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Bang M, Fan W, Wong ND. Liver fibrosis according to diabetes status and relation to cardiovascular risk and mortality in US adults. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 46:100457. [PMID: 39386080 PMCID: PMC11462167 DOI: 10.1016/j.ahjo.2024.100457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 09/01/2024] [Accepted: 09/02/2024] [Indexed: 10/12/2024]
Abstract
Study objective Liver fibrosis is associated with increased cardiovascular disease (CVD) risk and mortality. However, it is unknown how these risks compare in those with pre-diabetes (pre-DM) or diabetes (DM). We examined the association of FIB-4 levels, an indicator of liver fibrosis, with CVD risk and mortality according to DM status. Design and setting Prospective, longitudinal cohort study. Participants We examined 13,326 U.S. adults (6.7 % with DM) with FIB-4 measures classified as low (<1.30), intermediate (1.30- < 2.67), high (2.67- < 3.25), and very high (≥3.25). National Death Index linkage provided mortality status for CVD, liver-related, and all causes over 17.5 years. Main outcomes We calculated 10-year ASCVD risk in persons without known ASCVD. Cox regression examined the relation of FIB-4 with mortality by DM status. Results High/very high FIB-4 levels were greater in those with (2.2 %) vs. without (0.4 %) DM (p < 0.0001). Higher FIB-4 scores and DM were associated with greater estimated ASCVD risks (p < 0.0001); 44.5 % of those at high /very high FIB-4 levels had ≥20 % estimated ASCVD risk. CVD mortality hazard ratios (HRs) (95 % CI) associated with high/very high FIB-4 in those with pre-DM and DM were 8.76 (3.66-20.95), and 0.89 (0.22-3.53), respectively, and for total mortality were 5.46 (3.16-9.43), and 2.07 (0.90-4.74), respectively, which were attenuated after adjustment. Conclusions Our findings indicate the need for increased efforts to identify those at risk of liver fibrosis in adults with pre-DM or DM to prevent CVD and total mortality.
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Affiliation(s)
- Matthew Bang
- Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, USA
| | - Wenjun Fan
- Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, USA
| | - Nathan D. Wong
- Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, USA
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Barati M, Teimouri A, Feizi A, Iraj B, Karimifar M. Investigation of cardiovascular risk factors in diabetic and nondiabetic patients with nonalcoholic fatty liver disease. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2024; 29:51. [PMID: 39403226 PMCID: PMC11472873 DOI: 10.4103/jrms.jrms_830_23] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/02/2024] [Accepted: 02/21/2024] [Indexed: 05/27/2025]
Abstract
BACKGROUND The current study aims to assess cardiovascular risk factors (CVRFs) among diabetic versus nondiabetic nonalcoholic fatty liver disease (NAFLD) patients. NAFLD is the most common hepatic disorder worldwide which is directly associated with diverse CVRFs such as type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS). MATERIALS AND METHODS The current cross-sectional population-based study has been conducted on 1031 NAFLD patients. After excluding 340 prediabetes patients, the NAFLD patients were divided into T2DM and normal blood glucose (NBG). Then, CVRFs were compared between the two groups. RESULTS Out of 691 NAFLD cases included in the study, 337 (48.8%) patients had T2DM. In the T2DM and NBG groups, the body mass index (BMI) was 31.2 ± 4.6 and 29.9 ± 4.3 kg/m2, respectively (P = 0.001). The waist circumference was 102.2 ± 10.2 and 97.6 ± 10.6 cm, respectively (P < 0.001). The systolic blood pressure was 123.3 ± 15.6 and 119.6 ± 13.6 mmHg, respectively (P = 0.043). The triglyceride levels were 191.9 ± 104.7 and 176.5 ± 89.6 mg/dL, respectively (P = 0.042). Generally, these factors were significantly higher among the diabetic patients. Besides, cardiovascular disease (CVD), hypertension, and MS were statistically more prevalent in NAFLD patients with T2DM (P < 0.001) than nondiabetic NAFLD patients. In multiple logistic regression models, the odds ratio of CVD, hypertension, and MS was 2.18, 2.12, and 6.63 for patients with T2DM compared with NBG, respectively. Adjustment was made for age, sex, BMI, smoking, and physical activity. CONCLUSION CVRFs were higher in NAFLD patients with T2DM than NAFLD patients with NBG.
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Affiliation(s)
- Mona Barati
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azam Teimouri
- Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Awat Feizi
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Bijan Iraj
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mozhgan Karimifar
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Cao L, An Y, Liu H, Jiang J, Liu W, Zhou Y, Shi M, Dai W, Lv Y, Zhao Y, Lu Y, Chen L, Xia Y. Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis. BMC Med 2024; 22:101. [PMID: 38448943 PMCID: PMC10919055 DOI: 10.1186/s12916-024-03315-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 02/23/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.
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Affiliation(s)
- Limin Cao
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Yu An
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Huiyuan Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Jinguo Jiang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Wenqi Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yuhan Zhou
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Mengyuan Shi
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Wei Dai
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yanling Lv
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yuhong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yanhui Lu
- School of Nursing, Peking University, 38 Xueyuan Rd, Haidian District, Beijing, 100191, China.
| | - Liangkai Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Yang Xia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China.
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China.
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Gignac T, Trépanier G, Paquet V, Ferland S, Carreau AM. Glycated Hemoglobin Is Suboptimal for the Screening of Prediabetes and Type 2 Diabetes in Adults With Nonalcoholic Fatty Liver Disease. Can J Diabetes 2023; 47:603-610. [PMID: 37352972 DOI: 10.1016/j.jcjd.2023.06.002] [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: 12/20/2022] [Revised: 05/01/2023] [Accepted: 06/08/2023] [Indexed: 06/25/2023]
Abstract
OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D), but T2D screening tests are not well validated in this population. In this study, we assessed performance of glycated hemoglobin (A1C) and fasting plasma glucose (FPG) in glucose dysmetabolism screening and aimed to optimize detection thresholds for individuals with NAFLD. METHODS We retrospectively included oral glucose tolerance tests (OGTTs) from consecutive patients undergoing a specialized clinic for NAFLD, if A1C and/or fasting glucose was available within 3 months of OGTT. We compared performances of A1C and fasting glucose with the "gold standard" of OGTT using thresholds from the 2018 Diabetes Canada guidelines. A1C and FPG thresholds were optimized for detection of glucose dysmetabolism using receiver operating characteristic curves. RESULTS We included 63 OGTTs from individuals with NAFLD (52% female, age 48 [interquartile range 35 to 63] years, body mass index 34 [interquartile range 29 to 40] kg/m2). A1C had 16% (95% confidence interval [CI] 6% to 38%) sensitivity (Se) and 97% (95% CI 85% to 100%) specificity (Sp) for T2D detection, and 45% (95% CI 30% to 62%) Se and 100% (95% CI 83% to 100%) Sp for abnormal blood glucose detection. FPG had 67% (95% CI 45% to 83%) Se and 100% (95% CI 92% to 100%) Sp for T2D detection, and 74% (95% CI 59% to 85%) Se and 92% (95% CI 74% to 99%) Sp for abnormal blood glucose detection. Optimal A1C and FPG thresholds were 5.6% and 6.3 mmol/L for T2D detection, which are lower than current recommendations. CONCLUSIONS A1C is less sensitive than FPG and is suboptimal for T2D detection, suggesting that OGTT may be obtained if A1C is ≥5.6% or FPG is ≥6.3 mmol/L in individuals with NAFLD, to avoid underdiagnosis and treatment inertia.
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Affiliation(s)
- Théo Gignac
- Endocrinology/Nephrology Axis, Centre de Recherche du CHU de Québec-Université Laval, Québec City, Québec, Canada
| | - Gabrielle Trépanier
- Endocrinology/Nephrology Axis, Centre de Recherche du CHU de Québec-Université Laval, Québec City, Québec, Canada
| | - Véronique Paquet
- Endocrinology/Nephrology Axis, Centre de Recherche du CHU de Québec-Université Laval, Québec City, Québec, Canada; Division of Endocrinology, Department of Medicine, Centre Hospitalier Universitaire de Quebec, Université Laval, Québec City, Québec, Canada
| | - Stéphanie Ferland
- Endocrinology/Nephrology Axis, Centre de Recherche du CHU de Québec-Université Laval, Québec City, Québec, Canada; Division of Endocrinology, Department of Medicine, Centre Hospitalier Universitaire de Quebec, Université Laval, Québec City, Québec, Canada; Division of Gastroenterology, Department of Medicine, Centre Hospitalier Universitaire de Québec, Université Laval, Québec City, Québec, Canada
| | - Anne-Marie Carreau
- Endocrinology/Nephrology Axis, Centre de Recherche du CHU de Québec-Université Laval, Québec City, Québec, Canada; Division of Endocrinology, Department of Medicine, Centre Hospitalier Universitaire de Quebec, Université Laval, Québec City, Québec, Canada.
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Yip TCF, Wong GLH, Wong VWS, Goh GBB, Chan WK. Nonalcoholic Fatty Liver Disease: A Unique Entity or Part of the Metabolic Syndrome or Both. Med Clin North Am 2023; 107:449-463. [PMID: 37001947 DOI: 10.1016/j.mcna.2022.12.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. NAFLD is bidirectionally correlated with metabolic syndrome, which includes obesity, type 2 diabetes, hypertension, and dyslipidemia as major components. The presence of metabolic syndrome is associated with a higher prevalence of NAFLD, and vice versa. Also, the presence of metabolic syndrome in patients with NAFLD has been linked to a higher risk of cardiovascular diseases, liver-related complications, extrahepatic malignancies, and mortality, and possibly vice versa. Multidisciplinary care pathways including lifestyle modifications, control of metabolic risk, and potentially beneficial treatments are important to improve the clinical outcomes of patients with NAFLD.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - George Boon-Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, 20 College Road, Academia, Singapore 169856; Duke-NUS Medical School, Singapore.
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
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Liu Y, Liu L. Changes in the Epidemiology of Hepatocellular Carcinoma in Asia. Cancers (Basel) 2022; 14:cancers14184473. [PMID: 36139633 PMCID: PMC9496757 DOI: 10.3390/cancers14184473] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/09/2022] [Accepted: 09/13/2022] [Indexed: 11/23/2022] Open
Abstract
Simple Summary The incidence and mortality of hepatocellular carcinoma (HCC) in Asia are among the world leaders. By understanding the changes in prevalence and influencing factors of HCC, we can better understand the current situation in Asia and take measures to reduce the incidence. Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high morbidity and mortality, and the incidence is on the rise. HCC imposes a heavy healthcare burden on Asian countries due to the presence of multiple HCC risk factors in this area. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, non-alcoholic liver disease (NAFLD), aflatoxin and alcohol intake are the causes of HCC that cannot be ignored. Compared with the pre-vaccination era, universal vaccination of newborns reduces the incidence of HCC. Anti-viral therapy with nucleos(t)ide analogues also causes a decline in HCC incidence. Early screening and direct-acting antiviral agent are beneficial to the prevention and treatment of HCV. For HCC caused by NAFLD and other reasons, lifestyle changes are imperative. This paper introduces the epidemiological trends of HCC in Asia and highlight future efforts. Focusing on prevention may be the most effective way to improve the prognosis of this hard-to-treat cancer.
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Affiliation(s)
- Yao Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China
- Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China
- Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China
- Correspondence:
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Park J, Kwon HJ, Sohn W, Cho JY, Park SJ, Chang Y, Ryu S, Kim BI, Cho YK. Risk of liver fibrosis in patients with prediabetes and diabetes mellitus. PLoS One 2022; 17:e0269070. [PMID: 35653399 PMCID: PMC9162349 DOI: 10.1371/journal.pone.0269070] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/13/2022] [Indexed: 11/18/2022] Open
Abstract
The aim of this study was to assess the risk of liver fibrosis in those with no glucose intolerance, prediabetes, or diabetes. A cross-sectional study was conducted based on a cohort from a health examination program which included a magnetic resonance elastography (MRE). Participants were classified into three groups according to glucose tolerance: no glucose intolerance, prediabetes, and diabetes mellitus. Liver fibrosis was evaluated by liver stiffness measurement (LSM) value using two-dimensional real-time MRE. The risk of significant liver fibrosis was compared among three groups. A total of 2,090 subjects were included: no glucose intolerance (n = 889); prediabetes (n = 985); and diabetes (n = 216). Mean values of LSM in those with no glucose intolerance, prediabetes, and diabetes were 2.37 ± 0.43 kPa, 2.41 ± 0.34 kPa, and 2.65 ± 0.70 kPa, respectively (p<0.001). Proportions of significant fibrosis (LSM ≥2.97 kPa) in no glucose intolerance, prediabetes, and diabetes groups were 3.1%, 4.4%, and 16.7%, respectively (p<0.001). Compared with those with no glucose intolerance, those with diabetes had higher risk of significant fibrosis (adjusted odds ratio [aOR]: 3.02, 95% confidence interval [CI]: 1.57–5.81, p<0.001). However, there was no difference between prediabetes and no glucose intolerance (aOR: 1.05, 95% CI: 0.59–1.86, p = 0.876). A subgroup analysis also showed that prediabetes, unlike diabetes, was not associated with significant fibrosis in subjects with or without liver disease. Diabetes, but not prediabetes, is a risk factor for significant liver fibrosis. This finding is consistent regarldess of the pressence of liver disease.
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Affiliation(s)
- Jongsin Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Heon-Ju Kwon
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- * E-mail:
| | - Ju-Yeon Cho
- Department of Internal Medicine, Chosun University Hospital, Gwang-Ju, Republic of Korea
| | - Soo Jin Park
- Department of Surgery, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - Byung Ik Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yong Kyun Cho
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Zheng YT, Xiao TM, Wu CX, Cheng JY, Li LY. Correlation of Adiponectin Gene Polymorphisms rs266729 and rs3774261 With Risk of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2022; 13:798417. [PMID: 35399941 PMCID: PMC8983824 DOI: 10.3389/fendo.2022.798417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 02/22/2022] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Increasing evidence has suggested an association of adiponectin gene polymorphisms rs1501299, rs2241766, rs266729 and rs3774261 with risk of nonalcoholic fatty liver disease (NAFLD). This correlation has been extensively meta-analyzed for the first two polymorphisms, but not the second two. METHODS The PubMed, EMBASE, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant literature. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS A total of 10 case-control studies on rs266729 (2,619 cases and 1,962 controls) and 3 case-control studies on rs3774261 (562 cases and 793 controls) were included. Meta-analysis showed that rs266729 was associated with significantly higher NAFLD risk based on the following five models: allelic, OR 1.72, 95% CI 1.34-2.21, P < 0.001; recessive, OR 2.35, 95% CI 1.86-2.95, P < 0.001; dominant, OR 1.84, 95% CI 1.34-2.53, P < 0.001; homozygous, OR 2.69, 95% CI 1.84-3.92, P < 0.001; and heterozygous, OR 1.72, 95% CI 1.28-2.32, P < 0.001. This association between rs266729 and NAFLD risk remained significant for all five models among studies with Asian, Chinese and Caucasian samples. The rs2241766 polymorphism was associated with significantly higher NAFLD risk according to the recessive model (OR 1.87, 95% CI 1.15-3.04, P = 0.01). CONCLUSION Polymorphisms rs266729 and rs3774261 in the adiponectin gene may be risk factors for NAFLD. These findings may pave the way for novel therapeutic strategies, but they should be verified in large, well-designed studies.
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Busquets-Cortés C, Bennasar-Veny M, López-González AA, Fresneda S, Aguiló A, Yanez A. Fatty liver index and progression to type 2 diabetes: a 5-year longitudinal study in Spanish workers with pre-diabetes. BMJ Open 2021; 11:e045498. [PMID: 34433590 PMCID: PMC8388308 DOI: 10.1136/bmjopen-2020-045498] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE The main aim of the study was to evaluate the association between non-alcoholic fatty liver disease (NAFLD), estimated by fatty liver index (FLI), and the development of type 2 diabetes (T2D) in a large cohort of adult workers with pre-diabetes. DESIGN Prospective cohort study. SETTING Occupational health services from Spain. PARTICIPANTS 16 648 adult workers (aged 20-65 years) with pre-diabetes (fasting plasma glucose (FPG) of 100-125 mg/dL). OUTCOME AND MEASURES FLI was calculated based on measurements of triglycerides, body mass index, waist circumference and γ-glutamyltransferase. The population was classified into three categories: FLI<30 (no hepatic steatosis), FLI 30-60 (intermediate status) and FLI>60 (hepatic steatosis). Sociodemographic, anthropometric, dietary habits, physical activity and clinical data were collected from all subjects. The incidence rate of T2D was determined after 5 years of follow-up. RESULTS After 5 years of follow-up, 3706 of the 16 648 participants (22.2%) were diagnosed with T2D, corresponding to an annual rate of progression of 4.5%. FLI was strongly associated with T2D conversion. The incidence rates of T2D in the FLI<30, FLI 30-60 and FLI>60 groups were significantly different after 5 years of follow-up were 19/6,421 (0.3%), 338/4,318 (7.8%) and 3,349/5,909 (56.7%), respectively. This association remained significant for FLI>60 after adjustment for, age, diet, physical activity, FPG, blood pressure, social class and smoking habits (adjusted HR=6.879; 95% CI 5.873 to 8.057 for men, and HR=5.806; 95% CI 4.863 to 6.932 for women). CONCLUSION NAFLD assessed by FLI independently predicted the risk of conversion to T2D among people with pre-diabetes. FLI may be an easily determined and valuable early predictor for T2D in people with pre-diabetes. FLI-based assessment of NAFLD in subjects with pre-diabetes in routine clinical practice could allow the adoption of effective measures to prevent and reduce their progression to T2D.
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Affiliation(s)
- Carla Busquets-Cortés
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Escuela Universitaria ADEMA, Palma, Illes Balears, Spain
| | - Miquel Bennasar-Veny
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Global Health and Lifestyles research group, Insitut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Angel-Arturo López-González
- Escuela Universitaria ADEMA, Palma, Illes Balears, Spain
- Prevention of Occupational Risks in Health Services, Balearic Islands Health Services, Palma de Mallorca, Illes Balears, Spain
| | - Sergio Fresneda
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Global Health and Lifestyles research group, Insitut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain
| | - Antoni Aguiló
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Global Health and Lifestyles research group, Insitut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain
| | - Aina Yanez
- Nursing and Physiotherapy Department, University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain
- Global Health and Lifestyles research group, Insitut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain
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10
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Cheng YM, Kao JH, Wang CC. The metabolic profiles and body composition of lean metabolic associated fatty liver disease. Hepatol Int 2021; 15:405-412. [PMID: 33539004 DOI: 10.1007/s12072-021-10147-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/18/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND/PURPOSE Metabolic associated fatty liver disease (MAFLD) is the commonest cause of chronic liver disease, which is associated with obesity and diabetes. However, it also occurs in lean individuals especially in Asian populations. METHODS The participants of Tzu Chi MAFLD cohort (TCMC) including health controls or MAFLD patients were enrolled. MAFLD was defined as fatty liver in imaging without hepatitis B virus, hepatitis C virus infection, drug, alcohol or other known causes of chronic liver disease. Lean MAFLD was defined as MAFLD in lean subjects (BMI < 23 kg/m2). RESULTS A total of 880 subjects were included for final analysis. Of 394 MAFLD patients, 65 (16.5%) patients were diagnosed as lean MAFLD. Lean MAFLD patients were elder, higher percentage of female gender, lower ALT, diastolic blood pressure, triglyceride, and waist circumference but higher HDL than non-lean MAFLD patients. Using binary regression analysis, elder age and lower waist circumference were associated with lean MAFLD. Compared with lean healthy controls, lean MAFLD patients had higher BMI, waist circumference, and percentage of hypertension. In body composition, fatty tissue index (FTI), lean tissue index (LTI) ,and total body water (TBW) were lower in lean MAFLD than non-lean MAFLD patients; but they were comparable with lean healthy controls. CONCLUSIONS The prevalence of lean MAFLD was 16.5% in this study population and it was higher in elder age, especially of female subjects. Lean MAFLD patients had different metabolic profiles compared with lean healthy controls, but different body composition compared with non-lean MAFLD patients.
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Affiliation(s)
- Yu-Ming Cheng
- Department of Gastroenterology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, 289 Jianguo Rd., Xindian area, New Taipei City, Hualien, 23142, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Chi Wang
- Department of Gastroenterology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, 289 Jianguo Rd., Xindian area, New Taipei City, Hualien, 23142, Taiwan.
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11
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Lee HW, Wong GLH, Kwok R, Choi KC, Chan CKM, Shu SST, Leung JKY, Chim AML, Luk AOY, Ma RCW, Chan HLY, Chan JCN, Kong APS, Wong VWS. Serial Transient Elastography Examinations to Monitor Patients With Type 2 Diabetes: A Prospective Cohort Study. Hepatology 2020; 72:1230-1241. [PMID: 31991487 DOI: 10.1002/hep.31142] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 12/23/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Type 2 diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis. Current international guidelines recommend the use of noninvasive tests as initial assessments for NAFLD, but the role of noninvasive tests as monitoring tools has not been established. We aimed to study the role of transient elastography as a monitoring tool in patients with type 2 diabetes. APPROACH AND RESULTS We recruited patients with type 2 diabetes without viral hepatitis or excessive alcohol intake from a complication screening facility in Hong Kong in 2013-2014 and repeated the assessments in 2016-2018. The primary endpoint was an increase of liver stiffness measurement (LSM) to ≥10 kPa. The secondary endpoint was the change in the controlled attenuation parameter (CAP). A total of 611 patients with type 2 diabetes and a valid LSM (mean age, 57.7 ± 10.9 years; 342 men [56.0%]) were included in this study (568 also had a valid CAP). Overall, there was moderate correlation between the baseline and follow-up LSM (r = 0.689, P < 0.001). Among 487 patients with a baseline LSM <10 kPa, 21 (4.3%) had a follow-up LSM ≥10 kPa. Baseline body mass index, alanine aminotransferase (ALT), and ∆ALT were independent factors associated with LSM increase. Among 124 patients with a baseline LSM ≥10 kPa, 70 (56.5%) had a follow-up LSM <10 kPa. Among 198 patients with a CAP <248 dB/m at baseline, 103 (52.0%) had a CAP increased to ≥248 dB/m. CONCLUSIONS The prevalence and incidence of NAFLD in patients with type 2 diabetes are high. Although advanced fibrosis is common in this population, few patients progress to advanced fibrosis in 3 years. Future studies should define the optimal surveillance interval in patients with diabetes.
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Affiliation(s)
- Hye Won Lee
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, South Korea
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Raymond Kwok
- Department of Gastroenterology, Blacktown Hospital, Sydney, Australia
| | - Kai Chow Choi
- Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Carmen Ka-Man Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Sally She-Ting Shu
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Julie Ka-Yu Leung
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Angel Mei-Ling Chim
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Andrea On-Yan Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Ronald Ching-Wan Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Juliana Chung-Ngor Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Alice Pik-Shan Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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12
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Wang B, Li M, Zhao Z, Wang S, Lu J, Chen Y, Xu M, Wang W, Ning G, Bi Y, Wang T, Xu Y. Glycemic Measures and Development and Resolution of Nonalcoholic Fatty Liver Disease in Nondiabetic Individuals. J Clin Endocrinol Metab 2020; 105:5798911. [PMID: 32144419 DOI: 10.1210/clinem/dgaa112] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 03/04/2020] [Indexed: 12/21/2022]
Abstract
CONTEXT Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD); however, evidence regarding the link between blood glucose, especially below the threshold for T2D, and NAFLD is scarce. OBJECTIVE The objective of this work is to examine the associations of fasting glucose, oral glucose tolerance test (OGTT) 2-hour glucose, and hemoglobin A1c (HbA1c), and changes in these measures with development and resolution of NAFLD in nondiabetic individuals. METHODS This longitudinal cohort study comprised 4273 Chinese adults age 40 years or older and free of baseline T2D from 2010 to 2015. Blood sampling was performed during the OGTT test. NAFLD was ascertained by hepatic ultrasonography. Risk ratios (RRs) were calculated using modified Poisson regression models. RESULTS During a mean 4.4 years of follow-up, NAFLD occurred in 573 (17.9%) of the 3209 participants without baseline NAFLD and resolved in 304 (28.6%) of the 1064 participants with baseline NAFLD. OGTT 2-h glucose was positively associated with NAFLD incidence (RR per 1-SD increase: 1.16, 95% CI: 1.08-1.25), whereas fasting (RR: 0.86, 95% CI: 0.78-0.94) and 2-hour glucose (RR: 0.85, 95% CI: 0.77-0.93) were inversely associated with resolution of NAFLD. Glycemic deterioration conferred increased risk of developing NAFLD and decreased likelihood of resolution of NAFLD than maintaining normal glycemic regulation (NGR). The strongest associations were observed for individuals who developed T2D. Meanwhile, baseline or incident NAFLD significantly increased the risk of deterioration in glucose metabolism. CONCLUSIONS Increased glycemic levels within the nondiabetic range, as well as progression from NGR to T2D or prediabetes, were adversely associated with development and improvement of NAFLD.
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Affiliation(s)
- Bin Wang
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mian Li
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhiyun Zhao
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shuangyuan Wang
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jieli Lu
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhong Chen
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Xu
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiqing Wang
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guang Ning
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yufang Bi
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tiange Wang
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Xu
- Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, National Clinical Research Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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13
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Yip TCF, Wong GLH, Tse YK, Yuen BWY, Luk HWS, Lam MHB, Li MKK, Loo CK, Tsang OTY, Tsang SWC, Chan HLY, Wing YK, Wong VWS. High incidence of hepatocellular carcinoma and cirrhotic complications in patients with psychiatric illness: a territory-wide cohort study. BMC Gastroenterol 2020; 20:128. [PMID: 32349708 PMCID: PMC7189713 DOI: 10.1186/s12876-020-01277-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 04/15/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Because of high-risk behaviours, sedentary lifestyle and side effects of medications, psychiatric patients are at risk of viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. We aimed to study the incidence of hepatocellular carcinoma (HCC) and cirrhotic complications in psychiatric patients. METHODS We identified consecutive adult patients in all public hospitals and clinics in Hong Kong with psychiatric diagnoses between year 2003 and 2007 using the Clinical Data Analysis and Reporting System, which represents in-patient and out-patient data of approximately 80% of the 7.4-million local population. The patients were followed for liver-related events (HCC and cirrhotic complications) and deaths until December 2017. Age- and sex-standardized incidence ratio (SIR) of HCC in psychiatric patients to the general population was estimated by Poisson model. RESULTS We included 105,763 psychiatric patients without prior liver-related events in the final analysis. During a median (interquartile range) follow-up of 12.4 (11.0-13.7) years, 1461 (1.4%) patients developed liver-related events; 472 (0.4%) patients developed HCC. Compared with the general population, psychiatric patients had increased incidence of HCC (SIR 1.42, 95% confidence interval [CI] 1.28-1.57, P < 0.001). The SIR was highest in patients with drug-induced (SIR 3.18, 95% CI 2.41-4.11, P < 0.001) and alcohol-induced mental disorders (SIR 2.98, 95% CI 2.30-3.81, P < 0.001), but was also increased in patients with psychotic disorders (SIR 1.39, 95% CI 1.16-1.65, P < 0.001) and mood disorders (SIR 1.16, 95% CI 1.00-1.34, P = 0.047). Liver disease was the fifth most common cause of death in this population, accounting for 595 of 10,614 (5.6%) deaths. Importantly, 569 (38.9%) patients were not known to have liver diseases at the time of liver-related events. The median age at HCC diagnosis (61 [range 26-83] years) was older and the median overall survival (8.0 [95% CI 5.0-10.9] months) after HCC diagnosis was shorter in this cohort of psychiatric patients than other reports from Hong Kong. CONCLUSIONS HCC, cirrhotic complications, and liver-related deaths are common in psychiatric patients, but liver diseases are often undiagnosed. More efforts are needed to identify liver diseases in the psychiatric population so that treatments and screening for HCC and varices can be provided to patients in need.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Yee-Kit Tse
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Becky Wing-Yan Yuen
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Hester Wing-Sum Luk
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
| | - Marco Ho-Bun Lam
- Department of Psychiatry, Shatin Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | | | - Ching Kong Loo
- Department of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong, China
| | - Owen Tak-Yin Tsang
- Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, China
| | | | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Yun-Kwok Wing
- Department of Psychiatry, Shatin Hospital, The Chinese University of Hong Kong, Hong Kong, China.
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China.
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
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14
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Bredemolic Acid Ameliorates Selected Liver Function Biomarkers in a Diet-Induced Prediabetic Rat Model. Can J Gastroenterol Hepatol 2020; 2020:2475301. [PMID: 32149046 PMCID: PMC7053450 DOI: 10.1155/2020/2475301] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 12/21/2019] [Accepted: 01/06/2020] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Prediabetes is an intermediary hyperglycaemic state that precedes type 2 diabetes mellitus (T2DM) in which abnormal metabolism of glucose and lipids occurs in organs such as the liver. Evidence has shown that, about 70% of T2DM patients develop hepatic dysfunction which is found to begin during the prediabetic stage. Bredemolic acid, a pentacyclic triterpene, has been found to improve insulin sensitivity in diet-induced prediabetic rats. The effects of this compound on liver function, however, are unknown. This study was therefore designed to investigate the effects of BA on liver function in high fat-high carbohydrate (HFHC) diet-induced prediabetic rats. METHODS Thirty-six (36) male rats that weigh 150 g-180 g were divided into two groups, the non-prediabetic (n = 6) and the prediabetic groups (n = 6) and the prediabetic groups (n = 6) and the prediabetic groups (. RESULTS The induction of prediabetes resulted in increased release of liver enzymes (AST and ALT), increased liver glycogen and triglyceride, lipid peroxidation, and decreased sterol regulatory element-binding protein (SREBP1c) and antioxidant enzymes. However, the administration of BA decreased liver enzyme concentrations, decreased hepatic oxidative stress, and improved antioxidant enzymes such as SOD and GPx. CONCLUSION BA administration improved liver function in diet-induced prediabetic rats in the presence or absence of dietary intervention.
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15
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Hwang KB, Kyaw YY, Kang HR, Seong MS, Cheong J. Mitochondrial dysfunction stimulates HBV gene expression through lipogenic transcription factor activation. Virus Res 2019; 277:197842. [PMID: 31874211 DOI: 10.1016/j.virusres.2019.197842] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 12/12/2019] [Accepted: 12/18/2019] [Indexed: 12/17/2022]
Abstract
In previous studies, we showed two consistent findings regarding the functional relationship between hepatitis B virus (HBV) gene expression and hepatic lipid accumulation. One is that HBV X (HBx) protein expression induces hepatic lipid accumulation via specific transcriptional activation. The other is that hepatic rich lipids increase HBV gene expression. A variety of transcription factors, including nuclear receptors have been defined as regulators of HBV promoters and enhancers. However, the association between these metabolic events and HBV gene expression remains to be clearly elucidated. Here, we showed that lipid accumulation due to mitochondrial dysfunction is associated with an increase in HBV gene expression. Saturated fatty acids increase the expression of lipogenic factors cooperated with C/EBPα and LXRα. In addition, activation of PPARγ and SREBP-1 by fatty acids derived from hepatic lipid accumulation was found to increase HBV gene expression through mitochondrial dysfunction. These results provide that metabolic changes in the hepatic cells play a critical role in the HBV gene induction.
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Affiliation(s)
- Keum Bit Hwang
- Advanced Molecular Research Centre, Department of Medical Research, Yangon, Myanmar
| | - Yi Yi Kyaw
- Advanced Molecular Research Centre, Department of Medical Research, Yangon, Myanmar; Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea
| | - Hyo Rin Kang
- Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea
| | - Mi So Seong
- Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea
| | - JaeHun Cheong
- Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea.
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16
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Sattari M, Bril F, Egerman R, Kalavalapalli S, Cusi K. Relationship between non-alcoholic fatty liver disease during pregnancy and abnormal glucose metabolism during and after pregnancy. J Investig Med 2019; 68:743-747. [PMID: 31852748 DOI: 10.1136/jim-2019-001186] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2019] [Indexed: 12/17/2022]
Abstract
While non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of impaired glucose tolerance and type 2 diabetes mellitus (DM) in non-pregnant patients, the clinical significance of NAFLD during pregnancy is still unclear. We hypothesized that sonographic findings of NAFLD during pregnancy would be associated with gestational diabetes mellitus (GDM) and predict abnormal postpartum glucose metabolism. NAFLD was assessed by ultrasound during and after pregnancy. Standard 2-hour 75 g oral glucose tolerance test (OGTT) was used during pregnancy and post partum to establish GDM and the diagnosis of normal, impaired fasting glucose, or DM. We also measured plasma insulin, C peptide, and free fatty acids (FFA) concentration during an OGTT to evaluate glucose tolerance, insulin secretion and insulin resistance. Of the 84 subjects, 12 had sonographic evidence of NAFLD (5 of whom had OGTT post partum). There was a non-significant trend toward higher mean weight and body mass index during and after gestation in the NAFLD group, but no statistically significant differences in mean age, ethnicity, prepregnancy and postpregnancy hemoglobin A1C values, and postpartum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, insulin, or FFA. We did not find an association between sonographic evidence of NAFLD during the third trimester of pregnancy and abnormal glucose metabolism during or after pregnancy. This study also suggests that while AST and ALT are not reliable diagnostic tools for NAFLD during the postpartum period, ultrasound is a reasonably safe, practical, and cost-effective modality to assess maternal hepatic fat during pregnancy.
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Affiliation(s)
- Maryam Sattari
- Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Fernando Bril
- Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Robert Egerman
- Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.,Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Srilaxmi Kalavalapalli
- Endocrinology, Diabetes, and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Kenneth Cusi
- Endocrinology, Diabetes, and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA.,Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States.,Audie L. Murphy VAMC, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
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17
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Fibroscan and low-density lipoprotein as determinants of severe liver fibrosis in diabetic patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2019; 31:1540-1544. [PMID: 31135513 DOI: 10.1097/meg.0000000000001461] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Fibroscan is an effective and noninvasive tool to quantify fibrosis and steatosis in liver diseases including nonalcoholic fatty liver disease (NAFLD). Type-2-diabetes is a known risk factor for worse prognosis in NAFLD. In this study, we compare liver status in NAFDL diabetic and nondiabetic patients, identify potential risk factors, and determine the usefulness of Fibroscan in this population. PATIENTS AND METHODS The charts of all patients with NAFLD who underwent Fibroscan at our institution were reviewed. Fibroscan results, demographics, and clinical data were collected and analyzed using SPSS software. RESULTS Of the 248 NAFLD patients, 73 (29.4%) were diabetic and 175 (70.6%) were nondiabetic. As detected by the NAFLD' liver stiffness measure, 35 (47.94%) diabetic patients had severe liver fibrosis (F4) in contrast to only 46 (26.3%) nondiabetics. Diabetic patients also presented more with hypertension, dyslipidemia, coronary artery disease, and chronic kidney disease. Liver steatosis, liver function tests, and noninvasive scores did not vary significantly between the two groups, except for γ-glutamyltransferase, prothrombin time-international normalized ratio, and BMI-alanine aminotransferase ratio-diabetes score. Diabetic patients had significantly lower high-density lipoproteins and low-density lipoproteins. CONCLUSION Fibroscan results and low-density lipoprotein are potential diagnostic factors of liver fibrosis in diabetic patients with NAFLD. Further studies are necessary to verify liver fibrosis diagnostic tools and prognostic and genetic markers in diabetic patients.
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Chen LW, Chien CH, Kuo SF, Yu CY, Lin CL, Chien RN. Low vitamin D level was associated with metabolic syndrome and high leptin level in subjects with nonalcoholic fatty liver disease: a community-based study. BMC Gastroenterol 2019; 19:126. [PMID: 31311491 PMCID: PMC6636103 DOI: 10.1186/s12876-019-1040-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 06/30/2019] [Indexed: 02/06/2023] Open
Abstract
Background This study aimed to evaluate the association between serum vitamin D levels and nonalcoholic fatty liver disease (NAFLD) parameters, such as metabolic syndrome (MS), inflammatory cytokines (tumor necrosis factor, high sensitive C-reactive protein) and adipokines (adiponectin, leptin). Methods From August 2013 to August 2016, a community-based study was performed in the north-eastern region of Taiwan. All subjects received a demographic survey, blood testing and abdominal ultrasonography (US). The vitamin D level was evaluated by quartile divide or used the classification of deficiency (< 20 ng/ml), insufficiency (20–30 ng/ml) and sufficiency (> 30 ng/ml). Results Subjects were divided into NAFLD group and normal control (subjects number = 564 in each group) following abdominal US study and matching age and gender. The mean age was 57.1 years in NAFLD group and 57.5 in control group. Subjects in NAFLD group had a lower mean vitamin D than those in the control group (28.5 ± 9.5 ng/ml vs. 29.9 ± 10.2 ng/ml, P = 0.018). Subjects with serum vitamin D deficiency or insufficiency had higher odds for MS than those with sufficient vitamin D levels [deficiency vs. sufficiency, adjusted odds ratio (aOR) =1.860 (95% CI = 1.234–2.804), P = 0.003; insufficiency vs. sufficiency, aOR = 1.669 (95% CI = 1.237–2.251), P = 0.001]. Similarly, subjects in the lowest quartile of vitamin D had higher odds for MS than those in the highest quartile of vitamin D (aOR = 2.792, 95% CI = 1.719–4.538, P < 0.001). Vitamin D level was positively correlated with age and male, but negatively correlated with serum leptin level. Conclusion Subjects with low vitamin D level had higher odds for MS, but higher levels of leptin, compared to those with high vitamin D levels.
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Affiliation(s)
- Li-Wei Chen
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401.,Community Medicine Research Center, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401
| | - Cheng-Hung Chien
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401.,Community Medicine Research Center, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401
| | - Sheng-Fong Kuo
- Community Medicine Research Center, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401.,Metabolism and Endocrinology, Chang-Gung Memorial Hospital and University at Keelung, Keelung, Taiwan
| | - Chia-Ying Yu
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401.,Community Medicine Research Center, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401
| | - Chih-Lang Lin
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401.,Community Medicine Research Center, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401
| | - Rong-Nan Chien
- Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401. .,Community Medicine Research Center, Chang-Gung Memorial Hospital and University at Keelung, 12F, No 222, Mai-Jin Road, Keelung, Taiwan, 20401.
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Wong MCS, Huang JLW, George J, Huang J, Leung C, Eslam M, Chan HLY, Ng SC. The changing epidemiology of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol Hepatol 2019; 16:57-73. [PMID: 30158570 DOI: 10.1038/s41575-018-0055-0] [Citation(s) in RCA: 233] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This Review presents current epidemiological trends of the most common liver diseases in Asia-Pacific countries. Hepatitis B virus (HBV) remains the primary cause of cirrhosis; despite declining prevalence in most Asian nations, this virus still poses a severe threat in some territories and regions. Mortality resulting from HBV infection is declining as a result of preventive measures and antiviral treatments. The epidemiological transition of hepatitis C virus (HCV) infection has varied in the region in the past few decades, but the medical burden of infection and the prevalence of its related cancers are increasing. The lack of licensed HCV vaccines highlights the need for novel treatment strategies. The prevalence of nonalcoholic fatty liver disease (NAFLD) has risen in the past decade, mostly owing to increasingly urbanized lifestyles and dietary changes. Alternative herbal medicine and dietary supplements are major causes of drug-induced liver injury (DILI) in some countries. Complications arising from these chronic liver diseases, including cirrhosis and liver cancer, are therefore emerging threats in the Asia-Pacific region. Key strategies to control these liver diseases include monitoring of at-risk populations, implementation of national guidelines and increasing public and physician awareness, in concert with improving access to health care.
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Affiliation(s)
- Martin C S Wong
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jason L W Huang
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jacob George
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Junjie Huang
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Colette Leung
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Henry L Y Chan
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Siew C Ng
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
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20
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Wong VWS, Wong GLH, Chan RSM, Shu SST, Cheung BHK, Li LS, Chim AML, Chan CKM, Leung JKY, Chu WCW, Woo J, Chan HLY. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol 2018; 69:1349-1356. [PMID: 30142427 DOI: 10.1016/j.jhep.2018.08.011] [Citation(s) in RCA: 216] [Impact Index Per Article: 30.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 07/11/2018] [Accepted: 08/07/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Around 10-20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese patients with NAFLD and to identify factors that predict treatment response. METHODS A total of 154 community NAFLD patients were randomised to a 12-month lifestyle intervention programme involving regular exercise, or to standard care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed until Year 6. The Asian body mass index (BMI) cut-off of 25 kg/m2 was used to define non-obese NAFLD. RESULTS Patients were assigned to the intervention (n = 77) and control (n = 77) groups (39 and 38 in each group had baseline BMI <25 and ≥25 kg/m2, respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs. 18%, p <0.001; obese: 61% vs. 21%, p <0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3-5% weight reduction; the same could only be achieved in obese patients with 7-10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalisation than the control group. CONCLUSIONS Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population. LAY SUMMARY Some patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3-10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run.
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Affiliation(s)
- Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Ruth Suk-Mei Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Centre for Nutritional Studies, The Chinese University of Hong Kong, Hong Kong
| | - Sally She-Ting Shu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Bernice Ho-Ki Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Centre for Nutritional Studies, The Chinese University of Hong Kong, Hong Kong
| | - Liz Sin Li
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Centre for Nutritional Studies, The Chinese University of Hong Kong, Hong Kong
| | - Angel Mei-Ling Chim
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Carmen Ka-Man Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Julie Ka-Yu Leung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Winnie Chiu-Wing Chu
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong
| | - Jean Woo
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Centre for Nutritional Studies, The Chinese University of Hong Kong, Hong Kong
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
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Franch-Nadal J, Caballeria L, Mata-Cases M, Mauricio D, Giraldez-García C, Mancera J, Goday A, Mundet-Tudurí X, Regidor E. Fatty liver index is a predictor of incident diabetes in patients with prediabetes: The PREDAPS study. PLoS One 2018; 13:e0198327. [PMID: 29856820 PMCID: PMC5983533 DOI: 10.1371/journal.pone.0198327] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 05/17/2018] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES We evaluated the ability of the Fatty Liver Index (FLI), a surrogate marker of hepatic steatosis, to predict the development of type 2 diabetes (T2D) at 3 years follow-up in a Spanish cohort with prediabetes from a prospective observational study in primary care (PREDAPS). METHODS FLI was calculated at baseline for 1,142 adult subjects with prediabetes attending primary care centers, and classified into three categories: FLI <30 (no steatosis), FLI 30-60 (intermediate) and FLI ≥60 (hepatic steatosis). We estimated the incidence rate of T2D in each FLI category at 3 years of follow-up. The association between FLI and incident T2D was calculated using Cox regression models adjusted for age, sex, educational level, family history of diabetes, lifestyles, hypertension, lipid profile and transaminases. RESULTS The proportion of subjects with prediabetes and hepatic steatosis (FLI ≥60) at baseline was 55.7%. The incidence rate of T2D at 3 years follow-up was 1.3, 2.9 and 6.0 per 100 person-years for FLI<30, FLI 30->60 and FLI ≥60, respectively. The most significant variables increasing the risk of developing T2D were metabolic syndrome (hazard ratio [HR] = 3.02; 95% confidence interval [CI] = 2.14-4.26) and FLI ≥60 (HR = 4.52; 95%CI = 2.10-9.72). Moreover, FLI ≥60 was independently associated with T2D incidence: the HR was 4.97 (95% CI: 2.28-10.80) in the base regression model adjusted by sex, age and educational level, and 3.21 (95%CI: 1.45-7.09) in the fully adjusted model. CONCLUSIONS FLI may be considered an easy and valuable early indicator of high risk of incident T2D in patients with prediabetes attended in primary care, which could allow the adoption of effective measures needed to prevent and reduce the progression of the disease.
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Affiliation(s)
- Josep Franch-Nadal
- redGDPS Foundation, Madrid, Spain
- Unitat de Suport a la Recerca Barcelona Ciutat, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
- Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Madrid, Spain
- Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Llorenç Caballeria
- Department of Medicine, University of Barcelona, Barcelona, Spain
- Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), Madrid, Spain
- Unitat de Suport a la Recerca Barcelonès Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
| | - Manel Mata-Cases
- redGDPS Foundation, Madrid, Spain
- Unitat de Suport a la Recerca Barcelona Ciutat, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
- Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Madrid, Spain
| | - Didac Mauricio
- redGDPS Foundation, Madrid, Spain
- Unitat de Suport a la Recerca Barcelona Ciutat, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
- Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Madrid, Spain
- Department of Endocrinology and Nutrition, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain
| | - Carolina Giraldez-García
- redGDPS Foundation, Madrid, Spain
- Preventive Medicine Service, University Hospital Infanta Elena, Madrid, Spain
- Preventive Medicine, Public Health and History of Science Department, Complutense University of Madrid, Madrid, Spain
| | - José Mancera
- redGDPS Foundation, Madrid, Spain
- Health Center Ciudad Jardín, Málaga, Spain
| | - Albert Goday
- redGDPS Foundation, Madrid, Spain
- Endocrinology Service, Hospital del Mar, Barcelona, Spain
| | - Xavier Mundet-Tudurí
- redGDPS Foundation, Madrid, Spain
- Unitat de Suport a la Recerca Barcelona Ciutat, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
- Autonomous University of Barcelona, Bellaterra, Spain
| | - Enrique Regidor
- redGDPS Foundation, Madrid, Spain
- Preventive Medicine, Public Health and History of Science Department, Complutense University of Madrid, Madrid, Spain
- Epidemiology and Public Health Networking Biomedical Research Centre (CIBERESP), Madrid, Spain
- Health Research Institute, Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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Seko Y, Sumida Y, Tanaka S, Mori K, Taketani H, Ishiba H, Hara T, Okajima A, Umemura A, Nishikawa T, Yamaguchi K, Moriguchi M, Kanemasa K, Yasui K, Imai S, Shimada K, Itoh Y. Insulin resistance increases the risk of incident type 2 diabetes mellitus in patients with non-alcoholic fatty liver disease. Hepatol Res 2018. [PMID: 28628263 DOI: 10.1111/hepr.12925] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM Type 2 diabetes mellitus (T2DM) is a major complication of patients with non-alcoholic fatty liver disease (NAFLD). The aim of this retrospective study is to determine the risk factors for development of T2DM in patients with biopsy-proven NAFLD. METHODS One hundred and sixty two consecutive patients with biopsy-proven NAFLD who received a 75-g oral glucose tolerance test were enrolled as the total cohort. Among them, we analyzed 89 patients without T2DM diagnosed by oral glucose tolerance test to estimate the cumulative rate for development of T2DM as the follow-up cohort. RESULTS Of 162 patients, the glucose tolerance pattern were DM in 45 patients (27.8%), impaired glucose tolerance in 68 (42.0%), and normal glucose tolerance in 49 (30.2%). Patients with NAFL tended to be more likely to have normal glucose tolerance than those with non-alcoholic steatohepatitis (NASH). The serum levels of pre- and post-load insulin were significantly higher in the NASH group. Of 89 patients without T2DM, 13 patients newly developed T2DM during a follow-up period of 5.2 years. The cumulative rate of T2DM incidence was 8.8% at the end of the 5th year and 23.4% at the end of the 10th year. Multivariate analysis identified homeostasis model of assessment - insulin resistance (≥3.85, hazard ratio 40.1, P = 0.033) as an independent risk factor for development of T2DM. CONCLUSIONS Patients with NASH have an underlying potential of glucose intolerance. In NAFLD patients, insulin resistance is the most important risk factor for the incidence of T2DM. Appropriate therapy against insulin resistance could be needed for patients with NAFLD to prevent development of T2DM.
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Affiliation(s)
- Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Aichi, Japan
| | - Saiyu Tanaka
- Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
| | - Kojiroh Mori
- Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
| | - Hiroyoshi Taketani
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroshi Ishiba
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tasuku Hara
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akira Okajima
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Atsushi Umemura
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Taichiro Nishikawa
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kanji Yamaguchi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michihisa Moriguchi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuyuki Kanemasa
- Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
| | - Kohichiroh Yasui
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shunsuke Imai
- Department of Pathology, Nara City Hospital, Nara, Japan
| | - Keiji Shimada
- Department of Pathology, Nara City Hospital, Nara, Japan
| | - Yoshito Itoh
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Fan JG, Kim SU, Wong VWS. New trends on obesity and NAFLD in Asia. J Hepatol 2017; 67:862-873. [PMID: 28642059 DOI: 10.1016/j.jhep.2017.06.003] [Citation(s) in RCA: 789] [Impact Index Per Article: 98.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 05/31/2017] [Accepted: 06/07/2017] [Indexed: 12/12/2022]
Abstract
Traditionally, obesity and its related diseases have been considered a problem in Western countries. However, in the past two decades, urbanisation in many Asian countries has led to a sedentary lifestyle and overnutrition, setting the stage for the epidemic of obesity. This article reviews the epidemiological trend of obesity in Asia, with special emphasis on the emerging condition of non-alcoholic fatty liver disease (NAFLD). Currently, the population prevalence of NAFLD in Asia is around 25%, like many Western countries. While hepatocellular carcinoma and end-stage liver disease secondary to NAFLD remain uncommon, a rising trend has emerged. Around 8-19% of Asians with body mass indexes less than 25kg/m2 are also found to have NAFLD, a condition often described as "lean" or "non-obese" NAFLD. Although this condition is generally less severe than that in more obese patients, steatohepatitis and fibrotic disease are well recognized. Central adiposity, insulin resistance and weight gain are major risk factors, and genetic predisposition, such as the PNPLA3 polymorphism appears to be more important in the development of NAFLD in the non-obese population. Lifestyle modification remains the cornerstone of management for obesity and NAFLD, but few patients can achieve adequate weight reduction and even fewer can maintain the weight in the long run. While pharmacological agents have entered phase III development for steatohepatitis, Asian patients are under-represented in most drug trials. Future studies should define the optimal management of obesity and NAFLD in Asia.
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Affiliation(s)
- Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Seung-Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
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Yip TCF, Ma AJ, Yuen PC, Wong GLH. Editorial: progress towards a simple tool for screening for hepatic steatosis in the general population - authors' reply. Aliment Pharmacol Ther 2017; 46:560-561. [PMID: 28776735 DOI: 10.1111/apt.14234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
Linked ContentThis article is linked to Maj and Wong and Gallacher and McPherson papers. To view these articles visit https://doi.org/10.1111/apt.14172 and https://doi.org/10.1111/apt.14217.
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Affiliation(s)
- T C-F Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - A J Ma
- Department of Computer Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - P-C Yuen
- Department of Computer Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - G L-H Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
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Clinical and Metabolic Characterization of Lean Caucasian Subjects With Non-alcoholic Fatty Liver. Am J Gastroenterol 2017; 112:102-110. [PMID: 27527746 DOI: 10.1038/ajg.2016.318] [Citation(s) in RCA: 179] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 06/02/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity; however, 5-8% of lean subjects also have evidence of NAFLD. We aimed to investigate clinical, genetic, metabolic and lifestyle characteristics in lean Caucasian subjects with NAFLD. METHODS Data from 187 subjects allocated to one of the three groups according to body mass index (BMI) and hepatic steatosis on ultrasound were obtained: lean healthy (BMI≤25 kg/m2, no steatosis, N=71), lean NAFLD (BMI≤25 kg/m2, steatosis, N=55), obese NAFLD (BMI≥30 kg/m2, steatosis; N=61). All subjects received a detailed clinical and laboratory examination including oral glucose tolerance test. The serum metabolome was assessed using the Metabolomics AbsoluteIDQ p180 kit (BIOCRATES Life Sciences). Genotyping for single-nucleotide polymorphisms (SNPs) associated with NAFLD was performed. RESULTS Lean NAFLD subjects had fasting insulin concentrations similar to lean healthy subjects but had markedly impaired glucose tolerance. Lean NAFLD subjects had a higher rate of the mutant PNPLA3 CG/GG variant compared to lean controls (P=0.007). Serum adiponectin concentrations were decreased in both NAFLD groups compared to controls (P<0.001 for both groups) The metabolomics study revealed a potential role for various lysophosphatidylcholines (lyso-PC C18:0, lyso-PC C17:0) and phosphatidylcholines (PCaa C36:3; false discovery rate (FDR)-corrected P-value<0.001) as well as lysine, tyrosine, and valine (FDR<0.001). CONCLUSIONS Lean subjects with evidence of NAFLD have clinically relevant impaired glucose tolerance, low adiponectin concentrations and a distinct metabolite profile with an increased rate of PNPLA3 risk allele carriage.
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Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism 2016; 65:1096-108. [PMID: 26856933 PMCID: PMC4943559 DOI: 10.1016/j.metabol.2016.01.001] [Citation(s) in RCA: 378] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 01/04/2016] [Accepted: 01/05/2016] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are common conditions that regularly co-exist and can act synergistically to drive adverse outcomes. The presence of both NAFLD and T2DM increases the likelihood of the development of complications of diabetes (including both macro- and micro- vascular complications) as well as augmenting the risk of more severe NAFLD, including cirrhosis, hepatocellular carcinoma and death. The mainstay of NAFLD management is currently to reduce modifiable metabolic risk. Achieving good glycaemic control and optimising weight loss are pivotal to restricting disease progression. Once cirrhosis has developed, it is necessary to screen for complications and minimise the risk of hepatic decompensation. Therapeutic disease modifying options for patients with NAFLD are currently limited. When diabetes and NAFLD co-exist, there are published data that can help inform the clinician as to the most appropriate oral hypoglycaemic agent or injectable therapy that may improve NAFLD, however most of these data are drawn from observations in retrospective series and there is a paucity of well-designed randomised double blind placebo controlled studies with gold-standard end-points. Furthermore, given the heterogeneity of inclusion criteria and primary outcomes, as well as duration of follow-up, it is difficult to draw robust conclusions that are applicable across the entire spectrum of NAFLD and diabetes. In this review, we have summarised and critically evaluated the available data, with the aim of helping to inform the reader as to the most pertinent issues when managing patients with co-existent NAFLD and T2DM.
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Affiliation(s)
- Jonathan M Hazlehurst
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK, OX3 7LE
| | - Conor Woods
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK, OX3 7LE
| | - Thomas Marjot
- Department of Gastroenterology, Oxford University Hospitals NHS Trust, Oxford, UK, OX3 9DU
| | - Jeremy F Cobbold
- Department of Gastroenterology, Oxford University Hospitals NHS Trust, Oxford, UK, OX3 9DU
| | - Jeremy W Tomlinson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK, OX3 7LE.
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Kwok R, Choi KC, Wong GLH, Zhang Y, Chan HLY, Luk AOY, Shu SST, Chan AWH, Yeung MW, Chan JCN, Kong APS, Wong VWS. Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut 2016; 65:1359-68. [PMID: 25873639 DOI: 10.1136/gutjnl-2015-309265] [Citation(s) in RCA: 357] [Impact Index Per Article: 39.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 03/31/2015] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Type 2 diabetes is an important risk factor for non-alcoholic fatty liver disease (NAFLD), but current guidelines provide conflicting recommendations on whether diabetic patients should be screened for NAFLD. We therefore studied the strategy of screening diabetic patients by FibroScan. DESIGN Liver fat and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) by FibroScan at a diabetic centre for patients from primary care and hospital clinics. Probe-specific LSM cut-offs were used to detect advanced fibrosis. RESULTS Of 1918 patients examined, 1799 (93.8%) had valid CAP and 1884 (98.2%) had reliable LSM (1770 with the M probe and 114 with the XL probe). The proportion of patients with increased CAP and LSM was 72.8% (95% CI 70.7% to 74.8%) and 17.7% (95% CI 16.0% to 19.5%), respectively. By multivariable analysis, female gender, higher body mass index, triglycerides, fasting plasma glucose and alanine aminotransferase (ALT) and non-insulin use were associated with increased CAP. Longer duration of diabetes, higher body mass index, increased ALT and spot urine albumin:creatinine ratio and lower high-density lipoprotein-cholesterol were associated with increased LSM. Ninety-four patients (80% had increased LSM) underwent liver biopsy: 56% had steatohepatitis and 50% had F3-4 disease. CONCLUSIONS Diabetic patients have a high prevalence of NAFLD and advanced fibrosis. Those with obesity and dyslipidaemia are at particularly high risk and may be the target for liver assessment. Our data support screening for NAFLD and/or advanced fibrosis in patients with type 2 diabetes.
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Affiliation(s)
- Raymond Kwok
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Kai Chow Choi
- Nethersole School of Nursing, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong State Key Laboratory in Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Yuying Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong State Key Laboratory in Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Andrea On-Yan Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Sally She-Ting Shu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong State Key Laboratory in Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Anthony Wing-Hung Chan
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Ming-Wai Yeung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Juliana Chung-Ngor Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Alice Pik-Shan Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong State Key Laboratory in Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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28
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De Souza LR, Berger H, Retnakaran R, Vlachou PA, Maguire JL, Nathens AB, Connelly PW, Ray JG. Non-Alcoholic Fatty Liver Disease in Early Pregnancy Predicts Dysglycemia in Mid-Pregnancy: Prospective Study. Am J Gastroenterol 2016; 111:665-70. [PMID: 26977755 DOI: 10.1038/ajg.2016.43] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 01/02/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is mediated by insulin resistance, as is gestational diabetes mellitus (GDM). NAFLD has not been studied in relation to GDM. The objective of this study was to assess the association between first-trimester sonographic findings of NAFLD, and both dysglycemia and GDM in mid-pregnancy. METHODS We followed a prospective cohort design at a large obstetrics clinic in Toronto, Ontario with 476 women enrolled in early pregnancy. NAFLD was assessed by ultrasound at 11-14 weeks gestation, and standardized images were independently scored by two ultrasonographers for the presence of hepatorenal contrast (one finding) and/or blurring of the intrahepatic vessels (one finding), relative to neither being present. Logistic regression analysis was used to generate odds ratios (ORs) and 95% confidence interval (CI) for the relation between 0, 1, or 2 sonographic findings of NAFLD and the composite outcome of impaired fasting glucose, impaired glucose tolerance, or GDM at 24-28 weeks gestation, determined by a fasting 75-g oral glucose tolerance test. ORs were adjusted (aOR) for maternal age, ethnicity, first-degree relative with type 2 DM, body mass index (BMI) at 11-14 weeks gestation, and change in BMI from 11-14 to 24-28 weeks gestation. RESULTS Fifty out of 476 women (10.5%) developed the composite outcome. The presence of 1 (aOR 2.0, 95% CI: 1.0-4.1) or 2 (aOR 2.9, 95% CI: 1.0-18.4) sonographic features of NAFLD predicted the composite outcome. Limiting the analysis to ≥1 feature vs. none, the aOR was 2.2 (95% CI: 1.1-4.3). CONCLUSIONS Sonographic assessment of NAFLD is a semiquantitative measure, with limited ability to detect small amounts of hepatic steatosis, or to distinguish various stages of NAFLD. First-trimester sonographic evidence of NAFLD predicts dysglycemia in mid-pregnancy.
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Affiliation(s)
- Leanne R De Souza
- Department of Obstetrics and Gynecology, St Michael's Hospital, Toronto, Ontario, Canada.,Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Howard Berger
- Department of Obstetrics and Gynecology, St Michael's Hospital, Toronto, Ontario, Canada.,Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, Ontario, Canada
| | - Ravi Retnakaran
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Paraskevi A Vlachou
- Department of Medical Imaging, St Michael's Hospital, Toronto, Ontario, Canada
| | - Jonathon L Maguire
- Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, Ontario, Canada
| | - Avery B Nathens
- Department of Surgery, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
| | - Philip W Connelly
- Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, Ontario, Canada.,Department of Medicine, St Michael's Hospital, Toronto, Ontario, Canada
| | - Joel G Ray
- Department of Obstetrics and Gynecology, St Michael's Hospital, Toronto, Ontario, Canada.,Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.,Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, Ontario, Canada.,Department of Medicine, St Michael's Hospital, Toronto, Ontario, Canada.,Department of Health Policy Management Evaluation, University of Toronto, Toronto, Ontario, Canada
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de Lédinghen V, Wong GLH, Vergniol J, Chan HLY, Hiriart JB, Chan AWH, Chermak F, Choi PCL, Foucher J, Chan CKM, Merrouche W, Chim AML, Le Bail B, Wong VWS. Controlled attenuation parameter for the diagnosis of steatosis in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2016; 31:848-55. [PMID: 26514665 DOI: 10.1111/jgh.13219] [Citation(s) in RCA: 139] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 10/12/2015] [Accepted: 10/18/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan) is a recent method for non-invasive assessment of steatosis. Its usefulness in non-alcoholic fatty liver disease (NAFLD) is unknown. We prospectively investigated the performance of CAP for the diagnosis of steatosis in NAFLD, factors associated with discordances between CAP and steatosis grades, and relationships between CAP and clinical or biological parameters. METHODS All CAP examinations performed in NAFLD patients with a liver biopsy performed within 1 week of CAP measurement were included. Liver biopsies were assessed for activity and fibrosis stage, NAFLD activity score, and steatosis graded as follows: S0, steatosis < 5%; S1, 5-33%; S2, 34-66%; S3, >66%. RESULTS Two hundred sixty-one patients (59% male, age 56 years) from two ethnic groups were included. No patient had steatosis < 5%. The area under the receiver-operating characteristics curve of CAP for steatosis ≥S2 and S3 was 0.80 and 0.66, respectively. At a cut-off value of 310 dB/m, the sensitivity, specificity, and positive and negative predictive values for ≥S2 steatosis were 79%, 71%, 86%, and 71%, respectively. Discordance of at least one grade between CAP and steatosis was observed in 81 patients. By multivariate analysis, only steatosis S2S3 was associated with no discordance. By multivariate analysis, only BMI ≥ 30 kg/m(2) was significantly associated with CAP > 310 dB/m. CONCLUSION The association of CAP with steatosis, especially in patients with non-alcoholic steatohepatitis, and with elevated BMI could be useful for the diagnosis and follow-up of NAFLD patients.
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Affiliation(s)
- Victor de Lédinghen
- Investigation Center of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France.,INSERM U1053, Bordeaux University, Bordeaux, France
| | - Grace Lai-Hung Wong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Julien Vergniol
- Investigation Center of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Henry Lik-Yuen Chan
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Jean-Baptiste Hiriart
- Investigation Center of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Anthony Wing-Hung Chan
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
| | - Faiza Chermak
- Investigation Center of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Paul Cheung-Lung Choi
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
| | - Juliette Foucher
- Investigation Center of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Carmen Ka-Man Chan
- Investigation Center of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France.,INSERM U1053, Bordeaux University, Bordeaux, France
| | - Wassil Merrouche
- Investigation Center of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Angel Mei-Ling Chim
- Investigation Center of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France.,INSERM U1053, Bordeaux University, Bordeaux, France
| | - Brigitte Le Bail
- INSERM U1053, Bordeaux University, Bordeaux, France.,Department of Pathology, Pellegrin Hospital, Bordeaux University Hospital, Bordeaux, France
| | - Vincent Wai-Sun Wong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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30
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Wei Z, Li-Qun Z, Xiao-Ling H, Jian Q, Guo-Yue Y. Association of adiponectin gene polymorphisms and additional gene-gene interaction with nonalcoholic fatty liver disease in the Chinese Han population. Hepatol Int 2016; 10:511-7. [PMID: 26865047 DOI: 10.1007/s12072-015-9687-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 11/06/2015] [Indexed: 01/21/2023]
Abstract
PURPOSE To investigate the association between the single nucleotide polymorphisms (SNPs) of the adiponectin gene and nonalcoholic fatty liver disease (NAFLD) as well as the impact of the interaction of multiple SNPs on NAFLD risk, based on a Chinese population study. METHODS A total of 612 subjects (411 male, 201 female) were selected, including 302 NAFLD patients and 310 controls. Three SNPs were selected for genotyping in the case-control study: rs266729, rs822393, and rs1501299. A logistic regression model was used to examine the interaction between the SNPs and NAFLD. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction among SNPs. RESULTS Logistic analysis showed a significant association between genotypes of variants in rs266729 and rs822393 and increased NAFLD risk. The carriers of the homozygous mutant of two SNP polymorphisms revealed increased NAFLD risk compared to those with wild-type homozygotes; ORs (95 % CI) were 1.31 (1.14-1.81) (p = 0.001) and 1.18 (1.05-1.71) (p = 0.005), respectively. There was a significant two-locus model (p = 0.0010) involving rs266729 and rs822393, indicating a potential gene-gene interaction between rs266729 and rs822393. Overall, the two-locus models had a cross-validation consistency of 10 and testing accuracy of 62.17 %. Subjects with the CG or GG and CT or TT genotype have the highest NAFLD risk compared to subjects with the CC-CC genotype; the OR (95 % CI) was 2.52 (1.31-3.82), p < 0.001, after covariate adjustment. CONCLUSIONS Our results support an important association of the rs266729 (-11377 G/C) and rs822393 (-4522 C/T) polymorphism with increased risk of NAFLD. The interaction analysis showed a combined effect of rs266729 and rs822393 on NAFLD.
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Affiliation(s)
- Zhang Wei
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, No. 308 Jiefang Road, Zhenjiang, Jiangsu, 212001, China.
| | - Zhu Li-Qun
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, No. 308 Jiefang Road, Zhenjiang, Jiangsu, 212001, China
| | - Huo Xiao-Ling
- The Hospital of the 4th Division, Department of Gastroenterology, Xinjiang Production and Construction Corps, Yi'ning, 835000, China
| | - Qin Jian
- The Hospital of the 4th Division, Department of Gastroenterology, Xinjiang Production and Construction Corps, Yi'ning, 835000, China
| | - Yuan Guo-Yue
- Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China
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31
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Huang JF, Yeh ML, Yu ML, Huang CF, Dai CY, Hsieh MY, Hsieh MH, Huang CI, Lin ZY, Chen SC, Hsiao PJ, Shin SJ, Chuang WL. Hyperuricemia Inversely Correlates with Disease Severity in Taiwanese Nonalcoholic Steatohepatitis Patients. PLoS One 2015; 10:e0139796. [PMID: 26441244 PMCID: PMC4595446 DOI: 10.1371/journal.pone.0139796] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 09/16/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND & AIMS Asians are more susceptible to non-alcoholic steatohepatitis (NASH) as well as metabolic disorder than other ethnicities. We aimed to assess the interaction between metabolic factors and fibrosis in Taiwanese NASH patients. METHODS A total of 130 biopsy-proven Taiwanese NASH patients (94 males, age = 43.0 ± 13.0 years) were consecutively enrolled. Their demographic, metabolic profiles and histopathological manifestations were analyzed. RESULTS Twenty-four (18.5%) NASH patients were non-obese. Thirty-three (25.4%) patients had significant fibrosis (F2) or more: 22 (16.9%) patients were of F2, whilst 11 (8.5%) patients were of advanced fibrosis (F3-4). The prevalence of metabolic syndrome, diabetes and hypertension were 60.8%, 39.4%, and 61.5%, respectively. There was a significant inverse correlation between hyperuricemia and fibrosis stages, ranging from 48.4% of F0-1, 33.3% of F2, and 9.1% of F3-4, respectively (P = 0.01, linear trend). Multivariate logistic regression analysis showed that a decreased serum albumin level (OR = 40.0, 95% CI = 4.5-300, P = 0.001) and normal uric acid level (OR = 5.6, 95% CI = 1.5-21.7, P = 0.01) were the significant factors associated with significant fibrosis. CONCLUSIONS Hyperuricemia inversely predicts fibrosis stages. Females might carry a more disease severity than males in Taiwanese NASH patients.
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Affiliation(s)
- Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Chern Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pi-Jung Hsiao
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Endocrine Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shyi-Jang Shin
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Endocrine Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Tsai MS, Wang YC, Wang HH, Lee PH, Jeng LB, Kao CH. Pre-existing diabetes and risks of morbidity and mortality after liver transplantation: A nationwide database study in an Asian population. Eur J Intern Med 2015; 26:433-8. [PMID: 26048000 DOI: 10.1016/j.ejim.2015.05.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Revised: 04/23/2015] [Accepted: 05/17/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Whether diabetes mellitus (DM) is associated with a higher risk of perioperative mortality and mortality after liver transplantation (LTx) remains unclear. METHODS We compared the risk of postoperative mortality and morbidity in DM and non-DM patients undergoing LTx. We enrolled 558 DM patients who underwent LTx from 2000 to 2010. RESULTS DM was associated with elevated 90-day risk of post-LTx stroke. Otherwise, the DM cohort did not exhibit significantly higher risks of postoperative morbidities, such as septicemia, pneumonia, and wound infection, than the non-DM cohort. Cox proportional hazards regression model showed that patients with DM with coexisting renal manifestations were at a significantly high risk of 30-day and 90-day postoperative mortality. Further comorbidity stratification analysis showed that DM cohort exhibited higher risk of mortality than the non-DM cohort if the patients had liver cancer, or did not have hypertension, ischemic heart disease, and chronic obstructive pulmonary disease. CONCLUSION DM is associated with elevated risk of 90-day post-LTx. Moreover, DM patients with coexisting renal manifestations exhibited an increased postoperative risk of mortality after LTx.
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Affiliation(s)
- Ming-Shian Tsai
- Division of General Surgery, Department of Surgery, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Yu-Chiao Wang
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan
| | - Hsi-Hao Wang
- Division of Nephrology, Department of Internal Medicine, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Po-Huang Lee
- Division of General Surgery, Department of Surgery, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Long-Bin Jeng
- Department of Surgery, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.
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Tapan S, Sertoglu E, Kayadibi H, Uyanik M. Selection criteria for patients with non-alcoholic fatty liver disease and diabetes mellitus to achieve reliable results. Climacteric 2015; 18:329. [PMID: 25765619 DOI: 10.3109/13697137.2014.974533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Serkan Tapan
- Gulhane School of Medicine, Department of Medical Biochemistry , Ankara ;
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Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Dig Liver Dis 2015; 47:181-190. [PMID: 25739820 DOI: 10.1016/j.dld.2014.09.020] [Citation(s) in RCA: 504] [Impact Index Per Article: 50.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 09/19/2014] [Accepted: 09/21/2014] [Indexed: 02/07/2023]
Abstract
The conventional paradigm of nonalcoholic fatty liver disease representing the "hepatic manifestation of the metabolic syndrome" is outdated. We identified and summarized longitudinal studies that, supporting the association of nonalcoholic fatty liver disease with either type 2 diabetes mellitus or metabolic syndrome, suggest that nonalcoholic fatty liver disease precedes the development of both conditions. Online Medical databases were searched, relevant articles were identified, their references were further assessed and tabulated data were checked. Although several cross-sectional studies linked nonalcoholic fatty liver disease to either diabetes and other components of the metabolic syndrome, we focused on 28 longitudinal studies which provided evidence for nonalcoholic fatty liver disease as a risk factor for the future development of diabetes. Moreover, additional 19 longitudinal reported that nonalcoholic fatty liver disease precedes and is a risk factor for the future development of the metabolic syndrome. Finally, molecular and genetic studies are discussed supporting the view that aetiology of steatosis and lipid intra-hepatocytic compartmentation are a major determinant of whether fatty liver is/is not associated with insulin resistance and metabolic syndrome. Data support the novel paradigm of nonalcoholic fatty liver disease as a strong determinant for the development of the metabolic syndrome, which has potentially relevant clinical implications for diagnosing, preventing and treating metabolic syndrome.
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Affiliation(s)
- Amedeo Lonardo
- AUSL Modena and University of Modena and Reggio Emilia, Department of Biomedical, Metabolic and Neural Sciences, Division of Internal Medicine, NOCSAE - Baggiovara, Modena, Italy.
| | - Stefano Ballestri
- AUSL Modena, Department of Internal Medicine, Division of Internal Medicine, Hospital of Pavullo, Pavullo nel Frignano, Italy
| | - Giulio Marchesini
- "Alma Mater Studiorum" University, Unit of Metabolic Diseases and Clinical Dietetics, Bologna, Italy
| | - Paul Angulo
- University of Kentucky, Division of Digestive Diseases & Nutrition, Section of Hepatology, Medical Center, Lexington, KY, USA
| | - Paola Loria
- AUSL Modena and University of Modena and Reggio Emilia, Department of Biomedical, Metabolic and Neural Sciences, Division of Internal Medicine, NOCSAE - Baggiovara, Modena, Italy
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Buysschaert M, Medina JL, Bergman M, Shah A, Lonier J. Prediabetes and associated disorders. Endocrine 2015; 48:371-93. [PMID: 25294012 DOI: 10.1007/s12020-014-0436-2] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 09/20/2014] [Indexed: 12/14/2022]
Abstract
Prediabetes represents an elevation of plasma glucose above the normal range but below that of clinical diabetes. Prediabetes includes individuals with IFG, IGT, IFG with IGT and elevated HbA1c levels. Insulin resistance and β-cell dysfunction are characteristic of this disorder. The diagnosis of prediabetesis is vital as both IFG and IGT are indeed well-known risk factors for type 2 diabetes with a greater risk in the presence of combined IFG and IGT. Furthermore, as will be illustrated in this review, prediabetes is associated with associated disorders typically only considered in with established diabetes. These include cardiovascular disease, periodontal disease, cognitive dysfunction, microvascular disease, blood pressure abnormalities, obstructive sleep apnea, low testosterone, metabolic syndrome, various biomarkers, fatty liver disease, and cancer. As the vast majority of individuals with prediabetes are unaware of their diagnosis, it is therefore vital that the associated conditions are identified, particularly in the presence of mild hyperglycemia, so they may benefit from early intervention.
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Affiliation(s)
- Martin Buysschaert
- Department of Endocrinology and Diabetology, University Clinic Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
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Matsumoto N, Arase Y, Kawamura Y, Ohmoto-Sekine M, Amakawa K, Ogawa K, Tsuji H, Dong HS, Hara S, Akuta N, Suzuki F, Suzuki Y, Ikeda K, Kumada H, Kobayashi T. Significance of oral glucose tolerance tests in non-alcoholic fatty liver disease patients with a fasting plasma glucose level of <126 mg/dL and HbA1c level of ≤ 6.4% in Japan. Intern Med 2015; 54:875-80. [PMID: 25876566 DOI: 10.2169/internalmedicine.54.3437] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE The aim of this study was to clarify the indications for oral glucose tolerance tests (OGTT) in non-alcoholic fatty liver disease (NAFLD) subjects with a HbA1c level of ≤6.4%, fasting plasma glucose (FPG) level of <126 mg/dL and no history of diabetes. PATIENTS A total of 569 NAFLD subjects underwent 75-g OGTT. The plasma glucose and insulin levels were analyzed periodically for three hours during the OGTT examinations. Impaired fasting glucose (IFG) was defined as a plasma glucose level of ≥100 mg/dL to <126 mg/dL. Diabetes was defined as a two-hour post-load plasma glucose level of ≥200 mg/dL. Elevated insulin resistance was defined as a homeostasis model assessment-insulin resistance (HOMA-IR) of ≥2.5. Insulin secretory insufficiency was defined as an insulinogenic index of <0.4. RESULTS The prevalence of diabetes on the OGTT was 7.7% (44/569) among the NAFLD patients with an HbA1c level of ≤6.4%, FPG level of <126 mg/dL and no history of diabetes. A multivariate analysis showed that diabetes occurred more frequently when the subjects had IFG [odds ratio (OR) 5.13; 95% confidential interval (CI) 3.01-8.76; p<0.001] and an HbA1c level of 5.7-6.4% (OR 5.45; 95% CI 3.33-8.93; p<0.001). Of the NAFLD subjects with both IFG and an HbA1c level of 5.7-6.4%, 22.8% (28/123) exhibited a pattern of diabetes on OGTT. Regarding insulin dynamics, among the NAFLD subjects with both IFG and an HbA1c level of 5.7-6.4%, 25.2% (31/123) had elevated IR alone, 25.2% (31/123) had insulin secretory deficiency alone and 27.6% (34/123) had both elevated insulin resistance and insulin secretory deficiency. CONCLUSION NAFLD subjects with IFG and an HbA1c level of 5.7-6.4% should undergo OGTT in order to determine whether they have diabetes and/or abnormal insulin dynamics.
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Affiliation(s)
- Naoki Matsumoto
- Department of Health Management Center and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Japan
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Younossi ZM, Stepanova M, Saab S, Kalwaney S, Clement S, Henry L, Frost S, Hunt S. The impact of type 2 diabetes and obesity on the long-term outcomes of more than 85 000 liver transplant recipients in the US. Aliment Pharmacol Ther 2014; 40:686-94. [PMID: 25040315 DOI: 10.1111/apt.12881] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Revised: 06/25/2014] [Accepted: 06/27/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Type 2 diabetes is known to negatively impact the outcome of chronic liver disease. AIM To evaluate the impact of diabetes on the outcomes of liver transplants (LT). METHODS Study cohort included adults (>18 years) who received LT in the US between 1994 and 2013 (The Scientific Registry of Transplant Recipients). Pre- and post-transplant diabetes was recorded in patients with mortality follow-up. RESULTS We included 85 194 liver transplant recipients. Of those, 11.2% had history of pre-transplant diabetes. The most common indications for liver transplant were hepatitis C (36.4%), alcohol-related liver disease (20.6%), primary liver malignancy of unspecified aetiology (14.7%), cryptogenic cirrhosis (8.0%), hepatitis B (4.6%) and non-alcoholic steatohepatitis (3.9%). A total of 96.5% transplants were from deceased donors, and 7.9% donors had history of diabetes. During an average 6.5 years of follow-up, 31.3% recipients died and 8.8% had a graft failure. In multivariate survival analysis [at least 5 years of cohort follow-up (N = 35 870)], after adjustment for age, ethnicity, insurance type, history of chronic diseases, HCV infection and noncompliance, independent predictors of recipient mortality included the presence of pre-transplant diabetes [adjusted hazard ratio (95%CI) = 1.21 (1.12-1.30)] and developing diabetes post-transplant [1.06 (1.02-1.11)]. Donor's history of diabetes was also independently associated with higher mortality [1.10 (1.02-1.19)]. Furthermore, donor's history of diabetes was also associated with an increased the risk of liver graft failure [1.35 (1.24-1.47)]. CONCLUSIONS Presence of type 2 diabetes pre- and post-transplant, as well as presence of type 2 diabetes in the donors, are all associated with an increased risk of adverse post-transplant outcomes.
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Affiliation(s)
- Z M Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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Liu PJ, Ma F, Lou HP, Zhu YN, Chen Y. Relationship between serum uric acid levels and hepatic steatosis in non-obese postmenopausal women. Climacteric 2014; 17:692-9. [PMID: 24884478 DOI: 10.3109/13697137.2014.926323] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Serum uric acid levels have been reported to be associated with non-alcoholic fatty liver disease (NAFLD). However, very few studies specifically examining the relationship between serum uric acid (SUA) levels and NAFLD in postmenopausal women have been reported in China, especially in postmenopausal women with normal body mass index (BMI) in whom NAFLD is not uncommon. METHODS A cross-sectional study was employed of 528 Chinese normal-BMI postmenopausal women (aged 41-79 years) who participated in annual health check-ups. NAFLD is defined as a hepatic steatosis observed on liver ultrasonography in the absence of a second cause. Of all the participants, 121 women were diagnosed with hepatic steatosis (NAFLD group) and the others were without (non-NAFLD group). SUA quartiles were defined as follows: Q1, < 3.8 mg/dl; Q2, 3.8-4.4 mg/dl; Q3, 4.5-5.0 mg/dl; Q4, 5.1-6.0 mg/dl. Stepwise multivariable regression analysis was used to assess the relationships between SUA level and other variables. The association between SUA quartiles and hepatic steatosis was assessed using binary logistic regression. RESULTS Compared to the non-NAFLD group, the mean level of SUA was significantly higher in the NAFLD group (p < 0.01). The adjusted odds ratio (95% confidence interval) for the presence of hepatic steatosis in the highest SUA quartile vs. the lowest quartile was 2.774 (1.396-5.513) for all women (p < 0.01) after adjusting for the factors which were independently associated with uric acid level including waist circumference, high blood pressure, blood urea nitrogen, creatinine, γ-glutamyltransferase, and triglycerides. Most estimates changed little after further adjustment for age, metabolic syndrome, drinking status, and smoking status. The presence of hepatic steatosis significantly increased in the third and fourth quartiles of SUA. The prevalence of hepatic steatosis increased gradually with an increasing SUA quartile (p for trend < 0.01). CONCLUSION Higher SUA levels even within the normal range are positively and independently associated with the presence of hepatic steatosis in Chinese postmenopausal women with normal BMI.
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Affiliation(s)
- P J Liu
- * Department of Clinical Nutrition
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Affiliation(s)
- Naveed Sattar
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK
| | - Ewan Forrest
- Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow, UK
| | - David Preiss
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK
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Yilmaz Y, Senates E, Yesil A, Ergelen R, Colak Y. Not only type 2 diabetes but also prediabetes is associated with portal inflammation and fibrosis in patients with non-alcoholic fatty liver disease. J Diabetes Complications 2014; 28:328-31. [PMID: 24602757 DOI: 10.1016/j.jdiacomp.2014.01.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Revised: 01/23/2014] [Accepted: 01/24/2014] [Indexed: 02/06/2023]
Abstract
AIMS Growing evidence suggests that not only type 2 diabetes (T2D) but also prediabetes (PD) is common in patients with non-alcoholic fatty liver disease (NAFLD). However, few data exist on how PD impacts the histological characteristics of NAFLD patients. In this exploratory study, we sought to investigate the associations of PD and T2D with the severity of the histological features in patients with NAFLD. METHODS The population consisted of 280 patients with biopsy-proven NAFLD. The associations of PD and T2D with the severity of histological features of NAFLD were analyzed using multiple logistic (or ordinal logistic) regression models after adjustment for confounding factors. RESULTS PD and T2D was noted in 102 (36.4%) and 92 (32.8%) of patients, respectively. Of the 92 patients with T2D, ten (10.9%) were diagnosed de novo after the OGTT. PD and T2D were significantly associated with more severe portal inflammation (P<0.01); the adjusted odds ratios (ORs) of PD and T2D for having a higher grade of portal inflammation were 1.8 [95% CI, 1.1, 3.2] and 2.6 [95% CI, 1.3, 5.8]), respectively. A similar relationship was observed for liver fibrosis (P<0.001); specifically, the adjusted ORs of PD and T2D for having a higher grade of hepatic fibrosis were 2.4 [95% CI, 1.3, 3.7] and 3.8 [95% CI, 1.9, 6.1]), respectively. CONCLUSION Not only T2D but also PD is independently associated with portal inflammation and fibrosis in NAFLD patients. PD may be useful as a clinical indicator of patients who are likely to have already more severe histological findings.
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Affiliation(s)
- Yusuf Yilmaz
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey; Institute of Gastroenterology, Marmara University, Istanbul, Turkey.
| | - Ebubekir Senates
- Department of Gastroenterology, Dicle University, School of Medicine, Diyarbakir, Turkey
| | - Atakan Yesil
- Department of Gastroenterology, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey
| | - Rabia Ergelen
- Department of Radiology, Marmara University, School of Medicine, Istanbul, Turkey
| | - Yasar Colak
- Department of Gastroenterology, Istanbul Medeniyet University, Medical Faculty, Istanbul, Turkey
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Oka R, Aizawa T, Yagi K, Hayashi K, Kawashiri M, Yamagishi M. Elevated liver enzymes are related to progression to impaired glucose tolerance in Japanese men. Diabet Med 2014; 31:552-558. [PMID: 24151911 DOI: 10.1111/dme.12345] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Revised: 09/21/2013] [Accepted: 10/18/2013] [Indexed: 12/13/2022]
Abstract
AIMS To investigate whether the elevation of liver enzymes is associated with the progression from normal to impaired glucose tolerance. METHODS A historical cohort study was conducted in 594 male workers at public schools, who had normal glucose tolerance at baseline. The progression to impaired glucose tolerance and impaired fasting glycaemia during a mean follow-up of 3.1 years was measured using an oral glucose tolerance test. RESULTS Overall, 141 (23.7%) subjects developed impaired glucose tolerance and 68 (11.4%) subjects developed impaired fasting glycaemia, 23 of whom had combined impaired fasting glycaemia/impaired glucose tolerance. The incidence of impaired glucose tolerance increased significantly with increasing quartiles of serum aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase (P for trend <0.01). In Cox proportional hazards regression analysis, after adjusting for comprehensive risk factors, including plasma glucose levels, BMI and homeostatic model assessment of insulin resistance, the risk of progression to impaired glucose tolerance was significantly higher in the highest quartile of alanine aminotransferase than in the lowest quartile (hazard ratio 2.5; 95% CI 1.1-5.7). A significant association between alanine aminotransferase and the progression to impaired glucose tolerance was found after further adjustments for other liver enzymes or after the sample was limited to those with BMI < 25.0 kg/m(2) or with fasting plasma glucose < 5.5 mmol/l. CONCLUSIONS A higher level of alanine aminotransferase was independently associated with progression from normal to impaired glucose tolerance in Japanese men. The elevation of alanine aminotransferase may be a change that occurs early in the evolution of diabetes.
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Affiliation(s)
- R Oka
- Department of Internal Medicine, Hokuriku Central Hospital, Toyama, Japan
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Dogru T, Sertoglu E, Celebi G, Gurel H, Ercin CN. Endothelial dysfunction and carotid atherosclerosis in non-alcoholic fatty liver disease. Ups J Med Sci 2014; 119:58-9. [PMID: 24328674 PMCID: PMC3916721 DOI: 10.3109/03009734.2013.852276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
- Teoman Dogru
- Gulhane School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Erdim Sertoglu
- Ankara Mevki Military Hospital, Anittepe Dispensary, Biochemistry Laboratory, Ankara, Turkey
| | - Gurkan Celebi
- Gulhane School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Hasan Gurel
- Gulhane School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Cemal Nuri Ercin
- Gulhane School of Medicine, Department of Gastroenterology, Ankara, Turkey
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Abstract
Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease (NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.
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Chan WK, Bahar N, Razlan H, Vijayananthan A, Sithaneshwar P, Goh KL. Non-alcoholic fatty liver disease in a young multiracial Asian population: a worrying ethnic predilection in Malay and Indian males. Hepatol Int 2014. [PMID: 26202413 DOI: 10.1007/s12072-013-9510-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Previous studies on multiracial Malaysian populations found inordinately high prevalence of NAFLD among Malays and Indians. Whether the prevalence of NAFLD is different among young adults of different ethnic origins is not known. We aimed to determine racial differences in NAFLD in a young multiracial Malaysian population and associated factors. METHODS This was a cross-sectional study on medical students from the University of Malaya. Diagnosis of NAFLD was by transabdominal ultrasonography and following exclusion of significant alcohol intake and other causes of chronic liver disease. RESULTS Data of 469 subjects were analyzed (mean age 23.2 ± 2.4 years, 40.3 % male). The racial distribution was: Chinese 53.9 %, Malay 30.5 % and Indian 15.6 %. The overall prevalence of NAFLD was 7.9 %. Subjects with NAFLD were older, had greater BMI and WC, higher SBP and DBP, higher FBS, serum TG and LDL levels, and lower serum HDL level. The prevalence of NAFLD was higher among males compared to females (17.9 % vs. 3.3 %, p < 0.001). The highest prevalence of NAFLD was seen among Indian and Malay males at 33.3 and 25.5 %, respectively, compared to Chinese males at 6.8 % (p < 0.001). No significant difference was seen among females of different races. Independent factors associated with NAFLD were male gender, obesity and hypertriglyceridemia. CONCLUSIONS The difference in prevalence of NAFLD among the different ethnic groups can be observed as early as young adulthood. An inordinately high prevalence of NAFLD was observed among Malay and Indian males consistent with the higher prevalence of obesity in these groups.
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Affiliation(s)
- Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
| | - Norhaniza Bahar
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Hamizah Razlan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Anushya Vijayananthan
- Department of Bio-Medical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Pavai Sithaneshwar
- Clinical Diagnostic Laboratory, Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Khean-Lee Goh
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is commonly found in adults and adolescents with type 2 diabetes (T2DM). The cause-effect relations of these 2 conditions are complex and it is difficult to decipher whether one drives the other or vice versa. Genetic predispositions, along with obesity, are probably shared culprits of both. NAFLD may precede the diagnosis of diabetes and play a critical role of driving its development by way of increasing hepatic and whole body insulin resistance. On the other hand, T2DM is associated with hyperinsulinemia, a resistance to some of the effects of gut derived peptides and increased systemic free fatty acids, that can all promote hepatic lipid deposition. Thus, each condition may promote the development of the other and their mutual presence creates a vicious cycle. Upon studying this complex interplay from another angle, reduction of liver fat significantly improves glucose metabolism in patients with T2DM highlighting the tight pathophysiological link between them.
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Affiliation(s)
- Lior Hecht
- Department of Human Metabolism and Nutrition and the Section of Pediatric Endocrinology, Hadassah - Hebrew University School of Medicine, Jerusalem, Israel
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Korenaga K, Korenaga M, Teramoto F, Suzuki T, Nishina S, Sasaki K, Nakashima Y, Tomiyama Y, Yoshioka N, Hara Y, Moriya T, Hino K. Clinical usefulness of non-protein respiratory quotient measurement in non-alcoholic fatty liver disease. Hepatol Res 2013; 43:1284-94. [PMID: 23510120 DOI: 10.1111/hepr.12095] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2012] [Revised: 02/04/2013] [Accepted: 02/11/2013] [Indexed: 02/08/2023]
Abstract
AIM Little is known about the effects of non-alcoholic fatty liver disease (NAFLD) on energy metabolism, although this disease is associated with metabolic syndrome. We measured non-protein respiratory quotient (npRQ) using indirect calorimetry, which reflects glucose oxidation, and compared this value with histological disease severity in NAFLD patients. METHODS Subjects were 32 patients who were diagnosed with NAFLD histopathologically. Subjects underwent body composition analysis and indirect calorimetry, and npRQ was calculated. An oral glucose tolerance test was performed, and plasma glucose area under the curve (AUC glucose) was calculated. RESULTS There were no differences in body mass index, body fat percentage or visceral fat area among fibrosis stage groups. As fibrosis progressed, npRQ significantly decreased (stage 0, 0.895 ± 0.068; stage 1, 0.869 ± 0.067; stage 2, 0.808 ± 0.046; stage 3, 0.798 ± 0.026; P < 0.005). Glucose intolerance worsened and insulin resistance increased with fibrosis stage. npRQ was negatively correlated with AUC glucose (R = -0.6308, P < 0.001), Homeostasis Model of Assessment - Insulin Resistance (R = -0.5045, P < 0.005), fasting glucose (R = -0.4585, P < 0.01) and insulin levels (R = -0.4431, P < 0.05), suggesting that decreased npRQ may reflect impaired glucose tolerance due to insulin resistance, which was associated with fibrosis progression. Estimation of fibrosis stage using npRQ was as accurate as several previously established scoring systems using receiver-operator curve analysis. CONCLUSION npRQ was significantly decreased in patients with advanced NAFLD. Our data suggest that measurement of npRQ is useful for the estimation of disease severity in NAFLD patients.
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Affiliation(s)
- Keiko Korenaga
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
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Lomonaco R, Sunny NE, Bril F, Cusi K. Nonalcoholic fatty liver disease: current issues and novel treatment approaches. Drugs 2013; 73:1-14. [PMID: 23329465 DOI: 10.1007/s40265-012-0004-0] [Citation(s) in RCA: 115] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disorder in the Western world. It is commonly associated with insulin resistance, obesity, dyslipidaemia, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Nonalcoholic steatohepatitis (NASH) is characterized by steatosis with necroinflammation and eventual fibrosis, which can lead to end-stage liver disease and hepatocellular carcinoma. Its pathogenesis is complex, and involves a state of 'lipotoxicity' in which insulin resistance, with increased free fatty acid release from adipose tissue to the liver, play a key role in the onset of a 'lipotoxic liver disease' and its progression to NASH. The diagnosis of NASH is challenging, as most affected patients are symptom free and the role of routine screening is not clearly established. A complete medical history is important to rule out other causes of fatty liver disease (alcohol abuse, medications, other). Plasma aminotransferase levels and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for a definitive diagnosis. However, there is an active search for plasma biomarkers and imaging techniques that may non-invasively aid in the diagnosis. The treatment of NASH requires a multifaceted approach. The goal is to reverse obesity-associated lipotoxicity and insulin resistance via lifestyle intervention. Although there is no pharmacological agent approved for the treatment of NAFLD, vitamin E (in patients without T2DM) and the thiazolidinedione pioglitazone (in patients with and without T2DM) have shown the most consistent results in randomized controlled trials. This review concentrates on our current understanding of the disease, with a focus on the existing therapeutic approaches and potential future pharmacological developments for NAFLD and NASH.
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Affiliation(s)
- Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, 32610-0226, USA
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Hui E, Xu A, Bo Yang H, Lam KSL. Obesity as the common soil of non-alcoholic fatty liver disease and diabetes: Role of adipokines. J Diabetes Investig 2013; 4:413-25. [PMID: 24843689 PMCID: PMC4025109 DOI: 10.1111/jdi.12093] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2013] [Revised: 03/06/2013] [Accepted: 03/11/2013] [Indexed: 12/18/2022] Open
Abstract
Non‐alcoholic fatty liver disease (NAFLD) describes a spectrum of liver conditions from simple steatosis, steatohepatitis to end‐stage liver disease. The prevalence of NAFLD has been on the rise in many parts of the world, including Asia, and NAFLD is now the liver disease associated with the highest mortality, consequent to the increased risk of cardiovascular diseases and hepatocellular carcinoma. Whereas NAFLD is an independent risk factor for type 2 diabetes, increased hepatic and peripheral insulin resistance contribute to the pathogenesis of both NAFLD and diabetes, which are associated with enhanced cardiovascular risk. Studies in humans and animal models have suggested obesity as the common link of these two diseases, likely mediated by adipose tissue inflammation and dysregulated adipokine production in obesity. In the present review, we discuss recent advances in our understanding of the role of several novel adipokines (adiponectin, adipocyte fatty acid binding protein and fibroblast growth factor‐21) in the pathophysiology of NAFLD and diabetes, as well as their use as potential biomarkers and therapeutic targets for dysglycemia in NAFLD patients.
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Affiliation(s)
- Elaine Hui
- Endocrinology and Metabolism Division Department of Medicine the University of Hong Kong Hong Kong China
| | - Aimin Xu
- Research Centre of Heart, Brain, Hormone and Healthy Aging the University of Hong Kong Hong Kong China
| | - Hong Bo Yang
- Department of Endocrinology Peking Union Medical College Hospital Beijing China
| | - Karen S L Lam
- Endocrinology and Metabolism Division Department of Medicine the University of Hong Kong Hong Kong China ; Research Centre of Heart, Brain, Hormone and Healthy Aging the University of Hong Kong Hong Kong China
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Farrell GC, Wong VWS, Chitturi S. NAFLD in Asia--as common and important as in the West. Nat Rev Gastroenterol Hepatol 2013; 10:307-18. [PMID: 23458891 DOI: 10.1038/nrgastro.2013.34] [Citation(s) in RCA: 352] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
NAFLD--regarded as a consequence of the modern sedentary, food-abundant lifestyle prevalent in the West--was recorded in Japan nearly 50 years ago and its changing epidemiology during the past three decades is well-documented. NAFLD, and its pathologically more severe form NASH, occur in genetically susceptible people who are over-nourished. Asian people are particularly susceptible, partly owing to body composition differences in fat and muscle. Community prevalence ranges between 20% (China), 27% (Hong Kong), and 15-45% (South Asia, South-East Asia, Korea, Japan and Taiwan). This Review presents emerging data on genetic polymorphisms that predispose Asian people to NAFLD, NASH and cirrhosis, and discusses the clinical and pathological outcomes of these disorders. NAFLD is unlikely to be less severe in Asians than in other populations, but the associated obesity and diabetes pandemics have occurred more recently in Asia than in Europe and the USA, and occur with reduced degrees of adiposity. Cases of cryptogenic cirrhosis and hepatocellular carcinoma have also been attributed to NAFLD. Public health efforts to curb over-nutrition and insulin resistance are needed to prevent and/or reverse NAFLD, as well as its adverse health outcomes of type 2 diabetes, cardiovascular events, cirrhosis and liver cancer.
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Affiliation(s)
- Geoffrey C Farrell
- ANU Medical School, Australian National University and Gastroenterology and Hepatology Unit, The Canberra Hospital, Yamba Drive, Garran, ACT 2605, Australia.
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Kwok R, Wong VWS. Commentary: non-alcoholic fatty pancreas -- toward an uncharted territory. Aliment Pharmacol Ther 2013; 37:916. [PMID: 23551157 DOI: 10.1111/apt.12275] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2013] [Accepted: 02/18/2013] [Indexed: 12/08/2022]
Affiliation(s)
- R Kwok
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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