver Research, NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, Birmingham B15 2TT, UK.
  • CRUK Clinical Trials Unit, University of Birmingham, Birmingham, UK.
  • Medical Physics Department, University Hospitals Birmingham NHS Foundation Trust

Abstract

Background: Chronic hepatitis C (CHC) is associated with systemic insulin resistance, yet there are limited data on the tissue-specific contribution in vivo to this adverse metabolic phenotype, and the effect of HCV cure. Methods: We examined tissue-specific insulin sensitivity in a cohort study involving 13 patients with CHC compared to 12 BMI-matched healthy control subjects. All subjects underwent a two-step clamp incorporating the use of stable isotopes to measure carbohydrate and lipid flux (hepatic and global insulin sensitivity) with concomitant subcutaneous adipose tissue microdialysis and biopsy (subcutaneous adipose tissue insulin sensitivity). Investigations were repeated in seven patients with CHC following antiviral therapy with a documented sustained virological response. Results: Adipose tissue was more insulin resistant in patients with CHC compared to healthy controls, as evidence by elevated glycerol production rate and impaired insulin-mediated suppression of both circulating nonesterified fatty acids (NEFA) and adipose interstitial fluid glycerol release during the hyperinsulinaemic euglycaemic clamp. Hepatic and muscle insulin sensitivity were similar between patients with CHC and controls. Following viral eradication, hepatic insulin sensitivity improved as demonstrated by a reduction in endogenous glucose production rate. In addition, circulating NEFA decreased with sustained virological response (SVR) and insulin was more effective at suppressing adipose tissue interstitial glycerol release with a parallel increase in the expression of insulin signalling cascade genes in adipose tissue consistent with enhanced adipose tissue insulin sensitivity. Conclusion: Chronic hepatitis C patients have profound subcutaneous adipose tissue insulin resistance in comparison with BMI-matched controls. For the first time, we have demonstrated that viral eradication improves global, hepatic and adipose tissue insulin sensitivity.

Bibliographic note

© 2018 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.

Details

Original languageEnglish
Pages (from-to)440-448
Number of pages9
JournalClinical Endocrinology
Volume90
Issue number3
Early online date17 Jan 2019
Publication statusPublished - Mar 2019

Keywords

  • adipose tissue, HCV, hepatic, insulin resistance