Korean J Fam Pract. 2018; 8(4): 504-511  https://doi.org/10.21215/kjfp.2018.8.4.504
Association between Serum Liver Enzyme and Mortality in the Diabetes Patients of Korea
Chung-Woo Lee1, Do-Hoon Kim1,*, Seung-Hyun Lee1, Dong-Won Kim1, Hyonchong Kim1, SooGyeong Park1, Da-Eun Seul1, Joo-Hyun Park1, Shinhye Kim1, Moonyoung Choi1, Jin-Hyung Jung2, Kyungdo Han2
1Department of Family Medicine, Korea University College of Medicine; 2Department of Biostatics, College of Medicine, The Catholic University of Korea, Seoul, Korea
Do-Hoon Kim Tel: +82-31-412-4261, Fax: +82-31-412-5364 E-mail: kmcfm@hanmail.net ORCID: http://orcid.org/0000-0001-7421-4501
Received: June 23, 2017; Revised: September 14, 2017; Accepted: September 18, 2017; Published online: August 20, 2018.
© The Korean Academy of Family Medicine. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Serum liver enzyme levels have been commonly used as an indicator of liver damage, but recent studies have shown that gamma-glutamyl transferase (GGT), aspartate transaminase (AST), and alanine transaminase (ALT) levels may also affect all-cause mortality and cardiovascular mortality. In this study, we aimed to investigate the association between serum liver enzyme levels and mortality in patients with diabetes who were susceptible to cardiovascular disease.
Methods: In this study, using the national health insurance cohort data, we compared the mortality ratio of patients with diabetes who underwent health screening from 2003 to 2008 according to serum GGT, AST, and ALT quartiles.
Results: Of 35,996 participants, 21,946 were men, and the average age of the participants was 56 years. The average serum GGT, AST, and ALT levels of the participants were 36 IU/L, 25.9 IU/L, and 25.9 IU/L, respectively. Regarding GGT, significantly higher all-cause and cardiovascular mortality rates were observed in the fourth quartile than in the first quartile for both men and women. Regarding AST and ALT, both men and women had lower mortality rates in the second and third quartiles than in the first quartile, and both men and women had lower cardiovascular mortality in the second, third, and fourth quartiles than in the first quartile.
Conclusion: In patients with diabetes, elevated GGT levels are associated with increased mortality, while reduced AST and ALT levels to some extent may be associated with mortality, especially cardiovascular mortality. Therefore, it is necessary to pay attention to AST and ALT decreases with GGT increases in patients with diabetes.
Keywords: Liver Function Tests; Gamma-Glutamyl Transferase; Aspartate Transaminase; Alanine Transaminase; Diabetes Mellitus; Mortality
References
  1. Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin Chem 2000; 46: 2027-49.
    Pubmed
  2. Marchesini G, Targher G. Commentary: Liver enzymes and the risk of adverse cardiovascular outcomes--the lower, the better? Int J Epidemiol 2011;40: 1539-41.
    Pubmed CrossRef
  3. Kunutsor SK, Apekey TA, Seddoh D, Walley J. Liver enzymes and risk of allcause mortality in general populations: a systematic review and meta-analysis. Int J Epidemiol 2014; 43: 187-201.
    Pubmed CrossRef
  4. Kunutsor SK, Apekey TA, Cheung BM. Gamma-glutamyltransferase and risk of hypertension: a systematic review and dose-response meta-analysis of prospective evidence. J Hypertens 2015; 33: 2373-81.
    Pubmed CrossRef
  5. Kim DJ, Noh JH, Cho NH, Lee BW, Choi YH, Jung JH, et al. Serum gammaglutamyltransferase within its normal concentration range is related to the presence of diabetes and cardiovascular risk factors. Diabet Med 2005; 22:1134-40.
    Pubmed CrossRef
  6. Kunutsor SK, Apekey TA, Seddoh D. Gamma glutamyltransferase and metabolic syndrome risk: a systematic review and dose-response meta-analysis. Int J Clin Pract 2015; 69: 136-44.
    Pubmed CrossRef
  7. Lee DS, Evans JC, Robins SJ, Wilson PW, Albano I, Fox CS, et al. Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 2007; 27: 127-33.
    Pubmed CrossRef
  8. Nakagawa H, Isogawa A, Tateishi R, Tani M, Yoshida H, Yamakado M, et al. Serum gamma-glutamyltransferase level is associated with serum superoxide dismutase activity and metabolic syndrome in a Japanese population. J Gastroenterol 2012; 47: 187-94.
    Pubmed CrossRef
  9. Meisinger C, Döring A, Schneider A, Löwel H. Serum gamma-glutamyltransferase is a predictor of incident coronary events in apparently healthy men from the general population. Atherosclerosis 2006; 189: 297-302.
    Pubmed CrossRef
  10. Kunutsor SK, Khan H, Laukkanen JA. γ-Glutamyltransferase and risk of sudden cardiac death in middle-aged finnish men: a new prospective cohort study. J Am Heart Assoc 2016; 5(2): e002858.
    Pubmed KoreaMed CrossRef
  11. Wang J, Zhang D, Huang R, Li X, Huang W. Gamma-glutamyltransferase and risk of cardiovascular mortality: A dose-response meta-analysis of prospective cohort studies. PLoS One 2017; 12: e0172631.
    Pubmed KoreaMed CrossRef
  12. Sung KC, Ryu S, Kim BS, Cheong ES, Park DI, Kim BI, et al. γ-Glutamyl transferase is associated with mortality outcomes independently of fatty liver. Clin Chem 2015; 61: 1173-81.
    Pubmed CrossRef
  13. Ndrepepa G, Braun S, Cassese S, Fusaro M, Laugwitz KL, Schunkert H, et al. Relation of gamma-glutamyl transferase to cardiovascular events in patients with acute coronary syndromes. Am J Cardiol 2016; 117: 1427-32.
    Pubmed CrossRef
  14. Oh CM, Won YJ, Cho H, Lee JK, Park BY, Jun JK, et al. Alanine aminotransferase and gamma-glutamyl transferase have different dose-response relationships with risk of mortality by age. Liver Int 2016; 36: 126-35.
    Pubmed CrossRef
  15. Ford I, Mooijaart SP, Lloyd S, Murray HM, Westendorp RG, de Craen AJ, et al. The inverse relationship between alanine aminotransferase in the normal range and adverse cardiovascular and non-cardiovascular outcomes. Int J Epidemiol 2011; 40: 1530-8.
    Pubmed CrossRef
  16. Deetman PE, Alkhalaf A, Landman GW, Groenier KH, Kootstra-Ros JE, Navis G, et al. Alanine aminotransferase and mortality in patients with type 2 diabetes (ZODIAC-38). Eur J Clin Invest 2015; 45: 807-14.
    Pubmed CrossRef
  17. Williams KH, Sullivan DR, Nicholson GC, George J, Jenkins AJ, Januszewski AS, et al. Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes:Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Metabolism 2016; 65: 783-93.
    Pubmed CrossRef
  18. Le Couteur DG, Blyth FM, Creasey HM, Handelsman DJ, Naganathan V, Sambrook PN, et al. The association of alanine transaminase with aging, frailty, and mortality. J Gerontol A Biol Sci Med Sci 2010; 65: 712-7.
    Pubmed KoreaMed CrossRef
  19. Ramaty E, Maor E, Peltz-Sinvani N, Brom A, Grinfeld A, Kivity S, et al. Low ALT blood levels predict long-term all-cause mortality among adults. A historical prospective cohort study. Eur J Intern Med 2014; 25: 919-21.
    Pubmed CrossRef
  20. Sabin CA, Ryom L, Kovari H, Kirk O, de Wit S, Law M, et al. Association between ALT level and the rate of cardio/cerebrovascular events in HIV-positive individuals: the D: A: D study. J Acquir Immune Defic Syndr 2013; 63:456-63.
    Pubmed CrossRef
  21. Yun KE, Shin CY, Yoon YS, Park HS. Elevated alanine aminotransferase levels predict mortality from cardiovascular disease and diabetes in Koreans. Atherosclerosis 2009; 205: 533-7.
    Pubmed CrossRef
  22. Ruhl CE, Everhart JE. The association of low serum alanine aminotransferase activity with mortality in the US population. Am J Epidemiol 2013; 178:1702-11.
    Pubmed KoreaMed CrossRef
  23. Koehler EM, Sanna D, Hansen BE, van Rooij FJ, Heeringa J, Hofman A, et al. Serum liver enzymes are associated with all-cause mortality in an elderly population. Liver Int 2014; 34: 296-304.
    Pubmed CrossRef
  24. Yokoyama M, Watanabe T, Otaki Y, Takahashi H, Arimoto T, Shishido T, et al. Association of the aspartate aminotransferase to alanine aminotransferase ratio with BNP level and cardiovascular mortality in the general population:the yamagata study 10-year follow-up. Dis Markers 2016;2016:4857917.
    Pubmed KoreaMed CrossRef
  25. Zoppini G, Cacciatori V, Negri C, Stoico V, Lippi G, Targher G, et al. The aspartate aminotransferase-to-alanine aminotransferase ratio predicts allcause and cardiovascular mortality in patients with type 2 diabetes. Medicine (Baltimore) 2016; 95: e4821.
    Pubmed KoreaMed CrossRef
  26. Mahady SE, Wong G, Turner RM, Mitchell P, Macaskill P, Craig JC, et al. Elevated liver enzymes and mortality in older individuals: a prospective cohort study. J Clin Gastroenterol 2016. doi: 10.1097/MCG.0000000000000622.
    CrossRef
  27. Unalp-Arida A, Ruhl CE. Noninvasive fatty liver markers predict liver disease mortality in the U.S. population. Hepatology 2016; 63: 1170-83.
    Pubmed KoreaMed CrossRef
  28. Dong MH, Bettencourt R, Barrett-Connor E, Loomba R. Alanine aminotransferase decreases with age: the Rancho Bernardo Study. PLoS One 2010;5: e14254.
    Pubmed KoreaMed CrossRef
  29. Elinav E, Ben-Dov IZ, Ackerman E, Kiderman A, Glikberg F, Shapira Y, et al. Correlation between serum alanine aminotransferase activity and age: an inverted U curve pattern. Am J Gastroenterol 2005; 100: 2201-4.
    Pubmed CrossRef
  30. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39: 412-23.
    Pubmed KoreaMed CrossRef
  31. Elinav E, Ackerman Z, Maaravi Y, Ben-Dov IZ, Ein-Mor E, Stessman J. Low alanine aminotransferase activity in older people is associated with greater long-term mortality. J Am Geriatr Soc 2006; 54: 1719-24.
    Pubmed CrossRef
  32. Nakamura K, Okamura T, Kanda H, Hayakawa T, Okayama A, Ueshima H. The value of combining serum alanine aminotransferase levels and body mass index to predict mortality and medical costs: a 10-year follow-up study of National Health Insurance in Shiga, Japan. J Epidemiol 2006; 16:15-20.
    Pubmed CrossRef


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