title: NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome.
abstract: Nonalcoholic steatohepatitis (NASH) is often linked with disorders that are clearly associated with insulin resistance (IR): obesity, type 2 diabetes mellitus, and hypertriglyceridemia. We tested the hypotheses that (1) IR is an essential requirement for the development of NASH and (2) a high association between IR and liver disease is relatively specific for NASH. We measured body mass index (BMI), waist/hip ratio, and fasting serum lipid, insulin, C-peptide, and glucose levels in 66 patients with NASH (21 with advanced fibrosis and 45 with mild fibrosis). IR was determined by the homeostasis model assessment (HOMA). We also determined the strength of the association of NASH with insulin resistance syndrome (IRS) as defined by World Health Organization criteria. To assess whether the finding of IR was relatively specific to NASH rather than simply to obesity or liver disease, we compared the results of a subset of 36 patients with less-severe NASH with 36 age- and sex-matched patients with chronic hepatitis C virus (HCV) of comparable fibrotic severity. IR was confirmed in 65 patients (98%) with NASH, and 55 (87%) fulfilled minimum criteria for IRS. IR was found in lean as well as in overweight and obese patients. The IR values and the prevalence of IRS (75% vs. 8.3%) were significantly higher in those with NASH than in comparable cases of HCV. Hyperinsulinemia was attributable to increased insulin secretion rather than decreased hepatic extraction. In conclusion, most patients with NASH have IRS, and there is a near-universal association between NASH and IR irrespective of obesity. IR is present in mild as well as advanced cases of NASH but is unusual in chronic HCV of similar fibrotic severity.
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute, University of Sydney, New South Wales, Australia.
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Chitturi
authors.forename: Shehan
authors.initials: S
authors.lastname: Abeygunasekera
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Farrell
authors.forename: Jane
authors.initials: J
authors.lastname: Holmes-Walker
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hui
authors.forename: Caroline
authors.initials: C
authors.lastname: Fung
authors.forename: Rooshdiya
authors.initials: R
authors.lastname: Karim
authors.forename: Rita
authors.initials: R
authors.lastname: Lin
authors.forename: Dev
authors.initials: D
authors.lastname: Samarasinghe
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.forename: Martin
authors.initials: M
authors.lastname: Weltman
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005234:Fatty Liver / Q000150:complications* / Q000503:physiopathology; D005260:Female; D018149:Glucose Intolerance; D006505:Hepatitis / Q000150:complications* / Q000503:physiopathology; D019698:Hepatitis C, Chronic / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D024821:Metabolic Syndrome / Q000502:physiology*; D008875:Middle Aged
chemical_list: D007328:Insulin