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Article: Chronic Hepatitis C Is Associated With Peripheral Rather Than Hepatic Insulin Resistance

TitleChronic Hepatitis C Is Associated With Peripheral Rather Than Hepatic Insulin Resistance
Authors
Issue Date2010
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2010, v. 138 n. 3, p. 932-941.e3 How to Cite?
AbstractBackground & Aims: Chronic hepatitis C (CHC) is associated with insulin resistance (IR), liver steatosis (genotype 3), and increased diabetes risk. The site and mechanisms of IR are unclear. Methods: We compared cross-sectionally 29 nonobese, normoglycemic males with CHC (genotypes 1 and 3) to 15 adiposity and age-matched controls using a 2-step hyperinsulinemic-euglycemic clamp with [6,6- 2H 2] glucose to assess insulin sensitivity in liver and peripheral tissues and 1H-magnetic resonance spectroscopy to evaluate liver and intramyocellular lipid. Insulin secretion was assessed after intravenous glucose. Results: Insulin secretion was not impaired in CHC. Peripheral insulin sensitivity was 35% higher in controls vs CHC (P < .001) during high-dose (264.3 ± 25 [standard error] mU/L) insulin (P < .001); this was negatively associated with viral load (R 2 = .12; P = .05) and subcutaneous fat (R 2 = .41; P < .001). IR was similar in both genotypes despite 3-fold increased hepatic fat in genotype 3 (P < .001). Hepatic glucose production (P = .25) and nonesterified free fatty acid (P = .84) suppression with insulin were not different between CHC and controls inferring no adipocyte IR, and suggesting IR is mainly in muscle. In CHC, intramyocellular lipid was nonsignificantly increased but levels of glucagon (73.8 ± 3.6 vs 52.8 ± 3.1 ng/mL; P < .001), soluble tumor necrosis factor receptor 2 (3.1 ± 0.1 vs 2.3 ± 0.1 ng/mL; P < .001), and Lipocalin-2 (36.4 ± 2.9 vs 19.6 ± 1.6 ng/mL; P < .001) were elevated. Conclusions: CHC represents a unique infective/inflammatory model of IR, which is predominantly in muscle, correlates with subcutaneous, not visceral, adiposity, and is independent of liver fat. © 2010 AGA Institute.
Persistent Identifierhttp://hdl.handle.net/10722/125024
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170
ISI Accession Number ID
Funding AgencyGrant Number
National Health and Medical Research Council of Australia358398
GESA
University of Sydney
Hong Kong Research Council CRFHKU 2/07C
National Health and Medical Research Council
Diabetes UK
Funding Information:

Supported by grants from the National Health and Medical Research Council of Australia ( Grant 358398), GESA postgraduate medical research scholarship, Robert W. Storr Bequest to the University of Sydney, a University of Sydney Grant and Hong Kong Research Council CRF ( HKU 2/07C to A. X.). K. M. is supported by a National Health and Medical Research Council Postgraduate scholarship. M. T. is supported by a Diabetes UK RD Lawrence Fellowship.

References
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DC FieldValueLanguage
dc.contributor.authorMilner, Ken_HK
dc.contributor.authorvan der Poorten, Den_HK
dc.contributor.authorTrenell, Men_HK
dc.contributor.authorJenkins, ABen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorSmythe, Gen_HK
dc.contributor.authorDore, GJen_HK
dc.contributor.authorZekry, Aen_HK
dc.contributor.authorWeltman, Men_HK
dc.contributor.authorFragomeli, Ven_HK
dc.contributor.authorGeorge, Jen_HK
dc.contributor.authorChisholm, DJen_HK
dc.date.accessioned2010-10-31T11:07:13Z-
dc.date.available2010-10-31T11:07:13Z-
dc.date.issued2010en_HK
dc.identifier.citationGastroenterology, 2010, v. 138 n. 3, p. 932-941.e3en_HK
dc.identifier.issn0016-5085en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125024-
dc.description.abstractBackground & Aims: Chronic hepatitis C (CHC) is associated with insulin resistance (IR), liver steatosis (genotype 3), and increased diabetes risk. The site and mechanisms of IR are unclear. Methods: We compared cross-sectionally 29 nonobese, normoglycemic males with CHC (genotypes 1 and 3) to 15 adiposity and age-matched controls using a 2-step hyperinsulinemic-euglycemic clamp with [6,6- 2H 2] glucose to assess insulin sensitivity in liver and peripheral tissues and 1H-magnetic resonance spectroscopy to evaluate liver and intramyocellular lipid. Insulin secretion was assessed after intravenous glucose. Results: Insulin secretion was not impaired in CHC. Peripheral insulin sensitivity was 35% higher in controls vs CHC (P < .001) during high-dose (264.3 ± 25 [standard error] mU/L) insulin (P < .001); this was negatively associated with viral load (R 2 = .12; P = .05) and subcutaneous fat (R 2 = .41; P < .001). IR was similar in both genotypes despite 3-fold increased hepatic fat in genotype 3 (P < .001). Hepatic glucose production (P = .25) and nonesterified free fatty acid (P = .84) suppression with insulin were not different between CHC and controls inferring no adipocyte IR, and suggesting IR is mainly in muscle. In CHC, intramyocellular lipid was nonsignificantly increased but levels of glucagon (73.8 ± 3.6 vs 52.8 ± 3.1 ng/mL; P < .001), soluble tumor necrosis factor receptor 2 (3.1 ± 0.1 vs 2.3 ± 0.1 ng/mL; P < .001), and Lipocalin-2 (36.4 ± 2.9 vs 19.6 ± 1.6 ng/mL; P < .001) were elevated. Conclusions: CHC represents a unique infective/inflammatory model of IR, which is predominantly in muscle, correlates with subcutaneous, not visceral, adiposity, and is independent of liver fat. © 2010 AGA Institute.en_HK
dc.languageengen_HK
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastroen_HK
dc.relation.ispartofGastroenterologyen_HK
dc.subject.meshAcute-Phase Proteinsen_HK
dc.subject.meshAdiposityen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAustraliaen_HK
dc.subject.meshBiological Markers - blooden_HK
dc.subject.meshBlood Glucose - metabolismen_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshChinaen_HK
dc.subject.meshCross-Sectional Studiesen_HK
dc.subject.meshEnglanden_HK
dc.subject.meshGenotypeen_HK
dc.subject.meshGlucagon - blooden_HK
dc.subject.meshGlucose Clamp Techniqueen_HK
dc.subject.meshHepacivirus - geneticsen_HK
dc.subject.meshHepatitis C, Chronic - blood - diagnosis - physiopathologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInsulin - blooden_HK
dc.subject.meshInsulin Resistanceen_HK
dc.subject.meshIntra-Abdominal Fat - metabolism - physiopathologyen_HK
dc.subject.meshLipocalins - blooden_HK
dc.subject.meshLiver - metabolism - physiopathology - virologyen_HK
dc.subject.meshMagnetic Resonance Spectroscopyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMuscle, Skeletal - metabolism - physiopathology - virologyen_HK
dc.subject.meshProto-Oncogene Proteins - blooden_HK
dc.subject.meshRNA, Viral - blooden_HK
dc.subject.meshReceptors, Tumor Necrosis Factor, Type II - blooden_HK
dc.subject.meshSubcutaneous Fat - metabolism - physiopathologyen_HK
dc.subject.meshTime Factorsen_HK
dc.subject.meshViral Loaden_HK
dc.titleChronic Hepatitis C Is Associated With Peripheral Rather Than Hepatic Insulin Resistanceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0016-5085&volume=49&spage=1926&epage=34&date=2010&atitle=Chronic+Hepatitis+C+Is+Associated+With+Peripheral+Rather+Than+Hepatic+Insulin+Resistance.en_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/j.gastro.2009.11.050en_HK
dc.identifier.pmid19962985-
dc.identifier.scopuseid_2-s2.0-77449150552en_HK
dc.identifier.hkuros175934en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77449150552&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume138en_HK
dc.identifier.issue3en_HK
dc.identifier.spage932en_HK
dc.identifier.epage941.e3en_HK
dc.identifier.isiWOS:000275109900024-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectVascular dysfunction in obesity and diabetes: from risk prediction to therapeutic intervention-
dc.identifier.scopusauthoridMilner, K=24577068100en_HK
dc.identifier.scopusauthoridvan der Poorten, D=23111746900en_HK
dc.identifier.scopusauthoridTrenell, M=7801560103en_HK
dc.identifier.scopusauthoridJenkins, AB=7202457484en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridSmythe, G=7005143078en_HK
dc.identifier.scopusauthoridDore, GJ=7006650670en_HK
dc.identifier.scopusauthoridZekry, A=6701704541en_HK
dc.identifier.scopusauthoridWeltman, M=6701668963en_HK
dc.identifier.scopusauthoridFragomeli, V=35800790300en_HK
dc.identifier.scopusauthoridGeorge, J=7403558157en_HK
dc.identifier.scopusauthoridChisholm, DJ=54790548200en_HK

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