Department of Biochemistry, Modern Technical College, Sanepa, Lalitpur, Nepal, School of Medical Sciences, UNSW SYDNEY, NSW, Australia

Corresponding Author: Dr. Saroj Khatiwada, Modern Technical College, Sanepa, Lalitpur, Nepal, School of Medical Sciences, UNSW SYDNEY, NSW, Australia. E-mail: khatiwadasaroj22@gmail.com.

Note: This study was done at the Star Hospital, Sanepa, Lalitpur, Nepal.

	ABSTRACT
	INTRODUCTION
	MATERIALS
	RESULTS
	DISCUSSION
	LIMITATIONS
	ABBREVIATIONS
	ETHICS APPROVAL AND CONSENT TO PARTICIPATE
	CONFLICT OF INTEREST
	AUTHOR'S CONTRIBUTION
	ACKNOWLEDGEMENTS
	REFERENCES

	ABSTRACT

Background: This study was conducted to investigate the relationship between serum GGT (gamma glutamyl transferase) level and the components of metabolic syndrome in Nepalese metabolic syndrome patients. Methods: Anthropometric data and blood pressure was recorded for 100 metabolic syndrome patients. The height, weight, and waist circumference were recorded, and fasting blood samples were analysed for blood glucose, triglyceride, high density lipoprotein (HDL) cholesterol and GGT level. Results: Waist circumference, systolic BP, diastolic BP, blood glucose, triglyceride, and HDL cholesterol were 102.17 ± 8.12 Cm, 130.16 ± 14.70 mmHg, 84.45 ± 11.48 mmHg, 128.2 ± 50.4 mg/dL, 205.6 ± 101.4 mg/dL and 53.9 ± 15.9 mg/dL respectively. The median (with IQR) serum GGT level was 41.5 IU/L (21.2, 71.7). GGT level showed significant positive correlation with diastolic BP (r=0.311, p=0.002) and negative with HDL cholesterol (r=-0.359, p<0.001). Conclusions: Metabolic syndrome patients have serum GGT level in the upper normal range, it correlates with some components of metabolic syndrome.

	INTRODUCTION

   Several clinical features such as central obesity, insulin resistance and hyperlipidemia that directly promote the development of cardiovascular disease (CVD) collectively constitute Metabolic syndrome (MetS) (1). According to National Cholesterol Education Program’s Adult Treatment Panel III report (NCEP-ATP III), the metabolic syndrome is characterized by the presence of three or more of the components viz. increased fasting blood glucose, increased triglyceride, decreased HDL, high blood pressure and increased waist circumference (2).

   Because of the booming incidence of coronary heart disease in MetS patients during the past decades, MetS has drawn the interest of researchers and scientists around the globe (3). MetS, obesity, diabetes mellitus, and endocrine disorders especially in chronic diseases like diabetes mellitus and kidney diseases have been found rising in Nepal (4-6). Reports suggest that 20.7% of the Nepalese population have MetS based on National Cholesterol Education Program (NCEP) criteria (4). Thus, it seems important to study the factors associated with MetS and find the potential elements responsible for the rise of MetS in Nepal.

   It has been found that liver enzymes like gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are associated with MetS (7). Although, GGT is a less specific marker of liver function, higher GGT levels have also been linked with obesity, physical inactivity, hypertension, dyslipidemia, and hyperinsulinemia, implying that elevated GGT belongs in the cluster of the MetS (8). Many studies abroad have found GGT to be associated with MetS, however no such studies have been conducted in Nepalese MetS patients (9). Thus, there is paucity in the studies investigating relationship between GGT and the components of MetS in Nepal, and the clinical importance of estimating serum GGT in Nepalese MetS patients has not been studied, which led us to conduct the present study. We selected metabolic syndrome patients and investigated the association of serum GGT with diagnostic parameters of MetS.

	MATERIALS

   This study was conducted in 100 MetS patients from the Kathmandu valley, Nepal to find an association between GGT and the components of MetS in the Nepalese MetS patients. Patients were enrolled through the medicine department of Star Hospital, Kathmandu. MetS was diagnosed on the basis of revised NCEP ATP-III criteria (2). The exclusion criteria was; pregnant woman, chronic alcoholics or one who has consumed alcohol in past 24 hrs, hepatitis patients, and patients with acute or chronic pancreatitis. Consents were taken from each patient and the study was approved by the ethical committee of Nepal Health Research Council, Kathmandu.

   Each patient were assessed based on the inclusion criteria, and underwent height, weight, waist circumference, and blood pressure (BP) (systolic and diastolic) measurement. From each patient 5 ml fasting blood samples were collected following standard techniques. The samples were then analyzed for blood glucose, triglycerides, high density lipoprotein (HDL) cholesterol and GGT. Measurement of glucose, triglyceride, HDL cholesterol and GGT were done using standard spectrophotometric methods.

   The data obtained from the study were analyzed by using SPSS version 20. Continuous variables were expressed as mean ± SD (for normal distribution) and median with interquartile range (IQR) (for non-normal distribution). Independent t test and Man Whitney test were applied at 95% confidence interval to test for the significance. Spearman rho correlation coefficient was calculated to find the association of GGT with the components of MetS, and Pearson correlation coefficient was calculated to see association of triglyceride and HDL cholesterol with systolic BP and diastolic BP at 95% confidence interval. A p-value less than 0.05 was considered as statistically significant at 95% confidence interval.

	RESULTS

   The study comprised 100 MetS patients (46 males and 54 females). The mean age of study patients was 46.6 ± 12.1 years (males mean age 47.9 ± 12 years and females mean age 45.5 ± 12.2 years, p=0.332). Table 1 shows the components of MetS in the study patients according to gender. BMI in the study patients was 28.6 ± 3.6 Kg/m2. Waist circumference, systolic BP, diastolic BP, blood glucose, triglyceride, HDL cholesterol and serum GGT level in study patients were 102.17 ± 8.12 Cm, 130.16 ± 14.70 mmHg, 84.45 ± 11.48 mmHg, 128.2 ± 50.4 mg/dL, 205.6 ± 101.4 mg/dL, 53.9 ± 15.9 mg/dL, 41.5 IU/L (21.2, 71.7) respectively. No significant difference in the components of metabolic syndrome was observed among males and females.

   Correlation of GGT with the parameter of MetS according to gender is shown in Table 2. GGT showed significant positive correlation with diastolic BP (r=0.311, p=0.002) and negative with HDL cholesterol (r=-0.359, p<0.001). When separately analyzed, GGT has significant positive correlation with systolic BP, diastolic BP and negative correlation with HDL cholesterol in females, however, no such significant correlation was observed in males. Systolic and diastolic BP were significantly correlated (positive) with triglyceride level (r=0.197, p=0.049 and r=0.309, p=0.002 respectively) and negatively correlated with HDL cholesterol (r=-0.109, p=0.282 and r=-0.279, p=0.005 respectively).

	DISCUSSION

   Individuals with MetS are at high risk for CVDs and have a doubled cardiovascular associated mortality compared with those without the MetS (10). The root causes of the MetS are overweight/obesity, physical inactivity, and genetic factors (11). In the present study population, components of MetS; waist circumference, systolic BP, diastolic BP, blood glucose, triglyceride and HDL cholesterol were 102.17 ± 8.12 Cm, 130.16 ± 14.70 mmHg, 84.45 ± 11.48 mmHg, 128.2 ± 50.4 mg/dL, 205.6 ± 101.4 mg/dL and 53.9 ± 15.9 mg/dL respectively. Prevalence of MetS is rising among Nepalese communities; our previous study in eastern Nepal showed that such patients have higher level of inflammatory molecules such as high sensitive C reactive protein (hs-CRP) and uric acid than the general population and concomitant presence of such inflammatory molecules was found to increase the severity of MetS (12). Similar to the findings of Bonna et al., who observed that triglyceride levels increased with blood pressure, but the relation being weak in lean subjects, we found that systolic BP and diastolic BP had significant positive correlation with triglyceride level (13). Triglyceride is a risk factor for CVD and increases risk for development of atherogenic plaque that causes blood vessels atherosclerotic. These atherosclerotic blood vessels, because of its reduced lumen and arterial wall flexibility, acquire an increased peripheral blood pressure (14).

   Latest studies suggest for the association of liver enzymes with the MetS (7). GGT, a cell surface protein that contributes to the extracellular catabolism of glutathione (GSH), is one of parameters (enzyme) produced in many tissues, but most GGT in serum is derived from the liver (8). In the present study the median GGT was 41.5 IU/L which is at the upper range of normal GGT level (1-50 IU/L). Males had higher GGT level than females though not significant. Our results are in line with previous studies assessing GGT level in MetS patients. In the study by Bozbas et al., compared with controls, patients with MetS had significantly higher serum median GGT (21, IQ range [16-33] versus 19 [14-26] U/L, p=0.008) (15). In the study by Kasapoglu et al., mean values of ALT, AST and GGT levels were statistically significantly higher in MetS group than control (16). Study by Wei et al., found serum GGT concentrations significantly higher in subjects with metabolic syndrome compared to those without metabolic syndrome in both genders (p<0.05) (8).

   It is increasingly being shown that serum GGT level has strong relationship with components of MetS and high serum GGT predicts the future development of MetS (17). We observed significant positive correlation of serum GGT with diastolic BP and negative correlation with HDL cholesterol in females but not males. This is in agreement with the findings of Suh et al [17]. In a case control study by Bozbas et al., serum GGT level showed significant correlations with triglyceride (r=0.18, p=0.006) and HDL cholesterol (r=-0.19, p=0.004) (15). In a cohort study by André et al., the odds ratios for incident MetS increased across baseline GGT quartiles (1, 1.96, 2.25, and 3.81 in men, p<0.03; and 1, 1.23, 1.80, and 1.58 in women, p<0.05) (18).

   To our knowledge, this is the first study to investigate the association of liver enzyme, GGT with the components of MetS in the Nepalese MetS population. We found high level of serum GGT in MetS patients and a strong association between the components of MetS; diastolic BP and HDL cholesterol with the serum GGT level in Nepalese MetS patients.

	LIMITATIONS

   The sample size of the study was limited and GGT level in healthy population was not studied.

	ABBREVIATIONS

ALP	Alkaline phosphatase
ALT	aminotransferase
AST	Aspartate aminotransferase
BP	Blood pressure
CVD	Cardiovascular disease
GGT	Gamma glutamyl transferase
HDL	High density lipoprotein
hs-CRP	High sensitive C reactive protein
MetS	Metabolic syndrome
NCEP-ATP III	National Cholesterol Education Program's Adult Treatment Panel III

	ETHICS APPROVAL AND CONSENT TO PARTICIPATE

   The study was approved by the ethics committee of Nepal Health Research Council, Kathmandu, Nepal. Written consent was taken from the patients before participation.

	CONFLICT OF INTEREST

   The authors declare that no conflicting interests exist.

	AUTHOR'S CONTRIBUTION

   SK1, BC and SK2 designed the study. SK2 analyzed the samples and collected the data. SK1 performed analysis and drafted the manuscript. BC and SK2 revised the manuscript. All authors read and approved the final version of manuscript.

	ACKNOWLEDGEMENTS

   We kindly acknowledge all the participants of the study.

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