Skip to main content

Advertisement

SpringerLink
Log in

Increased serum gamma-glutamyltransferase levels are associated with ventricular instability in type 2 diabetes

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

The purpose of our study is to examine the association between serum GGT levels and ventricular instability in Chinese patients with T2DM. We conducted a cross-sectional, community-based study in Nanjing, China from June to November 2011. Among 10,050 patients aged 40–79 years, we enrolled 2444 with pre-diabetes, 2496 with T2DM, and 4521 without diabetes (non-diabetes). Electrocardiograms were performed to measure the QT interval corrected for heart rate (QTc) and QT interval dispersion (QTd). Serum GGT levels, metabolic parameters, body mass index, and blood pressure were also measured. We found that there were no significant associations of increased QTc/QTd with serum GGT levels in participants with pre-existing T2DM and non-diabetes, after adjusting for age, duration of diabetes, and metabolic parameters. Even after adjustment, higher risks of QTc ≥ 440 ms/√s and QTd ≥ 58 ms were found in participants with serum GGT levels ≥49 U/L compared with those with <15 U/L in the pre-diabetes (QTc: OR 1.96, 95 % CI 1.23–2.47; QTd: OR 1.34, 95 % CI 1.07–1.94) and newly diagnosed T2DM (QTc: OR 2.01, 95 % CI 1.39–2.51; QTd: OR 1.53, 95 % CI 1.03–1.99) groups. We conclude that Increased serum GGT levels are associated with some markers of ventricular repolarization abnormalities in the early stage of T2DM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. B.S. Rana, P.O. Lim, A.A. Naas, S.A. Ogston, R.W. Newton, R.T. Jung, A.D. Morris, A.D. Struthers, QT interval abnormalities are often present at diagnosis in diabetes and are better predictors of cardiac death than ankle brachial pressure index and autonomic function tests. Heart 91, 44–50 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. R. Marfella, F. Rossi, D. Giugliano, Hyperglycaemia and QT interval: time for re-evaluation. Diabetes Nutr. Metab. 14, 63–65 (2001)

    CAS  PubMed  Google Scholar 

  3. S. Giunti, G. Bruno, E. Lillaz, G. Gruden, V. Lolli, N. Chaturvedi, J.H. Fuller, M. Veglio, P. Cavallo-Perin, EURODIAB IDDM Complications Study Group: incidence and risk factors of prolonged QTc interval in type 1 diabetes: the EURODIAB Prospective Complications Study. Diabetes Care 30, 2057–2063 (2007)

    Article  PubMed  Google Scholar 

  4. A.A. Naas, N.C. Davidson, C. Thompson, R.T. Jung, R.W. Newton, A.D. Struthers, QT and QTc dispersion are accurate predictors of cardiac death in newly diagnosed non-insulin-dependent diabetes: cohort study. BMJ 316, 745–746 (1998)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. C. Cardoso, G. Salles, K. Bloch, W. Deccache, A.G. Siqueira-Filho, Clinical determinants of increased QT dispersion in patients with diabetes mellitus. Int. J. Cardiol. 79, 253–262 (2001)

    Article  CAS  PubMed  Google Scholar 

  6. M. Odermarsky, J. Lykkesfeldt, P. Liuba, Poor vitamin C status is associated with increased carotid intima-media thickness, decreased microvascular function, and delayed myocardial repolarization in young patients with type 1 diabetes. Am. J. Clin. Nutr. 90, 447–452 (2009)

    Article  CAS  PubMed  Google Scholar 

  7. A.P. Kellogg, K. Converso, T. Wiggin, M. Stevens, R. Pop-Busui, Effects of cyclooxygenase-2 gene inactivation on cardiac autonomic and left ventricular function in experimental diabetes. Am. J. Physiol. Heart Circ. Physiol. 296, H453–H461 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. G. Perseghin, F. De Cobelli, A. Esposito, E. Belloni, G. Lattuada, T. Canu, P.L. Invernizzi, F. Ragogna, A. La Torre, P. Scifo, G. Alberti, A. Del Maschio, L. Luzi, Left ventricular function and energy metabolism in middle-aged men undergoing long-lasting sustained aerobic oxidative training. Heart 95, 630–635 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. Z. Lu, J. Abe, J. Taunton, Y. Lu, T. Shishido, C. McClain, C. Yan, S.P. Xu, T.M. Spangenberg, H. Xu, Reactive oxygen species-induced activation of p90 ribosomal S6 kinase prolongs cardiac repolarization through inhibiting outward K+ channel activity. Circ. Res. 103, 269–278 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. A. Pannaccione, P. Castaldo, E. Ficker, L. Annunziato, M. Taglialatela, Histidines 578 and 587 in the S5-S6 linker of the human Ether-a-gogo related Gene-1K channels confer sensitivity to reactive oxygen species. J. Biol. Chem. 277, 8912–8919 (2002)

    Article  CAS  PubMed  Google Scholar 

  11. W.H. Tang, W.T. Cheng, G.M. Kravtsov, X.Y. Tong, X.Y. Hou, S.K. Chung, S.S. Chung, Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress. Am. J. Physiol. Cell. Physiol. 299, C643–C653 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. A. Fraser, R. Harris, N. Sattar, S. Ebrahim, D.G. Smith, D.A. Lawlor, Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women’s Heart and Health Study and meta-analysis. Diabetes Care 32, 741–750 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. N. Nakanishi, K. Suzuki, K. Tatara, Serum gamma-glutamyltransferase and risk of metabolic syndrome and type 2 diabetes in middle-aged Japanese men. Diabetes Care 27, 1427–1432 (2004)

    Article  CAS  PubMed  Google Scholar 

  14. S.G. Wannamethee, P.H. Whincup, A.G. Shaper, L. Lennon, N. Sattar, γ-glutamyltransferase, hepatic enzymes, and risk of incident heart failure in older men. Arterioscler. Thromb. Vasc. Biol. 32, 830–835 (2012)

    Article  CAS  PubMed  Google Scholar 

  15. A.M. Strasak, C.C. Kelleher, J. Klenk, L.J. Brant, E. Ruttmann, K. Rapp, H. Concin, G. Diem, K.P. Pfeiffer, H. Ulmer, Vorarlberg Health Monitoring and Promotion Program Study Group, Longitudinal change in serum gamma-glutamyltransferase and cardiovascular disease mortality: a prospective population-based study in 76,113 Austrian adults. Arterioscler. Thromb. Vasc. Biol. 28, 1857–1865 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. M. Emdin, A. Pompella, A. Paolicchi, Gamma-glutamyltransferase, atherosclerosis, and cardiovascular disease: triggering oxidative stress within the plaque. Circulation 112, 2078–2080 (2005)

    Article  PubMed  Google Scholar 

  17. A. Paolicchi, M. Emdin, E. Ghliozeni, E. Ciancia, C. Passino, G. Popoff, A. Pompella, Images in cardiovascular medicine. Human atherosclerotic plaques contain gamma-glutamyl transpeptidase enzyme activity. Circulation 109, 1440 (2004)

    Article  PubMed  Google Scholar 

  18. C. Lengyel, L. Virág, T. Bíró, N. Jost, J. Magyar, P. Biliczki, E. Kocsis, R. Skoumal, P.P. Nánási, M. Tóth, V. Kecskeméti, J.G. Papp, A. Varró, Diabetes mellitus attenuates the repolarization reserve in mammalian heart. Cardiovasc. Res. 73, 512–520 (2007)

    Article  CAS  PubMed  Google Scholar 

  19. G. Ning, Reaction study group. Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudial (REACTION) study. J. Diabetes 4, 172–173 (2012)

    Article  PubMed  Google Scholar 

  20. K. Wang, Y. Yang, Y. Wu, J. Chen, D. Zhang, X. Mao, X. Wu, X. Long, C. Liu, The association between insulin resistance and vascularization of thyroid nodules. J. Clin. Endocrinol. Metab. 100, 184–192 (2015)

    Article  CAS  PubMed  Google Scholar 

  21. D.H. Lee, D.R. Jacobs Jr, M. Gross, C.I. Kiefe, J. Roseman, C.E. Lewis, M. Steffes, Gammaglutamyltransferase is a predictor of incident diabetes and hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Clin. Chem. 49, 1358–1366 (2003)

    Article  CAS  PubMed  Google Scholar 

  22. P.M. Okin, R.B. Devereux, E.T. Lee, J.M. Galloway, B.V. Howard, Strong Heart Study, Electrocardiographic repolarization complexity and abnormality predict all-cause and cardiovascular mortality in diabetes: the strong heart study. Diabetes 53, 434–440 (2004)

    Article  CAS  PubMed  Google Scholar 

  23. M. Veglio, G. Bruno, M. Borra, G. Macchia, G. Bargero, N. D’Errico, G.F. Pagano, P. Cavallo-Perin, Prevalence of increased QT interval duration and dispersion in type 2 diabetic patients and its relationship with coronary heart disease: a population-based cohort. J. Int. Med 25, 317–324 (2002)

    Article  Google Scholar 

  24. J.S. Lim, J.H. Yang, B.Y. Chun, S. Kam, D.R. Jacobs Jr, D.H. Lee, Is serum gamma-glutamyltransferase inversely associated with serum antioxidants as a marker of oxidative stress? Free Radic. Biol. Med. 37, 1018–1023 (2004)

    Article  CAS  PubMed  Google Scholar 

  25. D.H. Lee, M.D. Gross, M.W. Steffes, D.R. Jacobs Jr, Is serum gammaglutamyltransferase a biomarker of xenobiotics, which are conjugated by glutathione? Arterioscler. Thromb. Vasc. Biol. 28, e26–e28 (2008)

    Article  CAS  PubMed  Google Scholar 

  26. K. Kolbe, R. Schonherr, G. Gessner, N. Sahoo, T. Hoshi, S.H. Heinemann, Cysteine 723 in the C-linker segment confers oxidative inhibition of hERG1 potassium channels. J. Physiol. 588, 2999–3009 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. M. Schönauer, A. Thomas, S. Morbach, J. Niebauer, U. Schönauer, H. Thiele, Cardiac autonomic diabetic neuropathy. Diabetes Vasc. Dis. Res. 5, 336–344 (2008)

    Article  Google Scholar 

  28. S. Matsushima, S. Kinugawa, T. Ide, H. Matsusaka, N. Inoue, Y. Ohta, T. Yokota, K. Sunagawa, H. Tsutsui, Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart. Am. J. Physiol.-Heart. C 291, H2237–H2245 (2006)

    Article  CAS  Google Scholar 

  29. J. Chen, J. Sroubek, Y. Krishnan, Y. Li, J. Bian, T.V. McDonald, PKA phosphorylation of HERG protein regulates the rate of channel synthesis. Am. J. Physiol. Heart Circ. Physiol. 296, H1244–H1254 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. D.A. Saint, The role of the persistent Na+ current during cardiac ischemia and hypoxia. J. Cardiovasc. Electrophysiol. 17, S96–S103 (2006)

    Article  PubMed  Google Scholar 

  31. Report and Recommendations of the San Antonio Conference on Diabetic Neuropathy: American Diabetes Association and American Academy of Neurology (Consensus Statement). Diabetes Care 11, 592–597 (1988)

  32. F.M. Brown, M. Watts, S.L. Rabinowe, Aggregation of subclinical autonomic nervous system dysfunction and autoantibodies in families with type I diabetes. Diabetes 40, 1611–1614 (1991)

    Article  CAS  PubMed  Google Scholar 

  33. J. Fleischer, Diabetic autonomic imbalance and glycemic variability. J. Mech. Sci. Technol. 6, 1207–1215 (2012)

    Google Scholar 

  34. G. Bujag, M. Miorelli, P. Turrini, P. Melacini, A. Nova, Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. Am. J. Cardiol. 72, 973–976 (1993)

    Article  Google Scholar 

  35. R. Kumar, M. Fisher, P.W. Macfarlane, Diabetes and the QT interval: time for debate. Br. J. Diabetes Vasc. Dis. 4, 146–150 (2004)

    Article  Google Scholar 

  36. J.B. Whitfield, Serum γ-glutamyltransferase and risk of disease. Clin. Chem. 53, 1–2 (2007)

    Article  CAS  PubMed  Google Scholar 

  37. G. Targher, L. Bertolini, F. Poli, S. Rodella, L. Scala, R. Tessari, L. Zenari, G. Falezza, Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 54, 354–3546 (2005)

    Article  Google Scholar 

Download references

Acknowledgments

The REACTION study was supported by grants from the Chinese Medical Association Foundation and Chinese Endocrine Society (Grant: 12020240314). This work was supported in part by the Special Foundation for Science and Technology Service Platform of Jiangsu Province (Grant: BM2012064). We thank all the participants in this study, along with Dr Tao Chen from Nanjing Medical University for assistance with statistical analysis. The authors have nothing to disclose.

Author information

Author notes

    Authors and Affiliations

    1. Department of Endocrinology, Affiliated Hospital on Integration of Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, 100, Hongshan Road, Nanjing, 210028, China

      Kun Wang, Yu Yang, Jie Chen, Danyu Zhang, Zhoujun Liu, Juan Xu, Meng Cao, Xiaodong Mao & Chao Liu

    2. Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, 87, Dingjiaqiao Road, Nanjing, 210009, China

      Ling Li

    3. Department of Endocrinology, The First People’s Hospital of Changzhou, Third Affiliated Hospital of Suzhou University, 185, Juqian Road, Changzhou, 213003, China

      Yang Wu

    Authors
    1. Kun Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Ling Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yang Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Yu Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Jie Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Danyu Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Zhoujun Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Juan Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Meng Cao
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Xiaodong Mao
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Chao Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Chao Liu.

    Ethics declarations

    Conflict of Interest

    The authors declare that they have no conflict of interest.

    Additional information

    Kun Wang and Ling Li have contributed equally to this study.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Wang, K., Li, L., Wu, Y. et al. Increased serum gamma-glutamyltransferase levels are associated with ventricular instability in type 2 diabetes. Endocrine 52, 63–72 (2016). https://doi.org/10.1007/s12020-015-0760-1

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12020-015-0760-1

    Keywords

    Search

    Navigation