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Lipids, Lipoproteins, and Cardiovascular Risk Factors |
-Glutamyltransferase Is a Predictor of Incident Diabetes and Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
1 Department of Preventive Medicine, College of Medicine, Kosin University, Pusan, Korea 602-202.
2 Division of Epidemiology, School of Public Health, and
3
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55454.
4 Institute for Nutrition Research, University of Oslo, N-0316 Oslo, Norway.
5 Division of Preventive Medicine, School of Medicine, and
6
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, AL 35205.
7 Birmingham Veterans Affairs Medical Center, Birmingham, AL 35233.
aAddress correspondence to this author at: Division of Epidemiology, School of Public Health, University of Minnesota, 1300 South 2nd St., Suite 300, Minneapolis, MN 55454. Fax 612-624-0315; e-mail jacobs{at}epi.umn.edu.
Background: 
-Glutamyltransferase (GGT), which maintains cellular concentrations of glutathione, may be a marker of oxidative stress, and GGT itself may produce oxidative stress. We performed a prospective study to examine whether serum GGT predicts diabetes and hypertension.
Methods: Study participants were 4844 black and white men and women 18–30 years of age in 1985–1986; they were reexamined 2, 5, 7, 10, and 15 years later. Year 0 GGT cutpoints were 12, 17, 25, and 36 U/L (overall 25th, 50th, 75th, and 90th percentiles; the laboratory cutpoints for abnormal are 40 U/L in women and 50 U/L in men). We deleted 32 participants with prevalent diabetes and 140 participants with prevalent hypertension from the respective incidence analyses.
Results: After adjustment for study center, race, sex, and age in proportional hazards regression, the hazard ratios across year 0 GGT categories were 1.0, 1.6, 1.7, 4.0 (95% confidence interval, 2.0–8.1), and 5.5 (2.7–11.1) for 15-year incident diabetes and 1.0, 1.2, 1.7 (1.2–2.2), 2.3 (1.7–3.2), and 2.3 (1.7–3.2) for hypertension. Additional adjustment for year 0 alcohol consumption, body mass index, cigarette smoking, and physical activity attenuated this relationship, but GGT remained a significant predictor.
Conclusions: Serum GGT within a range regarded as physiologically normal is associated with incident diabetes and hypertension. Considering known functionality of GGT, these associations are consistent with a role for oxidative stress in risk for diabetes and hypertension.
The following articles in journals at HighWire Press have cited this article:
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  D. Janicki-Deverts, S. Cohen, K. A. Matthews, M. D. Gross, and D. R. Jacobs Jr Socioeconomic Status, Antioxidant Micronutrients, and Correlates of Oxidative Damage: The Coronary Artery Risk Development in Young Adults (CARDIA) Study Psychosom Med, June 1, 2009; 71(5): 541 - 548. [Abstract] [Full Text] [PDF]
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E. S. Ford, M. B. Schulze, M. M. Bergmann, C. Thamer, H.-G. Joost, and H. Boeing Liver Enzymes and Incident Diabetes: Findings from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam Study Diabetes Care, June 1, 2008; 31(6): 1138 - 1143. [Abstract] [Full Text] [PDF]
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 D.-H. Lee, M. D. Gross, M. W. Steffes, and D. R. Jacobs Jr Is Serum Gamma-Glutamyltransferase a Biomarker of Xenobiotics, Which Are Conjugated by Glutathione? Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): e26 - e28. [Full Text] [PDF]
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A. Kotronen and H. Yki-Jarvinen Fatty Liver: A Novel Component of the Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 27 - 38. [Abstract] [Full Text] [PDF]
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 T. Ohira, A. Hozawa, C. Iribarren, M. L. Daviglus, K. A. Matthews, M. D. Gross, and D. R. Jacobs Jr. Longitudinal Association of Serum Carotenoids and Tocopherols with Hostility: The CARDIA Study Am. J. Epidemiol., January 1, 2008; 167(1): 42 - 50. [Abstract] [Full Text] [PDF]
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M. Shibata, Y. Kihara, M. Taguchi, M. Tashiro, and M. Otsuki Nonalcoholic Fatty Liver Disease Is a Risk Factor for Type 2 Diabetes in Middle-Aged Japanese Men Diabetes Care, November 1, 2007; 30(11): 2940 - 2944. [Abstract] [Full Text] [PDF]
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 M. P. Langford, T. B. Redens, N. R. Harris, S. Lee, S. K. Jain, S. Reddy, and R. McVie Plasma Levels of Cell-Free Apoptotic DNA Ladders and Gamma-Glutamyltranspeptidase (GGT) in Diabetic Children Experimental Biology and Medicine, October 1, 2007; 232(9): 1160 - 1169. [Abstract] [Full Text] [PDF]
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T. M. Wallace, K. M. Utzschneider, J. Tong, D. B. Carr, S. Zraika, D. D. Bankson, R. H. Knopp, and S. E. Kahn Relationship of Liver Enzymes to Insulin Sensitivity and Intra-Abdominal Fat Diabetes Care, October 1, 2007; 30(10): 2673 - 2678. [Abstract] [Full Text] [PDF]
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P. Andre, B. Balkau, S. Vol, M. A. Charles, E. Eschwege, and on behalf of the DESIR Study Group {gamma}-Glutamyltransferase Activity and Development of the Metabolic Syndrome (International Diabetes Federation Definition) in Middle-Aged Men and Women: Data From the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort Diabetes Care, September 1, 2007; 30(9): 2355 - 2361. [Abstract] [Full Text] [PDF]
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 J.-S. Lim, D.-H. Lee, J.-Y. Park, S.-H. Jin, and D. R. Jacobs Jr A Strong Interaction between Serum {gamma}-Glutamyltransferase and Obesity on the Risk of Prevalent Type 2 Diabetes: Results from the Third National Health and Nutrition Examination Survey Clin. Chem., June 1, 2007; 53(6): 1092 - 1098. [Abstract] [Full Text] [PDF]
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L. Kazemi-Shirazi, G. Endler, S. Winkler, T. Schickbauer, O. Wagner, and C. Marsik Gamma Glutamyltransferase and Long-Term Survival: Is It Just the Liver? Clin. Chem., May 1, 2007; 53(5): 940 - 946. [Abstract] [Full Text] [PDF]
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 J. M. Hodgson, N. C. Ward, V. Burke, L. J. Beilin, and I. B. Puddey Increased Lean Red Meat Intake Does Not Elevate Markers of Oxidative Stress and Inflammation in Humans J. Nutr., February 1, 2007; 137(2): 363 - 367. [Abstract] [Full Text] [PDF]
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S. M. Grundy Gamma-Glutamyl Transferase: Another Biomarker for Metabolic Syndrome and Cardiovascular Risk Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 4 - 7. [Full Text] [PDF]
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J. B. Whitfield Serum {gamma}-Glutamyltransferase and Risk of Disease Clin. Chem., January 1, 2007; 53(1): 1 - 2. [Full Text] [PDF]
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D. S. Lee, J. C. Evans, S. J. Robins, P. W. Wilson, I. Albano, C. S. Fox, T. J. Wang, E. J. Benjamin, R. B. D'Agostino, and R. S. Vasan Gamma Glutamyl Transferase and Metabolic Syndrome, Cardiovascular Disease, and Mortality Risk: The Framingham Heart Study Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 127 - 133. [Abstract] [Full Text] [PDF]
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S. Ryu, Y. Chang, D.-I. Kim, W. S. Kim, and B.-S. Suh {gamma}-Glutamyltransferase as a Predictor of Chronic Kidney Disease in Nonhypertensive and Nondiabetic Korean Men Clin. Chem., January 1, 2007; 53(1): 71 - 77. [Abstract] [Full Text] [PDF]
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 D.-H. Lee, K. Silventoinen, G. Hu, D. R. Jacobs Jr, P. Jousilahti, J. Sundvall, and J. Tuomilehto Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28 838 middle-aged men and women Eur. Heart J., September 2, 2006; 27(18): 2170 - 2176. [Abstract] [Full Text] [PDF]
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D.-H. Lee and D. R. Jacobs Jr Association between Serum Concentrations of Persistent Organic Pollutants and {gamma} Glutamyltransferase: Results from the National Health and Examination Survey 1999-2002 Clin. Chem., September 1, 2006; 52(9): 1825 - 1827. [Full Text] [PDF]
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D.-H. Lee, M.-H. Ha, S. Kam, B. Chun, J. Lee, K. Song, Y. Boo, L. Steffen, and D. R. Jacobs Jr. A Strong Secular Trend in Serum Gamma-Glutamyltransferase from 1996 to 2003 among South Korean Men Am. J. Epidemiol., January 1, 2006; 163(1): 57 - 65. [Abstract] [Full Text] [PDF]
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 S. Stranges, M. Trevisan, J. M. Dorn, J. Dmochowski, and R. P. Donahue Body Fat Distribution, Liver Enzymes, and Risk of Hypertension: Evidence From the Western New York Study Hypertension, November 1, 2005; 46(5): 1186 - 1193. [Abstract] [Full Text] [PDF]
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 O. Nilssen, M. Averina, T. Brenn, J. Brox, A. Kalinin, and V. Archipovski Alcohol consumption and its relation to risk factors for cardiovascular disease in the north-west of Russia: the Arkhangelsk study Int. J. Epidemiol., August 1, 2005; 34(4): 781 - 788. [Abstract] [Full Text] [PDF]
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 H. C. Kim, D. R. Kang, C. M. Nam, N. W. Hur, J. S. Shim, S. H. Jee, and I. Suh Elevated Serum Aminotransferase Level as a Predictor of Intracerebral Hemorrhage: Korea Medical Insurance Corporation Study Stroke, August 1, 2005; 36(8): 1642 - 1647. [Abstract] [Full Text] [PDF]
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D.-H. Lee, D. R. Jacobs Jr, M. Gross, and M. Steffes Serum {gamma}-Glutamyltransferase Was Differently Associated with Microalbuminuria by Status of Hypertension or Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study Clin. Chem., July 1, 2005; 51(7): 1185 - 1191. [Abstract] [Full Text] [PDF]
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D. A. Lawlor, N. Sattar, G. D. Smith, and S. Ebrahim The Associations of Physical Activity and Adiposity with Alanine Aminotransferase and Gamma-Glutamyltransferase Am. J. Epidemiol., June 1, 2005; 161(11): 1081 - 1088. [Abstract] [Full Text] [PDF]
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D. H. Lee, K. Silventoinen, D. R. Jacobs Jr., P. Jousilahti, and J. Tuomileto {gamma}-Glutamyltransferase, Obesity, and the Risk of Type 2 Diabetes: Observational Cohort Study among 20,158 Middle-Aged Men and Women J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5410 - 5414. [Abstract] [Full Text] [PDF]
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A. J.G. Hanley, K. Williams, A. Festa, L. E. Wagenknecht, R. B. D'Agostino Jr., J. Kempf, B. Zinman, and S. M. Haffner Elevations in Markers of Liver Injury and Risk of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study Diabetes, October 1, 2004; 53(10): 2623 - 2632. [Abstract] [Full Text] [PDF]
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D.-H. Lee, L. M Steffen, and D. R Jacobs Jr Association between serum {gamma}-glutamyltransferase and dietary factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study Am. J. Clinical Nutrition, April 1, 2004; 79(4): 600 - 605. [Abstract] [Full Text] [PDF]
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D.-H. Lee, M. D. Gross, and D. R. Jacobs Jr Association of Serum Carotenoids and Tocopherols with {gamma}-Glutamyltransferase: The Cardiovascular Risk Development in Young Adults (CARDIA) Study Clin. Chem., March 1, 2004; 50(3): 582 - 588. [Abstract] [Full Text] [PDF]
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M. Averina, O. Nilssen, T. Brenn, J. Brox, V. L. Arkhipovsky, and A. G. Kalinin Factors behind the Increase in Cardiovascular Mortality in Russia: Apolipoprotein AI and B Distribution in the Arkhangelsk Study 2000 Clin. Chem., February 1, 2004; 50(2): 346 - 354. [Abstract] [Full Text] [PDF]
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