All values are means+/-SE (unpaired Student T-tests). Results: Patients with NASH (age 54.4+/-2.1 years; 69% male; BMI 34.2+/-1.0 kg/m2]
had significantly higher fasting serum glucose, insulin and HOMA-IR than healthy controls (age 33.1+/- 2.2 years; 60% male; BMI 26.7+/-1.0 kg/m2). NASH patients had significant hepatic and muscle insulin resistance compared to controls, as demonstrated by lower % suppression of hepatic glucose production rate (41+/-4.3 vs.70+/-9.5 %; p<0.05) and lower glucose selleck chemicals llc disposal (0.85+/-0.1 vs.1.76+/-0.39 mg/kg/min; P<0.05). NASH patients have significant adipose insulin resistance, as demonstrated by higher insulin concentration required to 1/2-maximaIIy suppress circulating free fatty acids
(227+/-35.2 vs.65.2+/-14.0 pmol/L; p<0.001). Furthermore, in patients with NASH, interstitial fluid glycerol release from subcutaneous adipose tissue in response to both low-dose (379+/-42.6 vs.143+/-18.1 AUC μmol/l. h; p<0.0001) and high-dose insulin (261+/-30.7 vs.65.8+/-13.6 AUC μmol/l. h; p<0.0001) was significantly higher. NASH patients had significantly higher fasting circulating leptin: adiponectin ratio (3.22+/-0.49 vs.1.27+/-0.35 ng/μg p=0.003), TNFα (4.89+/-0.60 vs.1.32+/-0.14 pg/ml P<0.0001), hs-CRP (4.31+/-0.89 vs.1.47+/-0.47 μg/ml p<0.05), IL-6 (4.44+/-0.56 vs.2.59+/-0.51 pg/ml; p<0.05) and CCL-2 (224+/-14.4 vs.170+/-14.5 pg/ml; p<0.05) than controls. Conclusions: NASH patients have profound insulin resistance in the liver, muscle and adipose tissues.
Ku-0059436 cell line This study represents the first in-vivo description of dysfunctional subcutaneous adipose tissue in patients with NASH. Disclosures: Matthew J. Armstrong – Grant/Research Support: Novo Nordisk Ltd Stephen Gough – Advisory Committees or Review Panels: Novo Nordisk, Eli Lilly, Sanofi Aventis, Takeda, GSK; Sitaxentan Grant/Research Support: Novo Nordisk, Eli Lilly, Takeda; Speaking and Teaching: Novo Nordisk, Eli Lilly, Sanofi Aventis, GSK Philip N. Newsome – Grant/Research Support: Novo Nordisk The following people have nothing to disclose: Jonathan M. Hazlehurst, Diana Hull, Sarah Borrows, Kathy Guo, Jinglei Yu, Darren Barton, Piers Gaunt, Jeremy W. Tomlinson Background: Cytokeratin 18 (CK18) is a major intermediate filament protein in liver cells. Serum/plasma CK18 levels have been investigated as potential biomarkers for steatohepatitis, in patients with non-alcoholic fatty liver disease (NAFLD) /nonalcoholic steatohepatitis (NASH). The current study was performed to determine the usefulness of serum CK18 levels for evaluating long-term prognosis in NASH patients. Methods: The M30 enzyme-linked immunosorbent assay kit (Peviva) was used for estimating serum CK18 levels in 147 patients with NAFLD/NASH diagnosed by liver biopsies. A second liver biopsy (4.3±2.6 y) was required in 71 patients.