Journal List > Korean Diabetes J > v.33(3) > 1002292

TOOLS
Kim, Kim, Park, Cho, Lee, Ga, and Kim: The Effect of Gamma-Glutamyltransferase on Impaired Fasting Glucose or Type 2 Diabetes in Korean Men
Original Article
Korean Diabetes Journal

Korean Diabetes Journal 2009; 33(3): 215-224.

Published online: 30 June 2009

DOI: https://doi.org/10.4093/kdj.2009.33.3.215

The Effect of Gamma-Glutamyltransferase on Impaired Fasting Glucose or Type 2 Diabetes in Korean Men

Tae-Yeon Kim1, Do-Hoon Kim2, Chang-Hae Park2, Kyung-Hwan Cho2, Seung-Hwan Lee2, Hyuk Ga3, Hwan-cheol Kim4

1Department of Radiology, Ansan Hospital, Korea University College of Medicine, Ansan, Korea.

2Department of Family Medicine, Anam Hospital, Korea University College of Medicine, Seoul, Korea.

3Institute of Geriatric Medicine, Eun-Hye Hospital, Korea.

4Department of Occupational Medicine, Anam Hospital, Inha University College of Medicine, Incheon, Korea.

daumarong@hanmail.net

Received 19 March 2009       Accepted 18 May 2009

Copyright © 2009 Korean Diabetes Association

Abstract

Background

We sought to determine the association between serum gamma-glutamyltransferase (GGT) levels within the normal range and the risk for development of impaired fasting glucose (IFG) or type 2 diabetes.

Methods

This retrospective cohort study spanned four years (2002~2006) with 1,717 Korean men who underwent periodic health examinations at a university hospital in Incheon, Korea and were not diagnosed with IFG or type 2 diabetes. Fasting plasma glucose levels were measured at the annual health examination. IFG and diabetes were defined as a serum fasting glucose concentration of 100~125 mg/dL and more than 126 mg/dL, respectively. Cox's proportional hazards model was used to evaluate the association between serum GGT levels and development of IFG or type 2 diabetes.

Results

There was a strong dose-response relationship between serum GGT levels and the incidence of IFG and diabetes. A total of 570 cases (33.2%) of incident IFG and 50 cases (2.9%) of diabetes were found. After controlling potential predictors, the relative risks for the incidence of IFG for GGT levels ≤ 19, 20~25, 26~34, 35~50 and ≥ 51 were 1.00, 0.99, 1.17, 1.23 and 1.38 respectively (P for trend 0.015), and for the incidence of diabetes were 1.00, 1.44, 1.80, 2.55 and 2.58 respectively (P for trend 0.050).

Conclusion

The risk for development of IFG and type 2 diabetes increased in a dose-dependent manner as serum GGT increased within its normal range in Korean men.

Keywords: Gamma-Glutamyltransferase, Glucose intolerance, Type 2 diabetes mellitus

Figures and Tables

Fig. 1
Incidence of IFG (impaired fasting glucose) and type 2 diabetes mellitus according to serum GGT (gamma-glutamyltransferease) levels during 5 years of follow-up.
kdj-33-215-g001
Table 1
Baseline Characteristics of 1,717 Korean male, according to serum GGT levels
kdj-33-215-i001

*P-values are driven by ANOVA. Values were presented by mean ± SD or number (%). GGT, gamma-glutamyltransferase.

Table 2
The risk of incidence of IFG and type 2 diabetes mellitus according to serum GGT levels during 5 years of follow-up
kdj-33-215-i002

GGT, gamma-glutamyltransferase. IFG, impaired fasting glucose. *For linear Trend. Model 1; Age-adjusted. †Model 2; Multiple factors such as age, body mass index, amounts of smoking, alcohol consumption, regular physical exercise, family history of diabetes, fasting plasma glucose level, hemoglobin level, total cholesterol level, other liver enzymes (Aspartate transaminase/Alanine transaminase) at the beginning of the study. ‡Model 3; model 2 plus adjustment for all of the other liver enzymes (Aspartate transaminase/Alanine transaminase).

References

1. Zimmet P. Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted? J Intern Med. 2000. 247:301–310.
2. King H, Rewers M. WHO Ad Hoc Diabetes Reporting Group. Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. Diabetes Care. 1993. 16:157–177.
3. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998. 21:1414–1431.
4. Park SW, Kim DJ, Min KW, Baik SH, Choi KM, Park IB, Park JH, Son HS, Ahn CW, Oh JY, Lee J, Chung CH, Kim J, Kim H. Current status of diabetes management in Korea using National Health Insurance Database. J Korean Diabetes Assoc. 2007. 31:362–367.
5. Wannamethee G, Ebrahim S, Shaper AG. Gamma-glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes. Am J Epidemiol. 1995. 142:699–708.
6. Carlisle ML, King MR, Karp DR. Gamma-glutamyl transpeptidase activity alters the T cell response to oxidative stress and Fas-induced apoptosis. Int Immunol. 2003. 15:17–27.
7. Pintus F, Mascia P. 'ATS-SARDEGNA' Research Group. Distribution and population determinants of gamma-glutamyltransferase in a random sample of Sardinian inhabitants. Eur J Epidemiol. 1996. 12:71–76.
8. Whitehead TP, Robinson D, Allaway SL. The effects of cigarette smoking and alcohol consumption on serum liver enzyme activities: a dose-related study in men. Ann Clin Biochem. 1996. 33:530–535.
9. Kim KY, Kam S, Lee JH, Ha YA, Lee KE. A cross-sectional study on gamma-GTP and its related factors in male workers. Korean J Prev Med. 2002. 35:169–174.
10. Yamada Y, Noborisaka Y, Suzuki H, Ishizaki M, Yamada S. Alcohol consumption, serum gamma-glutamyltransferase levels, and coronary risk factors in a middle-aged occupational population. J Occup Health. 2003. 45:293–299.
11. Perry IJ, Wannamethee SG, Shaper AG. Prospective study of serum gamma-glutamyltransferase and risk of NIDDM. Diabetes Care. 1998. 21:732–737.
12. Nannipieri M, Gonzales C, Baldi S, Posadas R, Williams K, Haffner SM, Stern MP, Ferrannini E. Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study. Diabetes Care. 2005. 28:1757–1762.
13. Nakanishi N, Suzuki K, Tatara K. Serum gamma-glutamyltransferase and risk of metabolic syndrome and type 2 diabetes in middle-aged Japanese men. Diabetes Care. 2004. 27:1427–1432.
14. Andre P, Balkau B, Born C, Charles MA, Eschwege E. Three-year increase of gamma-glutamyltransferase level and development of type 2 diabetes in middle-aged men and women: the D.E.S.I.R. cohort. Diabetologia. 2006. 49:2599–2603.
15. Lee MY, Weon CS, Ko CH, Lee BJ, Lee Y, Kim MJ, Shin YK, Chung CH. Relations between serum gamma-glutamyltransferase and prevalence of diabetes mellitus. Korean J Med. 2004. 67:498–505.
16. Kim DJ, Noh JH, Cho NH, Lee BW, Choi YH, Jung JH, Min YK, Lee MS, Lee MK, Kim KW. Serum gamma-glutamyltransferase within its normal concentration range is related to the presence of diabetes and cardiovascular risk factors. Diabet Med. 2005. 22:1134–1140.
17. Shin JY, Lim JH, Koh DH, Kwon KS, Kim YK, Kim HC, Lee YC, Lee JH, Nam MS, Hong SB, Park SG. Serum gamma-glutamyltransferase levels and the risks of impaired fasting glucose in healthy men: a 2-year follow-up. J Prev Med Public Health. 2006. 39:353–358.
18. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003. 37:1202–1219.
19. Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, Kahn CR. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell. 2000. 6:87–97.
20. Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology. 2003. 144:5159–5165.
21. Joyce-Brady M, Jean JC, Hughey RP. gamma-glutamyltransferase and its isoform mediate an endoplasmic reticulum stress response. J Biol Chem. 2001. 276:9468–9477.
22. Paolisso G, D'Amore A, Volpe C, Balbi V, Saccomanno F, Galzerano D, Giugliano D, Varricchio M, D'Onofrio F. Evidence for a relationship between oxidative stress and insulin action in non-insulin -dependent (type II) diabetic patients. Metabolism. 1994. 43:1426–1429.
23. Paolisso G, Gambardella A, Tagliamonte MR, Saccomanno F, Salvatore T, Gualdiero P, D'Onofrio MV, Howard BV. Does free fatty acid infusion impair insulin action also through an increase in oxidative stress? J Clin Endocrinol Metab. 1996. 81:4244–4248.
24. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000. 408:239–247.
25. Stark AA, Russell JJ, Langenbach R, Pagano DA, Zeiger E, Huberman E. Localization of oxidative damage by a glutathione-gamma-glutamyl transpeptidase system in preneoplastic lesions in sections of livers from carcinogen-treated rats. Carcinogenesis. 1994. 15:343–348.
26. Drozdz R, Parmentier C, Hachad H, Leroy P, Siest G, Wellman M. gamma-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radic Biol Med. 1998. 25:786–792.
27. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature. 2001. 410:37–40.
28. Kaneto H, Xu G, Fujii N, Kim S, Bonner-Weir S, Weir GC. Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem. 2002. 277:30010–30018.
29. Campos SP, Baumann H. Insulin is a prominent modulator of the cytokine-stimulated expression of acute-phase plasma protein genes. Mol Cell Biol. 1992. 12:1789–1797.
30. Lopez-Bermejo A, Botas P, Funahashi T, Delgado E, Kihara S, Ricart W, Fernandez-Real JM. Adiponectin, hepatocellular dysfunction and insulin sensitivity. Clin Endocrinol (Oxf). 2004. 60:256–263.
31. Freeman DJ, Norrie J, Caslake MJ, Gaw A, Ford I, Lowe GD, O'Reilly DS, Packard CJ, Sattar N. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes. 2002. 51:1596–1600.
32. Kerner A, Avizohar O, Sella R, Bartha P, Zinder O, Markiewicz W, Levy Y, Brook GJ, Aronson D. Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2005. 25:193–197.
33. Krotkiewski M, Bjorntorp P, Sjostrom L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest. 1983. 72:1150–1162.
34. Wei M, Gaskill SP, Haffner SM, Stern MP. Waist circumference as the best predictor of noninsulin dependent diabetes mellitus (NIDDM) compared to body mass index, waist/hip ratio and other anthropometric measurements in Mexican Americans--a 7-year prospective study. Obes Res. 1997. 5:16–23.
35. Stevens J, Couper D, Pankow J, Folsom AR, Duncan BB, Nieto FJ, Jones D, Tyroler HA. Sensitivity and specificity of anthropometrics for the prediction of diabetes in a biracial cohort. Obes Res. 2001. 9:696–705.
36. Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation. 2003. 107:391–397.
37. Sattar N, Gaw A, Scherbakova O, Ford I, O'Reilly DS, Haffner SM, Isles C, Macfarlane PW, Packard CJ, Cobbe SM, Shepherd J. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation. 2003. 108:414–419.
38. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002. 123:745–750.
39. Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR Am J Roentgenol. 2007. 189:W320–W323.
40. Mulhall BP, Ong JP, Younossi ZM. Non-alcoholic fatty liver disease: an overview. J Gastroentero Hepatol. 2002. 17:1136–1143.
TOOLS
Similar articles