Gastroenterology
Volume 135, Issue 6 , Pages 1935-1944.e1 , December 2008

Aminotransferase Levels and 20-Year Risk of Metabolic Syndrome, Diabetes, and Cardiovascular Disease

  • Wolfram Goessling

      Affiliations

    • Division of Genetics and Gastroenterology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
    • Corresponding Author InformationAddress requests for reprints to: Wolfram Goessling, MD, PhD, Genetics Division, Brigham and Women's Hospital, NRB 4-058, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115. fax: (617) 525-4751
    • ,
  • Joseph M. Massaro

      Affiliations

    • Department of Biostatistics, Boston University, Boston, Massachusetts
    • ,
  • Ramachandran S. Vasan

      Affiliations

    • The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts
    • Division of Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
    • Division of Cardiology and Molecular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
    • ,
  • Ralph B. D'Agostino Sr

      Affiliations

    • Department of Mathematics and Statistics, Boston University, Boston, Massachusetts
    • ,
  • R. Curtis Ellison

      Affiliations

    • Division of Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
    • ,
  • Caroline S. Fox

      Affiliations

    • Division of Endocrinology, Metabolism, and Diabetes, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts

Received 28 February 2008 ,Accepted 4 September 2008.

References 

  1. Bellentani S, Saccoccio G, Masutti F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med. 2000;132:112–117
  2. Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001;50:1844–1850
  3. Cortez-Pinto H, Camilo ME, Baptista A, et al. Non-alcoholic fatty liver: another feature of the metabolic syndrome?. Clin Nutr. 1999;18:353–358
  4. Bedogni G, Miglioli L, Masutti F, et al. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology. 2005;42:44–52
  5. Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol. 2003;98:960–967
  6. Nanji AA, French SW, Freeman JB. Serum alanine aminotransferase to aspartate aminotransferase ratio and degree of fatty liver in morbidly obese patients. Enzyme. 1986;36:266–269
  7. Chang Y, Ryu S, Sung E, Jang Y. Higher concentrations of alanine aminotransferase within the reference interval predict nonalcoholic fatty liver disease. Clin Chem. 2007;53:686–692
  8. Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2003;124:71–79
  9. Ioannou GN, Weiss NS, Boyko EJ, et al. Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease. Gastroenterology. 2005;128:627–635
  10. Hanley AJ, Williams K, Festa A, et al. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes. 2005;54:3140–3147
  11. Schindhelm RK, Dekker JM, Nijpels G, et al. Alanine aminotransferase and the 6-year risk of the metabolic syndrome in Caucasian men and women: the Hoorn Study. Diabet Med. 2007;24:430–435
  12. Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30:1212–1218
  13. Targher G. Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. Diabet Med. 2007;24:1–6
  14. Goland S, Shimoni S, Zornitzki T, et al. Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease: echocardiographic and tissue Doppler imaging assessment. J Clin Gastroenterol. 2006;40:949–955
  15. Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865–873
  16. Targher G, Bertolini L, Padovani R, et al. Non-alcoholic fatty liver disease is associated with carotid artery wall thickness in diet-controlled type 2 diabetic patients. J Endocrinol Invest. 2006;29:55–60
  17. Targher G, Bertolini L, Poli F, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes. 2005;54:3541–3546
  18. Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med. 2000;342:1266–1271
  19. Zanella A, Conte D, Prati D, et al. Hepatitis C virus RNA and liver histology in blood donors reactive to a single antigen by second-generation recombinant immunoblot assay. Hepatology. 1995;21:913–917
  20. Prati D, Capelli C, Zanella A, et al. Influence of different hepatitis C virus genotypes on the course of asymptomatic hepatitis C virus infection. Gastroenterology. 1996;110:178–183
  21. Alberti A, Morsica G, Chemello L, et al. Hepatitis C viraemia and liver disease in symptom-free individuals with anti-HCV. Lancet. 1992;340:697–698
  22. Kunde SS, Lazenby AJ, Clements RH, Abrams GA. Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women. Hepatology. 2005;42:650–656
  23. 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
  24. Kim HC, Nam CM, Jee SH, et al. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ. 2004;328:983
  25. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37:1286–1292
  26. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395
  27. Dawber TR, Meadors GF, Moore FE. Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health. 1951;41:279–281
  28. Dawber TR, Kannel WB, Lyell LP. An approach to longitudinal studies in a community: the Framingham Study. Ann N Y Acad Sci. 1963;107:539–556
  29. Kannel WB, Feinleib M, McNamara PM, et al. An investigation of coronary heart disease in families (The Framingham offspring study). Am J Epidemiol. 1979;110:281–290
  30. Becker U, Deis A, Sorensen TI, et al. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996;23:1025–1029
  31. Bellentani S, Saccoccio G, Costa G, et al. Drinking habits as cofactors of risk for alcohol induced liver damage (The Dionysos Study Group). Gut. 1997;41:845–850
  32. Henry RJ, Chiamori N, Golub OJ, Berkman S. Revised spectrophotometric methods for the determination of glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, and lactic acid dehydrogenase. Am J Clin Pathol. 1960;34:381–398
  33. Cupples LA. DARB. Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Study, 30-year follow-up. In:  Kannel WB,  Garrison RJ editor. The Framingham Heart Study: An Epidemiological Investigation of Cardiovascular Disease. Washington, DC: Government Printing Office; 1987;p. 87–203NIH Publication, section 34
  34. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–2497
  35. Freiberg MS, Pencina MJ, D'Agostino RB, et al. BMI vs. waist circumference for identifying vascular risk. Obesity. 2008;16:463–469
  36. Siest G, Schiele F, Galteau MM, et al. Aspartate aminotransferase and alanine aminotransferase activities in plasma: statistical distributions, individual variations, and reference values. Clin Chem. 1975;21:1077–1087
  37. SAS/STAT User's Guide (Version 8). Cary, NC: SAS Institute Inc; 2000;
  38. Jeong SK, Nam HS, Rhee JA, et al. Metabolic syndrome and ALT: a community study in adult Koreans. Int J Obes Relat Metab Disord. 2004;28:1033–1038
  39. Kim HC, Choi KS, Jang YH, et al. Normal serum aminotransferase levels and the metabolic syndrome: Korean National Health and Nutrition Examination Surveys. Yonsei Med J. 2006;47:542–550
  40. Fraser A, Longnecker MP, Lawlor DA. Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999–2004. Gastroenterology. 2007;133:1814–1820
  41. Wannamethee SG, Shaper AG, Lennon L, Whincup PH. Hepatic enzymes, the metabolic syndrome, and the risk of type 2 diabetes in older men. Diabetes Care. 2005;28:2913–2918
  42. Vozarova B, Stefan N, Lindsay RS, et al. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes. 2002;51:1889–1895
  43. 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
  44. 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
  45. Lee DS, Evans JC, Robins SJ, et al. Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study. Arterioscler Thromb Vasc Biol. 2007;27:127–133
  46. Lee DH, Blomhoff R, Jacobs DR. Is serum gamma glutamyltransferase a marker of oxidative stress?. Free Radic Res. 2004;38:535–539
  47. Parekh S, Anania FA. Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease. Gastroenterology. 2007;132:2191–2207
  48. Pagano C, Soardo G, Esposito W, et al. Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur J Endocrinol. 2005;152:113–118
  49. Nishida M, Funahashi T, Shimomura I. Pathophysiological significance of adiponectin. Med Mol Morphol. 2007;40:55–67
  50. Vega GL, Chandalia M, Szczepaniak LS, Grundy SM. Metabolic correlates of nonalcoholic fatty liver in women and men. Hepatology. 2007;46:716–722
  51. Villanova N, Moscatiello S, Ramilli S, et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005;42:473–480
  52. Mallat A, Lotersztajn S. Endocannabinoids and their receptors in the liver. Am J Physiol Gastrointest Liver Physiol. 2007;294:G9–G12
  53. Lizardi-Cervera J, Chavez-Tapia NC, Perez-Bautista O, et al. Association among C-reactive protein, fatty liver disease, and cardiovascular risk. Dig Dis Sci. 2007;52:2375–2379
  54. Kew MC. Serum aminotransferase concentration as evidence of hepatocellular damage. Lancet. 2000;355:591–592
  55. Green RM, Flamm S. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology. 2002;123:1367–1384
  56. Kaplan MM. Alanine aminotransferase levels: what's normal?. Ann Intern Med. 2002;137:49–51
  57. Ioannou GN, Boyko EJ, Lee SP. The prevalence and predictors of elevated serum aminotransferase activity in the United States in 1999–2002. Am J Gastroenterol. 2006;101:76–82

 The authors disclose the following: Supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195). W.G. is supported by K08-DK071940 (NIDDK/NIH). R.S.V. is supported in part by 2K24HL04334 (NHLBI/NIH). W.G. and C.S.F. designed and conducted the study, analyzed and interpreted the data, and prepared the manuscript. They had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. J.M.M. performed all the statistical analyses. All authors reviewed and approved the manuscript.

PII: S0016-5085(08)01683-1

doi: 10.1053/j.gastro.2008.09.018

Gastroenterology
Volume 135, Issue 6 , Pages 1935-1944.e1 , December 2008

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