Eradicating hepatitis C virus ameliorates insulin resistance without change in adipose depots

被引:21
作者
Milner, K-L. [1 ,2 ]
Jenkins, A. B. [3 ]
Trenell, M. [4 ]
Tid-Ang, J. [1 ]
Samocha-Bonet, D. [1 ]
Weltman, M. [5 ,6 ]
Xu, A. [7 ]
George, J. [8 ,9 ]
Chisholm, D. J. [1 ]
机构
[1] Univ New S Wales, Garvan Inst Med Res, Sydney, NSW, Australia
[2] Univ New S Wales, Prince Wales Hosp, Dept Endocrinol, Sydney, NSW, Australia
[3] Univ Wollongong, Sch Hlth Sci, Wollongong, NSW, Australia
[4] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[5] Nepean Hosp, Dept Gastroenterol & Hepatol, Sydney, NSW, Australia
[6] Univ Sydney, Western Clin Sch, Sydney, NSW 2006, Australia
[7] Univ Hong Kong, Res Ctr Heart Brain Hormone & Hlth Ageing, Dept Med & Pharmacol, Hong Kong, Hong Kong, Peoples R China
[8] Univ Sydney, Westmead Millennium Inst, Storr Liver Unit, Sydney, NSW 2006, Australia
[9] Westmead Hosp, Sydney, NSW, Australia
基金
英国医学研究理事会;
关键词
liver steatosis; hyperinsulinaemic-euglycaemic clamp; magnetic resonance spectroscopy; chronic hepatitis C; adipokines; insulin resistance; MAGNETIC-RESONANCE-SPECTROSCOPY; BETA-CELL FUNCTION; TRIGLYCERIDE TRANSFER PROTEIN; ACID-BINDING PROTEIN; INTERFERON; GLUCOSE; FIBROSIS; OBESITY; IMPACT; SENSITIVITY;
D O I
10.1111/jvh.12143
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Chronic hepatitis C (CHC) is associated with lipid-related changes and insulin resistance; the latter predicts response to antiviral therapy, liver disease progression and the risk of diabetes. We sought to determine whether insulin sensitivity improves following CHC viral eradication after antiviral therapy and whether this is accompanied by changes in fat depots or adipokine levels. We compared 8 normoglycaemic men with CHC (genotype 1 or 3) before and at least 6months post viral eradication and 15 hepatitis C antibody negative controls using an intravenous glucose tolerance test and two-step hyperinsulinaemic-euglycaemic clamp with [6,6-H-2(2)] glucose to assess peripheral and hepatic insulin sensitivity. Magnetic resonance imaging and spectroscopy quantified abdominal fat compartments, liver and intramyocellular lipid. Peripheral insulin sensitivity improved (glucose infusion rate during high-dose insulin increased from 10.1 +/- 1.6 to 12 +/- 2.1mg/kg/min/, P=0.025), with no change in hepatic insulin response following successful viral eradication, without any accompanying change in muscle, liver or abdominal fat depots. There was corresponding improvement in incremental glycaemic response to intravenous glucose (pretreatment: 62.1 +/- 8.3 vs post-treatment: 56.1 +/- 8.5mm, P=0.008). Insulin sensitivity after viral clearance was comparable to matched controls without CHC. Post therapy, liver enzyme levels decreased but, interestingly, levels of glucagon, fatty acid-binding protein and lipocalin-2 remained elevated. Eradication of the hepatitis C virus improves insulin sensitivity without alteration in fat depots, adipokine or glucagon levels, consistent with a direct link of the virus with insulin resistance.
引用
收藏
页码:325 / 332
页数:8
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