Digestive Diseases and Sciences

, Volume 61, Issue 8, pp 2417–2425 | Cite as

Moderate Alcohol Use and Insulin Action in Chronic Hepatitis C Infection

  • Blaire E. Burman
  • Peter Bacchetti
  • Mandana Khalili
Original Article


Background and Aim

Chronic hepatitis C (HCV) is associated with metabolic abnormalities including insulin resistance (IR) and diabetes. While moderate alcohol consumption is known to have beneficial metabolic effects in the general population, such potential effects in HCV are unknown. We aimed to assess the association between graded alcohol intake and IR, insulin secretion, and metabolic syndrome in HCV.


Ninety-five non-diabetic HCV-infected patients underwent detailed metabolic testing. IR was directly measured via steady-state plasma glucose (SSPG) during a 240-min insulin suppression test. Total insulin secretion and insulinogenic index were determined by 75-g oral glucose tolerance test. Genotyping of CYP2E1 was performed to detect genetic polymorphisms influencing alcohol metabolism.


In this cohort, 61 % were abstinent from alcohol for the past 12 months, while 22 % were moderate, and 17 % heavy drinkers. Obesity and nonwhite ethnicity were the strongest predictors of IR. Moderate alcohol intake (vs none) was significantly associated with lower SSPG only among those with normal BMI (coef −72.9, 95 % CI −128.1 to −17.6, p = 0.01). Alcohol use was not associated with insulin secretion parameters when controlling for IR and other factors. Heavy alcohol intake (OR 3.2, 95 % CI 0.86–12.3) and nonwhite ethnicity (OR 7.1, 95 % CI 1.5–33.3) were associated with metabolic syndrome. Among nonwhites, the odds of metabolic syndrome were fivefold higher for heavy drinkers.


Moderate alcohol intake is associated with improved insulin sensitivity in HCV, although this benefit was limited to normal-weight individuals. The potential benefit of moderate alcohol on IR and its metabolic consequences in HCV warrants further longitudinal investigation.


Hepatitis C Insulin resistance Insulin secretion Metabolic syndrome Clamp testing 



Hepatitis C virus


Insulin resistance


Hepatitis B virus


Human immunodeficiency virus


National Institute on Alcohol Abuse and Alcoholism


Oral glucose tolerance test


Insulin suppression test


Steady-state plasma glucose


Area under the curve of insulin


Area under the curve of glucose


Body mass index


Alanine aminotransferase


High-density lipoprotein


Alcohol dehydrogenase


Aldehyde dehydrogenase


Homeostatic model assessment


Financial support

This work was in part supported by Hepatology Training Grant DK060414 (B.E.B.), R01 DK074673 (M.K.), K24AA022523 (M.K.), P30 DK026743 (UCSF Liver Center), and UL1 TR000004 (NIH/NCATS UCSF-CTSI).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to report.

Supplementary material

10620_2016_4119_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 kb)


  1. 1.
    Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999–2002. Ann Intern Med. 2006;144:705–714.CrossRefPubMedGoogle Scholar
  2. 2.
    Lieber CS. Hepatitis C and alcohol. J Clin Gastroenterol. 2003;36:100–102.CrossRefPubMedGoogle Scholar
  3. 3.
    Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349:825–832.CrossRefPubMedGoogle Scholar
  4. 4.
    Hutchinson SJ, Bird SM, Goldberg DJ. Influence of alcohol on the progression of hepatitis C virus infection: a meta-analysis. Clin Gastroenterol Hepatol. 2005;3:1150–1159.CrossRefPubMedGoogle Scholar
  5. 5.
    Singal AK, Anand BS. Mechanisms of synergy between alcohol and hepatitis C virus. J Clin Gastroenterol. 2007;41:761–772.CrossRefPubMedGoogle Scholar
  6. 6.
    Cheung O, Sterling RK, Salvatori J, et al. Mild alcohol consumption is not associated with increased fibrosis in patients with chronic hepatitis C. J Clin Gastroenterol. 2011;45:76–82.CrossRefPubMedGoogle Scholar
  7. 7.
    Howard AA, Arnsten JH, Gourevitch MN. Effect of alcohol consumption on diabetes mellitus: a systematic review. Ann Intern Med. 2004;140:211–219.CrossRefPubMedGoogle Scholar
  8. 8.
    Davies MJ, Baer DJ, Judd JT, Brown ED, Campbell WS, Taylor PR. Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial. JAMA. 2002;287:2559–2562.CrossRefPubMedGoogle Scholar
  9. 9.
    Hui JM, Sud A, Farrell GC, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology. 2003;125:1695–1704.CrossRefPubMedGoogle Scholar
  10. 10.
    Petta S, Camma C, Di Marco V, et al. Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. Am J Gastroenterol. 2008;103:1136–1144.CrossRefPubMedGoogle Scholar
  11. 11.
    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37:S81–S90.CrossRefGoogle Scholar
  12. 12.
    Szabo G. The 40th anniversary of the National Institute on Alcoholism and Alcohol Abuse: the impact on liver disease. Hepatology. 2010;52:10–12.CrossRefPubMedGoogle Scholar
  13. 13.
    Mukhtar NA, Bacchetti P, Ayala CE, et al. Insulin sensitivity and variability in hepatitis C virus infection using direct measurement. Dig Dis Sci. 2013;58:1141–1148.CrossRefPubMedGoogle Scholar
  14. 14.
    Greenfield MS, Doberne L, Kraemer F, Tobey T, Reaven G. Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes. 1981;30:387–392.CrossRefPubMedGoogle Scholar
  15. 15.
    Phillips DI, Clark PM, Hales CN, Osmond C. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med. 1994;11:286–292.CrossRefPubMedGoogle Scholar
  16. 16.
    Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement. Circulation. 2009;120:1640–1645.CrossRefPubMedGoogle Scholar
  17. 17.
    Beulens JW, Rimm EB, Hendriks HF, et al. Alcohol consumption and type 2 diabetes: influence of genetic variation in alcohol dehydrogenase. Diabetes. 2007;56:2388–2394.CrossRefPubMedGoogle Scholar
  18. 18.
    Neafsey P, Ginsberg G, Hattis D, Johns DO, Guyton KZ, Sonawane B. Genetic polymorphism in CYP2E1: population distribution of CYP2E1 activity. J Toxicol Environ Health Part B. 2009;12:362–388.CrossRefGoogle Scholar
  19. 19.
    Wan YJ, Poland RE, Lin KM. Genetic polymorphism of CYP2E1, ADH2, and ALDH2 in Mexican-Americans. Genet Test. 1998;2:79–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Wei M, Gibbons LW, Mitchell TL, Kampert JB, Blair SN. Alcohol intake and incidence of type 2 diabetes in men. Diabetes Care. 2000;23:18–22.CrossRefPubMedGoogle Scholar
  21. 21.
    Fuchs CS, Stampfer MJ, Colditz GA, et al. Alcohol consumption and mortality among women. N Engl J Med. 1995;332:1245–1250.CrossRefPubMedGoogle Scholar
  22. 22.
    Bell RA, Mayer-Davis EJ, Martin MA, D’Agostino RB Jr, Haffner SM. Associations between alcohol consumption and insulin sensitivity and cardiovascular disease risk factors: the Insulin Resistance and Atherosclerosis Study. Diabetes Care. 2000;23:1630–1636.CrossRefPubMedGoogle Scholar
  23. 23.
    Facchini F, Chen YD, Reaven GM. Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity. Diabetes Care. 1994;17:115–119.CrossRefPubMedGoogle Scholar
  24. 24.
    Sierksma A, Patel H, Ouchi N, et al. Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor-alpha, and insulin sensitivity. Diabetes Care. 2004;27:184–189.CrossRefPubMedGoogle Scholar
  25. 25.
    Peters MG, Terrault NA. Alcohol use and hepatitis C. Hepatology. 2002;36:S220–S225.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62:932–954.Google Scholar
  27. 27.
    Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444:840–846.CrossRefPubMedGoogle Scholar
  28. 28.
    Holbrook TL, Barrett-Connor E, Wingard DL. A prospective population-based study of alcohol use and non-insulin-dependent diabetes mellitus. Am J Epidemiol. 1990;132:902–909.PubMedGoogle Scholar
  29. 29.
    Kao WH, Puddey IB, Boland LL, Watson RL, Brancati FL. Alcohol consumption and the risk of type 2 diabetes mellitus: atherosclerosis risk in communities study. Am J Epidemiol. 2001;154:748–757.CrossRefPubMedGoogle Scholar
  30. 30.
    Younossi ZM, Zheng L, Stepanova M, Venkatesan C, Mir HM. Moderate, excessive or heavy alcohol consumption: each is significantly associated with increased mortality in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2013;37:703–709.CrossRefPubMedGoogle Scholar
  31. 31.
    Freiberg MS, Cabral HJ, Heeren TC, et al. Alcohol consumption and the prevalence of the Metabolic Syndrome in the US.: a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27:2954–2959.CrossRefPubMedGoogle Scholar
  32. 32.
    Baik I, Shin C. Prospective study of alcohol consumption and metabolic syndrome. Am J Clin Nutr. 2008;87:1455–1463.PubMedGoogle Scholar
  33. 33.
    Sun K, Ren M, Liu D, Wang C, Yang C, Yan L. Alcohol consumption and risk of metabolic syndrome: a meta-analysis of prospective studies. Clin Nutr. 2014;33:596–602. doi: 10.1016/j.clnu.2013.10.003.CrossRefPubMedGoogle Scholar
  34. 34.
    Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287:356–359.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Blaire E. Burman
    • 1
  • Peter Bacchetti
    • 2
  • Mandana Khalili
    • 1
    • 3
  1. 1.Department of Medicine, San Francisco General HospitalUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Department of Epidemiology and BiostatisticsUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.Liver CenterUniversity of California, San FranciscoSan FranciscoUSA

Personalised recommendations