Impact of Moderate Alcohol Discontinuation on Insulin Action and Secretion in Latinos With and Without Hepatitis C

Lindsay A Uribe, Peter Bacchetti, Nicholas Gelman, Esteban Burchard, Mark Fitch, Marc Hellerstein, Mandana Khalili, Lindsay A Uribe, Peter Bacchetti, Nicholas Gelman, Esteban Burchard, Mark Fitch, Marc Hellerstein, Mandana Khalili

Abstract

Background: Insulin resistance (IR) is associated with hepatitis C virus (HCV), and Latinos are both at risk of IR and are disproportionately affected by HCV. Moderate alcohol consumption improves insulin sensitivity and may modify HCV-associated IR. We investigated the impact of moderate alcohol discontinuation on insulin sensitivity and secretion in Latinos using direct measurements.

Methods: Twenty-five nondiabetic, noncirrhotic Latino adults without (n = 17) or with (n = 8) HCV underwent 3-day metabolic assessment before and after prescription of 6 weeks of moderate alcohol discontinuation. Peripheral IR was measured via steady-state plasma glucose (SSPG) and hepatic IR using endogenous glucose production during a 2-step 240-minute insulin suppression test. Insulin secretion was measured using graded glucose infusion test.

Results: Baseline mean age was 46 ± 11 years, 63% male, 29% had HCV, and mean body mass index was 27 ± 4 kg/m2 . Compared to non-HCV, HCV patients had a higher median SSPG (132 vs. 98.8 mg/dl, p = 1.0), hepatic IR (13.5 vs. 11.3, p = 0.24), and insulin secretion rate (ISR-AUC, 1,290 vs. 1,250 pmol/min, p = 0.98). After confirmed alcohol discontinuation, hepatic IR was the only parameter that changed significantly (increased, mean change 2.6 ± 4.8, p = 0.02). Higher baseline alanine aminotransferase (ALT) was also associated with a greater change in hepatic IR (average 4.0 points/ALT doubling, p = 0.004), and HCV was associated with a lesser change (average -7.3 points, p = 0.002), independent of ALT.

Conclusions: Short-term moderate alcohol discontinuation adversely impacted hepatic IR in Latinos which was influenced by level of ALT at baseline independent of etiology. Although reduction in ALT through weight loss and HCV eradication remains a priority in improving IR, the observed nonharmful effect of moderate alcohol use represents a potentially confounding variable that warrants further study.

Keywords: Alanine Aminotransferase; Hepatic Insulin Resistance; Hepatitis C Virus; Hispanic; Insulin Resistance.

Conflict of interest statement

Conflicts of interest: The authors have no conflicts of interest to report.

Copyright © 2017 by the Research Society on Alcoholism.

References

    1. AASLD/IDSA. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62:932–54.
    1. ABBASI F, MCLAUGHLIN T, LAMENDOLA C, REAVEN GM. The Relationship Between Glucose Disposal in Response to Physiological Hyperinsulinemia and Basal Glucose and Free Fatty Acid Concentrations in Healthy Volunteers. J Clin Endocrinol Metabol. 2000;85:1251–54.
    1. ADA. Standards of medical care in diabetes--2015: summary of revisions. Diabetes Care. 2015;38(Suppl):S4.
    1. ALTER MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007;13:2436–41.
    1. BEULENS JW, RIMM EB, HENDRIKS HF, HU FB, MANSON JE, HUNTER DJ, MUKAMAL KJ. Alcohol consumption and type 2 diabetes: influence of genetic variation in alcohol dehydrogenase. Diabetes. 2007;56:2388–94.
    1. BEULENS JW, VAN BEERS RM, STOLK RP, SCHAAFSMA G, HENDRIKS HF. The effect of moderate alcohol consumption on fat distribution and adipocytokines. Obesity (Silver Spring) 2006;14:60–6.
    1. BONNET F, DUCLUZEAU PH, GASTALDELLI A, LAVILLE M, ANDERWALD CH, KONRAD T, MARI A, BALKAU B. Liver enzymes are associated with hepatic insulin resistance, insulin secretion, and glucagon concentration in healthy men and women. Diabetes. 2011;60:1660–7.
    1. BRANDMAN D, BACCHETTI P, AYALA CE, MAHER JJ, KHALILI M. Impact of insulin resistance on HCV treatment response and impact of HCV treatment on insulin sensitivity using direct measurements of insulin action. Diabetes Care. 2012;35:1090–4.
    1. BURMAN BE, BACCHETTI P, KHALILI M. Moderate Alcohol Use and Insulin Action in Chronic Hepatitis C Infection. Dig Dis Sci. 2016;61:2417–25.
    1. CHEUNG O, STERLING RK, SALVATORI J, WILLIAMS K, HUBBARD S, LUKETIC VA, STRAVITZ TR, SANYAL AJ, CONTOS MJ, MILLS S, SHIFFMAN ML. Mild alcohol consumption is not associated with increased fibrosis in patients with chronic hepatitis C. J Clin Gastroenterol. 2011;45:76–82.
    1. CHOUDHRY S, COYLE NE, TANG H, SALARI K, LIND D, CLARK SL, TSAI HJ, NAQVI M, PHONG A, UNG N, MATALLANA H, AVILA PC, CASAL J, TORRES A, NAZARIO S, CASTRO R, BATTLE NC, PEREZ-STABLE EJ, KWOK PY, SHEPPARD D, SHRIVER MD, RODRIGUEZ-CINTRON W, RISCH N, ZIV E, BURCHARD EG. Population stratification confounds genetic association studies among Latinos. Hum Genet. 2006;118:652–64E. pub 2005 Nov 8.
    1. CHRISTIANSEN MP, LINFOOT PA, NEESE RA, HELLERSTEIN MK. Effect of dietary energy restriction on glucose production and substrate utilization in type 2 diabetes. Diabetes. 2000;49:1691–9.
    1. CHURILLA JR, JOHNSON TM, CURLS R, RICHARDSON MR, BOYER WR, DEVORE SR, ALNOJEIDI AH. Association between alcohol consumption patterns and metabolic syndrome. Diabetes Metab Syndr. 2014;8:119–23.
    1. DAHL H, HAMMARBERG A, FRANCK J, HELANDER A. Urinary ethyl glucuronide and ethyl sulfate testing for recent drinking in alcohol-dependent outpatients treated with acamprosate or placebo. Alcohol Alcohol. 2011;46:553–7.
    1. 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;287:2559–62.
    1. FACCHINI F, CHEN YD, REAVEN GM. Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity. Diabetes Care. 1994;17:115–9.
    1. HAUKELAND JW, KONOPSKI Z, LINNESTAD P, AZIMY S, MARIT LOBERG E, HAALAND T, BIRKELAND K, BJORO K. Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease. Scand J Gastroenterol. 2005;40:1469–77.
    1. HUI JM, SUD A, FARRELL GC, BANDARA P, BYTH K, KENCH JG, MCCAUGHAN GW, GEORGE J. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected] Gastroenterology. 2003;125:1695–704.
    1. IMAZEKI F, YOKOSUKA O, FUKAI K, KANDA T, KOJIMA H, SAISHO H. Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: comparison with hepatitis B virus-infected and hepatitis C virus-cleared patients. Liver Int. 2008;28:355–62.
    1. KIM SH, ABBASI F, LAMENDOLA C, REAVEN GM. Effect of moderate alcoholic beverage consumption on insulin sensitivity in insulin-resistant, nondiabetic individuals. Metabolism. 2009;58:387–92.
    1. KIM SH, LIU A, ARIEL D, ABBASI F, LAMENDOLA C, GROVE K, TOMASSO V, OCHOA H, REAVEN G. Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study. Diabetes Care. 2014;37:1944–50.
    1. KLEVENS RM, HU DJ, JILES R, HOLMBERG SD. Evolving epidemiology of hepatitis C virus in the United States. Clin Infect Dis. 2012;55(Suppl 1):S3–9.
    1. KOPPES LL, DEKKER JM, HENDRIKS HF, BOUTER LM, HEINE RJ. Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes Care. 2005;28:719–25.
    1. LEITE NC, SALLES GF, ARAUJO AL, VILLELA-NOGUEIRA CA, CARDOSO CR. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int. 2009;29:113–9.
    1. LORENZO C, SERRANO-RIOS M, MARTINEZ-LARRAD MT, GABRIEL R, WILLIAMS K, GONZALEZ-VILLALPANDO C, STERN MP, HAZUDA HP, HAFFNER SM. Was the historic contribution of Spain to the Mexican gene pool partially responsible for the higher prevalence of type 2 diabetes in mexican-origin populations? The Spanish Insulin Resistance Study Group, the San Antonio Heart Study, and the Mexico City Diabetes Study. Diabetes Care. 2001;24:2059–64.
    1. MILNER KL, VAN DER POORTEN D, TRENELL M, JENKINS AB, XU A, SMYTHE G, DORE GJ, ZEKRY A, WELTMAN M, FRAGOMELI V, GEORGE J, CHISHOLM DJ. Chronic hepatitis C is associated with peripheral rather than hepatic insulin resistance. Gastroenterology. 2010;138:932–41. e1–3.
    1. MONTO A, PATEL K, BOSTROM A, PIANKO S, POCKROS P, MCHUTCHISON JG, WRIGHT TL. Risks of a range of alcohol intake on hepatitis C-related fibrosis. Hepatology. 2004;39:826–34.
    1. MOUCARI R, ASSELAH T, CAZALS-HATEM D, VOITOT H, BOYER N, RIPAULT MP, SOBESKY R, MARTINOT-PEIGNOUX M, MAYLIN S, NICOLAS-CHANOINE MH, PARADIS V, VIDAUD M, VALLA D, BEDOSSA P, MARCELLIN P. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008;134:416–23.
    1. MUKHTAR NA, BACCHETTI P, AYALA CE, MELGAR J, CHRISTENSEN S, MAHER JJ, KHALILI M. Insulin sensitivity and variability in hepatitis C virus infection using direct measurement. Dig Dis Sci. 2013;58:1141–8.
    1. NAMMI S, ROUFOGALIS BD. Light-to-moderate ethanol feeding augments AMPK-alpha phosphorylation and attenuates SREBP-1 expression in the liver of rats. J Pharm Pharm Sci. 2013;16:342–51.
    1. 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 B Crit Rev. 2009;12:362–88.
    1. NIAAA. What is “low-risk” drinking? National Institute on Alcohol Abuse and Alcoholism; [Accessed July 15, 2016]. . [Online]. Available: .
    1. OWEI I, UMEKWE N, WAN J, DAGOGO-JACK S. Plasma lipid levels predict dysglycemia in a biracial cohort of nondiabetic subjects: Potential mechanisms. Exp Biol Med (Maywood) 2016
    1. PETERS MG, TERRAULT NA. Alcohol use and hepatitis C. Hepatology. 2002;36:S220–5.
    1. POLI A, MARANGONI F, AVOGARO A, BARBA G, BELLENTANI S, BUCCI M, CAMBIERI R, CATAPANO AL, COSTANZO S, CRICELLI C, DE GAETANO G, DI CASTELNUOVO A, FAGGIANO P, FATTIROLLI F, FONTANA L, FORLANI G, FRATTINI S, GIACCO R, LA VECCHIA C, LAZZARETTO L, LOFFREDO L, LUCCHIN L, MARELLI G, MARROCCO W, MINISOLA S, MUSICCO M, NOVO S, NOZZOLI C, PELUCCHI C, PERRI L, PIERALLI F, RIZZONI D, STERZI R, VETTOR R, VIOLI F, VISIOLI F. Moderate alcohol use and health: a consensus document. Nutr Metab Cardiovasc Dis. 2013;23:487–504.
    1. PRITCHARD JK, STEPHENS M, DONNELLY P. Inference of population structure using multilocus genotype data. Genetics. 2000;155:945–59.
    1. RODRIGUEZ-TORRES M. Latinos and chronic hepatitis C: a singular population. Clin Gastroenterol Hepatol. 2008;6:484–90.
    1. SCHRIEKS IC, HEIL AL, HENDRIKS HF, MUKAMAL KJ, BEULENS JW. The effect of alcohol consumption on insulin sensitivity and glycemic status: a systematic review and meta-analysis of intervention studies. Diabetes Care. 2015;38:723–32.
    1. SCHWARZ JM, NEESE RA, TURNER S, DARE D, HELLERSTEIN MK. Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection. J Clin Invest. 1995;96:2735–43.
    1. SERFATY L. Metabolic Manifestations of Hepatitis C Virus: Diabetes Mellitus, Dyslipidemia. Clin Liver Dis. 2017;21:475–486.
    1. SOBELL LC, SOBELL MB. Timeline Follow-Back: A technique for assessing self-reported alcohol consumption. In: Litten RZ, Allen JP, editors. Measuring Alcohol Consumption: Psychosocial and Biological Methods. Totowa, NJ: Humana Press; 1992. pp. 41–72.
    1. TOMIE FURUYA D, BINSACK R, ONISHI ME, MONTEIRO SERAPHIM P, FABRES MACHADO U. Low ethanol consumption induces enhancement of insulin sensitivity in liver of normal rats. Life Sci. 2005;77:1813–24.
    1. TSAI HJ, CHOUDHRY S, NAQVI M, RODRIGUEZ-CINTRON W, BURCHARD EG, ZIV E. Comparison of three methods to estimate genetic ancestry and control for stratification in genetic association studies among admixed populations. Hum Genet. 2005;118:424–33.
    1. WAN YJ, POLAND RE, LIN KM. Genetic polymorphism of CYP2E1, ADH2, and ALDH2 in Mexican-Americans. Genet Test. 1998;2:79–83.
    1. WHITE DL, RATZIU V, EL-SERAG HB. Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis. J Hepatol. 2008;49:831–44.

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