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Faramarzi E, Mehrtabar S, Molani-Gol R, Dastgiri S. The relationship between hepatic enzymes, prediabetes, and diabetes in the Azar cohort population. BMC Endocr Disord 2025; 25:41. [PMID: 39953488 PMCID: PMC11827479 DOI: 10.1186/s12902-025-01871-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 02/06/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND Early prediabetes screening holds immense significance in decreasing the incidence of diabetes. Therefore, we aimed to evaluate the association of hepatic enzymes with prediabetes and diabetes in the Azar cohort population in Iran. METHODS This cross-sectional study utilized data from the Azar cohort study, initiated in 2014, with 14,865 participants aged 35-70 years. This study defines prediabetes, according to the American Diabetes Association (ADA), as fasting blood sugar (FBS) of 100-125 mg/dl. An FBS ≥ 126 mg/dL or a history of diabetes indicates diabetes. Serum liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) were measured, and associations with prediabetes and diabetes were analyzed using binary logistic regression. RESULTS In a study of 14,865 participants, 16% had prediabetes and 14.1% had diabetes. The serum levels of ALT, AST, GGT, and ALP were significantly higher (P < 0.05) in the prediabetic and diabetic patients. The adjusted logistic regression model showed a dose-response increase for all hepatic enzymes, with the highest ORs in the fourth quartile for both prediabetes and diabetes. The highest OR for prediabetes and diabetes was in the fourth GGT quartile. CONCLUSION Our findings suggest that serum ALT, GGT, and ALP levels are strongly associated with prediabetes and diabetes. These hepatic enzymes may be considered easy and valuable early indicators of diabetes risk, prompting timely interventions to slow disease progression.
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Affiliation(s)
- Elnaz Faramarzi
- Liver and Gastrointestinal Diseases Research Center Tabriz, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saba Mehrtabar
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roghayeh Molani-Gol
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Saeed Dastgiri
- Tabriz Health Services Management Research Center School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Lai Z, Li Z, Huang M, Wang Y, Li L, Liu F, Yang T, Liu Y, Xu Q, Gao S, Yu C. Associations Between GGT/ALT Ratio and Carotid Plaque in Inpatients With Coronary Artery Disease: A RCSCD-TCM Study. Angiology 2025; 76:40-50. [PMID: 37632145 DOI: 10.1177/00033197231197441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/27/2023]
Abstract
This study investigated the relationship between gamma-glutamyltransferase/alanine aminotransferase (GGT/ALT) ratio and carotid plaques in patients with coronary artery disease (CAD). This multicenter retrospective study included 8,255 patients with CAD who were divided according to GGT/ALT quartiles: Q1 (GGT/ALT ≤ 1.00), Q2 (1.00 < GGT/ALT ≤ 1.41), Q3 (1.41 < GGT/ALT ≤ 2.05), and Q4 (GGT/ALT > 2.05). Logistic regression was used to analyze the relationship between GGT/ALT, carotid plaques, and carotid plaque echogenicity. GGT/ALT ratio (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.11-1.21; P < .001) was significantly associated with carotid plaque risk. The degree of relevance was higher in men (OR: 1.71; 95% CI: 1.35-2.15; P < .001) than in women (OR: 1.56; 95% CI: 1.28-1.91; P < .001). The ORs value of carotid plaque risk was higher in middle-aged patients (OR: 2.23; 95% CI: 1.78-2.80; P < .001) than in older patients (OR: 1.77; 95% CI: 1.44-2.18; P < .001). The GGT/ALT ratio was significantly associated with different carotid plaque echogenicity, and the highest OR values were for isoechoic plaques (OR: 1.18; 95% CI: 1.12-1.24; P < .001). These findings suggest that the GGT/ALT ratio might be associated with a high risk of developing carotid plaques and different types of plaque echoes and was more significantly associated with isoechoic plaques.
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Affiliation(s)
- Ziqin Lai
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
| | - Zhu Li
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Binjiang District, Hangzhou, China
| | - Mengnan Huang
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
| | - Yang Wang
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
| | - Lin Li
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
| | - Fanfan Liu
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
| | - Tong Yang
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
| | - Yijia Liu
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
| | - Qiang Xu
- Second Teaching Hospital of Tianjin University of TCM, Tianjin, China
| | - Shan Gao
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
| | - Chunquan Yu
- Tianjin University of Traditional Chinese Medicine, Tuanbo New Town, China
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Ma X, Wu H, Huang H, Tang P, Zeng X, Huang D, Liu S, Qiu X. The role of liver enzymes in the association between ozone exposure and diabetes risk: a cross-sectional study of Zhuang adults in China. ENVIRONMENTAL SCIENCE. PROCESSES & IMPACTS 2024; 26:765-777. [PMID: 38517292 DOI: 10.1039/d3em00463e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/23/2024]
Abstract
Background: Growing evidence has demonstrated the role of ambient air pollutants in driving diabetes incidence. However, epidemiological evidence linking ozone (O3) exposure to diabetes risk has been scarcely studied in Zhuang adults in China. We aimed to investigate the associations of long-term exposure to O3 with diabetes prevalence and fasting plasma glucose (FPG) and estimate the mediating role of liver enzymes in Zhuang adults. Methods: We recruited 13 843 ethnic minority adults during 2018-2019 based on a cross-sectional study covering nine districts/counties in Guangxi. Generalized linear mixed models were implemented to estimate the relationships between O3 exposure and diabetes prevalence and FPG. Mediation effect models were constructed to investigate the roles of liver enzymes in the associations of O3 exposure with diabetes prevalence and FPG. Subgroup analyses were conducted to identify potential effect modifications. Results: Long-term exposure to O3 was positively associated with diabetes prevalence and FPG levels in Zhuang adults, with an excess risk of 7.32% (95% confidence interval [CI]: 2.56%, 12.30%) and an increase of 0.047 mmol L-1 (95% CI: 0.032, 0.063) for diabetes prevalence and FPG levels, respectively, for each interquartile range (IQR, 1.18 μg m-3) increment in O3 concentrations. Alanine aminotransferase (ALT) significantly mediated 8.10% and 29.89% of the associations of O3 with FPG and diabetes prevalence, respectively, and the corresponding mediation proportions of alkaline phosphatase (ALP) were 8.48% and 30.00%. Greater adverse effects were observed in females, obese subjects, people with a low education level, rural residents, non-clean fuel users, and people with a history of stroke and hypertension in the associations of O3 exposure with diabetes prevalence and/or FPG levels (all P values for interaction < 0.05). Conclusion: Long-term exposure to O3 is related to an increased risk of diabetes, which is partially mediated by liver enzymes in Chinese Zhuang adults. Promoting clean air policies and reducing exposure to environmental pollutants should be a priority for public health policies geared toward preventing diabetes.
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Affiliation(s)
- Xiaoyun Ma
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22, Shuangyong Road, Nanning, Guangxi, China.
- Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Han Wu
- Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Huishen Huang
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22, Shuangyong Road, Nanning, Guangxi, China.
| | - Peng Tang
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22, Shuangyong Road, Nanning, Guangxi, China.
| | - Xiaoyun Zeng
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22, Shuangyong Road, Nanning, Guangxi, China.
| | - Dongping Huang
- Department of Sanitary Chemistry, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Shun Liu
- Department of Maternal, Child and Adolescent Health, School of Public Health, Guangxi Medical University, No. 22, Shuangyong Road, Nanning, Guangxi, China.
| | - Xiaoqiang Qiu
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22, Shuangyong Road, Nanning, Guangxi, China.
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Anupam S, Goel S, Bhatti K, Mehta DK, Das R. Serum Gamma Glutamyl Transferase: Understanding its Contribution as a Potential Predictor of the Occurrence of Type 2 Diabetes. Curr Diabetes Rev 2024; 21:e240124226080. [PMID: 38275034 DOI: 10.2174/0115733998260996231122054907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 08/22/2023] [Accepted: 10/13/2023] [Indexed: 01/27/2024]
Abstract
INTRODUCTION The liver and kidneys are the primary locations of the glutathione metabolism enzyme gamma-glutamyl transferase (GGT). The two main factors contributing to an increase are hepatic illnesses and excessive alcohol use. This study set out to test a theory on the predictive importance of the association between GGT and Type 2 diabetes mellitus. (T2DM). METHODS In order to do this, we combed through PubMed, Google Scholar, Medline, and Science Direct for a wide range of information from previous studies. Attributes were established at the outset and compared to GGT concentration. RESULT GGT, present in most cells, absorbs glutathione for intracellular antioxidant defences. This study links GGT to hepatic enzymes including HDL, LDL, and triglyceride. LDL, triglycerides, AST, and ALT increased with GGT concentration, but LDL decreased. Because of obesity, GGT production rises with BMI. We found that greater GGT levels were associated with more T2DM after analysing data from multiple sources. CONCLUSION This literature review concludes that GGT is related to other factors such as BMI, HDL, AST, and triglycerides in the development of diabetes mellitus. Serum GGT was found to be a potential predictor of metabolic syndrome and T2DM.
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Affiliation(s)
- Sristi Anupam
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Simran Goel
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Karun Bhatti
- Department of Medicine, M.M. Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Dinesh Kumar Mehta
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Rina Das
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
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Khalid S, Bashir S, Basharat S, Mehboob R, Anwar T, Hashim M, Orfali R, Hussain SA, Gilkaramenthi R, Jibreel EA, Asdaq SMB, Ghazanfar S. Association of cholesterol with hepatorenal markers and quality of life in diabetic patients before and after magnesium and potassium supplements. Saudi Pharm J 2023; 31:101865. [PMID: 38028213 PMCID: PMC10663893 DOI: 10.1016/j.jsps.2023.101865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 11/04/2023] [Indexed: 12/01/2023] Open
Abstract
Background Magnesium and potassium are two critical minerals that have been linked to the treatment of diabetes and its consequences. A lack of magnesium has been linked to insulin resistance and diabetes, whereas potassium has been found to promote insulin sensitivity and glucose metabolism. The study aimed to determine the relationship between cholesterol, liver and kidney markers, and quality of life in diabetic patients before and after magnesium and potassium supplementation. Methods It was a single-blind randomized controlled study at Lahore Garrison University and Lahore Medical Research Centre (LMRC). The study included 200 diabetes participants. Four groups were made based on supplements. Blood samples of all diabetes patients were obtained to assess their quality of life before and after using Mg + and K + supplements, as well as the association between cholesterol, liver, and kidney markers. Results The participants' average age was 51.0 ± 11.08. 139 (69.5 %) of the 200 participants were female, whereas 26 (30.5 %) were male. There was no correlation between the quality of life measure and the patients' cholesterol levels before and after the magnesium and potassium supplementation. Furthermore, the kidney and liver indicators were not dependent on the diabetes individuals' cholesterol levels. Conclusions The study concluded that none of the four groups noticed a significant effect of magnesium and potassium therapies on the patient's quality of life or cholesterol levels. However, more research is needed to determine if liver and kidney problems are linked to cholesterol levels before and after medication, as the current study found no significant correlation between the two parameters.
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Affiliation(s)
- Sidra Khalid
- University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
| | - Shahid Bashir
- University Institute of Food Science and Technology, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan/ Faculty of Allied Health and Biological Sciences, Ibadat International University, Islamabad, Pakistan
| | - Shahnai Basharat
- University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
| | - Riffat Mehboob
- Lahore Medical Research CenterLLP/ RotoGen BIOTECH Pvt. Ltd., Lahore, Pakistan
| | - Tehreem Anwar
- Lahore Medical Research CenterLLP/ RotoGen BIOTECH Pvt. Ltd., Lahore, Pakistan
| | - Mariam Hashim
- Lahore Medical Research CenterLLP/ RotoGen BIOTECH Pvt. Ltd., Lahore, Pakistan
| | - Raha Orfali
- Department of Pharmacognosy, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia
| | - Syed Arif Hussain
- Respiratory Care Department, College of Applied Sciences, AlMaarefa University, Dariyah 13713, Riyadh, Saudi Arabia
| | - Rafiulla Gilkaramenthi
- Department of Emergency Medical Services, College of Applied Sciences, AlMaarefa University, Riyadh, Saudi Arabia
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Li Y, Wang J, Han X, Hu H, Wang F, Yu C, Yuan J, Yao P, Li X, Yang K, Miao X, Wei S, Wang Y, Chen W, Liang Y, Zhang X, Guo H, Yang H, Wu T, He M. Serum alanine transaminase levels predict type 2 diabetes risk among a middle-aged and elderly Chinese population. Ann Hepatol 2020; 18:298-303. [PMID: 31040092 DOI: 10.1016/j.aohep.2017.02.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 02/07/2017] [Accepted: 02/14/2017] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND AIM It is indicated that high levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are associated with increased incident type 2 diabetes risk. However, whether serum ALT levels could improve the discrimination of type 2 diabetes remains unclear. METHODS The data was derived from the Dongfeng-Tongji cohort study, which was established in 2008 and followed until October 2013. A total of 17,173 participants free of type 2 diabetes at baseline were included and 1159 participants developed diabetes after 4.51 (0.61) years of follow-up. Cox proportional hazard regression model was used to calculate the hazard ratios (HRs) for the association between ALT and AST levels with incident diabetes risk. Receiver-operating characteristic (ROC) curves analysis was used to evaluate the predictive accuracy of models incorporating traditional risk factors with and without ALT. RESULTS Compared with the lowest quartile of ALT and AST levels, the highest quartile had a significantly higher risk of developing type 2 diabetes (HR: 2.17 [95% CI: 1.78-2.65] and 1.29 [1.08-1.54], respectively) after adjustment for potential confounders. The addition of ALT levels into the traditional risk factors did not improve the predictive ability of type 2 diabetes, with AUC increase from 0.772 to 0.774; P=0.86. CONCLUSIONS Although elevated ALT or AST levels increased incident type 2diabetes risk, addition of ALT levels into the prediction model did not improve the discrimination of type 2 diabetes.
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Affiliation(s)
- Yaru Li
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jing Wang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xu Han
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hua Hu
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Fei Wang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Caizheng Yu
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jing Yuan
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ping Yao
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiulou Li
- Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China
| | - Kun Yang
- Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China
| | - Xiaoping Miao
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Sheng Wei
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Youjie Wang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Weihong Chen
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuan Liang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaomin Zhang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huan Guo
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Handong Yang
- Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China
| | - Tangchun Wu
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Meian He
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Islam S, Rahman S, Haque T, Sumon AH, Ahmed AZM, Ali N. Prevalence of elevated liver enzymes and its association with type 2 diabetes: A cross-sectional study in Bangladeshi adults. Endocrinol Diabetes Metab 2020; 3:e00116. [PMID: 32318634 PMCID: PMC7170449 DOI: 10.1002/edm2.116] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 01/22/2020] [Accepted: 01/25/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Type 2 diabetes (T2D) is a major public health concern affecting millions of people worldwide. The relationship between liver enzymes and T2D has been reported in limited studies; however, there is still a lack of evidence for the Bangladeshi population. This study aimed to evaluate the prevalence of elevated liver enzymes and examine its association with the prevalence of T2D in Bangladeshi adults. METHODS A total of 270 individuals (110 diabetic and 160 nondiabetic) were enrolled in the study. Alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) activities were measured in blood serum collected from them. T2D was defined as fasting blood glucose (FBG) ≥126 mg/dL or self-reported recent use of insulin or antidiabetic medications. Association between liver enzymes and T2D was evaluated by multinomial logistic regression analysis. RESULTS Overall, 61.2% of participants in T2D and 37.1% of participants in the nondiabetes group had at least one or more elevated liver enzymes. The mean concentrations of serum ALT, AST, ALP and GGT were significantly higher in the T2D group compared to the nondiabetes group. The prevalence of elevated liver enzymes was significantly higher in the diabetes group compared to the nondiabetes group (P < .01). In regression analysis, serum GGT activity showed an independent association with the prevalence of T2D. CONCLUSIONS A high prevalence of elevated liver enzymes was observed in subjects having diabetes. Increased serum GGT activity was independently associated with the prevalence of T2D among Bangladeshi adults. More studies of this nature should be carried out in developing countries to get proper insights into the involvement of liver enzymes in T2D.
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Affiliation(s)
- Shiful Islam
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | - Sadaqur Rahman
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | - Tangigul Haque
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | - Abu Hasan Sumon
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | | | - Nurshad Ali
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
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Bacanlı M, Aydın S, Anlar HG, Çal T, Arı N, Ündeğer Bucurgat Ü, Başaran AA, Başaran N. Can ursolic acid be beneficial against diabetes in rats? ACTA ACUST UNITED AC 2018. [DOI: 10.1515/tjb-2017-0289] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Abstract
Objective:
Diabetes mellitus, a heteregenous metabolic and chronic disease, is a growing health problem especially in developing countries. It is claimed that diabetes associated with increased formation of free radicals and decrease in antioxidant potential and also alterations in lipid profile and enzyme levels. Ursolic acid is commonly used in traditional Chinese medicine due to its beneficial effects. The aim of this study was to investigate the effects of ursolic acid on streptozotocin-induced diabetes in Wistar albino rats.
Methods:
DNA damage was evaluated in the blood and liver cells of rats by alkaline comet assay. The activities of antioxidant enzymes, oxidative stress parameters, biochemical parameters, hepatic enzyme levels and lipid profile parameters were also evaluated.
Results:
The results of this study demonstrate that diabetes caused genotoxic damage, changes in hepatic enzyme and lipid profile, biochemical and antioxidant enzyme activities and oxidative stress parameters in rats. Ursolic acid was found to be protective against diabetes induced effects in blood and liver samples of rats.
Conclusions:
According to our results, it seems that ursolic acid may be beneficial against diabetes and its adverse effects in rats.
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Xie J, Zhang S, Yu X, Yang Y, Liu Z, Yuan G, Hu S. Association between Liver Enzymes with Metabolically Unhealthy Obese Phenotype. Lipids Health Dis 2018; 17:198. [PMID: 30134916 PMCID: PMC6106819 DOI: 10.1186/s12944-018-0847-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 08/10/2018] [Indexed: 01/07/2023] Open
Abstract
Background Obesity could be classified into two phenotypes: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). This study investigated the ability of liver enzymes to identify obesity phenotype. Methods We conducted a cross-sectional study in 2197 obese adults (age > 40 years and BMI ≥25 kg/m2) in a rural area of central China. Results In this population, 75% of the participants have more than one cardiometabolic risk factor. Both GGT and ALT were strongly related to the MUHO phenotype. The association between the fourth quartile of GGT and MUHO risk was strong and independent of confounder risk factors in both genders (adjusted ORs, 1.73 (95%CI 1.03–2.92) for male and 1.82 (95%CI 1.29–2.57) for female). The association between the fourth quartile of ALT and MUHO risk was strong and independent in female, but not in male (adjusted ORs, 1.65 (95%CI 0.86–3.19) for male and 1.88 (95%CI 1.29–2.75) for female). Additionally, AST was not associated with MUHO phenotype. Conclusions Both GGT and ALT are effective markers for identifying MUHO in this population. Furthermore, the ability of GGT may be superior to ALT in male.
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Affiliation(s)
- Junhui Xie
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Shujun Zhang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Xuefeng Yu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China.
| | - Yan Yang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Zhelong Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Shuhong Hu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
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Radaelli MG, Martucci F, Perra S, Accornero S, Castoldi G, Lattuada G, Manzoni G, Perseghin G. NAFLD/NASH in patients with type 2 diabetes and related treatment options. J Endocrinol Invest 2018; 41:509-521. [PMID: 29189999 DOI: 10.1007/s40618-017-0799-3] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Accepted: 11/17/2017] [Indexed: 02/06/2023]
Abstract
Type 2 diabetes may reduce life expectancy and patients' quality of life due to its micro- and macro-vascular complications and to the higher risk of several types of cancer. An emerging important factor is represented by the hepatic involvement; it is recognized that excessive hepatic fat accumulation represents a typical feature of diabetic patients and that it also plays an important pathogenic role. It is now evident that non-alcoholic fatty liver disease (NAFLD), generally perceived as a benign condition, may have on the contrary an important deleterious impact for diabetic patients increasing the risk to develop cardiovascular complications but also serious hepatic diseases, in particular non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Lifestyle intervention, bariatric surgery and several drug therapies have now accumulated evidence of efficacy in treating NASH. On the other hand, their durability and safety in the long-term is yet to be proven and their use may be sometimes associated with side effects or higher risk of adverse events limiting the regular administration or contraindicating it. Professional health care providers, building awareness about the importance of these hepatic complications, should put more efforts in primary prevention using a behavioral therapy needing a multidisciplinary approach, in secondary prevention applying on a regular basis in the clinical setting available predictive algorithms to identify the patients at higher cardiovascular and hepatologic risk, and in tertiary prevention treating, when not contraindicated, the diabetic patients preferentially with drugs with proven benefit on NAFLD/NASH.
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Affiliation(s)
- M G Radaelli
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - F Martucci
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - S Perra
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - S Accornero
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - G Castoldi
- Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano Bicocca, Milan, MI, Italy
| | - G Lattuada
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - G Manzoni
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - G Perseghin
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy.
- Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano Bicocca, Milan, MI, Italy.
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11
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Nikniaz L, Nikniaz Z, Tabrizi JS, Sadeghi-Bazargani H, Farahbakhsh M. Is within-normal range liver enzymes associated with metabolic syndrome in adults? Clin Res Hepatol Gastroenterol 2018; 42:92-98. [PMID: 28866090 DOI: 10.1016/j.clinre.2017.06.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 04/17/2017] [Accepted: 06/02/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Considering the clear association between metabolic syndrome and future cardiovascular disease, early detection of metabolic syndrome is important. This study was conducted to assess the correlation between metabolic syndrome components and within-normal-range of liver enzymes in Iranian adults. METHODS This cross-sectional study was comprised of 700 Iranian adults in the districts of East Azerbaijan-Iran in 2015. The levels of lipid profile and glucose were measured by enzymatic colorimetric methods. Weight, height, waist circumferences were measured with standard protocols. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) were assessed using the ultraviolet method. The Pearson correlation and Logistic regression were used to for statistical analysis. RESULTS With increasing the number of metabolic abnormalities, the mean ALT level was increased significantly (Ptrend=0.04). In women, the increase in AST and ALT with increasing the number of metabolic abnormalities was statistically significant (PAST=0.01; PALT<0.001). In men, ALT level had significantly positive correlation with waist circumference (r=0.14, P<0.05), serum TG (r=0.16, P<0.05) and fasting plasma glucose (r=0.17, P<0.01). In women, there was a significant correlation between AST level and serum TG (r=0.15, P<0.05). A significant positive and negative correlation were found respectively between serum ALT and AST/ALT ratio and waist circumference, serum TG and fasting blood glucose. Women in the 4th quartile of ALT were 4.43 fold at an increased risk for metabolic syndrome outcome when compared to those in the first quartile [OR (95% CI): 4.43 (1.69, 11.63)]. In women, with increasing the quartiles of ALT within normal limits, the percent of participants with metabolic syndrome also increased significantly (Ptrend=0.04). CONCLUSIONS Based on the results, the use of ALT and AST:ALT ratio as continuous biomarkers for early signaling of dysmetabolism especially in women could be encouraged.
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Affiliation(s)
- Leila Nikniaz
- Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zeinab Nikniaz
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Jafar Sadegh Tabrizi
- Tabriz Health Services Management Research Center, Faculty of Management and Medical Informatics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Homayoun Sadeghi-Bazargani
- Road and Traffic Injury Research Center, Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mostafa Farahbakhsh
- Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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12
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Chen SCC, Tsai SP, Jhao JY, Jiang WK, Tsao CK, Chang LY. Liver Fat, Hepatic Enzymes, Alkaline Phosphatase and the Risk of Incident Type 2 Diabetes: A Prospective Study of 132,377 Adults. Sci Rep 2017; 7:4649. [PMID: 28680048 PMCID: PMC5498613 DOI: 10.1038/s41598-017-04631-7] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Accepted: 05/18/2017] [Indexed: 12/19/2022] Open
Abstract
Previous studies have reported inconsistent results of the associations of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) with incident type 2 diabetes (diabetes hereafter). We aimed to resolve the controversy by taking nonalcoholic fatty liver disease (NAFLD) into account. The study population comprised 132,377 non-diabetic individuals (64,875 men and 67,502 women) aged 35–79 who had two or more health examinations during 1996–2014. A total of 6,555 incident diabetes (3,734 men and 2,821 women) were identified, on average, over 5.8 years of follow-up. Cox regression was used to calculate the hazard ratio (HR) for incident diabetes, adjusting for classical confounders. The risk of incident diabetes was significantly associated with NAFLD [HR = 2.08 (men) and 2.65 (women)]. Elevated ALT, AST, GGT and ALP were also significantly associated with the increased risk of diabetes, with HRs of 1.27, 1.23, 1.58 and 1.37, respectively, in men, and 1.56, 1.18, 1.48 and 1.44, respectively in women. Our results suggest that NAFLD, ALT, AST, GGT and ALP are independent predictors for incident diabetes in both men and women.
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Affiliation(s)
- Sean Chun-Chang Chen
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, 110, Taiwan
| | - Shan Pou Tsai
- MJ Health Management Institution, Taipei, 114, Taiwan
| | - Jing-Yun Jhao
- MJ Health Management Institution, Taipei, 114, Taiwan.,MJ Health Research Foundation, Taipei, 114, Taiwan
| | - Wun-Kai Jiang
- MJ Health Management Institution, Taipei, 114, Taiwan.,MJ Health Research Foundation, Taipei, 114, Taiwan
| | | | - Ly-Yun Chang
- MJ Health Management Institution, Taipei, 114, Taiwan. .,MJ Health Research Foundation, Taipei, 114, Taiwan. .,Institute of Sociology, Academia Sinica, Taipei, 115, Taiwan.
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13
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Zidani S, Benakmoum A, Ammouche A, Benali Y, Bouhadef A, Abbeddou S. Effect of dry tomato peel supplementation on glucose tolerance, insulin resistance, and hepatic markers in mice fed high-saturated-fat/high-cholesterol diets. J Nutr Biochem 2017; 40:164-171. [DOI: 10.1016/j.jnutbio.2016.11.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Revised: 11/01/2016] [Accepted: 11/07/2016] [Indexed: 11/17/2022]
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14
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Noordam R, Vermond D, Drenth H, Wijman CA, Akintola AA, van der Kroef S, Jansen SWM, Huurman NC, Schutte BAM, Beekman M, Slagboom PE, Mooijaart SP, van Heemst D. High Liver Enzyme Concentrations are Associated with Higher Glycemia, but not with Glycemic Variability, in Individuals without Diabetes Mellitus. Front Endocrinol (Lausanne) 2017; 8:236. [PMID: 28955304 PMCID: PMC5601417 DOI: 10.3389/fendo.2017.00236] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 08/28/2017] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Elevated concentrations of liver enzymes have been associated with an increased risk of developing type 2 diabetes mellitus. However, it remains unclear to which specific aspects of diurnal glucose metabolism these associate most. We aimed to investigate the associations between liver enzyme concentrations and 24 h-glucose trajectories in individuals without diabetes mellitus from three independent cohorts. METHODS This cross-sectional study included 436 participants without diabetes mellitus from the Active and Healthy Aging Study, the Switchbox Study, and the Growing Old Together Study. Fasting blood samples were drawn to measure gamma-glutamyltransferase (GGT), alanine transaminase, and aspartate transaminase. Measures of glycemia (e.g., nocturnal and diurnal mean glucose levels) and glycemic variability (e.g., mean amplitude of glucose excursions) were derived from continuous glucose monitoring. Analyses were performed separately for the three cohorts; derived estimates were additionally meta-analyzed. RESULTS After meta-analyses of the three cohorts, elevated liver enzyme concentrations, and specifically elevated GGT concentrations, were associated with higher glycemia. More specific, participants in the highest GGT tertile (GGT ≥37.9 U/L) had a 0.39 mmol/L (95% confidence interval: 0.23, 0.56) higher mean nocturnal glucose (3:00 to 6:00 a.m.) and a 0.23 mmol/L (0.10, 0.36) higher diurnal glucose (6:00 to 0:00 a.m.) than participants in the lowest GGT tertile (GGT <21.23 U/L). However, elevated liver enzyme concentrations were not associated with a higher glycemic variability. CONCLUSION Though elevated liver enzyme concentrations did not associate with higher glycemic variability in participants without diabetes mellitus, specifically, elevated GGT concentrations associated with higher glycemia.
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Affiliation(s)
- Raymond Noordam
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
- *Correspondence: Raymond Noordam,
| | - Debbie Vermond
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
- Leyden Academy on Vitality and Ageing, Leiden, Netherlands
| | - Hermijntje Drenth
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
- Leyden Academy on Vitality and Ageing, Leiden, Netherlands
| | - Carolien A. Wijman
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
| | - Abimbola A. Akintola
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
| | - Sabrina van der Kroef
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
| | - Steffy W. M. Jansen
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
| | - Neline C. Huurman
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
| | - Bianca A. M. Schutte
- Department of Medical Statistics and Bioinformatics, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands
| | - Marian Beekman
- Department of Medical Statistics and Bioinformatics, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands
| | - P. Eline Slagboom
- Department of Medical Statistics and Bioinformatics, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands
| | - Simon P. Mooijaart
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
- Institute for Evidence-Based Medicine in Old Age, IEMO, Leiden, Netherlands
| | - Diana van Heemst
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
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15
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Ballestri S, Zona S, Targher G, Romagnoli D, Baldelli E, Nascimbeni F, Roverato A, Guaraldi G, Lonardo A. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. J Gastroenterol Hepatol 2016; 31:936-44. [PMID: 26667191 DOI: 10.1111/jgh.13264] [Citation(s) in RCA: 523] [Impact Index Per Article: 58.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 12/05/2015] [Accepted: 12/07/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM The magnitude of the risk of incident type 2 diabetes (T2D) and metabolic syndrome (MetS) among patients with nonalcoholic fatty liver disease (NAFLD) is poorly known. We gauged the risk of developing T2D and MetS in patients with NAFLD diagnosed by either serum liver enzymes (aminotransferases or gamma-glutamyltransferase [GGT]) or ultrasonography. METHODS Pertinent prospective studies were identified through extensive electronic database research, and studies fulfilling enrolment criteria were included in the meta-analysis. RESULTS Overall, in a pooled population of 117020 patients (from 20 studies), who were followed-up for a median period of 5 years (range: 3-14.7 years), NAFLD was associated with an increased risk of incident T2D with a pooled relative risk of 1.97 (95% confidence interval [CI], 1.80-2.15) for alanine aminotransferase, 1.58 (95% CI, 1.43-1.74) for aspartate aminotransferase, 1.86 (95% CI, 1.71-2.03) for GGT (last vs first quartile or quintile), and 1.86 (95% CI, 1.76-1.95) for ultrasonography, respectively. Overall, in a pooled population of 81411 patients (from eight studies) who were followed-up for a median period of 4.5 years (range: 3-11 years), NAFLD was associated with an increased risk of incident MetS with a pooled relative risk of 1.80 (95% CI, 1.72-1.89) for alanine aminotransferase (last vs first quartile or quintile), 1.98 (95% CI, 1.89-2.07) for GGT, and 3.22 (95% CI, 3.05-3.41) for ultrasonography, respectively. CONCLUSIONS Nonalcoholic fatty liver disease, as diagnosed by either liver enzymes or ultrasonography, significantly increases the risk of incident T2D and MetS over a median 5-year follow-up.
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Affiliation(s)
| | - Stefano Zona
- University of Modena and Reggio Emilia, Metabolic Clinic, Infectious and Tropical Disease Unit, Policlinico Hospital, Modena, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy
| | - Dante Romagnoli
- Azienda USL, Outpatient Liver Clinic and Internal Medicine, NOCSAE, Modena, Italy
| | - Enrica Baldelli
- Azienda USL, Outpatient Liver Clinic and Internal Medicine, NOCSAE, Modena, Italy
| | - Fabio Nascimbeni
- Azienda USL, Outpatient Liver Clinic and Internal Medicine, NOCSAE, Modena, Italy
| | | | - Giovanni Guaraldi
- University of Modena and Reggio Emilia, Metabolic Clinic, Infectious and Tropical Disease Unit, Policlinico Hospital, Modena, Italy
| | - Amedeo Lonardo
- Azienda USL, Outpatient Liver Clinic and Internal Medicine, NOCSAE, Modena, Italy
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16
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Xie JH, Liu Q, Yang Y, Liu ZL, Hu SH, Zhou XR, Yuan G, Zhang MX, Tao J, Yu XF. Correlation of liver enzymes with diabetes and pre-diabetes in middle-aged rural population in China. ACTA ACUST UNITED AC 2016; 36:53-58. [PMID: 26838740 DOI: 10.1007/s11596-016-1541-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 11/12/2015] [Indexed: 01/08/2023]
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17
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Wang YL, Koh WP, Yuan JM, Pan A. Association between liver enzymes and incident type 2 diabetes in Singapore Chinese men and women. BMJ Open Diabetes Res Care 2016; 4:e000296. [PMID: 27738514 PMCID: PMC5030569 DOI: 10.1136/bmjdrc-2016-000296] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 08/23/2016] [Accepted: 08/30/2016] [Indexed: 12/18/2022] Open
Abstract
AIMS To assess the association between liver enzymes and the risk of type 2 diabetes (T2D) in a Chinese population. METHODS A nested case-control study comprising 571 T2D cases and 571 matched controls was conducted within the Singapore Chinese Health Study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were quantified in baseline plasma collected from them, while γ-glutamyltransferase (GGT) was assayed among 255 T2D cases with baseline hemoglobin A1c <6.5% and 255 matched controls. Participants were free of diagnosed diabetes, cardiovascular disease, and cancer at blood collections (1999-2004). Incident self-reported T2D cases were identified at follow-up II interview (2006-2010). Controls were matched to cases on age, sex, dialect group, and date of blood collection. RESULTS Higher levels of ALT and GGT were significantly associated with increased risk of T2D (p for trend <0.001 for ALT, p for trend=0.03 for GGT), and the ORs (95% CIs) comparing highest versus lowest tertiles of ALT and GGT were 2.00 (1.01 to 3.96) and 2.38 (1.21 to 4.66), respectively. A null association was observed for AST, ALP, and LDH with T2D risk. Adding GGT (<23 vs ≥23 IU/L) or ALT (<21 vs ≥21 IU/L) to a prediction model resulted in significant gain in net reclassification improvement and integrated discrimination improvement of T2D prediction (all p<0.001). CONCLUSIONS Higher levels of GGT and ALT are associated with increased T2D risk. GGT ≥23 IU/L and ALT ≥21 IU/L may identify people at higher risk of developing T2D in this Chinese population.
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Affiliation(s)
- Ye-Li Wang
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
| | - Woon-Puay Koh
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
- Duke-NUS Graduate Medical School Singapore, Singapore, Singapore
| | - Jian-Min Yuan
- Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - An Pan
- Department of Epidemiology and Statistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
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18
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Vimaleswaran KS, Cavadino A, Verweij N, Nolte IM, Mateo Leach I, Auvinen J, Veijola J, Elliott P, Penninx BW, Snieder H, Järvelin MR, van der Harst P, Cohen RD, Boucher BJ, Hyppönen E. Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study. Eur J Endocrinol 2015; 173:863-72. [PMID: 26526553 DOI: 10.1530/eje-15-0839] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND AND OBJECTIVE Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242). DESIGN AND METHODS The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. RESULTS In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations). CONCLUSION In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.
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Affiliation(s)
- Karani S Vimaleswaran
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
| | - Alana Cavadino
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
| | - Niek Verweij
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia
| | - Ilja M Nolte
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia
| | - Irene Mateo Leach
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia
| | - Juha Auvinen
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
| | - Juha Veijola
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
| | - Paul Elliott
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia
| | - Brenda W Penninx
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
| | - Harold Snieder
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia
| | - Marjo-Riitta Järvelin
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
| | - Pim van der Harst
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
| | - Robert D Cohen
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia
| | - Barbara J Boucher
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia
| | - Elina Hyppönen
- Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
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Wang C, Zhao P, Luo P, Liu W, Wang H, Zhao Q. Prevalence and risk factors of coronary artery disease in patients with chronic viral hepatitis. Postgrad Med 2015; 127:786-90. [PMID: 26436306 DOI: 10.1080/00325481.2015.1094366] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Patients with chronic viral hepatitis usually present metabolic abnormalities and hemodynamic changes, which are known factors associated with the development of coronary artery disease (CAD). This study aims to determine the risk factors of incident CAD in these patients. METHODS We identified 193 patients who subsequently developed CAD amongst 37,840 cases diagnosed as chronic viral hepatitis from January 2007 through December 2013. RESULTS In these patients, 141 had hepatitis B virus infections and 52 had hepatitis C virus infections. There was a male preponderance (65.9%). The median age at the diagnosis of hepatitis was 51 years. In the univariate analysis, patients aged ≥ 51 years had shorter median periods from the diagnosis of hepatitis to the onset of CAD than patients aged < 51 years (50 versus 96 months, p < 0.001), and patients with hypertension had shorter median durations compared to those without hypertension (48 versus 96 months, p < 0.001). Statistical significance also existed between patients with different etiologies (p = 0.004). In the multivariate analysis by Cox regression, age at the diagnosis of hepatitis (p < 0.001; hazard ratio (HR), 1.041; 95% CI, 1.027-1.056) and hypertension (with versus without, p < 0.001; HR, 1.925; 95% CI, 1.419-2.611) were revealed. CONCLUSIONS Age at diagnosis of hepatitis and hypertension appeared to be independent risk factors of incident CAD in these patients. This topic deserves further studies.
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Affiliation(s)
- Chunya Wang
- a 1 Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University , Beijing 100029, China
| | - Pan Zhao
- b 2 Clinical Trial Center, Beijing 302 Hospital (302 Hospital of PLA) , Beijing 100039, China
| | - Ping Luo
- a 1 Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University , Beijing 100029, China
| | - Weiwei Liu
- c 3 Department of Statistics, Academy of Military Medical Science , Beijing 100850, China
| | - Hao Wang
- d 4 Medical Record Center, Beijing 302 Hospital (302 Hospital of PLA) , Beijing 100039, China
| | - Quanming Zhao
- e 5 Department of Special Medical Service, Beijing Anzhen Hospital, Capital Medical University , Beijing 100029, China
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Lin MS, Lin HS, Chung CM, Lin YS, Chen MY, Chen PH, Hu JH, Chou WN, Huang JC, Huang TJ. Serum aminotransferase ratio is independently correlated with hepatosteatosis in patients with HCV: a cross-sectional observational study. BMJ Open 2015; 5:e008797. [PMID: 26369802 PMCID: PMC4577874 DOI: 10.1136/bmjopen-2015-008797] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 08/06/2015] [Accepted: 08/21/2015] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES The incidence of non-alcoholic fatty liver disease (NAFLD) is significant in hepatitis C virus (HCV) carriers due to multiple mechanisms, and this worsens the progression of chronic liver diseases, such as cirrhosis and hepatocellular carcinoma, and death. The purpose of this study was to examine whether the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio correlates with the status of hepatosteatosis. DESIGN A cross-sectional observational study. SETTING Community-based annual examination in northern Taiwan. PARTICIPANTS A total of 1354 participants (age 20 years or over) were enrolled after excluding participants with HCV seronegative, laboratory or questionnaires loss, moderate alcohol consumption, liver cirrhosis, tumours and postlobectomy. OUTCOME MEASURES Fatty liver was diagnosed according to echogenic findings. NAFLD included grades 1-3 fatty liver and high-degree NAFLD defined grades 2-3 fatty liver. RESULTS 580 males and 774 females with a mean age of 47.2 (SD=16.1) years were cross-sectionally studied. The participants with NAFLD have significantly higher levels of ALT/AST ratio, fasting glucose, triglyceride and systolic/diastolic blood pressure than non-NAFLD participants. The association between NAFLD and ALT/AST was significant even when adjusting for the metabolic syndrome (aOR 1.90; 95% CI 1.37 to 2.65; p<0.001). In patients with a high degree of NAFLD, the ALT/AST ratio was still a significant predictor for hepatosteatosis (aOR 2.44; 95% CI 1.58 to 3.77; p<0.001). CONCLUSIONS The ALT/AST ratio could be a strong risk of hepatosteatosis in patients with chronic HCV infection.
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Affiliation(s)
- Ming-Shyan Lin
- Division of Cardiology, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Huang-Shen Lin
- Division of Infectious Diseases, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chang-Ming Chung
- Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yu-Sheng Lin
- Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Mei-Yen Chen
- School of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan
| | - Po-Han Chen
- Division of Orthopedic, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Jing-Hong Hu
- Division of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Wen-Nan Chou
- Division of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Jui-Chu Huang
- Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Tung-Jung Huang
- Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan
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Beigi T, Shafaei A, Khoshnia M, Marjani A. Serum Fetuin A Level, Liver Enzymes Activities and Insulin Resistance in Patients with Type 2 Diabetes. JOURNAL OF MEDICAL SCIENCES 2015. [DOI: 10.3923/jms.2015.229.234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
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Chen S, Guo X, Zhang X, Yu S, Yang H, Jiang M, Sun G, Sun Y. Association between elevated serum alanine aminotransferase and cardiometabolic risk factors in rural Chinese population: a cross-sectional study. BMC Cardiovasc Disord 2015; 15:65. [PMID: 26160405 PMCID: PMC4702363 DOI: 10.1186/s12872-015-0060-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Accepted: 06/29/2015] [Indexed: 01/05/2023] Open
Abstract
Background Elevated alanine aminotransferase (ALT) levels may be associated with metabolic syndrome and cardiovascular diseases. This study aimed to investigate the association between elevated ALT levels and cardiometabolic risk factors in a rural Chinese population. Methods This was a cross-sectional study conducted from July 2012 to August 2013, including 11,573 subjects (5,357 men and 6,216 women) aged ≥35 years in rural areas of Liaoning Province. A physical examination was performed and metabolic indicators were examined under standard protocols. Subjects were divided into those with elevated ALT levels (>40U/L) and those with normal ALT levels (≤40U/L). Results Participants with elevated ALT levels had higher levels of almost all cardiometabolic risk factors than those with normal ALT levels. In individuals with elevated ALT levels, weight, height, waist circumference, and body mass index (BMI), which are indicators for general and abdominal obesity, were significantly higher (p < 0.001) than those in individuals with normal ALT levels. There was no significant difference in race, current smoking, or physical activity between the two groups. Other cardiometabolic risk factors, such as systolic blood pressure, diastolic blood pressure, and fasting plasma glucose, TC, TG, low-density lipoprotein cholesterol, and serum uric acid levels, were higher in participants with elevated ALT levels than in those with normal ALT levels. Logistic regression analysis showed that male sex, younger age, and the presence of high TC, high TG, and low high-density lipoprotein cholesterol levels, current smoking status, BMI ≥25 kg/m2, abdominal obesity, hyperuricemia, and HtgW phenotype were significantly (p < 0.05) associated with elevated ALT levels. Sex-related differences were also investigated. For men, hypertension (OR 1.33, 95 % CI 1.08–1.62), high TC levels (OR 1.63, 95 % CI 1.23–2.17), high TG levels (OR 1.62, 95 % CI 1.25–2.09), BMI ≥25 kg/m2 (OR 1.52, 95 % CI 1.07–2.18), and hyperuricemia (OR 1.92, 95 % CI 1.52–2.40) were significantly (p < 0.05) related to elevated serum ALT levels, but this was not observed in women. Conclusions There are significant relationships of elevated ALT levels with cardiometabolic risk factors and several sex-related differences in rural Chinese. Elevated serum ALT levels are associated with a worse cardiac risk profile.
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Affiliation(s)
- Shuang Chen
- Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, 110001, Shenyang, People's Republic of China.
| | - Xiaofan Guo
- Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, 110001, Shenyang, People's Republic of China.
| | - Xingang Zhang
- Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, 110001, Shenyang, People's Republic of China.
| | - Shasha Yu
- Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, 110001, Shenyang, People's Republic of China.
| | - Hongmei Yang
- Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, 110001, Shenyang, People's Republic of China.
| | - Mohan Jiang
- Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, 110001, Shenyang, People's Republic of China.
| | - Guozhe Sun
- Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, 110001, Shenyang, People's Republic of China.
| | - Yingxian Sun
- Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, 110001, Shenyang, People's Republic of China.
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Liang J, Gong Y, Wang Y, Qiu Q, Zou C, Dou L, Liu X, Song H. Serum gamma-glutamyltransferase is associated with impaired fasting glucose in Chinese adults: the Cardiometabolic Risk in Chinese (CRC) study. Cell Biochem Biophys 2015; 70:1823-8. [PMID: 25030409 DOI: 10.1007/s12013-014-0136-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Recently, several studies found raised serum γ-glutamyltransferase (GGT), and traditional marker of liver damage was associated with the risk of type 2 diabetes. The purpose of this study was to investigate the relationship between GGT and impaired fasting glucose (IFG), and evaluate the modification effects of age, BMI, prehypertension, and lipids in a large sample of Chinese adults. The study samples are from a community-based health examination survey in China. The sample for our analysis included 7,309 participants. IFG was defined as FBG from 6.1 to 7.0 mmol/L. Serum GGT, lipids, blood pressure, and glucose were measured. The odds ratios (ORs, 95 % CI) of IFG across increasing quintiles of GGT were 1.00, 0.91 (0.49-1.72), 1.27 (0.68-2.38), 2.31 (1.29-4.15), and 2.42 (1.32-4.42) (P for trend < 0.0001), adjusting for age, sex, BMI, blood pressure, glucose, and lipids. We found significant interactions between age, BMI, and GGT on IFG risk. When the joint effects were examined, we found an additional effect of triglycerides (TG) and GGT levels on IFG. Our data indicate that serum GGT concentration was associated with the risk of IFG, and the association was modified by TG level.
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Affiliation(s)
- Jun Liang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Institute of Diabetes, Affiliated Hospital of Medical College of Southeast University, 199# South Jiefang Road, Xuzhou, 221009, Jiangsu, China,
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Ko SH, Baeg MK, Han KD, Ko SH, Ahn YB. Increased liver markers are associated with higher risk of type 2 diabetes. World J Gastroenterol 2015; 21:7478-7487. [PMID: 26139993 PMCID: PMC4481442 DOI: 10.3748/wjg.v21.i24.7478] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Revised: 03/02/2015] [Accepted: 04/28/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association between liver markers and the risk of type 2 diabetes (T2DM) and impaired fasting glucose (IFG).
METHODS: A total of 8863 participants (3408 men and 5455 women) over 30 years of age were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2011). The associations of serum liver markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT, and gamma-glutamyltransferase (GGT) with T2DM and IFG were analyzed using logistic regression models. Participants were divided into sex-specific quartiles on the basis of liver markers.
RESULTS: The prevalence of T2DM and IFG were 11.3% and 18.3%. Increasing quartiles of ALT and GGT were positively and AST/ALT were negatively correlated with T2DM and IFG. Analysis of the liver marker combinations showed that if any two or more markers were in the highest risk quartile, the risks of both T2DM and IFG increased significantly. The risk was greatest when the highest ALT and GGT and lowest AST/ALT quartile were combined, with the risk of T2DM at 3.21 (95%CI: 1.829-5.622, P < 0.001) in men and 4.60 (95%CI: 3.217-6.582, P < 0.001) in women. Men and women with the highest AST and ALT and lowest AST/ALT quartile had a 1.99 and 2.40 times increased risk of IFG.
CONCLUSION: Higher levels of GGT and ALT and lower AST/ALT within the physiological range are independent, additive risk factors of T2DM and IFG.
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Arase Y, Heianza Y, Hara S, Ohmoto-Sekine Y, Amakawa K, Tsuji H, Ogawa K, Saito K, Kodama S, Ikeda K, Kumada H, Kobayashi T, Sone H. Potential impact of joint association of alanine aminotransferase and gamma-glutamyltransferase on insulin resistance in Japan: The Toranomon Hospital Health Management Center Study 19 (TOPICS 19). Hepatol Res 2015; 45:247-58. [PMID: 24720401 DOI: 10.1111/hepr.12343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 04/03/2014] [Accepted: 04/08/2014] [Indexed: 02/08/2023]
Abstract
AIM To investigate the potential impact of joint association of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) on insulin resistance and β-cell dysfunction in healthy Japanese individuals with a normal range of liver enzymes. METHODS This study included 1010 individuals (545 men and 465 women) aged 20-89 years who underwent an oral glucose tolerance test for health screening. Participants were divided into four groups on the basis of median values for ALT and GGT: (i) both ALT and GGT low (both-low); (ii) ALT high and GGT low (ALT-high); (iii) ALT low and GGT high (GGT-high); and (iv) both ALT and GGT high (both-high). Logistic regression analysis was used to investigate the relationship between liver enzyme and insulin dynamics, such as Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) and insulinogenic index (IGI). The insulin resistance was defined when HOMA-IR was 2.5 or more. IGI of less than 0.4 was considered to be decreased early-phase insulin secretion. RESULTS Mean values of HOMA-IR in men was 1.5 in the both-low group, 1.8 in ALT-high, 1.8 in GGT-high and 2.8 in both-high. The mean HOMA-IR in women was 1.3 in the both-low group, 1.3 in ALT-high, 1.6 in GGT-high and 2.0 in both-high. HOMA-IR in the both-high group was significantly higher than that in the both-low group regardless of the difference of sex. Multivariate analysis showed that insulin resistance occurred when the patient had high liver enzymes. CONCLUSION Combining the two liver function markers would be effective for identifying individuals with insulin resistance.
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Affiliation(s)
- Yasuji Arase
- Department of Health Management Center and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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Ahmadi M, Moosazadeh M, Vardanjani HME, Dehghan A. Prevalence of obesity and overweight and their related factors among the adults of Mazandaran Province, Iran, in 2010. Electron Physician 2014; 6:955-61. [PMID: 25763175 PMCID: PMC4324264 DOI: 10.14661/2014.955-961] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 05/21/2014] [Accepted: 09/25/2014] [Indexed: 12/03/2022] Open
Abstract
Background: Obesity is an unpleasant outcome of changes in the behavior and lifestyle, and it leads to premature inability and loss of job in most cases. This study aimed at determining the prevalence of obesity and overweight conditions and some related factors among the adults in Mazandaran Province, Iran. Methods: This cross-sectional study was conducted in 2010. The data collection tool was a standard questionnaire provided by the World Health organization (WHO).The sample of this study was selected from all people in the age range of 15 to 64 who lived in the urban and rural areas of Mazandaran Province. The researchers studied 1000 people (500 males and 500 females). The data were analyzed using mean, standard deviation, chi-squared, linear regression, and Logistic regression in SPSS version 16 software. Results: The average and the standard deviation of Body Mass Index (BMI) of the participants was 27.36±6.04 (25.76±4.5 for males and 28.95±6.9 for females), and the average prevalence of overweight was 34% (males: 35.8%, females: 32.2%); the average incidence of obesity was 28.4% (males: 17.8%, females: 39%).It was found that age groups of 35–44 (OR: 3.1, CI: 95%: 1.7–5.8), 45–54 (OR: 3.1, CI: 95%: 1.7–5.8), and 55–64 (OR: 4.02, CI: 95%: 2.1–7.5) and being a housewife (OR: 2.3, 95% CI: 1.03–5.1) were predictive of BMI values equal to or greater than 30. Conclusion: The results of this study showed that the prevalence of overweight and obesity was significant among people of Mazandaran Province. Therefore, it is recommended that educational-research centers and health authorities look for appropriate strategies to reduce the prevalence of this problem.
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Affiliation(s)
- Mohammad Ahmadi
- MD, Researcher, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mahmood Moosazadeh
- MPH and Ph.D. in Epidemiology, Research Center for Modeling in Health, Institute of Future Studies in Health, Kerman university of Medical Sciences, Kerman, Iran
| | - Hossein Molavi-E Vardanjani
- Ph.D. Candidate in Epidemiology, department of biostatistics and Epidemiology, Kerman University of Medical Sciences, Kerman, Iran
| | - Azizallah Dehghan
- Ph.D. Candidate in Epidemiology, department of biostatistics and Epidemiology, Kerman University of Medical Sciences, Kerman, Iran
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Liu X, Hamnvik OPR, Chamberland JP, Petrou M, Gong H, Christophi CA, Christiani DC, Kales SN, Mantzoros CS. Circulating alanine transaminase (ALT) and γ-glutamyl transferase (GGT), but not fetuin-A, are associated with metabolic risk factors, at baseline and at two-year follow-up: the prospective Cyprus Metabolism Study. Metabolism 2014; 63:773-82. [PMID: 24726813 PMCID: PMC4104665 DOI: 10.1016/j.metabol.2014.03.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Revised: 03/10/2014] [Accepted: 03/13/2014] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To comparatively evaluate traditional liver tests and fetuin A as predictors of cardiometabolic risk, we studied associations between serum alanine transaminase (ALT), γ-glutamyl transferase (GGT), aspartate aminotransferase (AST) and fetuin-A and anthropometric, metabolic, and cardiovascular parameters cross-sectionally at baseline, and prospectively, after 2-years of follow-up. RESEARCH DESIGN AND METHODS 616 randomly enrolled young healthy participants in the Cyprus Metabolism Study, including all 93 subjects who participated in the follow-up study 2 years after baseline assessment, were included in this study. RESULTS In the cross-sectional study, serum ALT and GGT were strongly correlated with anthropometric, cardiovascular, and metabolic variables, while serum AST was only correlated with waist circumference and waist-to-hip ratio. Fetuin-A was correlated with anthropometric variables, systolic blood pressure (SBP), insulin, and homeostasis model of assessment-insulin resistance (HOMA-IR) in the unadjusted model. In the fully adjusted model, both serum ALT and GGT levels remained positively correlated with total and low-density lipoprotein (LDL) cholesterol. GGT levels also remained correlated with triglycerides. ALT levels remained strongly positively correlated with insulin (r=0.17, p<.0001) and HOMA-IR (r=0.16, p=0.0001). Serum fetuin-A levels were no longer significantly correlated with any variables. Prospectively, ALT and GGT were predictors of anthropometric variables and LDL cholesterol, while baseline levels of AST and fetuin-A were not predictors of any variables at 2-year follow-up. CONCLUSIONS We confirmed associations of ALT and GGT levels but failed to demonstrate an independent association between fetuin-A and cardiometabolic risk factors in young healthy men. Traditional liver tests (LFTs) are thus better than fetuin-A predictors of metabolic risk factors cross-sectionally and prospectively in young healthy adults.
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Affiliation(s)
- Xiaowen Liu
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
| | - Ole-Petter R Hamnvik
- Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - John P Chamberland
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Section of Endocrinology, Boston VA Healthcare System, Boston, MA
| | - Michael Petrou
- Cyprus International Institute for Environmental and Public Health in association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus
| | - Huizhi Gong
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
| | - Costas A Christophi
- Cyprus International Institute for Environmental and Public Health in association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus; Department of Environmental Health, Harvard School of Public Health, Boston, MA
| | - David C Christiani
- Department of Environmental Health, Harvard School of Public Health, Boston, MA
| | - Stefanos N Kales
- Department of Environmental Health, Harvard School of Public Health, Boston, MA.
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Environmental Health, Harvard School of Public Health, Boston, MA; Section of Endocrinology, Boston VA Healthcare System, Boston, MA
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Ahn HR, Shin MH, Nam HS, Park KS, Lee YH, Jeong SK, Choi JS, Kweon SS. The association between liver enzymes and risk of type 2 diabetes: the Namwon study. Diabetol Metab Syndr 2014; 6:14. [PMID: 24502834 PMCID: PMC3918101 DOI: 10.1186/1758-5996-6-14] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Accepted: 02/04/2014] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND We examined the association between liver enzymes and development of type 2 diabetes in a general Korean population. METHODS A total of 10,667 subjects (4,201 males and 6,466 females) aged 45 to 74 years participated in a baseline examination between 2004 and 2007. Among the subjects, 8,157 (3,231 males and 4,926 females) underwent follow-up examination from 2007 to 2011, for a median follow-up period of 4.2 years. Type 2 diabetes was defined as intake of anti-diabetic agents, insulin treatment, fasting glucose concentration of more than 126 mg/dl, or hemoglobin A1c of more than 6.5% at re-examination. Associations of liver enzymes with incidence of type 2 diabetes were analyzed using logistic regression models. RESULTS During the follow-up period, 548 subjects (235 males, 313 females) developed type 2 diabetes. After adjusting for comprehensive diabetes risk factor, the risk of type 2 diabetes was significantly higher in the highest alanine aminotransferase (ALT) quartile than in the lowest quartile (odds ratio (OR): 1.95, 95% confidence interval (CI): 1.18-3.21 in males; OR: 1.49, 95% CI: 1.03-2.16 in females). Similar results were observed for gamma-glutamyltransferase (GGT) quartiles, but in the fully adjusted analysis, the OR for the highest versus lowest quartiles was significant only for females (OR: 1.58, 95% CI: 0.95-2.63 in males; OR: 1.85, 95% CI: 1.23-2.79 in females). CONCLUSIONS Our results suggest that serum ALT concentrations were independently associated with type 2 diabetes in both sexes, and that GGT was also independently associated but only in females.
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Affiliation(s)
- Hye-Ran Ahn
- Department of Preventive Medicine, Chonnam National University Medical School, 5, Hak-dong, Dong-gu, Gwangju 501-746, Korea
| | - Min-Ho Shin
- Department of Preventive Medicine, Chonnam National University Medical School, 5, Hak-dong, Dong-gu, Gwangju 501-746, Korea
| | - Hae-Sung Nam
- Department of Preventive Medicine and Public Health, School of Medicine, Chungnam National University, Daejun, Korea
| | - Kyeong-Soo Park
- Department of Preventive Medicine, College of Medicine, Seonam University, Namwon, Korea
| | - Young-Hoon Lee
- Department of Preventive Medicine & Institute of Wonkwang Medical Science, Wonkwang University school of Medicine, Iksan, Korea
| | - Seul-Ki Jeong
- Department of Neurology & Research Institute of Clinical Medicine, Chonbuk National University Medical School & Chonbuk National University Hospital, Jeonju, Korea
| | - Jin-Su Choi
- Department of Preventive Medicine, Chonnam National University Medical School, 5, Hak-dong, Dong-gu, Gwangju 501-746, Korea
| | - Sun-Seog Kweon
- Department of Preventive Medicine, Chonnam National University Medical School, 5, Hak-dong, Dong-gu, Gwangju 501-746, Korea
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Kunutsor SK, Abbasi A, Apekey TA. Aspartate aminotransferase - risk marker for type-2 diabetes mellitus or red herring? Front Endocrinol (Lausanne) 2014; 5:189. [PMID: 25408682 PMCID: PMC4219379 DOI: 10.3389/fendo.2014.00189] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Accepted: 10/17/2014] [Indexed: 12/17/2022] Open
Affiliation(s)
- Setor K. Kunutsor
- Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- *Correspondence:
| | - Ali Abbasi
- MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge Biomedical Campus, University of Cambridge School of Clinical Medicine, Cambridge, UK
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Tanefa A. Apekey
- Sport, Health and Nutrition Department, Leeds Trinity University, Leeds, UK
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Schneider ALC, Lazo M, Ndumele CE, Pankow JS, Coresh J, Clark JM, Selvin E. Liver enzymes, race, gender and diabetes risk: the Atherosclerosis Risk in Communities (ARIC) Study. Diabet Med 2013; 30:926-33. [PMID: 23510198 PMCID: PMC3715563 DOI: 10.1111/dme.12187] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/14/2013] [Indexed: 01/01/2023]
Abstract
AIMS To examine the associations of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase(AST), and gamma-glutamyl transferase (GGT) with diabetes risk and to determine whether associations differ by race and/or gender. We hypothesized that all liver enzymes would be associated with diabetes risk and that associations would differ by race and gender. METHODS Prospective cohort of 7495 white and 1842 black participants without diabetes in the Atherosclerosis Risk in Communities Study. Poisson and Cox models adjusted for demographic, socio-behavioural, and metabolic and health-related factors were used. RESULTS During a median of 12 years of follow-up, 2182 incident cases of diabetes occurred. Higher liver enzyme levels were independently associated with diabetes risk: adjusted hazard ratios (95% confidence intervals) were 1.68 (1.49-1.89), 1.16 (1.02-1.31) and 1.95 (1.70-2.24) comparing the highest with the lowest quartiles of ALT, AST, and GGT, respectively. Gamma-Glutamyl transferase was most strongly related to diabetes risk, even at levels considered within the normal range (≤ 60 U/l) in clinical practice. Adjusted incidence rates by quartiles of liver enzymes were similar by gender but higher in black versus white participants. Nonetheless, relative associations of ALT, AST, and GGT with diabetes were similar by race (P for interactions > 0.05). CONCLUSIONS Compared with ALT and AST, GGT was more strongly associated with diabetes risk. Our findings suggest that abnormalities in liver enzymes precede the diagnosis of diabetes by many years and that individuals with elevated liver enzymes, even within the normal range as defined in clinical practice, are at high risk for diabetes.
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Affiliation(s)
- A L C Schneider
- Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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Kunutsor SK, Apekey TA, Walley J. Liver aminotransferases and risk of incident type 2 diabetes: a systematic review and meta-analysis. Am J Epidemiol 2013; 178:159-71. [PMID: 23729682 DOI: 10.1093/aje/kws469] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
We evaluated the associations of liver aminotransferases with risk of type 2 diabetes (T2D) in general populations by conducting a systematic review and meta-analysis of published prospective studies. Studies were identified in a literature search of PubMed, EMBASE, and Web of Science from 1950 through October 2012. Of the 2,729 studies reviewed, 17 studies involving 60,359 participants and 3,890 incident T2D events were included. All of the studies assessed associations between alanine aminotransferase (ALT) level and T2D, with heterogeneous findings (I(2) = 88%, 95% confidence interval (CI): 82, 92; P < 0.001). The pooled fully adjusted relative risk of T2D was 1.26 (95% CI: 1.14, 1.41) per 1-standard-deviation change in log baseline ALT level. This association became nonsignificant after trim-and-fill correction for publication bias. Nine studies evaluated associations between aspartate aminotransferase (AST) levels and T2D risk, with a corresponding relative risk of 1.02 (95% CI: 0.99, 1.04). The relative risk of T2D per 5-IU/L increase in ALT level was 1.16 (95% CI: 1.08, 1.25). Available data indicate moderate associations of ALT with risk of T2D events, which may be attributable to publication bias. There was no evidence for an increased risk of T2D with AST. Large prospective studies may still be needed to establish the magnitude and nature of these associations.
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Affiliation(s)
- Setor K Kunutsor
- Strangeways Research Laboratory, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge,Worts Causeway, Cambridge CB1 8RN, UK.
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Lee JH, Um MH, Park YK. The Association of Metabolic Syndrome and Serum γ-Glutamyl Transpeptidase: A 4-Year Cohort Study of 3,698 Korean Male Workers. Clin Nutr Res 2013; 2:67-75. [PMID: 23429457 PMCID: PMC3572816 DOI: 10.7762/cnr.2013.2.1.67] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 01/01/2013] [Accepted: 01/06/2013] [Indexed: 01/14/2023] Open
Abstract
The aim of the present study was to examine the causal-effect of baseline (year 2004) serum γ-glutamyl transpeptidase (GGT) level with the prevalence of metabolic syndrome (MS) in year 2008. The study was comprised of male workers who underwent a regular health check-up in 2004 and 2008. MS was diagnosed according to the American Association of Clinical Endocrinologists (AACE) criteria. In the subgroup analysis according to serum GGT level, triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) showed a significant increasing tendency (p < 0.001). In addition, unexpectedly results were consistent in non-drinkers (p < 0.001). GGT level was significantly associated with risk factors of MS (waist circumference [WC]: r = 0.18, p < 0.001; fasting blood glucose [FBG]: r = 0.16, p < 0.001; TG: r = 0.29, p < 0.001). As the secondary biomarker, homeostasis model assessment of insulin sensitivity (HOMA-S) and TC had significant correlations with GGT level (HOMA-S: r = -0.14, p < 0.001; TC: r = 0.21, p < 0.001). In the 4-year prospective analysis, the predictive effect of baseline GGT concentrations on change in MS status was evaluated using Cox proportional model. Elevated GGT concentrations measured in 2004 were associated with the risk of MS incidence after 4 years (GGT: HR 1.7 [95% CI: 1.2-2.3]) (p < 0.01). This observation indicates that an elevated GGT level could be suggested as a subsidiary marker for MS and partially reflects dyslipidemia as a component of MS.
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Affiliation(s)
- Jung Hyun Lee
- Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-791, Korea
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Suh YJ, Park SK, Choi JM, Ryoo JH. The clinical importance of serum γ-glutamyltransferase level as an early predictor of obesity development in Korean men. Atherosclerosis 2013; 227:437-41. [PMID: 23395520 DOI: 10.1016/j.atherosclerosis.2013.01.029] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2012] [Revised: 01/11/2013] [Accepted: 01/20/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVE Serum γ-glutamyl transferase (GGT) levels are known to be positively associated with obesity. We aimed at verifying an association between baseline GGT levels and the development of obesity in Korean men. PATIENTS AND METHODS This prospective cohort study was performed on 18,510 initially non-obese Korean men. The total follow-up period was 66,993.3 person years and the average follow-up period was 3.62 years (standard deviation [SD], 1.44). Cox proportional hazards model was used to determine hazard ratios for the risk of obesity development. RESULTS We found a strong positive association between serum GGT levels at baseline and obesity development, after adjusting for multiple covariates. The risk of obesity development was found to be significantly and dose-dependently associated with serum GGT level. Moreover, estimated hazard ratios for severe obesity (BMI (body mass index) ≥30 kg/m(2)) attributable to serum GGT levels were much higher than those for obesity (BMI ≥ 25 kg/m(2)). The significant association was also found for WC (waist circumference)-defined obesity (WC > 90 cm). CONCLUSIONS Our findings, which were obtained from a large cohort, indicate that serum GGT is an early predictor of obesity development. Furthermore, this association was remained significant after adjusting for multiple baseline covariates.
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Affiliation(s)
- Young Ju Suh
- Institute of Clinical Research, School of Medicine, Inha University, Incheon, Republic of Korea
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Wang CS, Chang TT, Yao WJ, Wang ST, Chou P. Impact of increasing alanine aminotransferase levels within normal range on incident diabetes. J Formos Med Assoc 2012; 111:201-8. [DOI: 10.1016/j.jfma.2011.04.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2010] [Revised: 04/13/2011] [Accepted: 04/15/2011] [Indexed: 10/28/2022] Open
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Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2011; 43:617-49. [PMID: 21039302 DOI: 10.3109/07853890.2010.518623] [Citation(s) in RCA: 909] [Impact Index Per Article: 64.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND. NAFLD ranges from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). The natural history of NAFLD and the optimal strategy to identify subjects with progressive liver disease are unclear. Objectives. To assess the evidence in: (1) natural history of NAFLD; and (2) non-invasive methods to differentiate NAFLD histological subtypes. DESIGN AND SETTING. Among 4185 articles published on MEDLINE, Cochrane Library, EMBASE, Pubmed, national and International meeting abstracts through July 2010, 40 articles assessing the natural history of NAFLD and 32 articles evaluating the diagnostic accuracy of non-invasive tests against liver biopsy (LB) were included. MEASUREMENTS. Two reviewers retrieved articles and evaluated study quality by appropriate scores. Main outcomes were pooled using random- or fixed-effects models. RESULTS. NAFLD has an increased overall mortality (OR: 1.57, 95% CI: 1.18-2.10), deriving from liver-related and cardiovascular disease, and a 2-fold risk of diabetes. Compared to SS, NASH has a higher liver-related (OR for NASH: 5.71, 2.31-14.13; OR for NASH with advanced fibrosis: 10.06, 4.35-23.25), but not cardiovascular mortality (OR: 0.91, 0.42-1.98). Three non-invasive methods received independent validation: pooled AUROC, sensitivity and specificity of cytokeratin-18 for NASH are 0.82 (0.78-0.88), 0.78 (0.64-0.92), 0.87 (0.77-0.98). For NASH with advanced fibrosis, pooled AUROC, sensitivity and specificity of NAFLD fibrosis score and Fibroscan are 0.85 (0.80-0.93), 0.90 (0.82-0.99), 0.97 (0.94-0.99) and 0.94 (0.90-0.99), 0.94 (0.88-0.99) and 0.95 (0.89-0.99). CONCLUSIONS. NAFLD warrants screening for cardio-metabolic risk and for progressive liver disease. The combination of three noninvasive tests with LB may optimally individuate patients with NASH, with or without advanced fibrosis.
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Abstract
Based on the "lipotoxic" hypothesis, the free fatty acid flux from the excessive amount of adipose tissue toward the peripheral tissues would induce the development of insulin resistance especially when the triglyceride storage or the concentration of intermediate fat metabolites (diacylglycerides, ceramides) within the cytoplasm of these cells become excessive. Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis and advanced fibrosis. NAFLD is associated with general and intra-abdominal obesity and with a reduced ability of insulin to stimulate metabolic pathways in the liver itself and in other tissues. There are animal models and models in human diseases sustaining the hypothesis that a primary hepatic disease may determine the development of type 2 diabetes (T2DM). Epidemiologic data generated on surrogate markers of NAFLD (transaminases and γ-glutamyltransferase), semiquantitative assessment of fatty liver (ultrasound), and surrogate algorithms of NAFLD also support a causative effect of NAFLD on the risk to develop T2DM. In spite of the presence of these indirect associations, a clear-cut link between NAFLD and abnormal β-cell function is yet to be reported. Therefore, more data are warranted to prove what is considered a likely causative relationship between NAFLD and T2DM.
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Affiliation(s)
- Guido Lattuada
- Department of Sport, Nutrition and Health, Università degli Studi di Milano, via Kramer 4/A, 20129 Milan, Italy
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Villegas R, Xiang YB, Elasy T, Cai Q, Xu W, Li H, Fazio S, Linton MF, Raiford D, Zheng W, Shu XO. Liver enzymes, type 2 diabetes, and metabolic syndrome in middle-aged, urban Chinese men. Metab Syndr Relat Disord 2011; 9:305-11. [PMID: 21495862 DOI: 10.1089/met.2011.0016] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND We examined associations between elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with physical activity and obesity measures in middle-aged urban Chinese men. The associations between elevated aminotransferases with impaired fasting glucose, newly diagnosed type 2 diabetes (T2D), and metabolic syndrome were also evaluated in this population. METHODS The study included 3,978 urban Chinese men 40-74 years of age from a population-based cohort study, the Shanghai Men's Health Study, who were free of T2D at baseline and had provided fasting blood samples. Elevated AST and ALT levels were defined as >40 U/L. Anthropometric measurements and information on lifestyle factors and disease history were collected by in-person interviews. RESULTS A total of 11.13% and 5.85% study participants had elevated serum ALT and AST levels, respectively. Both body mass index (BMI) and waist-to-hip ratio (WHR) were positively associated with elevated ALT and AST. We found stronger associations between ALT and BMI/WHR than between AST and BMI/WHR. Physical activity was inversely associated with ALT and AST, but the association was attenuated after adjustment for BMI and WHR. Elevated serum aminotransferase levels were associated with T2D and metabolic syndrome. CONCLUSIONS In this representative sample of middle-aged Chinese men, elevated ALT and AST were associated with a prevalence of metabolic syndrome and T2D. These findings suggest that the relationship between obesity and T2D might involve liver injury. Physical activity might reduce the levels of ALT and AST, probably mediated through weight reduction.
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Affiliation(s)
- Raquel Villegas
- Department of Medicine, Vanderbilt Epidemiology Center, Nashville, Tennessee, USA.
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Berisha SZ, Serre D, Schauer P, Kashyap SR, Smith JD. Changes in whole blood gene expression in obese subjects with type 2 diabetes following bariatric surgery: a pilot study. PLoS One 2011; 6:e16729. [PMID: 21423737 PMCID: PMC3053356 DOI: 10.1371/journal.pone.0016729] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2010] [Accepted: 01/11/2011] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND A pilot study was performed in order to investigate the effects of bariatric surgery on whole blood gene expression profiles in obese subjects with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS Whole blood from eleven obese subjects with type 2 diabetes was collected in PAXgene tubes prior to and 6-12 months after bariatric surgery. Total RNA was isolated, amplified, labeled and hybridized to Illumina gene expression microarrays. Clinical and expression data were analyzed using a paired t-test, and correlations between changes in clinical trait and transcript levels were calculated. Pathways were identified using Ingenuity Pathway Analysis and DAVID gene ontology software. Overall, bariatric surgery resulted in significant reduction of body mass index, fasting plasma glucose, fasting plasma insulin, and normalization of glycosylated hemoglobin levels. The expression levels of 204 transcripts, representing 200 unique genes, were significantly altered after bariatric surgery. Among the significantly regulated genes were GGT1, CAMP, DEFA1, LCN2, TP53, PDSS1, OLR1, CNTNAP5, DHCR24, HHAT and SARDH, which have been previously implicated in lipid metabolism, obesity and/or type 2 diabetes. Selected findings were replicated by quantitative real-time-PCR. The changes in expression of seven transcripts, WDR35, FLF45244, DHCR24, TIGD7, TOPBP1, TSHZ1, and FAM8A1 were strongly correlated with the changes in body weight, fasting plasma glucose and glycosylated hemoglobin content. The top pathways associated with gene expression changes after bariatric surgery was lipid metabolism, small molecule biochemistry and gene expression. Two antimicrobial peptides were among the transcripts with the largest changes in gene expression after bariatric surgery. CONCLUSIONS/SIGNIFICANCE Data from this pilot study suggest that whole blood expression levels of specific transcripts may be useful as biomarkers associated with susceptibility for type 2 diabetes and/or therapeutic response.
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Affiliation(s)
- Stela Z. Berisha
- Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
- Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio, United States of America
| | - David Serre
- Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States of America
| | - Philip Schauer
- Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
| | - Sangeeta R. Kashyap
- Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, Cleveland, Ohio, United States of America
| | - Jonathan D. Smith
- Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States of America
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Forbes S, Taylor-Robinson SD, Patel N, Allan P, Walker BR, Johnston DG. Increased prevalence of non-alcoholic fatty liver disease in European women with a history of gestational diabetes. Diabetologia 2011; 54:641-7. [PMID: 21153530 DOI: 10.1007/s00125-010-2009-0] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2010] [Accepted: 11/12/2010] [Indexed: 12/22/2022]
Abstract
AIMS/HYPOTHESIS Non-alcoholic fatty liver disease (NAFLD) is common in type 2 diabetes but it is unknown whether NAFLD is prevalent in European women at risk of type 2 diabetes. We studied the prevalence of, and risk factors for, NAFLD in European women with previous gestational diabetes (GDM) at high risk of type 2 diabetes. METHODS A total of 110 women with previous GDM and 113 without previous GDM, with non-diabetic glucose tolerance were recruited retrospectively from antenatal databases. Participants underwent liver ultrasound scan examination, anthropometry and blood sampling for liver function tests and to determine levels of fasting lipids, NEFA and insulin and glucose concentrations in order to derive insulin sensitivity and insulin secretion indices (HOMA%S and HOMA%B, respectively). RESULTS There was no significant difference in BMI in women with previous GDM compared with those without previous GDM (28.9 ± 0.6 vs. 27.9 ± 0.6 kg/m(2), respectively; p = 0.12). Women with previous GDM had higher fasting and 2 h glucose concentrations following a 75 g OGTT ([mean ± SEM] fasting glucose 5.3 ± 0.1 vs. 5.1 ± 0.1 mmol/l, p = 0.02; 2 h glucose 6.8 ± 0.2 vs. 5.8 ± 0.3 mmol/l, p = 0.02), dyslipidaemia (LDL-cholesterol 3.3 ± 0.1 vs. 2.8 ± 0.1 mmol/l; HDL-cholesterol [median {interquartile range}] 1.3 [1.2-1.6] vs. 1.8 [1.5-1.9] mmol/l; triacylglycerol 1.3 [0.9-1.6] vs. 1.0 [0.7-1.7] mmol/l, all p ≤ 0.03), higher insulin secretion and lower insulin sensitivity. NAFLD prevalence was greater in women with previous GDM compared with those without previous GDM: 38% (95% CI 28-47%) vs. 17% (95% CI 10-24%), p = 0.001. In multiple logistic regression analysis, lower insulin sensitivity and raised serum alanine transaminase concentrations were associated with NAFLD. CONCLUSIONS/INTERPRETATION NAFLD is prevalent in European women with previous GDM. Impaired insulin sensitivity and increased liver transaminase activity are closely associated with NAFLD in these women.
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Affiliation(s)
- S Forbes
- Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
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C-reactive protein and gamma-glutamyltransferase concentrations in relation to the prevalence of type 2 diabetes diagnosed by glucose or HbA1c criteria in Chinese adults in Qingdao, China. EXPERIMENTAL DIABETES RESEARCH 2010; 2010:761715. [PMID: 21076541 PMCID: PMC2976070 DOI: 10.1155/2010/761715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/13/2010] [Revised: 10/12/2010] [Accepted: 10/12/2010] [Indexed: 12/30/2022]
Abstract
Aims. To investigate the association of C-reactive protein (CRP) and gamma glutamyltransferase (GGT) concentrations with newly diagnosed diabetes defined by either glucose or HbA1c criteria in Chinese adults. Methods. A population-based cross-sectional study was conducted in 2006. Data from 1167 men and 1607 women aged 35–74 years were analyzed. Diabetes was defined according to either glucose or HbA1c criteria alone. Results. Compared with nondiabetes, multivariate-adjusted OR (95%CI) was 1.13 (0.90,1.42) in men and 1.21 (1.00,1.45) in women for CRP and 1.42 (1.18,1.72) and 1.57 (1.31,1.87) for GGT, respectively. Neither CRP nor GGT was associated with the presence of diabetes defined by the HbA1c criterion. Conclusions. The effect of elevated CRP on diabetes defined by the glucose criterion was mediated through obesity, but elevated GGT was an independent risk factor for diabetes in this Chinese population. None of the two was, however, associated with the elevated HbA1c concentrations.
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Balkau B, Lange C, Vol S, Fumeron F, Bonnet F. Nine-year incident diabetes is predicted by fatty liver indices: the French D.E.S.I.R. study. BMC Gastroenterol 2010; 10:56. [PMID: 20529259 PMCID: PMC2898845 DOI: 10.1186/1471-230x-10-56] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2010] [Accepted: 06/07/2010] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Fatty liver is known to be linked with insulin resistance, alcohol intake, diabetes and obesity. Biopsy and even scan-assessed fatty liver are not always feasible in clinical practice. This report evaluates the predictive ability of two recently published markers of fatty liver: the Fatty Liver Index (FLI) and the NAFLD fatty liver score (NAFLD-FLS), for 9-year incident diabetes, in the French general-population cohort: Data from an Epidemiological Study on the Insulin Resistance syndrome (D.E.S.I.R). METHODS At baseline, there were 1861 men and 1950 women, non-diabetic, aged 30 to 65 years. Over the follow-up, 203 incident diabetes cases (140 men, 63 women) were identified by diabetes-treatment or fasting plasma glucose > or = 7.0 mmol/l. The FLI includes: BMI, waist circumference, triglycerides and gamma glutamyl transferase, and the NAFLD-FLS: the metabolic syndrome, diabetes, insulin, alanine aminotransferase, and asparate aminotransferase. Logistic regression was used to determine the odds ratios for incident diabetes associated with categories of the fatty liver indices. RESULTS In comparison to those with a FLI < 20, the age-adjusted odds ratio (95% confidence interval) for diabetes for a FLI > or = 70 was 9.33 (5.05-17.25) for men and 36.72 (17.12-78.76) for women; these were attenuated to 3.43 (1.61-7.28) and 11.05 (4.09 29.81), after adjusting on baseline glucose, insulin, hypertension, alcohol intake, physical activity, smoking and family antecedents of diabetes; odds ratios increased to 4.71 (1.68-13.16) and 22.77 (6.78-76.44) in those without an excessive alcohol intake. The NAFLD-FLS also predicted incident diabetes, but with odds ratios much lower in women, similar in men. CONCLUSIONS These fatty liver indexes are simple clinical tools for evaluating the extent of liver fat and they are predictive of incident diabetes. Physicians should screen for diabetes in patients with fatty liver.
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Affiliation(s)
- Beverley Balkau
- INSERM CESP Center for Research in Epidemiology and Population Health, Villejuif, France.
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Balkau B, Lange C, Vol S, Fumeron F, Bonnet F. Nine-year incident diabetes is predicted by fatty liver indices: the French D.E.S.I.R. study. BMC Gastroenterol 2010. [PMID: 20529259 DOI: 10.1186/1471/230x-10-56] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Fatty liver is known to be linked with insulin resistance, alcohol intake, diabetes and obesity. Biopsy and even scan-assessed fatty liver are not always feasible in clinical practice. This report evaluates the predictive ability of two recently published markers of fatty liver: the Fatty Liver Index (FLI) and the NAFLD fatty liver score (NAFLD-FLS), for 9-year incident diabetes, in the French general-population cohort: Data from an Epidemiological Study on the Insulin Resistance syndrome (D.E.S.I.R). METHODS At baseline, there were 1861 men and 1950 women, non-diabetic, aged 30 to 65 years. Over the follow-up, 203 incident diabetes cases (140 men, 63 women) were identified by diabetes-treatment or fasting plasma glucose > or = 7.0 mmol/l. The FLI includes: BMI, waist circumference, triglycerides and gamma glutamyl transferase, and the NAFLD-FLS: the metabolic syndrome, diabetes, insulin, alanine aminotransferase, and asparate aminotransferase. Logistic regression was used to determine the odds ratios for incident diabetes associated with categories of the fatty liver indices. RESULTS In comparison to those with a FLI < 20, the age-adjusted odds ratio (95% confidence interval) for diabetes for a FLI > or = 70 was 9.33 (5.05-17.25) for men and 36.72 (17.12-78.76) for women; these were attenuated to 3.43 (1.61-7.28) and 11.05 (4.09 29.81), after adjusting on baseline glucose, insulin, hypertension, alcohol intake, physical activity, smoking and family antecedents of diabetes; odds ratios increased to 4.71 (1.68-13.16) and 22.77 (6.78-76.44) in those without an excessive alcohol intake. The NAFLD-FLS also predicted incident diabetes, but with odds ratios much lower in women, similar in men. CONCLUSIONS These fatty liver indexes are simple clinical tools for evaluating the extent of liver fat and they are predictive of incident diabetes. Physicians should screen for diabetes in patients with fatty liver.
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Affiliation(s)
- Beverley Balkau
- INSERM CESP Center for Research in Epidemiology and Population Health, Villejuif, France.
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Alanine aminotransferase and γ-glutamyltransferase as markers for elevated insulin resistance-associated metabolic abnormalities in obese Japanese men younger than 30 years of age. Obes Res Clin Pract 2010; 4:e1-e82. [DOI: 10.1016/j.orcp.2009.09.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2009] [Revised: 08/30/2009] [Accepted: 09/23/2009] [Indexed: 01/14/2023]
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Jimba S, Nakagami T, Oya J, Wasada T, Endo Y, Iwamoto Y. Increase in gamma-glutamyltransferase level and development of established cardiovascular risk factors and diabetes in Japanese adults. Metab Syndr Relat Disord 2009; 7:411-8. [PMID: 19419267 DOI: 10.1089/met.2008.0082] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND We investigated the predictive value of changes in serum gamma-glutamyltransferase (GGT) for the development of cardiovascular disease (CVD) risk factors in Japanese. METHODS A total of 1514 adult participants in a general health examination program were followed for 3 years until January, 2006. The subjects were divided into two groups according to whether their serum GGT level had decreased (< or =0 U/L) or increased (> or =1 U/L) from the baseline level of GGT during the study period. The logistic regression model was used to analyze the relationship between increases in GGT levels and the incidence of diabetes (DM), impaired fasting glucose (IFG), dyslipidemia, and hypertension (HT). RESULTS The mean value of GGT level was significantly higher at baseline than the 3-year follow-up point (47 +/- 41 versus 41 +/- 51, P < 0.0001), and the average 3-year GGT change was -5.7 +/- 32.3 U/L. The subjects with an increased GGT over the 3 years had an increased risk of developing DM, IFG, high triglyceride (TG) levels, and HT, in comparison with that of the subjects with a decreased GGT level, with an odds ratios (OR) of 6.13 (95% confidence interval [CI], 2.83-13.25), 2.70 (1.68-4.34), 2.65 (1.76-3.99), and 1.54 (1.12-2.13), respectively, after adjusting for age, sex, and alcohol habits. Further adjustments for baseline GGT, alanine aminotransferase (ALT), body mass index (BMI), and 3-year changes in BMI did not alter these associations. CONCLUSIONS The increased change in GGT over 3 years was a significant and an independent risk factor for the development of high TG, HT, IFG, and DM in Japanese.
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Affiliation(s)
- Sachiyo Jimba
- Diabetes Center, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
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Fraser A, Harris R, Sattar N, Ebrahim S, Davey Smith G, Lawlor DA. Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women's Heart and Health Study and meta-analysis. Diabetes Care 2009; 32:741-50. [PMID: 19131466 PMCID: PMC2660465 DOI: 10.2337/dc08-1870] [Citation(s) in RCA: 283] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To estimate and compare associations of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) with incident diabetes. RESEARCH DESIGN AND METHODS ALT and GGT were studied as determinants of diabetes in the British Women's Heart and Health Study, a cohort of 4,286 women 60-79 years old (median follow-up 7.3 years). A systematic review and a meta-analysis of 21 prospective, population-based studies of ultrasonography, which diagnosed nonalcoholic fatty liver disease (NAFLD), ALT, and GGT as determinants of diabetes, were conducted, and associations of ALT and GGT with diabetes were compared. RESULTS Ultrasonography-diagnosed NAFLD was associated with more than a doubling in the risk of incident diabetes (three studies). ALT and GGT both predicted diabetes. The fully adjusted hazard ratio (HR) for diabetes per increase in one unit of logged ALT was 1.83 (95% CI 1.57-2.14, I(2) = 8%) and for GGT was 1.92 (1.66-2.21, I(2) = 55%). To directly compare ALT and GGT as determinants of diabetes, the fully adjusted risk of diabetes in the top versus bottom fourth of the ALT and GGT distributions was estimated using data from studies that included results for both markers. For ALT, the HR was 2.02 (1.59-2.58, I(2) = 27%), and for GGT the HR was 2.94 (1.98-3.88, I(2) = 20%), suggesting that GGT may be a better predictor (P = 0.05). CONCLUSIONS Findings are consistent with the role of liver fat in diabetes pathogenesis. GGT may be a better diabetes predictor than ALT, but additional studies with directly determined liver fat content, ALT, and GGT are needed to confirm this finding.
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Affiliation(s)
- Abigail Fraser
- Departmentof Social Medicine, Medical Research Council Centre for Causal Analysis in Translational Epidemiology, University of Bristol, Bristol, UK.
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Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology 2009; 136:477-85.e11. [PMID: 19100265 DOI: 10.1053/j.gastro.2008.10.052] [Citation(s) in RCA: 265] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2008] [Revised: 09/18/2008] [Accepted: 10/09/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Elevated serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) activities are markers of liver injury, but may also be associated with other diseases and death. In a prospective, national, population-based sample, we examined whether elevated ALT and GGT were associated with increased risk of all-cause and disease-specific mortality. METHODS Death certificate-based 12-year mortality was analyzed among 14,950 adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994, who were negative for markers of viral hepatitis B and C. Abnormal ALT was defined as >30 U/L in men or >19 U/L in women, and abnormal GGT as >51 U/L in men or >33 U/L in women. RESULTS Cumulative mortality was 13.9% from all causes, including 4.2% from cardiovascular disease, 4.2% from neoplasms, 0.44% from diabetes, and 0.13% from liver disease. In multivariate-adjusted analyses, elevated ALT was not associated with all-cause mortality (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.88-1.6). ALT elevation was associated with deaths from liver disease (HR, 8.2; 95% CI, 2.1-31.9), but not from cardiovascular disease (HR, 0.90; 95% CI, 0.56-1.4), neoplasms (HR, 1.0; 95% CI, 0.65-1.5), or diabetes (HR, 2.4; 95% CI, 0.65-9.1). All-cause mortality increased with elevated GGT (HR, 1.5; 95% CI, 1.2-1.8), as did mortality from liver disease (HR, 13.0; 95% CI, 2.4-71.5), neoplasms (HR, 1.5; 95% CI, 1.01-2.2), and diabetes (HR, 3.3; 95% CI, 1.4-7.6), but not from cardiovascular disease (HR, 1.3; 95% CI, 0.80-2.0). CONCLUSIONS In the US population, elevated GGT was associated with mortality from all causes, liver disease, cancer, and diabetes, while ALT was associated only with liver disease mortality.
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Affiliation(s)
- Constance E Ruhl
- Social & Scientific Systems, Inc, Silver Spring, Maryland 20910, USA.
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Kim CH, Park JY, Lee KU, Kim JH, Kim HK. Association of serum gamma-glutamyltransferase and alanine aminotransferase activities with risk of type 2 diabetes mellitus independent of fatty liver. Diabetes Metab Res Rev 2009; 25:64-9. [PMID: 19065605 DOI: 10.1002/dmrr.890] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Although elevated serum concentrations of gamma-glutamyltrans- ferase (GGT) or alanine aminotransferase (ALT) have been associated with type 2 diabetes mellitus, it is unclear whether each is an independent predictor of type 2 diabetes or merely a surrogate marker for fatty liver or hepatic injury. METHODS We assessed clinical and laboratory findings in 3556 non-diabetic subjects (2217 men, 1339 women; age, 45.7 +/- 8.1 (range 20-79) years) without fatty liver or clinically significant hepatic dysfunction who underwent voluntary medical check-ups at a 5-year interval. RESULTS The odds ratio of developing type 2 diabetes increased significantly with increasing GGT and ALT levels at baseline. In multiple logistic regression models adjusted for age, sex, alcohol consumption, smoking, body mass index (BMI), triglycerides, high-density lipoprotein (HDL)-cholesterol, fasting glucose, and ALT, the highest quartile of GGT remained significantly associated with type 2 diabetes. Compared with the first GGT quartile, the odds ratios of the second, third, and fourth GGT quartiles were 0.64 (95% CI, 0.25-1.65), 1.12 (0.45-2.78), and 3.07 (1.21-7.76), respectively. The adjusted odds ratios for the second, third, and fourth ALT quartiles in the same logistic regression model were 2.40 (0.83-6.94), 2.85 (1.03-7.90), and 4.31 (1.56-11.88), respectively. The risk of type 2 diabetes was additive with respect to GGT and ALT quartiles. CONCLUSIONS Increased serum GGT and ALT levels are independent, additive risk factors for the development of type 2 diabetes mellitus in subjects without fatty liver or hepatic dysfunction.
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Affiliation(s)
- Chul-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
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Balkau B, Lange C, Fezeu L, Tichet J, de Lauzon-Guillain B, Czernichow S, Fumeron F, Froguel P, Vaxillaire M, Cauchi S, Ducimetière P, Eschwège E. Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 2008; 31:2056-61. [PMID: 18689695 PMCID: PMC2551654 DOI: 10.2337/dc08-0368] [Citation(s) in RCA: 183] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To provide a simple clinical diabetes risk score and to identify characteristics that predict later diabetes using variables available in the clinic setting as well as biological variables and polymorphisms. RESEARCH DESIGN AND METHODS Incident diabetes was studied in 1,863 men and 1,954 women, 30-65 years of age at baseline, with diabetes defined by treatment or by fasting plasma glucose >or=7.0 mmol/l at 3-yearly examinations over 9 years. Sex-specific logistic regression equations were used to select variables for prediction. RESULTS A total of 140 men and 63 women developed diabetes. The predictive clinical variables were waist circumference and hypertension in both sexes, smoking in men, and diabetes in the family in women. Discrimination, as measured by the area under the receiver operating curves (AROCs), were 0.713 for men and 0.827 for women, a little higher than for the Finish Diabetes Risk (FINDRISC) score, with fewer variables in the score. Combining clinical and biological variables, the predictive equation included fasting glucose, waist circumference, smoking, and gamma-glutamyltransferase for men and fasting glucose, BMI, triglycerides, and diabetes in family for women. The number of TCF7L2 and IL6 deleterious alleles was predictive in both sexes, but after including the above clinical and biological variables, this variable was only predictive in women (P < 0.03) and the AROC statistics increased only marginally. CONCLUSIONS The best clinical predictor of diabetes is adiposity, and baseline glucose is the best biological predictor. Clinical and biological predictors differed marginally between men and women. The genetic polymorphisms added little to the prediction of diabetes.
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Affiliation(s)
- Beverley Balkau
- INSERM U780-IFR69, Villejuif, France/University Paris-Sud, Orsay, France.
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Tohidi M, Harati H, Hadaegh F, Mehrabi Y, Azizi F. Association of liver enzymes with incident type 2 diabetes: A nested case control study in an Iranian population. BMC Endocr Disord 2008; 8:5. [PMID: 18533046 PMCID: PMC2438361 DOI: 10.1186/1472-6823-8-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2007] [Accepted: 06/05/2008] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND To investigate the association of Aspartate aminotransferase (AST), Alanin aminotranferase (ALT) and Gamma glutamyl transferase (GGT) with incident type 2 diabetes. METHODS In a nested case-control study, AST, ALT, GGT as well as classic diabetes risk factors, insulin and C-reactive protein (CRP) were measured in 133 non-diabetic subjects at baseline of which 68 were cases and 65 were controls. Incident diabetes was defined by the WHO 1999 criteria. Conditional logistic regression was used to calculate the odds ratio (OR) of incident diabetes associated with different hepatic markers. We used factor analysis for clustering of classic diabetes risk factors. RESULTS In Univariate analysis both ALT and GGT were associated with diabetes with ORs of 3.07(1.21-7.79) and 2.91(1.29-6.53) respectively. After adjustment for CRP and insulin, ALT and GGT were still predictive of incident diabetes. When the model was further adjusted for anthropometric, blood pressure and metabolic factors, only ALT was independently associated with diabetes [OR = 3.18 (1.02-9.86)]. No difference was found between the area under the receiver operating characteristic curves of the models with and without ALT (0.820 and 0.802 respectively, P = 0.4) CONCLUSION ALT is associated with incident type 2 diabetes independent of classic risk factors. However, its addition to the classic risk factors does not improve the prediction of diabetes.
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Affiliation(s)
- Maryam Tohidi
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University (M.C), Tehran, Iran
| | - Hadi Harati
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University (M.C), Tehran, Iran
| | - Farzad Hadaegh
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University (M.C), Tehran, Iran
| | - Yadolladh Mehrabi
- School of Public Health, Shahid Beheshti University (M.C), Tehran, Iran
| | - Fereidoun Azizi
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University (M.C), Tehran, Iran
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Jiamjarasrangsi W, Sangwatanaroj S, Lohsoonthorn V, Lertmaharit S. Increased alanine aminotransferase level and future risk of type 2 diabetes and impaired fasting glucose among the employees in a university hospital in Thailand. DIABETES & METABOLISM 2008; 34:283-9. [DOI: 10.1016/j.diabet.2008.01.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2007] [Revised: 01/08/2008] [Accepted: 01/21/2008] [Indexed: 01/14/2023]
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