Tzu Chi Medical Journal
Volume 20, Issue 4 , Pages 275-279, December 2008

Association of Insulin Resistance with Alanine Aminotransferase Activity in Patients with Nonalcoholic Fatty Liver Disease

  • Chia-Chi Wang

      Affiliations

    • Department of Gastroenterology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan
  • ,
  • Wai-Wah Wu

      Affiliations

    • Department of Gastroenterology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan
  • ,
  • Ching-Sheng Hsu

      Affiliations

    • Department of Gastroenterology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan
  • ,
  • Pin-Chao Wang

      Affiliations

    • Department of Gastroenterology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan
  • ,
  • Hans Hsienhong Lin

      Affiliations

    • Department of Gastroenterology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan
  • ,
  • Jia-Horng Kao

      Affiliations

    • Department of Internal Medicine, Hepatic Research Center and Department of Medical Research, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
    • Corresponding Author InformationCorresponding author. Department of Internal Medicine, Hepatic Research Center and Department of Medical Research, National Taiwan University College of Medicine and National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei, Taiwan

Received 20 February 2008; received in revised form 27 March 2008; accepted 5 May 2008.

Article Outline

Abstract 

Objective

Elevated liver enzymes have been recognized as a predictor for the development of metabolic syndrome and type 2 diabetes mellitus in patients with nonalcoholic fatty liver disease (NAFLD). However, the association of insulin resistance with alanine aminotransferase (ALT) activity remains largely unknown.

Patients and Methods

A total of 454 subjects attending the health examination center were enrolled from September 2005 through December 2006. Of them, 203 patients (male/female, 113/90; mean age, 50.9 years) were identified to have NAFLD. Their insulin resistance index was determined using the homeostasis model assessment (HOMA-IR). Elevated ALT level was defined as > 30 IU/L for male and > 19 IU/L for female subjects according to the new cut-off values.

Results

There were 113 subjects in the elevated ALT group and 90 in the normal ALT group. Age, gender and the prevalence of diabetes mellitus, hypertension and smoking history were comparable between these two groups. The elevated ALT group had higher readings for body mass index, triglyceride, total cholesterol, low-density lipoprotein cholesterol, insulin and HOMA-IR than the normal ALT group using univariate analyses. Multivariate logistic regression analyses showed that only log(HOMA-IR) was positively associated with elevated ALT level in the NAFLD patients (adjusted odds ratio, 5.04; 95% confidence interval, 1.56–16.27).

Conclusion

Our data showed that there was an association between insulin resistance and serum ALT levels in NAFLD patients, independent of other metabolic factors. However, further longitudinal studies are needed to clarify the causal relationship between insulin resistance and increased ALT activity in patients with NAFLD.

Keywords:  Alanine aminotransferase , Insulin resistance , Non-alcoholic fatty liver disease

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References 

  1. Chitturi S , Farrell GC , George J . Non-alcoholic steatohepatitis in the Asia-Pacific region: future shock? . J Gastroenterol Hepatol . 2004;19:368–374
  2. Matteoni CA , Younossi ZM , Gramlich T , Boparai N , Liu YC , McCullough AJ . Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity . Gastroenterology . 1999;116:1413–1419
  3. Marchesini G , Brizi M , Bianchi G , et al.   Nonalcoholic fatty liver disease: a feature of the metabolic syndrome . Diabetes . 2001;50:1844–1850
  4. Marchesini G , Bugianesi E , Forlani G , et al.   Non-alcoholic fatty liver, steatohepatitis and the metabolic syndrome . Hepatology . 2003;37:917–923
  5. Clark JM , Diehl AM . Hepatic steatosis and type 2 diabetes mellitus . Curr Diab Rep . 2002;2:210–215
  6. Brea A , Mosquera D , Martin E , Arizti A , Cordero JL , Ros E . Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study . Arterioscler Thromb Vasc Biol . 2005;25:1045–1050
  7. Day CP , James OF . Steatohepatitis: a tale of two “hits”? . Gastroenterology . 1998;114:842–845
  8. Scheig R . Evaluation of tests used to screen patients with liver disorders . Prim Care . 1996;23:551–560
  9. Hanley AJ , Williams K , Festa A , et al.   Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study . Diabetes . 2004;53:2623–2632
  10. Hanley AJ , Williams K , Festa A , Wagenknecht LE , D'Agostino RB Jr , Haffner SM . Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study . Diabetes . 2005;54:3140–3147
  11. Farrell GC , Chitturi S , Lau GK , Sollano JD; Asia-Pacific Working Party on NAFLD . Guideline for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary . J Gastroenterol Hepatol . 2007;22:775–777
  12. Bonora E , Targher G , Alberiche M , et al.   Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity . Diabetes Care . 2000;23:57–63
  13. Prati D , Taioli E , Zanella A , et al.   Updated definitions of healthy ranges for serum alanine aminotransferase levels . Ann Intern Med . 2002;137:1–10
  14. Osawa H , Mori Y . Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical amplitudes . J Clin Ultrasound . 1986;24:25–29
  15. Saadeh S , Younossi ZM , Remer EM , et al.   The utility of radiographic imaging in nonalcoholic fatty liver disease . Gastroenterology . 2002;123:745–750
  16. Marchesini G , Avagnina S , Barantani EG , et al.   Aminotransferase and gamma-glutamyltranspeptidase levels in obesity are associated with insulin resistance and the metabolic syndrome . J Endocrinol Invest . 2005;28:333–339
  17. Chung RT , Casson DR , Murray G , Song S , Grinspoon S , Hadigan C . Alanine aminotransferase levels predict insulin resistance in HIV lipodystrophy . J Acquir Immune Defic Syndr . 2003;34:534–536
  18. de Luis DA , Aller R , Izaola O , Sagrado MG , Con de R , Bellido D . Influence of insulin resistance and adipocytokines on elevated serum aminotransferase in obese patients . Arch Med Res . 2008;39:110–114
  19. Dessein PH , Woodiwiss AJ , Joffe BI , Norton GR . Aminotransferases are associated with insulin resistance and atherosclerosis in rheumatoid arthritis. BMC Cardiovasc Disord 2007;7:31. 20. Shen YH, Yang WS, Lee TH, Lee LT, Chen CY, Huang KC. Bright liver and alanine aminotransferase are associated with metabolic syndrome in adults . Obes Res . 2005;13:1238–1245
  20. Belfort R , Harrison SA , Brown K , et al.   A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis . N Engl J Med . 2006;355:2297–2307
  21. Sheth SG , Gordon FD , Chopra S . Nonalcoholic steatohepatitis . Ann Intern Med . 1997;126:137–145
  22. Su CC , Wang K , Hsia TL , Chen CS , Tung TH . Association of nonalcoholic fatty liver disease with abnormal aminotransferase and postprandial hyperglycemia . J Clin Gastroenterol . 2006;40:551–554
  23. Hanley AJ , Wagenknecht LE , Festa A , D'Agostino RB Jr , Haffner SM . Alanine aminotransferase and directly measured insulin sensitivity in a multiethnic cohort: the Insulin Resistance Atherosclerosis Study . Diabetes Care . 2007;30:1819–1827
  24. Schindhelm RK , Dekker JM , Nijpels G , et al.   Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study . Atherosclerosis . 2007;191:391–396
  25. Chen CH , Huang MH , Yang JC , et al.   Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults . J Clin Gastroenterol . 2006;40:745–752
  26. The IDF Consensus Worldwide Definition of the Metabolic Syndrome . International Diabetes Federation; 2006;
  27. Oh SY , Cho YK , Kang MS , et al.   The association between increased alanine aminotransferase activity and metabolic factors in nonalcoholic fatty liver disease . Metabolism . 2006;55:1604–1609
  28. Salazar MR , Carbajal HA , Curciarello JO , Aizpurua M , Adrover RE , Riondet B . Alanine-aminotransferase: an early marker for insulin resistance? . Medicina (B Aires) . 2007;67:125–130
  29. Fraser A , Ebrahim S , Smith GD , Lawlor DA . A comparison of association of alanine aminotransferase and gammaglutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes . Hepatology . 2007;46:158–165
  30. Mittendorfer B . Insulin resistance: sex matter . Curr Opin Clin Nutr Metab Care . 2005;8:367–372

PII: S1016-3190(08)60050-6

doi:10.1016/S1016-3190(08)60050-6

Tzu Chi Medical Journal
Volume 20, Issue 4 , Pages 275-279, December 2008