Gamma Glutamyl transferase [GGT] also known as Gamma Glutamyl Transpeptidase has long been used in the diagnosis of hepato-biliary diseases, primarily fatty liver and cholestasis. It is also an excellent diagnostic marker of alcoholic liver disease . GGT is expressed in the liver, kidney, cerebrovascular endothelium and pericytes and is an enzyme responsible for the extracellular catabolism of antioxidant glutathione and acts as a pro-oxidant in the extracellular space. Elevated serum GGT levels may be a reflection of high degree of oxidative stress and oxidative stress is known to be associated with central obesity.
International Journal of Medical and Health Sciences Journal Home Page: http://www.ijmhs.net ISSN:2277-4505 Original article Serum Gamma Glutamyl Transferase levels in Obese South Indian adults with reference to atherogenic lipid risk factors and lipid peroxides Niranjan Gopal*1, Ajeet Selvam2, Srinivasan A R3, Saha S4, Prakash H Muddegowda5 1 Assistant Professor,3,4Professor,Department of Biochemistry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth [SBV] University, Pillaiyarkuppam, Puducherry- 607402, India. 2 Final year MBBS, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth [SBV] University, Pillaiyarkuppam, Puducherry-607402, India. 5 Assistant Professor, Department of Pathology, VMKV Medical College, Salem. ABSTRACT Background: Obesity has reached epidemic proportions especially in South India. In recent years, Waist circumference (WC), which reflects central obesity, has been regarded as an independent predictor of risk. Generation of free radicals occurs in central obesity and depletes intracellular glutathione, thereby inducing the production and release of Gamma Glutamyl Transferase [GGT] into circulation. High GGT levels are known to be associated with Type 2 Diabetes mellitus, hypertension and related vascular complications. Hence, this study was planned with a view to exploring the nexus among these components of metabolic syndrome and serum GGT levels, especially as the characteristic biochemical events are not fully understood and addressed yet. Materials and methods: In this prospective study we included 41 obese and 39 non-obese adults who were non-smokers and non-alcoholics, between the ages of 20 and 40 years. Lipid profile, Malondialdehyde (MDA), Fasting Plasma Glucose (FPG), blood pressure (BP) and GGT activity were measured in both the groups. Data were compared with un-paired student t-test. Pearson’s correlation was used to find the association of serum GGT levels with other variables in obese individuals. Results: Atherogenic dyslipidemia was documented in obese individuals which was associated with significantly elevated levels of serum GGT (p<0.001). High levels of serum GGT were also associated significantly with increase in BP (p<0.001), Lipid peroxidation [(serum MDA), (p<0.05)] and atherogenic lipid ratios [(TC/HDL, LDL/HDL) (p<0.001)]. Conclusions: Elevated serum GGT levels are associated with the components of metabolic syndrome and high degree of lipid peroxidation in obese South Indian adults. KEYWORDS: Obesity, GGT, Atherosclerosis, Lipid profile, Oxidative stress. Int J Med Health Sci. April 2012,Vol-1;Issue-2 35 INTRODUCTION levels, especially in South Indian population, where there is a paucity of published reports. Gamma Glutamyl transferase [GGT] also known as Gamma Glutamyl Transpeptidase has long been used in the diagnosis of hepato-biliary Aim and objectives diseases, primarily fatty liver and cholestasis. It is 1. To explore the association of GGT levels with also an excellent diagnostic marker of alcoholic fasting plasma glucose, waist circumference, liver disease . GGT is expressed in the liver, blood pressure, lipid peroxidation, lipid profile kidney, cerebrovascular endothelium and and lipid ratios in the obese south Indian pericytes and is an enzyme responsible for the population. extracellular catabolism of antioxidant glutathione 2. To compare the above mentioned parameters and acts as a pro-oxidant in the extracellular with non-obese age and gender matched space. Elevated serum GGT levels may be a healthy control group. reflection of high degree of oxidative stress and oxidative stress is known to be associated with central obesity. Serum Malondialdehyde (MDA) MATERIALS AND METHODS is a well known marker of degree of lipid peroxidation in vivo. . High levels of GGT have Sample size: In this prospective study, we included also been found to be associated with various 41 obese individuals (cases) and 39 healthy non- atherosclerotic risk factors such as Diabetes obese (controls) adults who were non-smokers and mellitus, hyperlipidemia, and hypertension, non-alcoholics, between the ages of 20 and 40 independent of alcohol consumption and hepatic years. dysfunction. Moreover, certain documented Exclusion criteria [for both the groups]: Subjects evidences are available suggesting a direct link with liver diseases like alcoholic liver disease, between increased GGT activity and occurrence cholestasis and hepatitis were excluded from the or progression of atherosclerosis [3-6]. study. People who were on anti epileptics and other Obesity has reached epidemic proportions in India drugs were also excluded from the study. A proper in the 21st century with morbid obesity affecting informed consent was obtained from all the 5% of the Indian population. Obesity when subjects. This was a prospective case control study unchecked does lead to a host of lifestyle diseases conducted in the Department of Biochemistry at a . The root cause of all diseases like Diabetes tertiary centre with equipped clinical laboratory mellitus, hypertension, coronary artery disease facilities. and stroke has been traced to obesity [8-10]. Study Parameters: Waist circumference was measured using standard measuring tape at the level Waist circumference (WC) which reflects central of the upper hip bone with the tape being snug obesity is an independent and better predictor of without compressing on the skin. Blood pressure risk compared to body mass index and waist hip was measured by standard sphygmomanometer ratio. Males with WC more than 40 inches and (Manual) in supine posture; while the lipid profile females more than 35 inches are known to be at a and GGT were estimated with the auto analyzer higher risk. A high WC is known to be associated [Hitachi-902 chemistry analyzer] using procedures with an increased risk of type 2 Diabetes mellitus approved by International Federation of Clinical (Type 2 DM), dyslipidemia, hypertension and Chemistry and Laboratory Medicine [IFCC]. Five coronary vascular disease. There are ethnic and ml of fasting (post-absorptive) venous blood sample age related differences in body fat distribution that was collected from the subjects and the following modify the predictive validity of WC as a parameters were estimated. surrogate marker of abdominal fat [11, 12]. With Fasting plasma glucose: glucose oxidase and the increasing association among obesity, peroxidase method. hypertension, fatty liver and atherosclerosis in the GGT: Carboxy substrate method background, we proposed this study to compare Total cholesterol: cholesterol the various risk factors, as related to obesity, in esterase/oxidase method the light of GGT Triacyl glycerol: Lipase-glycerol kinase method. Int J Med Health Sci. April 2012,Vol-1;Issue-2 36 LDL cholesterol: is calculated by was considered as significant for all statistical Friedwald’s equation purposes. SPSS version17 for Windows was used HDL cholesterol: polyanion precipitation for all statistical analysis. (SPSS Inc.,Chicago, method USA). VLDL was calculated by the formula VLDL= TAGs/5 RESULTS Serum MDA by OxiSelect™ Thiobarbituric The age and gender distribution of the study acid reactive species (TBARS) Assay Kit for population is depicted in Table 1. There was MDA Quantitation by colorimetry. no significant difference in the mean age and gender of participants between the two Statistical analysis: Data were expressed as mean groups. All physiological and Biochemical +/- SD; un-paired student t- test was used to parameters were expressed as mean±SD; compare the data. For exploring the association results were compared by using un-paired between serum GGT levels and other variables Student t test. Pearson’s correlation was used. A p value <0.05 Table 1: Age and gender distribution of the study population variables Cases Controls (n=41) (n=39) Gender Male 24 (58.53%) 21 (53.84%) Female 17 (41.46%) 18 (46.15%) Age group 20-30 28 (68.29%) 26 (66.67%) (years) 30-40 13 (31.70%) 13 (33.34%) Table 2: Comparison of Age, blood pressure and waist circumference between the cases and controls. Controls Cases (n=41) p value Variables (n=39) [Mean ± SD] [Mean ± SD] Age (years) 35.8 ± 4.82 33.8 ± 6.06 0.09 SBP (mm/Hg) 145±14.81 120±2.79 0.0006* DBP (mm/Hg) 93.4 ±10.24 79.7 ± 2.12 0.0004* WC (inches) 45.6 ± 7.15 33.3 ±3.99 0.0006* SBP = Systolic Blood Pressure, DBP = Diastolic Blood Pressure, WC = Waist Circumference, SD = Standard Deviation, *p value <0.001. Waist circumference, systolic and diastolic blood 0.001. But there was no significant difference in pressures were significantly high in obese subjects the mean ages of the participants between the two compared to the control group with p value < groups. (Table 2). Int J Med Health Sci. April 2012,Vol-1;Issue-2 37 Table 3: Comparison of serum lipids between the cases and controls. Control p value Cases (n=41) Parameters (n=39) [Mean ± SD] [Mean ± SD] Total cholesterol 0.0004† 215.1 ±35.22 164 ±48.21 (mg/dL) Triacylglycerols 0.021* 166.1 ± 63.98 112 ±52.24 (mg/dL) LDL-Cholesterol 0.0004† 139 ±31.04 100.4 ±40.71 (mg/dL) HDL-Cholesterol 0.0008† 31.6 ±5.90 41 ±8.50 (mg/dL) VLDLCholesterol 0.0006† 45.8 ±14.03 22.4 ±10.45 (mg/dL) LDL=Low Density Lipoprotein, VLDL=Very Low Density Lipoprotein, HDL= High Density Lipoprotein. *p value <0.05, † p value < 0.001. Table-3 shows that total cholesterol, were significantly low in cases. Alteration in triacylglycerols and LDL cholesterol levels the fasting lipid profile indicates pro- were significantly high in cases as compared atherogenic dyslipidemia in obese subjects. to controls; while HDL-cholesterol levels Table 4: Comparison of lipid ratios between the cases and controls. Controls Cases (n=41) p value Lipid Ratios (n=39) [Mean ± SD] [Mean ± SD] TC/HDL 8.2 ±2.4 5.11 ± 1.04 0.0004* LDL/HDL 4.5±1.25 2.5±1.35 0.0007* TC= Total Cholesterol, LDL=Low Density Lipoprotein, VLDL=Very Low Density Lipoprotein, HDL= High Density Lipoprotein. *p value < 0.001. Table-4 shows that the lipid ratios were ratios support pro-atherogenic dyslipidemia in significantly higher in obese individuals as obese subjects. compared to controls. Alterations in the lipid Table 5: Comparison of serum GGT, MDA and Fasting Plasma Glucose levels between the cases and controls Control Cases (n=41) p value Parameters (n=39) [Mean ± SD] [Mean ± SD] Serum GGT (IU/L) 33.3±25.50 19.7±7.7 0.002* Serum MDA (µmol/L) 2.19 ± 2.2 1.58 ± 1.6 0.003* FPG (mg/dl) 86.5 ± 14.7 81.5 ± 11.4 0.08 GGT = Gamma glutamyl transferase, FPG = Fasting Plasma Glucose, MDA=Malondialdehyde. *p value < 0.05. Int J Med Health Sci. April 2012,Vol-1;Issue-2 38 Table-5 depicts GGT levels in cases which = 0.03). But there was no statistically were significant. (p value = 0.002). Serum significant difference in Fasting Plasma MDA levels were significantly high in obese Glucose between the two groups. individuals compared to the control group (p Table 6: Correlation of serum GGT levels with other variables in cases WC SBP DBP FPG MDA VARIABLES r 0.62 0.54 0.45 0.23 0.33 Serum GGT p 0.000* 0.001* 0.002* 0.08 0.03* WC = Waist Circumference (Inches), SBP = Systolic Blood Pressure (mmHg), DBP = Diastolic Blood Pressure (mmHg), FPG = Fasting Plasma Glucose (mg/dl), MDA= Malondialdehyde (µmol/L), GGT = Gamma Glutamyl Transferase (IU/L). *p value < 0.05. Table 7: Correlation of serum GGT levels with serum lipids in cases. VLDL TC LDL TAG HDL VARIABLES 0.69 -0.43 r 0.69 0.64 0.71 Serum GGT 0.002* 0.002* p 0.000* 0.000* 0.000* TC= Total Cholesterol (mg/dl), LDL=Low Density Lipoprotein (mg/dl), VLDL=Very Low Density Lipoprotein(mg/dl), HDL= High Density Lipoprotein (mg/dl), GGT = Gamma Glutamyl Transferase (IU/L). *p value < 0.05. Tables 6 and 7 shows the results of Pearson’s when we correlated serum GGT levels with correlation analysis between the serum GGT all the variables, with the exception of FPG levels and other variables. Statistically levels. A significant negative correlation was significant positive correlation was observed observed with serum HDL levels. DISCUSSION In the present study, levels of serum GGT higher among the cases. It is known that GGT were measured in obese subjects (cases) and has a protective effect in maintaining compared with that of healthy non-obese appropriate intracellular glutathione levels, control population who were life time non- which is a powerful antioxidant. Therefore, it alcoholics. Pukka et al., in their study showed is possible that the generation of free radicals, that GGT levels rise with age in both sexes which can occur in central obesity, may . In this study, the mean age of the cases deplete intracellular glutathione and thus was not significantly different from that of induce the activity of GGT into the controls (Table 1). Alcoholics and the circulation. Oxidative stress with the subjects with age >60 years in both sexes attendant low-grade inflammation has been were excluded from our study. The major implicated in a number of pathological difference between the two groups was the conditions, including aging, atherosclerosis waist circumference which was significantly and Diabetes mellitus [14-18]. Int J Med Health Sci. April 2012,Vol-1;Issue-2 39 It is known that GGT catalyzes the oxidation hypertension, Type 2 DM and coronary artery of LDL and conversion of LDL to oxidised disease. LDL, a process involved in the pathogenesis of atherosclerosis [19, 20]. The study This study clearly demonstrates that demonstrates that dyslipidemia, high systolic documentation of high serum GGT levels in and diastolic blood pressure in obese individuals may not be attributed only to individuals are associated with elevated levels alcoholism  but, it could serve as an of GGT- a putative marker of sub-clinical indicator of higher oxidative stress, atherosclerosis. Although there was no inflammation and fatty liver in obese significant difference in FPG levels between individuals. Therefore, GGT could function as the two groups, the previous studies have an early predictor and reliable marker of sub- confirmed elevated GGT levels in Type 2 clinical atherosclerosis and its complications. DM cases [4, 5]. This depicts the fact that In routine practice sophisticated techniques elevated GGT levels with accompanying such as echocardiography, colour doppler and dyslipidemia and hypertension could be used other radiological imaging modalities are as diagnostic predictors, independent of utilized to detect vascular abnormalities pronounced elevation in FPG. Our study resulting from atherosclerosis. However, the clearly demonstrates low HDL, high LDL, modalities are hampered by lack of high total cholesterol/HDL ratio and high availability in primary and secondary health LDL/HDL ratio in cases when compared to care centres, besides the cost factor. the control group. Moreover, we also Morbidity associated with vascular changes documented significant positive correlation of still goes undetected, especially in view of the serum GGT with the components of lower socio-economic status of the metabolic syndrome. Estimation of serum population. Estimation of GGT levels in GGT levels can thus help us to assess the risk serum could reflect a pragmatic approach. of impending complications like However, further studies on a larger hypertension, atherosclerosis, Type 2 DM and population would provide a better insight. coronary artery disease in obese individuals. Elevation of serum GGT activity is a risk CONCLUSION factor for myocardial infarction and stroke [21-23]. We conclude that there is a significant association of elevated serum GGT levels Hence, necessary non-pharmacological with the anthropometric, physiological and interventions can be initiated in these subjects biochemical components of metabolic that include lifestyle and dietary syndrome namely; WC, blood pressure, modifications. High serum GGT is associated impaired FPG, atherogenic dyslipidemia. with oxidative stress [13-18]. Even in this High serum GGT is also associated with a study we documented a high degree of lipid higher degree of lipid peroxidation in peroxidation in obese individuals. individuals with central obesity. GGT in Supplementation of anti-oxidants will serum could thus be used as a screening test definitely help in reducing the risk of various especially in primary and secondary health complications related to atherosclerosis and care centres to assess the risk of developing Type 2 DM. GGT estimation can be a useful various complications related to central and cost-effective screening procedure obesity. especially in rural population to assess the risk of developing various complications IMPLICATIONS & SCOPE FOR related to atherosclerosis. Hence, GGT could FUTURE STUDY be a simple, sensitive and reliable diagnostic tool that can be included in the routine There is a paucity of published data in this armamentarium of investigations pertaining field, on South Indian population, where there to the individuals on treatment for is a rising incidence of morbid obesity related complications especially diabetes mellitus, Int J Med Health Sci. April 2012,Vol-1;Issue-2 40 atherosclerosis and coronary artery disease. aged Japanese men. Diabetes Care Documentation of high serum GGT levels 2004;27: 1427 –1432. could help us to advocate pharmacological and non-pharmacological interventions to 6. Paolicchi A, Emdin M, Passino C, prevent the further complications in Lorenzini E, Titta F, Marchi S, et al. Beta- individuals with central obesity. Lifestyle and Lipoprotein- and LDL-associated serum γ- dietary modifications, in addition to Glutamyl transferase in patients with supplementation of anti-oxidants, could coronary atherosclerosis. Atherosclerosis reduce the incidence of various complications 2006;186:80-85. related to atherosclerosis and Type 2 DM. 7. Varghese RT, Vijaykumar K. Prevalence However; further studies on a larger pattern of obesity across different age population are needed in South India on groups in a rural setting in Kerala. Calicut direct association of GGT with the degree of Medical Journal 2008;6(1):e3. atherosclerotic process. The effects of life 8. Agrawal PK. Emerging obesity in North style changes and supplementation of anti- Indian States: A serious threat for health. oxidants on serum GGT can also be explored. Paper presented at: IUSSP Conference; 2002, June 10-12;Bangkok. Acknowledgements: Authors gratefully 9. Jousilahti P, Rastenyte D, Tuomilehto J. acknowledge ICMR for the grant of STS 2011 Serum g-glutamyl 12. transferase, self- fellowship. We thank Dr. D R Gunasekaran, Vice reported alcohol drinking, and the risk of chancellor, SBV University and Dr. N stroke. Stroke 2000; 31:1851-5. Ananthakrishnan, Prof and Head Dept of 10. Lee DH, Jacobs DR Jr, Gross M, Kiefe Gastroenterology, MGMCRI for their kind CI, Roseman J, 11. Lewis CE, et al. support and encouragement. Gamma-glutamyl transferase is a predictor of incident diabetes and hypertension : the REFERENCES Coronary Artery Risk Development in 1. Hietala J, Puukka K, Koivisto H, Anttila P, Young Adults (CARDIA) Study. Clin Niemela O. Serum gamma-glutamyl Chem 2003; 49:1358-66. transferase in alcoholics, moderate 11. Guidelines on Overweight and Obesity: drinkers and abstainers: effect on GT Electronic textbook [cited 16 Jan 2011]. reference intervals at population level. Availablefrom:http://www.nhlbi.nih.gov/g Alcohol and Alcoholism 2005;40:511–4. uidelines/obesity/e_txtbk/txgd/4142.hm. 2. Emdin M, Pompella A, Paolicchi A. Gamma glutamyl transferase, 12. Moniz C, Nicolaides K H, Keys D, atherosclerosis, and cardiovascular Rodeck CH. y-glutamyl transferase disease: triggering oxidative stress within activity in fetal serum, maternal serum, the plaque. Circulation 2005;112:2078-80. and amniotic fluid during gestation. J Clin 3. Demirkran B, Guray Y, Guray U, Turak O, Pathol 1984;37:700-703. Hajro E, Korkmaz S. The relationship 13. Puukka K, Hietala J, Koivisto H.Anttila P, between saphenous coronary bypass graft Bluiqu R,Nimelao.Additive effects of occlusion and serum gamma glutamyl moderate drinking and obesity on serum transferase activity. Turk Kardiyol Derm gamma-glutamyl transferase. The Ars 2010;38(5):321-6. American Journal of Clinical Nutrition 4. Stranges S, Trevisan M, Dorn JM, 2006; 83:1351-1354. Dmochowski J, Donahue RP. Body fat distribution, liver enzymes, and risk for 14. Lee DH, Blomhoff R, Jacobs DR Jr. Is hypertension. Hypertension 2005;46:1186- serum gamma glutamyltransferase a 93. marker of oxidative stress?. Free Radic 5. Nakanishi N, Suzuki K, Tatara K. Serum – Res. 2004;38(6):535-539. glutamyltransferase and risk of metabolic 15. Karp DR, Shimooku K, Lipsky PE: syndrome and type 2 diabetes in middle- Expression of gamma-glutamyl Int J Med Health Sci. April 2012,Vol-1;Issue-2 41 transpeptidase protects ramos B cells from 21. Emiroglu Y M, Esen O B, Bulut M. oxidation-induced cell death. J Biol Gamma glutamyltransferase levels and its Chem.2001; 276:3798–3804. protein in patients with acute coronary 16. Joyce-Brady M, Jean JC, Hughey syndromes.association with high sensitive RP:Gamma-glutamyl transferase and its C-reactive North American Journal of isoformmediate an endoplasmic reticulum Medical Sciences.2010; 2:306-310. stress response. J Biol 22. Meisinger C, Doring A, Schneider A, Chem.2001;276:94689477. Lowel H. KORA Study Group. Serum 17. West IC: Radicals and oxidative stress in gamma-glutamyltransferase is a predictor diabetes. Diabet Med.2000; 17:171–180. of incident coronary events in apparently 18. Pandur S, Pankiv S, Johannessen M, healthy men from the general population. Moens U, Huseby NE. Gamma Atherosclerosis.2006; 189: 297-302. glutamyltransferase is upregulated after 23. Ruttmann E, Brant LJ, Concin H, Diem G, oxidative stress through the Ras signal Rapp K, Ulmer 10. H, Vorarlberg Health transduction pathway in rat colon Monitoring and Promotion Program Study carcinoma cells.Free Radic Group. Gammaglutamyltransferase as a Res.2007;41(12):1376-1384. risk factor for cardiovascular disease 19. Kang YH, Min HK, Son SM, Kim IJ, Kim mortality : an epidemiological YK. The association of serum gamma investigation ina cohort of 163,944 glutamyltransferase with components of Austrian adults. the metabolic syndrome in the Korean Circulation.2005;112:2130-2137. adults.Diabetes Res Clin Pract. 2007; 77: 306-313. _________________________________________________________ 20. Paolicchi A, Emdin M, Passino C, et al. Lipoprotein- and LDL-associated serum γ- glutamyltransferase in patients with *Corresponding author:Dr. Niranjan Gopal coronary atherosclerosis. Atherosclerosis E-mail: email@example.com 2006;186:80-85. Int J Med Health Sci. April 2012,Vol-1;Issue-2 42
Pages to are hidden for
"Serum Gamma Glutamyl Transferase levels in Obese South Indian adults with reference to atherogenic lipid risk factors and lipid peroxides"Please download to view full document