Endocrinology and Metabolism

Original Articles

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study: Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun; Endocrinol Metab. 2023;38(6):770-781. Published online November 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1726

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Abstract PDF Supplementary Material PubReader ePub: Background
Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population.
Methods
Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model.
Results
During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m², and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death.
Conclusion
Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Cumulative Exposure to High γ-Glutamyl Transferase Level and Risk of Diabetes: A Nationwide Population-Based Study: Ji-Yeon Park, Kyungdo Han, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim, Seung-Hwan Lee; Endocrinol Metab. 2022;37(2):272-280. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1416

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Abstract PDF Supplementary Material PubReader ePub

Background
Elevated γ-glutamyl transferase (γ-GTP) level is associated with metabolic syndrome, impaired glucose tolerance, and insulin resistance, which are risk factors for type 2 diabetes. We aimed to investigate the association of cumulative exposure to high γ-GTP level with risk of diabetes.
Methods
Using nationally representative data from the Korean National Health Insurance system, 346,206 people who were free of diabetes and who underwent 5 consecutive health examinations from 2005 to 2009 were followed to the end of 2018. High γ-GTP level was defined as those in the highest quartile, and the number of exposures to high γ-GTP level ranged from 0 to 5. Hazard ratio (HR) and 95% confidence interval (CI) for diabetes were analyzed using the multivariable Cox proportional-hazards model.
Results
The mean follow-up duration was 9.2±1.0 years, during which 15,183 (4.4%) patients developed diabetes. There was a linear increase in the incidence rate and the risk of diabetes with cumulative exposure to high γ-GTP level. After adjusting for possible confounders, the HR of diabetes in subjects with five consecutive high γ-GTP levels were 2.60 (95% CI, 2.47 to 2.73) in men and 3.05 (95% CI, 2.73 to 3.41) in women compared with those who never had a high γ-GTP level. Similar results were observed in various subgroup and sensitivity analyses.
Conclusion
There was a linear relationship between cumulative exposure to high γ-GTP level and risk of diabetes. Monitoring and lowering γ-GTP level should be considered for prevention of diabetes in the general population.

Citations

Citations to this article as recorded by

Validation of Estimated Small Dense Low-Density Lipoprotein Cholesterol Concentration in a Japanese General Population
Keisuke Endo, Ryo Kobayashi, Makito Tanaka, Marenao Tanaka, Yukinori Akiyama, Tatsuya Sato, Itaru Hosaka, Kei Nakata, Masayuki Koyama, Hirofumi Ohnishi, Satoshi Takahashi, Masato Furuhashi
Journal of Atherosclerosis and Thrombosis.2023;[Epub] CrossRef
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study
Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun
Endocrinology and Metabolism.2023; 38(6): 770. CrossRef
Elevated gamma‐glutamyl transferase to high‐density lipoprotein cholesterol ratio has a non‐linear association with incident diabetes mellitus: A second analysis of a cohort study
Haofei Hu, Yong Han, Mijie Guan, Ling Wei, Qijun Wan, Yanhua Hu
Journal of Diabetes Investigation.2022; 13(12): 2027. CrossRef
Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio: A valuable predictor of type 2 diabetes mellitus incidence
Wangcheng Xie, Bin Liu, Yansong Tang, Tingsong Yang, Zhenshun Song
Frontiers in Endocrinology.2022;[Epub] CrossRef

Clinical Study
Association between Serum Gamma-Glutamyltransferase and Prevalence of Metabolic Syndrome Using Data from the Korean Genome and Epidemiology Study: Mi Young Lee, Dae Sung Hyon, Ji Hye Huh, Hae Kyung Kim, Sul Ki Han, Jang Young Kim, Sang Baek Koh; Endocrinol Metab. 2019;34(4):390-397. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.390

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Abstract PDF PubReader ePub

Background

The aim of this study was to determine whether there is a positive correlation between gamma-glutamyltransferase (GGT) levels and the prevalence of metabolic syndrome and whether GGT can be used as an easily checkable metabolic index using data from the large-scale Korean Genome and Epidemiology Study (KoGES).

Methods

We obtained data of 211,725 participants of the KoGES. The collected data included age, sex, height, weight, waist circumference, and various biochemical characteristics, including serum GGT levels. The data of study participants who ingested more than 40 g/day of alcohol and who were diagnosed with metabolic syndrome at baseline was excluded. We analyzed the prevalence of metabolic syndrome according to GGT quartiles in both genders.

Results

The GGT level was significantly higher in subjects with metabolic syndrome compared to normal subjects (37.92±48.20 mg/dL vs. 25.62±33.56 mg/dL). The prevalence of metabolic syndrome showed a stepwise increase with GGT quartiles in both male and female subjects. Compared to the lowest GGT quartile, the odds ratio was 1.534 (95% confidence interval [CI], 1.432 to 1.643), 1.939 (95% CI, 1.811 to 2.076), and 2.754 (95% CI, 2.572 to 2.948) in men and 1.155 (95% CI, 1.094 to 1.218), 1.528 (95% CI, 1.451 to 1.609), and 2.022 (95% CI, 1.921 to 2.218) in women with increasing GGT quartile. The cutoff value of GGT predicting risk of metabolic syndrome was 27 IU/L in men and 17 IU/L in women.

Conclusion

We suggested that GGT could be an easily checkable marker for the prediction of metabolic syndrome.

Citations

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Associating Liver Enzymes and Their Interactions with Metabolic Syndrome Prevalence in a Japanese Working Population
Aziz Jamal, Akira Babazono, Ning Liu, Rieko Yamao, Takako Fujita, Sung-a Kim, Yunfei Li
Metabolic Syndrome and Related Disorders.2024; 22(1): 27. CrossRef
Liver fat content assessed by conventional B-mode ultrasound and metabolic profile in non-diabetic patients: Implications for clinical practice
Rosanna Villani, Grazia Pia Magnati, Giulia Tuccari, Moris Sangineto, Antonino Davide Romano, Tommaso Cassano, Gaetano Serviddio
Ultrasound.2023; 31(3): 177. CrossRef
Serum γ-glutamyltransferase level and incidence risk of metabolic syndrome in community dwelling adults: longitudinal findings over 12 years
Jiwon Kwak, In-Ho Seo, Yong-Jae Lee
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
Gamma-Glutamyl Transferase as a Diagnostic Marker of Metabolic Syndrome
Bobbili Tarun Kesava Naidu, Kakarlapudi Santosh Raju, Janapareddi V BhaskaraRao, Nallapati Sunil Kumar
Cureus.2023;[Epub] CrossRef
Metabolic syndrome and transaminases: systematic review and meta-analysis
Elena Raya-Cano, Rafael Molina-Luque, Manuel Vaquero-Abellán, Guillermo Molina-Recio, Rocío Jiménez-Mérida, Manuel Romero-Saldaña
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
Association between Serum Gamma-glutamyl Transferase and Metabolic Syndrome: A Case–control Study
Akshay Shelar, Nalini Humaney, Akshay Chhajed, Krunal Domki, Ajay Narwade
Journal of Datta Meghe Institute of Medical Sciences University.2023; 18(4): 651. CrossRef
“Big Data” Approaches for Prevention of the Metabolic Syndrome
Xinping Jiang, Zhang Yang, Shuai Wang, Shuanglin Deng
Frontiers in Genetics.2022;[Epub] CrossRef
Can Gamma-glutamyl Transferase Predict Unhealthy Metabolic Phenotypes Among Healthcare Workers in Azar Cohort Study?
Mohammadhossein Somi, Seyed Sina Zakavi, Alireza Ostadrahimi, Negin Frounchi, Neda Gilani, Sarvin Sanaie, Elnaz Faramarzi
Hepatitis Monthly.2022;[Epub] CrossRef
Association between liver enzymes and metabolic syndrome in Canadian adults: results from the Canadian health measures survey - cycles 3 &4
Luan Manh Chu, Chandima Karunanayake, Palok Aich, Markus Hecker, Punam Pahwa
Journal of Diabetes & Metabolic Disorders.2022; 21(2): 1699. CrossRef
Repeatedly elevated γ-glutamyltransferase levels are associated with an increased incidence of digestive cancers: A population-based cohort study
Chang-Hoon Lee, Kyungdo Han, Da Hye Kim, Min-Sun Kwak
World Journal of Gastroenterology.2021; 27(2): 176. CrossRef
Index of Cardiac Age Index and Cardiometabolic Biomarkers in Adults with Metabolic Syndrome
Eun Jung Choi, Sang Yeoup Lee
Metabolic Syndrome and Related Disorders.2021; 19(5): 288. CrossRef
Simple metabolic markers associated with tophaceous gout
Wei Liu, Hui Song, Siliang Man, Hongchao Li, Siming Gao
Clinical Rheumatology.2021; 40(12): 5047. CrossRef
Expression Status and Prognostic Significance of Gamma-Glutamyl Transpeptidase Family Genes in Hepatocellular Carcinoma
Shan Tian, Jiao Li, Yingyun Guo, Weiguo Dong, Xin Zheng
Frontiers in Oncology.2021;[Epub] CrossRef
Nonalcoholic fatty liver disease and the risk of insulin-requiring gestational diabetes
Sang Youn You, Kyungdo Han, Seung-Hawn Lee, Mee Kyoung Kim
Diabetology & Metabolic Syndrome.2021;[Epub] CrossRef

Clinical Study
Serum γ-Glutamyl Transferase Is Inversely Associated with Bone Mineral Density Independently of Alcohol Consumption: Han Seok Choi, Kwang Joon Kim, Yumie Rhee, Sung-Kil Lim; Endocrinol Metab. 2016;31(1):64-71. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.64

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Abstract PDF PubReader

Background

γ-Glutamyl transferase (GGT) is a well-known marker of chronic alcohol consumption or hepatobiliary diseases. A number of studies have demonstrated that serum levels of GGT are independently associated with cardiovascular and metabolic disorders. The purpose of this study was to test if serum GGT levels are associated with bone mineral density (BMD) in Korean adults.

Methods

A total of 462 subjects (289 men and 173 women), who visited Severance Hospital for medical checkup, were included in this study. BMD was measured using dual energy X-ray absorptiometry. Cross-sectional association between serum GGT and BMD was evaluated.

Results

As serum GGT levels increased from the lowest tertile (tertile 1) to the highest tertile (tertile 3), BMD decreased after adjusting for confounders such as age, body mass index, amount of alcohol consumed, smoking, regular exercise, postmenopausal state (in women), hypertension, diabetes mellitus, and hypercholesterolemia. A multiple linear regression analysis showed a negative association between log-transformed serum GGT levels and BMD. In a multiple logistic regression analysis, tertile 3 of serum GGT level was associated with an increased risk for low bone mass compared to tertile 1 (odds ratio, 2.271; 95% confidence interval, 1.340 to 3.850; P=0.002).

Conclusion

Serum GGT level was inversely associated with BMD in Korean adults. Further study is necessary to fully elucidate the mechanism of the inverse relationship.

Citations

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Association of gamma-glutamyl transferase variability with risk of osteoporotic fractures: A nationwide cohort study
Dongyeop Kim, Jee Hyun Kim, Heajung Lee, Iksun Hong, Yoonkyung Chang, Tae-Jin Song, Mohamed El-Sayed Abdel-Wanis
PLOS ONE.2023; 18(6): e0277452. CrossRef
Gamma-glutamyl-transferase is associated with incident hip fractures in women and men ≥ 50 years: a large population-based cohort study
W. Brozek, H. Ulmer, A. Pompella, G. Nagel, A. Leiherer, O. Preyer, H. Concin, E. Zitt
Osteoporosis International.2022; 33(6): 1295. CrossRef
Elevated gamma-glutamyl transpeptidase level is associated with an increased risk of hip fracture in postmenopausal women
Kyoung Jin Kim, Namki Hong, Min Heui Yu, Seunghyun Lee, Sungjae Shin, Sin Gon Kim, Yumie Rhee
Scientific Reports.2022;[Epub] CrossRef
Elevated serum γ-glutamyl transferase is associated with low muscle function in adults independent of muscle mass
Seunghyun Lee, Dawon Song, Sungjae Shin, Namki Hong, Yumie Rhee
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A fluorine-18 labeled radiotracer for PET imaging of γ-glutamyltranspeptidase in living subjects
Dingyao Gao, Yinxing Miao, Siqin Ye, Chunmei Lu, Gaochao Lv, Ke Li, Chunjing Yu, Jianguo Lin, Ling Qiu
RSC Advances.2021; 11(31): 18738. CrossRef
The dark side of gamma-glutamyltransferase (GGT): Pathogenic effects of an ‘antioxidant’ enzyme
Alessandro Corti, Eugenia Belcastro, Silvia Dominici, Emilia Maellaro, Alfonso Pompella
Free Radical Biology and Medicine.2020; 160: 807. CrossRef
Clinical and body composition predictors of bone turnover and mineral content in obese postmenopausal women
Rim Cherif, Feten Mahjoub, Hela Sahli, Elhem Cheour, Mohsen Sakly, Nebil Attia
Clinical Rheumatology.2019; 38(3): 739. CrossRef
Association between liver enzymes and bone mineral density in Koreans: a cross-sectional study
Ho Jeong Do, Joon-Shik Shin, Jinho Lee, Yoon Jae Lee, Me-riong Kim, Dongwoo Nam, Eun-Jung Kim, Yeoncheol Park, Kristin Suhr, In-Hyuk Ha
BMC Musculoskeletal Disorders.2018;[Epub] CrossRef
Articles inEndocrinology and Metabolismin 2016
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Endocrinology and Metabolism.2017; 32(1): 62. CrossRef

Alanine Aminotransferase as a Predictor of Metabolic Syndrome in Koreans.: Ji Hae Kwon, Yong Seong An, Yang Ho Kang, Seok Man Son, In Ju Kim, Yong Ki Kim; J Korean Endocr Soc. 2008;23(6):404-412. Published online December 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.6.404

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Abstract PDF

AIMS: Alanine aminotransferase (ALT) is associated with insulin resistance, and is independent of the general metabolic measures. Gamma-glutamyltransferase (GGT) is regarded as a predictor of diabetes mellitus. We analyzed which of ALT or GGT is better tool to preestimate the development of metabolic syndrome. METHOD: A total of 1203 Koreans who visited the Institute of Health in Pusan National University Hospital from January 2005 to August 2006 were enrolled in this cross-sectional study. Their median age was 51 years old, and the prevalence of metabolic syndrome was 16.4% (n = 197). We excluded the subjects with diabetes mellitus, hypertension and viral hepatitis or those subjects with a level of alanine aminotransferase (ALT) or gamma-glutamyltransferase (r-GGT) > 80 IU/L. RESULTS: For all the patients in the metabolic syndrome group, the median homeostatic assessment of insulin resistance (HOMA-IR), the waist circumference, the fasting blood glucose level, the systolic and diastolic blood pressure were all associated with the ALT level (P < 0.05). For the nonmetabolic syndrome group, all the metabolic risk factors were associated with the ALT level (P < 0.05). On logistic regression analysis, after correction for age, alcohol intake, HOMA-IR and body mass index, the logALT maintained a highly predictive value for metabolic syndrome, and this was better than the logGGT [odds ratio (OR) of logALT: 18.489, odds ratio of logGGT: 2.024] (P < 0.001). The risk of developing metabolic syndrome was significantly higher in the above 50 percentile and the above 75 percentile of ALT than in the lowest quartile. [for men - OR: 3.6; 95% confidence interval (CI), 2.2-5.9; OR: 6.9; 95% CI: 4.3-10.9] [for women - OR: 2.7; 95% CI: 1.5-4.7; OR: 6.5; 95% CI: 3.8-11] (P < 0.001). The cut-off value of ALT by the ROC curve was 24 IU/L for men (sensitivity: 64.3%, specificity: 66%, negative predictive value: 99.5%) and 20 IU/L for women (sensitivity: 78.9%, specificity: 61.4%, negative predictive value: 84.9%). CONCLUSIONS: Even although patients can have an ALT level that's included within the upper normal level, we may consider the probability that these patients will have metabolic syndrome. Furthermore, in our analysis, the ALT level is a better predictor of metabolic syndrome than the GGT level.

Citations

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Nutritional Status of Hypertensive Men in Gyeongnam Area
Hae-Jin Park, Ye-Ji Choi, Sung-Hee Kim
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