Accessible Requires Authentication Published by De Gruyter June 10, 2014

Increased levels of serum γ-glutamyltransferase and uric acid on metabolic, hepatic and kidney parameters in subjects at high altitudes

Gustavo F. Gonzales and Vilma Tapia

Abstract

Background: Currently there are no studies on γ-glutamyltransferase (γGT) levels at high altitude or on the relationship between γGT, uric acid and several dysfunctions. The aim of the study was to determine the association between serum γGT and uric acid levels in subjects at high altitude with hemoglobin, glycemia, and lipidic, hepatic and kidney markers.

Methods: The present study was performed in 487 subjects aged 30–75 years living at 4100 m of altitude. A venous blood sample was drawn from each subject to measure hemoglobin, glucose, and lipid levels and markers of liver and kidney function. Quartiles for serum γGT and uric acid were calculated and associated with different physiological variables. A p-value <0.05 was considered statistically significant.

Results: Serum γGT values were higher in men (38.35± 2.54 IU/L) than in women (30.33±1.76 IU/L) (p<0.01). Similarly, serum uric acid levels were higher in men (5.78± 0.12 mg/dL) than in women (4.29±0.08 mg/dL; p<0.001). Serum γGT levels in the top quartile were associated with higher glycemia, overweight/obesity, increased levels of non-high-density lipoprotein (non-HDL) cholesterol, triglycerides, alanine aminotransferase, alkaline phosphatase, uric acid, creatinine, and hemoglobin. Levels of uric acid in the top quartile were associated with overweight/obesity, elevated non-HDL cholesterol, triglycerides, creatinine, γGT and hemoglobin. Higher arterial blood pressure was associated with high levels of uric acid but not with γGT levels.

Conclusions: At high altitude, increased γGT levels were associated with hyperglycemia; increased uric acid levels were associated with overweight/obesity, hemoglobin, dyslipidemia, high blood pressure and kidney disease.


Corresponding author: Dr. Gustavo F. Gonzales, Department of Biological and Physiological Sciences, Faculty of Sciences and Philosophy, and High Altitude Research Institute, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, Lima 31, Peru, Phone: +51-1-3190000 ext. 2535, E-mail:

Acknowledgments

This study was supported by a grant from the Fogarty Program of the National Institutes of Health of the United States (NIH Research Grant 5-D43TW005746-04 funded by the Fogarty International Center, National Institutes on Environmental Health Services, National Institute for Occupational Safety and Health, and the Agency for Toxic Substances and Disease Registry). We acknowledge Manuel Gasco, Ana Huambachano, Carmen Maldonado, Ana Lucía Chirinos, Narda Malpartida, Vanessa Vásquez and Jessica Nieto for their support in the fieldwork.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. West MB, Segu ZM, Feasley CL, Kang P, Klouckova I, Li C, et al. Analysis of site-specific glycosylation of renal and hepatic γ-glutamyl transpeptidase from normal human tissue. J Biol Chem 2010;285:29511–24. Search in Google Scholar

2. Tsai J, Ford ES, Li C, Zhao G. Past and current alcohol consumption patterns and elevations in serum hepatic enzymes among US adults. Addict Behav 2012;37:78–84. Search in Google Scholar

3. Thapa PB, Maharjan DK, Suwal B, Byanjankar B, Singh DR. Serum gamma glutamyl transferase and alkaline phosphatase in acute cholecystitis. J Nepal Health Res Counc 2010;8:78–81. Search in Google Scholar

4. Kawamoto R, Tabara Y, Kohara K, Miki T, Kusunoki T, Takayama S, et al. Hemoglobin is associated with serum high molecular weight Adiponectin in Japanese Community-Dwelling Persons. J Atheroscler Thromb 2011;18:182–9. Search in Google Scholar

5. Ryu S, Chang Y, Zhang Y, Kim SG, Cho J, Son HJ, et al. A cohort study of hyperuricemia in middle-aged South Korean men. Am J Epidemiol 2012;175:133–43. Search in Google Scholar

6. Simão AM, Dichi JB, Barbosa DS, Cecchini R, Dichi I. Influence of uric acid and gamma-glutamyltransferase on total antioxidant capacity and oxidative stress in patients with metabolic syndrome. Nutrition 2008;24:675–81. Search in Google Scholar

7. González-Pérez B, Salas-Flores R, Echegollen-Guzmán A, Pizarro-Chávez S, Guillén-Mata GA. [Elevated liver enzymes, impaired fasting glucose and undiagnosed diabetes] [In Spanish]. Rev Med Inst Mex Seguro Soc 2011;49:247–52. Search in Google Scholar

8. Kawamoto R, Tabara Y, Kohara K, Miki T, Ohtsuka N, Kusunoki T, et al. Serum gamma-glutamyl transferase within its normal concentration range is related to the presence of impaired fasting glucose and diabetes among Japanese community-dwelling persons. Endocr Res 2011;36:64–73. Search in Google Scholar

9. Bonnet F, Ducluzeau PH, Gastaldelli A, Laville M, Anderwald CH, Konrad T, et al; RISC Study Group. Liver enzymes are associated with hepatic insulin resistance, insulin secretion, and glucagon concentration in healthy men and women. Diabetes 2011;60:1660–7. Search in Google Scholar

10. Jung CH, Yu JH, Bae SJ, Koh EH, Kim MS, Park JY, et al. Serum gamma-glutamyltransferase is associated with arterial stiffness in healthy individuals. Clin Endocrinol (Oxf) 2011;75:328–34. Search in Google Scholar

11. Yilmaz Y. Liver function tests: association with cardiovascular outcomes. Word J Hepatol 2010;2:143–5. Search in Google Scholar

12. De Carvalho JA, Piva SJ, Hausen BS, Bochi GV, Kaefer M, Coelho AC, et al. Assessment of urinary γ-glutamyltransferase and alkaline phosphatase for diagnosis of diabetic nephropathy. Clin Chim Acta 2011;412:1407–11. Search in Google Scholar

13. Zapolski T, Waciński P, Kondracki B, Rychta E, Buraczyńska MJ, Wysokiński A. Uric acid as a link between renal dysfunction and both pro-inflammatory and prothrombotic state in patients with metabolic syndrome and coronary artery disease. Kardiol Pol 2011;69:319–26. Search in Google Scholar

14. López-Suarez A, Elvira-Gonzalez J, Bascunana-Quirell A, Rosal-Obrador J, Michán-Doña A, Escribano-Serrano J, et al. [Serum urate levels and urinary uric acid excretion in subjects with metabolic syndrome]. Med Clin (Barc) 2006;126:321–4. Search in Google Scholar

15. Baracco R, Mohanna S, Seclen S. A comparison of the prevalence of metabolic syndrome and its components in high and low altitude populations in Peru. Metab Syndr Relat Disord 2006;4:1–6. Search in Google Scholar

16. Sobrevilla LA, Salazar F. High altitude hyperuricemia. Proc Soc Exp Biol Med 1968;129:890–5. Search in Google Scholar

17. Jefferson JA, Escudero E, Hurtado ME, Kelly JP, Swenson ER, Wener MH, et al. Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia. Am J Kidney Dis 2002;39:1135–42. Search in Google Scholar

18. Wu T, Wang X, Wei C, Cheng H, Wang X, Li Y, et al. Hemoglobin levels in Qinghai-Tibet: different effects of gender for Tibetans vs. Han. J Appl Physiol 2005;98:598–604. Search in Google Scholar

19. Liu L. Epidemiology of hypertension and cardiovascular disease – China experience. Clin Exp Hypertens A 1990;12:831–44. Search in Google Scholar

20. Smith C. Blood pressure of Sherpa men in modernizing Nepal. Am J Human Biol 1999;11:469–79. Search in Google Scholar

21. Dominguez Coello S, Cabrera De León A, Bosa Ojeda F, Perez Mendez LI, Diaz Gonzalez L, Aguirre-Jaime AJ. High density lipoprotein cholesterol increases with living altitude. Int J Epidemiol 2000;29:65–70. Search in Google Scholar

22. Aitbaev KA. The levels of high density lipoprotein cholesterol and other lipids in the native population of the mountain region of Kirghizia (In Russian). Vorp Med Khim 1985;31:58–61. Search in Google Scholar

23. Santos JL, Perez-Bravo F, Carrasco E, Calvillán M, Albala C. Low prevalence of type 2 diabetes despite high average body mass index in the Aymara natives from Chile. Nutrition 2001;17:305–9. Search in Google Scholar

24. Solís J, Guerra-García R. Prevalencia de diabetes mellitus en hospitalizados de las grandes alturas. Arch Biol Andina 1979;9:21–30. Search in Google Scholar

25. Sinha S, Singh SN, Ray US. Total antioxidant status at high altitude in lowlanders and native highlanders: role of uric acid. High Alt Med Biol 2009;10:269–74. Search in Google Scholar

26. Bilen H, Kilicasian A, Akcay G, Albayrak F. Performance of glucose dehydrogenase (GDH) based and glucose oxidase (GOX) based blood glucose meter systems at moderately high altitude. J Med Eng Technol 2007;31:152–6. Search in Google Scholar

27. Gonzales GF, Gasco M, Tapia V, Gonzales-Castañeda C. High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men. Am J Physiol Endocrinol Metab 2009;296:E1319–25. Search in Google Scholar

28. Mueller A, Haeberle L, Zollver H, Claassen T, Kronawitter D, Oppelt PG, et al. Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals. J Sex Med 2010;7:3190–8. Search in Google Scholar

29. Hosoyamada M, Takiue Y, Shibasaki T, Saito H. The effect of testosterone upon the urate reabsorptive transport system in mouse kidney. Nucleosides Nucleotides Nucleic Acids 2010;29:574–9. Search in Google Scholar

30. Bozbas H, Yildirir A, Karacaglar E, Demir O, Ulus T, Eroglu S, et al. Increased serum gamma-glutamyltransferase activity in patients with metabolic syndrome. Arch Turk Soc Cardiol 2011;39:122–8. Search in Google Scholar

31. Turgut O, Tandogan I. Gamma-glutamyltransferase to determine cardiovascular risk: shifting the paradigm forward. J Atheroscler Thromb 2011;18:177–81. Search in Google Scholar

32. Oh HJ, Kim TH, Sohn YW, Kim YS, Oh YR, Cho EY, et al. Association of serum alanine aminotransferase and γ-glutamyltransferase levels within the reference range with metabolic syndrome and nonalcoholic fatty liver disease. Korean J Hepatol 2011;17:27–36. Search in Google Scholar

33. Zoppini G, Targher G, Trombetta M, Lippi G, Muggeo M. Relationship of serum γ-glutamyltransferase to atherogenic dyslipidemia and glycemic control in type 2 diabetes. Obesity 2008;17:370–4. Search in Google Scholar

34. 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;28:2913–8. Search in Google Scholar

35. Castillo O, Woolcott OO, Gonzales E, Tello V, Tello L, Villarreal C, et al. Residents at high altitude show a lower glucose profile than sea-level residents throughout 12-hour blood continuous monitoring. High Alt Med Biol 2007;8:307–11. Search in Google Scholar

36. Rodrigues SL, Baldo MP, Capingana P, Magalhães P, Dantas EM, Molina MD, et al. Gender distribution of serum uric acid and cardiovascular risk factors: population based study. Arq Bras Cardiol 2012;98:13–21. Search in Google Scholar

37. Høstmark AT, Tomten SE, Berg JE. Serum albumin and blood pressure: a population-based, cross-sectional study. J Hypertens 2005;23:725–30. Search in Google Scholar

38. Rafieian-Kopaei M, Behradmanesh S, Kheiri S, Nasri H. Association of serum uric acid with level of blood pressure in type 2 diabetic patients. Iran J Kidney Dis 2014;8:152–4. Search in Google Scholar

39. Zhang J, Xiang G, Xiang L, Sun H. Serum uric acid is associated with arterial stiffness in men with newly diagnosed type 2 diabetes mellitus. J Endocrinol Invest 2014; Epub ahead of print 9 Jan 2014. DOI:. Search in Google Scholar

40. Jalalzadeh M, Nurcheshmeh Z, Mohammadi R, Mousavinasab N, Ghadiani MH. The effect of allopurinol on lowering blood pressure in hemodialysis patients with hyperuricemia. J Res Med Sci 2012;17:1039–46. Search in Google Scholar

41. Vinueza R, Boissonnet CP, Acevedo M, Uriza F, Benitez FJ, Silva H, et al. Dyslipidemia in seven Latin American cities: CARMELA study. Prev Med 2010;50:106–11. Search in Google Scholar

42. Kannel WB, Vasan RS. Triglycerides as vascular risk factors: new epidemiologic insights. Curr Opin Cardiol 2009;24:345–50. Search in Google Scholar

43. Jefferson JA, Simoni J, Escudero E, Hurtado ME, Swenson ER, Wesson DE, et al. Increased oxidative stress following acute and chronic high altitude exposure. High Alt Med Biol 2004;5:61–9. Search in Google Scholar

44. Mircescu G, CapuşaʠC, Stoian I, Vârgolici B, Barbulescu C, Ursea N. Global assessment of serum antioxidant status in hemodialysis patients. J Nephrol 2005;18:599–605. Search in Google Scholar

45. Jin M, Yang F, Yang I, Yin Y, Luo JJ, Wang H, et al. Uric acid, hyperuricemia and vascular diseases. Front Biosci 2012;17:656–69. Search in Google Scholar

46. Braghiroli A, Sacco C, Erbetta M, Ruga V, Donner CF. Overnight urinary uric acid: creatinine ratio for detection of sleep hypoxemia. Validation study in chronic obstructive pulmonary disease and obstructive sleep apnea before and after treatment with nasal continuous positive airway pressure. Am Rev Respir Dis 1993;148:173–8. Search in Google Scholar

47. Gonzales GF, Tapia V. Association of high altitude-induced hypoxemia to lipid profile and glycemia in men and women living at 4100 m in the Peruvian Central Andes. Endocrinol Nutr 2013;60:79–86. Search in Google Scholar

Received: 2013-12-11
Accepted: 2014-4-20
Published Online: 2014-6-10
Published in Print: 2015-1-1

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