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Zhyzhneuskaya SV, Al‐Mrabeh AH, Peters C, Barnes AC, Hollingsworth KG, Welsh P, Sattar N, Lean MEJ, Taylor R. Clinical utility of liver function tests for resolution of metabolic dysfunction-associated steatotic liver disease after weight loss in the Diabetes Remission Clinical Trial. Diabet Med 2025; 42:e15462. [PMID: 39645664 PMCID: PMC11823348 DOI: 10.1111/dme.15462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 09/26/2024] [Accepted: 10/18/2024] [Indexed: 12/10/2024]
Abstract
AIMS Ectopic fat is reduced by effective weight management, but difficult to assess clinically. METHODS We evaluated paired data on 42 participants in the intervention group of the Diabetes Remission Clinical Trial (DiRECT) at baseline, 12 and 24 months after weight loss as indicators of liver fat content measured by 3-point Dixon MRI. RESULTS Baseline liver fat was elevated at 13.0 [7.8-23.3]% with fasting plasma glucose 7.9 [7.1-10.1] mmol/L. Prevalence of baseline MASLD was 86.4%. After weight loss of 11.9 ± 1.2 kg (0-37 kg) at 12 months, remission of MASLD occurred in 74% and liver fat normalised for many (1.8 [1.2-5.2]%; p < 0.0001) as did fasting glucose (5.9 [5.5-7.2] mmol/L; p < 0.0001). Alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) decreased at 12 months by 38 [19-60]% (p < 0·0001) and 38 [16-53]% (p < 0.0001) respectively. The positive predictive value for decrease in liver fat, with baseline values of >40 IU/L, was 100% for ALT and 87.5% for GGT. As expected, change in liver fat correlated with change in ALT (r = 0.64; p < 0.0001), GGT (r = 0.38; p = 0.013), AST (r = 0.36; p = 0.018), fatty liver index (r = 0.50; p < 0.0001) and hepatic steatosis index (r = 0.44; p < 0.0001). CONCLUSION Metabolic dysfunction-associated steatotic liver disease, an important marker of ill-health is improved by intentional weight loss. If enzyme levels are raised at baseline, following weight loss, changes in ALT and GGT usefully reflect change in liver fat content, with high positive predictive value. Monitoring liver enzymes can provide a simple way to assess change in liver fat following weight loss in day-to-day clinical practice.
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Affiliation(s)
- S. V. Zhyzhneuskaya
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
- University Hospital of North Durham, County Durham and Darlington NHS Foundation TrustDurhamUK
| | - A. H. Al‐Mrabeh
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
- Centre for Cardiovascular Science, Queen's Medical Research Institute, University of EdinburghEdinburghUK
| | - C. Peters
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
| | - A. C. Barnes
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle UniversityNewcastle upon TyneUK
| | - K. G. Hollingsworth
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
| | - P. Welsh
- School of Cardiovascular and Metabolic Health, College of Medical Veterinary and Life Sciences, University of GlasgowGlasgowUK
| | - N. Sattar
- School of Cardiovascular and Metabolic Health, College of Medical Veterinary and Life Sciences, University of GlasgowGlasgowUK
| | - M. E. J. Lean
- Human Nutrition, School of Medicine, Dentistry and Nursing, College of Medical Veterinary and Life Sciences, University of GlasgowGlasgowUK
| | - R. Taylor
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
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Tang SS, Zhao XF, An XD, Sun WJ, Kang XM, Sun YT, Jiang LL, Gao Q, Li ZH, Ji HY, Lian FM. Classification and identification of risk factors for type 2 diabetes. World J Diabetes 2025; 16:100371. [PMID: 39959280 PMCID: PMC11718467 DOI: 10.4239/wjd.v16.i2.100371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 10/24/2024] [Accepted: 11/26/2024] [Indexed: 12/30/2024] Open
Abstract
The risk factors for type 2 diabetes mellitus (T2DM) have been increasingly researched, but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors, which are categorized in this paper into five categories: Social determinants, lifestyle, checkable/testable risk factors, history of illness and medication, and other factors, which are discussed in a narrative review. Meanwhile, this paper points out the problems of the current research, helps to improve the systematic categorisation and practicality of T2DM risk factors, and provides a professional research basis for clinical practice and industry decision-making.
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Affiliation(s)
- Shan-Shan Tang
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
| | - Xue-Fei Zhao
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Xue-Dong An
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Wen-Jie Sun
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Xiao-Min Kang
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Yu-Ting Sun
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Lin-Lin Jiang
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Qing Gao
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Ze-Hua Li
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Hang-Yu Ji
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
| | - Feng-Mei Lian
- Department of Endocrinology, Guang’anmen Hospital, Beijing 100053, China
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Zhao H, Ji B, Wang X, Shi S, Sheng J, Ma X, Ban B, Gao G. Association between SPISE and NAFLD in patients with type 2 diabetes. Front Med (Lausanne) 2025; 12:1454938. [PMID: 39911865 PMCID: PMC11794499 DOI: 10.3389/fmed.2025.1454938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 01/06/2025] [Indexed: 02/07/2025] Open
Abstract
Aims Non-alcoholic fatty liver disease (NAFLD) is closely related to type 2 diabetes (T2D), with reduced insulin sensitivity being a key factor in their disrupted metabolic processes. The single point insulin sensitivity estimator (SPISE) is a novel index. This study aims to explore the association between SPISE and NAFLD in T2D population. Methods This study included a total of 2,459 patients with T2D. SPISE was calculated based on high density lipoprotein-cholesterol (HDL-c), triglycerides (TG), and body mass index (BMI). Participants were categorized into NAFLD and non-NAFLD groups based on the results of ultrasonographic diagnosis. The relationship between SPISE and NAFLD was analyzed separately for each gender. Results The overall prevalence of NAFLD is 38.5%. In females and males, the SPISE was significantly reduced in the NAFLD group compared to the non-NAFLD group (both P < 0.05). The prevalence of NAFLD showed a significant reduction across quartiles of the SPISE in both genders (both P < 0.05).Additionally, univariate correlation analysis showed a negative correlation between SPISE and NAFLD (both P < 0.05). In multivariate regression analysis, a reduced SPISE was identified as an independent risk factor for NAFLD (odds ratios of 0.572 and 0.737, 95% CI of 0.477-0.687 and 0.587-0.926, respectively).Moreover, the area under the receiver operating characteristic (ROC) curve for SPISE was 0.209 in females and 0.268 in males (95% CI of 0.175-0.244 and 0.216-0.320, respectively). These results are more meaningful than those of other variables. Conclusion SPISE is significantly reduced in NAFLD patients with T2D. Compared to other indicators, SPISE demonstrates superior predictive value in diagnosing NAFLD, and it is independent of gender.
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Affiliation(s)
- Hongyan Zhao
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
- Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, China
| | - Baolan Ji
- Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, China
| | - Xin Wang
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
| | - Shuwei Shi
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
- Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, China
| | - Jie Sheng
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
- Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, China
| | - Xuan Ma
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
- Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, China
| | - Bo Ban
- Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Guanqi Gao
- Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, China
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Sumida Y, Toyoda H, Yasuda S, Kimoto S, Sakamoto K, Nakade Y, Ito K, Osonoi T, Yoneda M. Comparison of Efficacy between Pemafibrate and Omega-3-Acid Ethyl Ester in the Liver: the PORTRAIT Study. J Atheroscler Thromb 2024; 31:1620-1633. [PMID: 38777770 PMCID: PMC11537790 DOI: 10.5551/jat.64896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 04/15/2024] [Indexed: 05/25/2024] Open
Abstract
AIM No pharmacotherapeutic treatment has been established for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This trial compared the effects of pemafibrate and omega-3-acid ethyl ester on hepatic function in patients with hypertriglyceridemia complicated by MASLD. METHODS Patients with hypertriglyceridemia complicated by MASLD were enrolled, randomly assigned to the pemafibrate or omega-3-acid ethyl ester group, and followed for 24 weeks. The primary endpoint was the change in alanine aminotransferase (ALT) from baseline to week 24. The secondary endpoints included other hepatic enzymes, lipid profiles, and hepatic fibrosis biomarkers. RESULTS A total of 80 patients were enrolled and randomized. The adjusted mean change in ALT from baseline to week 24 was significantly lower in the pemafibrate group (-19.7±5.9 U/L) than in the omega-3-acid ethyl ester group (6.8±5.5 U/L) (intergroup difference, -26.5 U/L; 95% confidence interval, -42.3 to -10.7 U/L; p=0.001). Pemafibrate significantly improved the levels of other hepatic enzymes (aspartate aminotransferase and gamma-glutamyl transpeptidase), lipid profiles (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol), and hepatic fibrosis biomarkers (Mac-2 binding protein glycan isomer and Fibrosis-4 index). No cases of discontinuation due to adverse drug reactions were identified in either group, and there were no safety concerns. CONCLUSIONS Pemafibrate is recommended over omega-3-acid ethyl ester for lipid management and MASLD treatment in patients with hypertriglyceridemia complicated by MASLD. The study results may contribute to the development of future treatment strategies for patients with MASLD/MASH.
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Affiliation(s)
- Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | | | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital
| | - Satoshi Kimoto
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | - Kazumasa Sakamoto
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | - Yukiomi Nakade
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | - Kiyoaki Ito
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
| | | | - Masashi Yoneda
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University
- Goryokai Clinic
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Taylor R. Understanding the cause of type 2 diabetes. Lancet Diabetes Endocrinol 2024; 12:664-673. [PMID: 39038473 DOI: 10.1016/s2213-8587(24)00157-8] [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] [Received: 03/11/2024] [Revised: 05/23/2024] [Accepted: 05/23/2024] [Indexed: 07/24/2024]
Abstract
Type 2 diabetes has long been thought to have heterogenous causes, even though epidemiological studies uniformly show a tight relationship with overnutrition. The twin cycle hypothesis postulated that interaction of self-reinforcing cycles of fat accumulation inside the liver and pancreas, driven by modest but chronic positive calorie balance, could explain the development of type 2 diabetes. This hypothesis predicted that substantial weight loss would bring about a return to the non-diabetic state, permitting observation of the pathophysiology determining the transition. These changes were postulated to reflect the basic mechanisms of causation in reverse. A series of studies over the past 15 years has elucidated these underlying mechanisms. Together with other research, the interaction of environmental and genetic factors has been clarified. This knowledge has led to successful implementation of a national programme for remission of type 2 diabetes. This Review discusses the paucity of evidence for heterogeneity in causes of type 2 diabetes and summarises the in vivo pathophysiological changes, which cause this disease of overnutrition. Type 2 diabetes has a homogenous cause expressed in genetically heterogenous individuals.
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Affiliation(s)
- Roy Taylor
- Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
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Liu Y, Liang X, Hu Y, Zhang N, Zhu X, Feng Y, Qin Z, Wang Z, Kangzhuo B, Xiao X, Zhao X. Temporal relationship between hepatic steatosis and fasting blood glucose elevation: a longitudinal analysis from China and UK. BMC Public Health 2024; 24:1865. [PMID: 38997689 PMCID: PMC11241918 DOI: 10.1186/s12889-024-19177-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 06/17/2024] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect. METHODS This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects. RESULTS In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (βCMEC = 0.068, βUK-Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (βCMEC = 0.027, βUK-Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D. CONCLUSIONS Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.
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Affiliation(s)
- Yujie Liu
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, CN, 610041, China
| | - Xian Liang
- Chengdu Center for Disease Control and Prevention, Chengdu, China
| | - Yifan Hu
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, CN, 610041, China
| | - Ning Zhang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, CN, 610041, China
| | - Xingren Zhu
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, CN, 610041, China
| | - Yuemei Feng
- School of Public Health, Kunming Medical University, Kunming, China
| | - Zixiu Qin
- School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China
| | - Zihao Wang
- Chongqing Center for Disease Control and Prevention, Chongqing, China
| | - Baima Kangzhuo
- High Altitude Health Science Research Center of Tibet University, Lhasa, Tibet, China
| | - Xiong Xiao
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, CN, 610041, China.
| | - Xing Zhao
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, CN, 610041, China
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Park KY, Hwang HS, Han K, Park HK. Changes in Fatty Liver Disease and Incident Diabetes Mellitus in Young Korean Adults. Am J Prev Med 2024; 66:717-724. [PMID: 38008134 DOI: 10.1016/j.amepre.2023.11.021] [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] [Received: 06/09/2023] [Revised: 11/20/2023] [Accepted: 11/20/2023] [Indexed: 11/28/2023]
Abstract
INTRODUCTION This study sought to assess the association between the changes in nonalcoholic fatty liver disease (NAFLD) and risk of type 2 diabetes in young individuals with prediabetes. METHODS Data from the Korean National Health Insurance System database were collected from 2009 to 2019 and analyzed in 2022. A total of 446,813 young adults aged 20-39 years with prediabetes who underwent two National Health Screening examinations from 2009 to 2012 were followed up. NAFLD was defined as a fatty liver index≥60 without liver disease or history of alcohol abuse. Multivariable Cox proportional hazards regression was used to calculate the HR and CIs for type 2 diabetes according to NAFLD changes. RESULTS During a median follow-up of 8.3 years, 26,464 (5.9%) young individuals developed type 2 diabetes. Multivariable adjusted HR of type 2 diabetes according to the NAFLD change was 5.38 (95% CI 5.08-5.70) in individuals with persistent NAFLD when compared to those who never had NAFLD. Even in individuals who were consistently nonobese, resolved NAFLD, new NAFLD, and persistent NAFLD were associated with>3-fold increased risk of type 2 diabetes compared to nonobese individuals without NAFLD. The risk of type 2 diabetes also increased in obese individuals without NAFLD by 2-fold when compared to nonobese individuals without NAFLD. CONCLUSIONS NAFLD that either existed persistently or ever existed plays a critical role in the development of type 2 diabetes in young adults with or without obesity. Nonobese individuals with NAFLD warrant special attention.
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Affiliation(s)
- Kye-Yeung Park
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, South Korea
| | - Hwan-Sik Hwang
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, South Korea.
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea.
| | - Hoon-Ki Park
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, South Korea
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Chan KE, Ong EYH, Chung CH, Ong CEY, Koh B, Tan DJH, Lim WH, Yong JN, Xiao J, Wong ZY, Syn N, Kaewdech A, Teng M, Wang JW, Chew N, Young DY, Know A, Siddiqui MS, Huang DQ, Tamaki N, Wong VWS, Mantzoros CS, Sanyal A, Noureddin M, Ng CH, Muthiah M. Longitudinal Outcomes Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-analysis of 129 Studies. Clin Gastroenterol Hepatol 2024; 22:488-498.e14. [PMID: 37775028 DOI: 10.1016/j.cgh.2023.09.018] [Citation(s) in RCA: 34] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 08/30/2023] [Accepted: 09/01/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND & AIMS The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. METHODS To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. RESULTS One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD. CONCLUSIONS The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.
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Affiliation(s)
- Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Elden Yen Hng Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Charlotte Hui Chung
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Christen En Ya Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Benjamin Koh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Zhen Yu Wong
- Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Margaret Teng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Jiong-Wei Wang
- Department of Surgery, Cardiovascular Research Institute (CVRI), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Nanomedicine Translational Research Programme, Centre for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Nicholas Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Dan Yock Young
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Alfred Know
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Hospital Singapore, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Christos S Mantzoros
- Division of Endocrinology, Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts
| | - Arun Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | | | - Cheng Han Ng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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Andreozzi F, Mancuso E, Mazza E, Mannino GC, Fiorentino TV, Arturi F, Succurro E, Perticone M, Sciacqua A, Montalcini T, Pujia A, Sesti G. One-hour post-load glucose levels are associated with hepatic steatosis assessed by transient elastography. Diabetes Obes Metab 2024; 26:682-689. [PMID: 37953652 DOI: 10.1111/dom.15358] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 10/11/2023] [Accepted: 10/19/2023] [Indexed: 11/14/2023]
Abstract
AIM To examine the association between 1-hour plasma glucose (PG) concentration and markers of non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). METHODS We performed TE in 107 metabolically well-characterized non-diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. RESULTS Controlled attenuation parameter correlated significantly with 1-hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2-hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high-density lipoprotein cholesterol (r = -0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1-hour PG (β = 0.274, P = 0.008) and fasting insulin levels (β = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1-hour PG was the sole predictor of CAP variation (β = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1-hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43-11.13; P = 0.008) than individuals with 1-hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1-hour PG and LS. CONCLUSION Our data confirm that 1-hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low-impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy.
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Affiliation(s)
- Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elettra Mancuso
- Department of Science of Health, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elisa Mazza
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Gaia Chiara Mannino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Franco Arturi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Maria Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Tiziana Montalcini
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
- Department of Clinical and Experimental Medicine, University Magna Greaecia of Catanzaro, Catanzaro, Italy
| | - Arturo Pujia
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
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10
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Kim JH, Lyu YS, Kim MK, Kim SY, Baek KH, Song KH, Han K, Kwon HS. Repeated detection of non-alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults. Diabetes Obes Metab 2024; 26:180-190. [PMID: 37872007 DOI: 10.1111/dom.15304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/14/2023] [Accepted: 09/15/2023] [Indexed: 10/25/2023]
Abstract
AIM This study aimed to investigate the effects of repeated detection of non-alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults. MATERIALS AND METHODS In this nationwide population-based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20-39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0-4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points. RESULTS The multivariable-adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57-2.921), 3.45 (3.221-3.694), 4.588 (4.303-4.892) and 6.126 (5.77-6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores. CONCLUSIONS Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.
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Affiliation(s)
- Jin Hwa Kim
- Department of Endocrinology and Metabolism, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of Korea
| | - Young Sang Lyu
- Department of Endocrinology and Metabolism, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Yong Kim
- Department of Endocrinology and Metabolism, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of Korea
| | - Ki-Hyun Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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11
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Park KY, Park JH, Han K, Yu SH, Lee CB, Kim DS, Park HK, Hwang HS, Hong S. Fatty Liver Change in Older Adults as an Important Risk Factor for Type 2 Diabetes: A Nationwide Cohort Study. Mayo Clin Proc 2023; 98:1809-1819. [PMID: 37804267 DOI: 10.1016/j.mayocp.2023.02.033] [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] [Received: 07/04/2022] [Revised: 01/16/2023] [Accepted: 02/28/2023] [Indexed: 10/09/2023]
Abstract
OBJECTIVE To examine the association between changes in fatty liver disease (FLD) over time and the risk of type 2 diabetes in elderly individuals with prediabetes. METHODS A total of 156,984 elderly individuals with prediabetes who underwent national health screening in 2009 and 2011 were followed up through December 31, 2019. The FLD status was defined as a change in the fatty liver index. Prediabetes was defined as impaired fasting glucose levels at baseline. Multivariable Cox proportional hazards regression was used to calculate the hazard ratio and CIs for type 2 diabetes according to the changes in FLD. RESULTS During a median of 8.35 years of follow-up, type 2 diabetes developed in 29,422 (18.7%) elderly individuals with prediabetes. Multivariable adjusted hazard ratio of type 2 diabetes according to FLD change was 2.22 (95% CI, 2.11 to 2.34) in individuals with persistent FLD compared with those who have never had FLD. Although overall weight loss of 5% or more was associated with a 7% lower risk of type 2 diabetes in total participants, fatty liver status was important. Even with weight loss, those with a history of fatty liver-resolved FLD, new FLD, or persistent FLD-had an increased risk of type 2 diabetes. The risk of type 2 diabetes did not increase in individuals with sustained FLD-free status, regardless of weight change. CONCLUSION The presence and change of FLD are important factors for the development of type 2 diabetes in elderly individuals with prediabetes.
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Affiliation(s)
- Kye-Yeung Park
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, South Korea
| | - Jung Hwan Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea
| | - Sung Hoon Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University Guri Hospital, South Korea
| | - Chang Beom Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University Guri Hospital, South Korea
| | - Dong Sun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea
| | - Hoon-Ki Park
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, South Korea
| | - Hwan-Sik Hwang
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, South Korea
| | - Sangmo Hong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University Guri Hospital, South Korea.
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12
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Mathrani A, Lu LW, Sequeira-Bisson IR, Silvestre MP, Hoggard M, Barnett D, Fogelholm M, Raben A, Poppitt SD, Taylor MW. Gut microbiota profiles in two New Zealand cohorts with overweight and prediabetes: a Tū Ora/PREVIEW comparative study. Front Microbiol 2023; 14:1244179. [PMID: 38033566 PMCID: PMC10687470 DOI: 10.3389/fmicb.2023.1244179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 10/20/2023] [Indexed: 12/02/2023] Open
Abstract
Obesity-related metabolic diseases such as type 2 diabetes (T2D) are major global health issues, affecting hundreds of millions of people worldwide. The underlying factors are both diverse and complex, incorporating biological as well as cultural considerations. A role for ethnicity - a measure of self-perceived cultural affiliation which encompasses diet, lifestyle and genetic components - in susceptibility to metabolic diseases such as T2D is well established. For example, Asian populations may be disproportionally affected by the adverse 'TOFI' (Thin on the Outside, Fat on the Inside) profile, whereby outwardly lean individuals have increased susceptibility due to excess visceral and ectopic organ fat deposition. A potential link between the gut microbiota and metabolic disease has more recently come under consideration, yet our understanding of the interplay between ethnicity, the microbiota and T2D remains incomplete. We present here a 16S rRNA gene-based comparison of the fecal microbiota of European-ancestry and Chinese-ancestry cohorts with overweight and prediabetes, residing in New Zealand. The cohorts were matched for mean fasting plasma glucose (FPG: mean ± SD, European-ancestry: 6.1 ± 0.4; Chinese-ancestry: 6.0 ± 0.4 mmol/L), a consequence of which was a significantly higher mean body mass index in the European group (BMI: European-ancestry: 37.4 ± 6.8; Chinese-ancestry: 27.7 ± 4.0 kg/m2; p < 0.001). Our findings reveal significant microbiota differences between the two ethnicities, though we cannot determine the underpinning factors. In both cohorts Firmicutes was by far the dominant bacterial phylum (European-ancestry: 93.4 ± 5.5%; Chinese-ancestry: 79.6 ± 10.4% of 16S rRNA gene sequences), with Bacteroidetes and Actinobacteria the next most abundant. Among the more abundant (≥1% overall relative sequence abundance) genus-level taxa, four zero-radius operational taxonomic units (zOTUs) were significantly higher in the European-ancestry cohort, namely members of the Subdoligranulum, Blautia, Ruminoclostridium, and Dorea genera. Differential abundance analysis further identified a number of additional zOTUs to be disproportionately overrepresented across the two ethnicities, with the majority of taxa exhibiting a higher abundance in the Chinese-ancestry cohort. Our findings underscore a potential influence of ethnicity on gut microbiota composition in the context of individuals with overweight and prediabetes.
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Affiliation(s)
- Akarsh Mathrani
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Louise W. Lu
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
| | - Ivana R. Sequeira-Bisson
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
| | - Marta P. Silvestre
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
- Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS), NOVA University of Lisbon, Lisbon, Portugal
| | - Michael Hoggard
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
| | - Daniel Barnett
- Department of Statistics, University of Auckland, Auckland, New Zealand
| | - Mikael Fogelholm
- Department of Food and Nutrition, Faculty of Agriculture and Forestry, University of Helsinki, Helsinki, Finland
| | - Anne Raben
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
- Clinical Research, Copenhagen University Hospital – Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Sally D. Poppitt
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Michael W. Taylor
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
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13
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En Li Cho E, Ang CZ, Quek J, Fu CE, Lim LKE, Heng ZEQ, Tan DJH, Lim WH, Yong JN, Zeng R, Chee D, Nah B, Lesmana CRA, Bwa AH, Win KM, Faulkner C, Aboona MB, Lim MC, Syn N, Kulkarni AV, Suzuki H, Takahashi H, Tamaki N, Wijarnpreecha K, Huang DQ, Muthiah M, Ng CH, Loomba R. Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Gut 2023; 72:2138-2148. [PMID: 37491159 DOI: 10.1136/gutjnl-2023-330110] [Citation(s) in RCA: 98] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/20/2023] [Indexed: 07/27/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with type 2 diabetes mellitus (T2DM) as a major predictor. Insulin resistance and chronic inflammation are key pathways in the pathogenesis of T2DM leading to NAFLD and vice versa, with the synergistic effect of NAFLD and T2DM increasing morbidity and mortality risks. This meta-analysis aims to quantify the prevalence of NAFLD and the prevalence of clinically significant and advanced fibrosis in people with T2DM. METHODS MEDLINE and Embase databases were searched from inception until 13 February 2023. The primary outcomes were the prevalence of NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis in people with T2DM. A generalised linear mixed model with Clopper-Pearson intervals was used for the analysis of proportions with sensitivity analysis conducted to explore heterogeneity between studies. RESULTS 156 studies met the inclusion criteria, and a pooled analysis of 1 832 125 patients determined that the prevalence rates of NAFLD and NASH in T2DM were 65.04% (95% CI 61.79% to 68.15%, I2=99.90%) and 31.55% (95% CI 17.12% to 50.70%, I2=97.70%), respectively. 35.54% (95% CI 19.56% to 55.56%, I2=100.00%) of individuals with T2DM with NAFLD had clinically significant fibrosis (F2-F4), while 14.95% (95% CI 11.03% to 19.95%, I2=99.00%) had advanced fibrosis (F3-F4). CONCLUSION This study determined a high prevalence of NAFLD, NASH and fibrosis in people with T2DM. Increased efforts are required to prevent T2DM to combat the rising burden of NAFLD. PROSPERO REGISTRATION NUMBER CRD42022360251.
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Affiliation(s)
- Elina En Li Cho
- Department of Medicine, National University Hospital, Singapore
| | - Chong Zhe Ang
- Department of Medicine, National University Hospital, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Clarissa Elysia Fu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Lincoln Kai En Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Zane En Qi Heng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Rebecca Zeng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Douglas Chee
- Department of Medicine, National University Hospital, Singapore
| | - Benjamin Nah
- Department of Medicine, National University Hospital, Singapore
| | | | - Aung Hlaing Bwa
- Department of Medical Research, Union of Myanmar, Naypyidaw, Myanmar
| | - Khin Maung Win
- Department of Medical Research, Union of Myanmar, Naypyidaw, Myanmar
| | - Claire Faulkner
- Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Majd B Aboona
- Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Mei Chin Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Diagnostic Imaging, National University Health System, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Anand V Kulkarni
- Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Hiroyuki Suzuki
- Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | | | - Nobuharu Tamaki
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, Musashino Red Cross Hospital, Musashino, Japan
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, University of Michigan, Michigan, Michigan, USA
| | - Daniel Q Huang
- Department of Medicine, National University Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Mark Muthiah
- Department of Medicine, National University Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Rohit Loomba
- Department of Medicine, University of California San Diego, La Jolla, California, USA
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14
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Jung DJ. Association between fatty liver disease and hearing impairment in Korean adults: a retrospective cross-sectional study. JOURNAL OF YEUNGNAM MEDICAL SCIENCE 2023; 40:402-411. [PMID: 37376734 PMCID: PMC10626306 DOI: 10.12701/jyms.2023.00304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/03/2023] [Accepted: 05/11/2023] [Indexed: 06/29/2023]
Abstract
BACKGROUND We hypothesized that fatty liver disease (FLD) is associated with a high prevalence of hearing loss (HL) owing to metabolic disturbances. This study aimed to evaluate the association between FLD and HL in a large sample of the Korean population. METHODS We used a dataset of adults who underwent routine voluntary health checkups (n=21,316). Fatty liver index (FLI) was calculated using Bedogni's equation. The patients were divided into two groups: the non-FLD (NFLD) group (n=18,518, FLI <60) and the FLD group (n=2,798, FLI ≥60). Hearing thresholds were measured using an automatic audiometer. The average hearing threshold (AHT) was calculated as the pure-tone average at four frequencies (0.5, 1, 2, and 3 kHz). HL was defined as an AHT of >40 dB. RESULTS HL was observed in 1,370 (7.4%) and 238 patients (8.5%) in the NFLD and FLD groups, respectively (p=0.041). Compared with the NFLD group, the odds ratio for HL in the FLD group was 1.16 (p=0.040) and 1.46 (p<0.001) in univariate and multivariate logistic regression analyses, respectively. Linear regression analyses revealed that FLI was positively associated with AHT in both univariate and multivariate analyses. Analyses using a propensity score-matched cohort showed trends similar to those using the total cohort. CONCLUSION FLD and FLI were associated with poor hearing thresholds and HL. Therefore, active monitoring of hearing impairment in patients with FLD may be helpful for early diagnosis and treatment of HL in the general population.
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Affiliation(s)
- Da Jung Jung
- Department of Otorhinolaryngology-Head and Neck Surgery, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
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15
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Kouvari M, Sergi D, Zec M, Naumovski N. Editorial: Nutrition in prevention and management of non-alcoholic fatty liver disease. Front Nutr 2023; 10:1212363. [PMID: 37521411 PMCID: PMC10374431 DOI: 10.3389/fnut.2023.1212363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 07/04/2023] [Indexed: 08/01/2023] Open
Affiliation(s)
- Matina Kouvari
- Discipline of Nutrition and Dietetics, Faculty of Health, University of Canberra, Canberra, ACT, Australia
- Functional Foods and Nutrition Research (FFNR) Laboratory, University of Canberra, Bruce, Ngunnawal Country, ACT, Australia
| | - Domenico Sergi
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Manja Zec
- School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, United States
| | - Nenad Naumovski
- Discipline of Nutrition and Dietetics, Faculty of Health, University of Canberra, Canberra, ACT, Australia
- Functional Foods and Nutrition Research (FFNR) Laboratory, University of Canberra, Bruce, Ngunnawal Country, ACT, Australia
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16
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Park SH, Park J, Kwon SY, Lee YB, Kim G, Hur KY, Koh J, Jee JH, Kim JH, Kang M, Jin SM. Increased risk of incident diabetes in patients with MAFLD not meeting the criteria for NAFLD. Sci Rep 2023; 13:10677. [PMID: 37393407 PMCID: PMC10314928 DOI: 10.1038/s41598-023-37858-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 06/28/2023] [Indexed: 07/03/2023] Open
Abstract
We aimed to compare the risk of incident diabetes according to fatty liver disease (FLD) definition, focusing on the comparison between those who met criteria for either metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) but not the other. This was a 5.0-year (interquartile range, 2.4-8.2) retrospective longitudinal cohort study of 21,178 adults who underwent at least two serial health checkup examinations. The presence of hepatic steatosis was determined by abdominal ultrasonography at the first health examination. Cox proportional hazard analyses were used to compare the risk of incident diabetes among five groups. Incident diabetes cases occurred in 1296 participants (6.1%). When non-FLD without metabolic dysfunction (MD) group was set as a reference, the risk of incident diabetes increased in the order of NAFLD-only, non-FLD with MD, both FLD, and MAFLD-only groups. The presence of excessive alcohol consumption and/or hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, FLD, and MD synergistically increased the risk of incident diabetes. MAFLD-only group showed a greater increase in incidence of diabetes than non-FLD with MD and NAFLD-only groups. The interaction among excessive alcohol consumption, HBV/HCV infection, MD, and hepatic steatosis on the development of diabetes should not be overlooked.
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Affiliation(s)
- So Hee Park
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Jiyun Park
- Division of Endocrine and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, Gyeonggi-do, 14396, Republic of Korea
| | - So Yoon Kwon
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - You-Bin Lee
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Janghyun Koh
- Department of Health Promotion Center, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Jae Hwan Jee
- Department of Health Promotion Center, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Mira Kang
- Department of Health Promotion Center, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
- Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
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Deravi N, Dehghani Firouzabadi F, Moosaie F, Asadigandomani H, Arab Bafrani M, Yoosefi N, Poopak A, Dehghani Firouzabadi M, Poudineh M, Rabizadeh S, Kamel I, Nakhjavani M, Esteghamati A. Non-alcoholic fatty liver disease and incidence of microvascular complications of diabetes in patients with type 2 diabetes: a prospective cohort study. Front Endocrinol (Lausanne) 2023; 14:1147458. [PMID: 37342261 PMCID: PMC10277724 DOI: 10.3389/fendo.2023.1147458] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 05/17/2023] [Indexed: 06/22/2023] Open
Abstract
Objective To investigate the association between non-alcoholic fatty liver disease (NAFLD) and liver enzymes with the incidence of microvascular complications (neuropathy, retinopathy, and nephropathy) in a cohort of Iranian patients with type 2 diabetes. Methods For a total population of 3123 patients with type 2 diabetes, a prospective study was designed for 1215 patients with NAFLD and 1908 gender and age-matched control patients without NAFLD. The two groups were followed for a median duration of 5 years for the incidence of microvascular complications. The association between having NAFLD, the level of liver enzymes, aspartate aminotransferase to platelet ratio index (APRI), Fibrosis-4 (FIB-4) value, and the incidence risk of diabetic retinopathy, neuropathy, and nephropathy were assessed through logistic regression analysis. Results NAFLD was found to be associated with incidence of diabetic neuropathy and nephropathy (Odds ratio: 1.338 (95% confidence interval: 1.091-1.640) and 1.333 (1.007-1.764), respectively). Alkaline-phosphatase enzyme was found to be associated with higher risks of diabetic neuropathy and nephropathy ((Risk estimate: 1.002 (95% CI: 1.001-1.003) and 1.002 (1.001-1.004), respectively)). Moreover, gamma-glutamyl transferase was associated with a higher risk of diabetic nephropathy (1.006 (1.002-1.009). Aspartate aminotransferase and alanine aminotransferase were inversely associated with the risk of diabetic retinopathy (0.989 (0.979-0.998) and 0.990 (0.983-0.996), respectively). Furthermore, ARPI_T (1), ARPI_T (2), and ARPI_T (3) were shown to be associated with NAFLD (1.440 (1.061-1.954), 1.589 (1.163-2.171), and 2.673 (1.925, 3.710), respectively). However, FIB-4 score was not significantly associated with risk of microvascular complications. Conclusion Despite the benign nature of NAFLD, patients with type 2 diabetes should be always assessed for NAFLD to ensure early diagnosis and entry into proper medical care. Regular screenings of microvascular complications of diabetes is also suggested for these patients.
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Affiliation(s)
- Niloofar Deravi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Student Research committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Fatemeh Moosaie
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hassan Asadigandomani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Melika Arab Bafrani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Niyoosha Yoosefi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Poopak
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Dehghani Firouzabadi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohadeseh Poudineh
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Soghra Rabizadeh
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ibrahim Kamel
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esteghamati
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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18
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Mettananda C, Egodage T, Dantanarayana C, Fernando R, Ranaweera L, Luke N, Ranawaka C, Kottahachchi D, Pathmeswaran A, de Silva HJ, Dassanayake AS. Identification of patients with type 2 diabetes with non-alcoholic fatty liver disease who are at increased risk of progressing to advanced fibrosis: a cross-sectional study. BMJ Open 2023; 13:e063959. [PMID: 36639212 PMCID: PMC9843224 DOI: 10.1136/bmjopen-2022-063959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
INTRODUCTION Identification of advanced hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) is important as this may progress to cirrhosis and hepatocellular carcinoma. The risk of hepatic fibrosis is especially high among patients with diabetes with NAFLD. Annual screening of patients with diabetes for fatty liver and calculation of Fibrosis-4 (FIB-4) score and exclusion of significant fibrosis with vibration-controlled transient elastography (VCTE) have been recommended. However, VCTE is expensive and may not be freely available in resource-limited settings. We aim to identify predictors of significant liver fibrosis who are at increased risk of progression to advanced liver fibrosis and to develop a prediction model to prioritise referral of patients with diabetes and NAFLD for VCTE. METHODS AND ANALYSIS This cross-sectional study is conducted among all consenting adults with type 2 diabetes mellitus with NAFLD at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All patients get the FIB-4 score calculated. Those with FIB-4 ≥1.3 undergo VCTE (with FibroScan by Echosens). Risk associations for progression to advanced liver fibrosis/cirrhosis will be identified by comparing patients with significant fibrosis (liver stiffness measure (LSM) ≥8 kPa) and without significant fibrosis (LSM <8 kPa). A model to predict significant liver fibrosis will be developed using logistic regression. ETHICS AND DISSEMINATION Ethical approval has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (P/66/07/2021). Results of the study will be disseminated as scientific publications in reputable journals.
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Affiliation(s)
- Chamila Mettananda
- Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - Thimira Egodage
- Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - Channaka Dantanarayana
- Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - Rumal Fernando
- Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - Lakmali Ranaweera
- Gastroenterology unit, North Colombo Teaching Hospital, Ragama, Sri Lanka
| | - Nathasha Luke
- Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - Chamila Ranawaka
- Gastroenterology unit, North Colombo Teaching Hospital, Ragama, Sri Lanka
| | - Dulani Kottahachchi
- Department of Physiology, University of Kelaniya Faculty of Medicine, Ragama, Sri Lanka
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Faria LC, Diniz MDFHS, Giatti L, Schmidt MI, Goulart AC, Duncan BB, Barreto SM. Liver steatosis as a predictor of incident diabetes in adults: a prospective evaluation in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). CAD SAUDE PUBLICA 2023. [PMID: 37477601 DOI: 10.1590/0102-311xen090522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2023] Open
Abstract
Increasing epidemiological evidence suggests a bidirectional relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, and that NAFLD may precede and/or promote the development of diabetes. This study aimed to investigate whether liver steatosis is associated with the incidence of diabetes in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The ELSA-Brasil is an occupational cohort study of active or retired civil servants, aged 35-74 years, in six capital cities in Brazil. We excluded participants with diabetes at baseline, those who reported excessive alcohol consumption or with missing information on relevant covariates, and those with self-referred hepatitis or cirrhosis. In total, 8,166 individuals participated, and the mean duration of follow-up was 3.8 years. The Cox proportional regression model was used to estimate the adjusted hazard ratio (HR) for the associations. Abdominal ultrasonography was used to detect liver steatosis. In the follow-up period, the cumulative incidence of diabetes was 5.25% in the whole sample, 7.83% and 3.88% in the groups with and without hepatic steatosis, respectively (p < 0.001). Compared to those without steatosis, individuals with hepatic steatosis had an increased risk of developing diabetes (HR = 1.31; 95%CI: 1.09-1.56) after adjustment for potential confounders, including body mass index (BMI). Hepatic steatosis was an independent predictor of incident diabetes in the ELSA-Brasil cohort study. Physicians should encourage changes in lifestyle and screen for diabetes in patients with fatty liver.
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Affiliation(s)
| | | | - Luana Giatti
- Hospital das Clínicas da Universidade Federal de Minas Gerais, Brasil
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20
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Association of serum brain-derived neurotrophic factor with hepatic enzymes, AST/ALT ratio, and FIB-4 index in middle-aged and older women. PLoS One 2022; 17:e0273056. [PMID: 35998179 PMCID: PMC9398011 DOI: 10.1371/journal.pone.0273056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 08/01/2022] [Indexed: 11/19/2022] Open
Abstract
Substantial evidence suggests an important role of liver function in brain health. Liver function is clinically assessed by measuring the activity of hepatic enzymes in the peripheral blood. Brain-derived neurotrophic factor (BDNF) is an important regulator of brain function. Therefore, we hypothesized that blood BDNF levels are associated with liver function and fibrosis. To test this hypothesis, in this cross-sectional study, we investigated whether serum BDNF concentration is associated with liver enzyme activity, aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio, and fibrosis-4 (FIB-4) index in middle-aged and older women. We found that serum BDNF level showed a significant positive association with ALT and γ-glutamyltranspeptidase (GGT) activity and negative association with FIB-4 index, and a trend of negative association with the AST/ALT ratio after adjustment for age. Additionally, these associations remained statistically significant even after adjustment for body mass index (BMI) and fasting blood glucose level. These results demonstrate associations of serum BDNF levels with liver enzymes and hepatic fibrosis-related indices, which may underlie liver-brain interactions.
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21
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Wajsbrot NB, Leite NC, Salles GF, Villela-Nogueira CA. Non-alcoholic fatty liver disease and the impact of genetic, epigenetic and environmental factors in the offspring. World J Gastroenterol 2022; 28:2890-2899. [PMID: 35978876 PMCID: PMC9280730 DOI: 10.3748/wjg.v28.i25.2890] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 03/20/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is strongly associated with metabolic deregulation. More recently, a significant impact of parental NAFLD in the offspring was demonstrated and has been widely discussed. However, pathogenetic pathways implicated in the inheritance by the offspring and relatives are still under debate. Probably, multiple mechanisms are involved as well as in NAFLD pathogenesis itself. Among the multifactorial involved mechanisms, genetic, epigenetic and environmental backgrounds are strongly related to NAFLD development in the offspring. Thus, based on recent evidence from the available literature concerning genetic, epigenetic and environmental disease modifiers, this review aimed to discuss the relationship between parental NAFLD and its impact on the offspring.
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Affiliation(s)
- Natalia Balassiano Wajsbrot
- Division of Hepatology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 20941-913, Brazil
| | - Nathalie Carvalho Leite
- Division of Hepatology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 20941-913, Brazil
| | - Gil F Salles
- Department of Internal Medicine, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro 22750-240, Brazil
| | - Cristiane A Villela-Nogueira
- Department of Internal Medicine, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro 22750-240, Brazil
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22
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Petrov MS, Taylor R. Intra-pancreatic fat deposition: bringing hidden fat to the fore. Nat Rev Gastroenterol Hepatol 2022; 19:153-168. [PMID: 34880411 DOI: 10.1038/s41575-021-00551-0] [Citation(s) in RCA: 99] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2021] [Indexed: 02/07/2023]
Abstract
Development of advanced modalities for detection of fat within the pancreas has transformed understanding of the role of intra-pancreatic fat deposition (IPFD) in health and disease. There is now strong evidence for the presence of minimal (but not negligible) IPFD in healthy human pancreas. Diffuse excess IPFD, or fatty pancreas disease (FPD), is more frequent than type 2 diabetes mellitus (T2DM) (the most common disease of the endocrine pancreas) and acute pancreatitis (the most common disease of the exocrine pancreas) combined. FPD is not strictly a function of high BMI; it can result from the excess deposition of fat in the islets of Langerhans, acinar cells, inter-lobular stroma, acinar-to-adipocyte trans-differentiation or replacement of apoptotic acinar cells. This process leads to a wide array of diseases characterized by excess IPFD, including but not limited to acute pancreatitis, chronic pancreatitis, pancreatic cancer, T2DM, diabetes of the exocrine pancreas. There is ample evidence for FPD being potentially reversible. Weight loss-induced decrease of intra-pancreatic fat is tightly associated with remission of T2DM and its re-deposition with recurrence of the disease. Reversing FPD will open up opportunities for preventing or intercepting progression of major diseases of the exocrine pancreas in the future.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
| | - Roy Taylor
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
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23
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Kim J, Kwon HS. Not Control but Conquest: Strategies for the Remission of Type 2 Diabetes Mellitus. Diabetes Metab J 2022; 46:165-180. [PMID: 35385632 PMCID: PMC8987695 DOI: 10.4093/dmj.2021.0377] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 03/02/2022] [Indexed: 12/14/2022] Open
Abstract
A durable normoglycemic state was observed in several studies that treated type 2 diabetes mellitus (T2DM) patients through metabolic surgery, intensive therapeutic intervention, or significant lifestyle modification, and it was confirmed that the functional β-cell mass was also restored to a normal level. Therefore, expert consensus introduced the concept of remission as a common term to express this phenomenon in 2009. Throughout this article, we introduce the recently updated consensus statement on the remission of T2DM in 2021 and share our perspective on the remission of diabetes. There is a need for more research on remission in Korea as well as in Western countries. Remission appears to be prompted by proactive treatment for hyperglycemia and significant weight loss prior to irreversible β-cell changes. T2DM is not a diagnosis for vulnerable individuals to helplessly accept. We attempt to explain how remission of T2DM can be achieved through a personalized approach. It may be necessary to change the concept of T2DM towards that of an urgent condition that requires rapid intervention rather than a chronic, progressive disease. We must grasp this paradigm shift in our understanding of T2DM for the benefit of our patients as endocrine experts.
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Affiliation(s)
- Jinyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Corresponding author: Hyuk-Sang Kwon https://orcid.org/0000-0003-4026-4572 Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 10 63(yuksam)-ro, Yeongdeungpo-gu, Seoul 07345, Korea E-mail:
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24
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Miyake T, Matsuura B, Furukawa S, Ishihara T, Yoshida O, Miyazaki M, Watanebe K, Shiomi A, Nakaguchi H, Yamamoto Y, Koizumi Y, Tokumoto Y, Hirooka M, Takeshita E, Kumagi T, Abe M, Ikeda Y, Iwata T, Hiasa Y. Fatty liver with metabolic disorder, such as metabolic dysfunction-associated fatty liver disease, indicates high risk for developing diabetes mellitus. J Diabetes Investig 2022; 13:1245-1252. [PMID: 35167194 PMCID: PMC9248428 DOI: 10.1111/jdi.13772] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/27/2022] [Accepted: 02/13/2022] [Indexed: 11/26/2022] Open
Abstract
Introduction Nonalcoholic fatty liver disease (NAFLD) is diagnosed after excluding other liver diseases. The pathogenesis of NAFLD when complicated by other liver diseases has not been established completely. Metabolic dysfunction‐associated fatty liver disease (MAFLD) involves more metabolic factors than NAFLD, regardless of complications with other diseases. This study aimed to clarify the effects of fatty liver occurring with metabolic disorders, such as MAFLD without diabetes mellitus (DM), on the development of DM. Materials and Methods We retrospectively assessed 9,459 participants who underwent two or more annual health check‐ups. The participants were divided into the MAFLD group (fatty liver disease with overweight/obesity or non‐overweight/obesity complicated by metabolic disorders), simple fatty liver group (fatty liver disease other than MAFLD group), metabolic disorder group (metabolic disorder without fatty liver disease), and normal group (all other participants). Results The DM onset rates in the normal, simple fatty liver, metabolic disorder, and MAFLD groups were 0.51, 1.85, 2.52, and 7.36%, respectively. In the multivariate analysis, the MAFLD group showed a significantly higher risk of DM onset compared with other three groups (P < 0.01). Additionally, the risk of DM onset was significantly increased in fatty liver disease with overweight/obesity or pre‐diabetes (P < 0.01). Conclusions Fatty liver with metabolic disorders, such as MAFLD, can be used to identify patients with fatty liver disease who are at high risk of developing DM. Additionally, patients with fatty liver disease complicated with overweight/obesity or prediabetes are at an increased risk of DM onset and should receive more attention.
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Affiliation(s)
- Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Bunzo Matsuura
- Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Shinya Furukawa
- Health Services Center, Ehime University, Bunkyo, Matsuyama, Ehime, Japan
| | - Toru Ishihara
- Ehime General Health Care Association, Misake, Matsuyama, Ehime, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Masumi Miyazaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Kyoko Watanebe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Akihito Shiomi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Hironobu Nakaguchi
- Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Yasunori Yamamoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Eiji Takeshita
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Teru Kumagi
- Postgraduate Medical Education Center, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Yoshio Ikeda
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Takeshi Iwata
- Ehime General Health Care Association, Misake, Matsuyama, Ehime, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
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25
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Sebastiani G, Patel K, Ratziu V, Feld JJ, Neuschwander-Tetri BA, Pinzani M, Petta S, Berzigotti A, Metrakos P, Shoukry N, Brunt EM, Tang A, Cobbold JF, Ekoe JM, Seto K, Ghali P, Chevalier S, Anstee QM, Watson H, Bajaj H, Stone J, Swain MG, Ramji A. Current considerations for clinical management and care of non-alcoholic fatty liver disease: Insights from the 1st International Workshop of the Canadian NASH Network (CanNASH). CANADIAN LIVER JOURNAL 2022; 5:61-90. [PMID: 35990786 PMCID: PMC9231423 DOI: 10.3138/canlivj-2021-0030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 09/07/2021] [Indexed: 08/30/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects approximately 8 million Canadians. NAFLD refers to a disease spectrum ranging from bland steatosis to non-alcoholic steatohepatitis (NASH). Nearly 25% of patients with NAFLD develop NASH, which can progress to liver cirrhosis and related end-stage complications. Type 2 diabetes and obesity represent the main risk factors for the disease. The Canadian NASH Network is a national collaborative organization of health care professionals and researchers with a primary interest in enhancing understanding, care, education, and research around NAFLD, with a vision of best practices for this disease state. At the 1st International Workshop of the CanNASH network in April 2021, a joint event with the single topic conference of the Canadian Association for the Study of the Liver (CASL), clinicians, epidemiologists, basic scientists, and community members came together to share their work under the theme of NASH. This symposium also marked the initiation of collaborations between Canadian and other key opinion leaders in the field representative of international liver associations. The main objective is to develop a policy framework that outlines specific targets, suggested activities, and evidence-based best practices to guide provincial, territorial, and federal organizations in developing multidisciplinary models of care and strategies to address this epidemic.
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Affiliation(s)
- Giada Sebastiani
- Division of Gastroenterology and Hepatology, Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada
| | - Keyur Patel
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Vlad Ratziu
- Assistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Sorbonne University, Paris, France
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | | | - Massimo Pinzani
- UCL Institute for Liver and Digestive Health, Division of Medicine - Royal Free Hospital, London, UK
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, Università di Palermo, Palermo, Italy
| | - Annalisa Berzigotti
- Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, University of Bern, Switzerland
| | - Peter Metrakos
- Cancer Research Program, McGill University Health Centre Research Institute, Montréal, Québec, Canada
| | - Naglaa Shoukry
- Centre de Recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada
| | | | - An Tang
- Department of Radiology, Centre Hospitalier de l'Université de Montréal (CHUM), Québec, Canada
| | - Jeremy F Cobbold
- Department of Gastroenterology, Oxford University Hospitals NHS Trust, Oxford, UK
| | - Jean-Marie Ekoe
- Montreal Institute for Clinical Research, Division of Endocrinology and Department of Nutrition, Université de Montréal, Montréal, Québec, Canada
| | - Karen Seto
- Canadian Liver Foundation, Markham, Ontario, Canada
| | - Peter Ghali
- University of Florida, Gainesville, Florida, USA
| | | | - Quentin M Anstee
- Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | | | - Harpreet Bajaj
- LMC Diabetes and Endocrinology, Brampton, Ontario, Canada
| | - James Stone
- Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Mark G Swain
- Calgary Liver Unit, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Alnoor Ramji
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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26
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Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease. Biomedicines 2022; 10:biomedicines10010197. [PMID: 35052876 PMCID: PMC8773613 DOI: 10.3390/biomedicines10010197] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/14/2022] [Accepted: 01/16/2022] [Indexed: 02/04/2023] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD), the main cause of chronic liver disease worldwide, is a progressive disease ranging from fatty liver to steatohepatitis (metabolic-associated steatohepatitis; MASH). Nevertheless, it remains underdiagnosed due to the lack of effective non-invasive methods for its diagnosis and staging. Although MAFLD has been found in lean individuals, it is closely associated with obesity-related conditions. Adipose tissue is the main source of liver triglycerides and adipocytes act as endocrine organs releasing a large number of adipokines and pro-inflammatory mediators involved in MAFLD progression into bloodstream. Among the adipocyte-derived molecules, fatty acid binding protein 4 (FABP4) has been recently associated with fatty liver and additional features of advanced stages of MAFLD. Additionally, emerging data from preclinical studies propose FABP4 as a causal actor involved in the disease progression, rather than a mere biomarker for the disease. Therefore, the FABP4 regulation could be considered as a potential therapeutic strategy to MAFLD. Here, we review the current knowledge of FABP4 in MAFLD, as well as its potential role as a therapeutic target for this disease.
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Zhang ZH, Ke JF, Lu JX, Liu Y, Wang AP, Li LX. Serum Retinol-Binding Protein Levels Are Associated with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Real-World Study. Diabetes Metab J 2022; 46:129-139. [PMID: 34372627 PMCID: PMC8831806 DOI: 10.4093/dmj.2020.0222] [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: 09/01/2020] [Accepted: 11/20/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM. METHODS This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed. RESULTS After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients. CONCLUSION Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.
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Affiliation(s)
- Zhi-Hui Zhang
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Jiang-Feng Ke
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Jun-Xi Lu
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Yun Liu
- Department of Information, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Medical Information, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
| | - Ai-Ping Wang
- Department of Endocrinology, Eastern Theater Air Force Hospital of PLA, Nanjing, China
| | - Lian-Xi Li
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
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28
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Meritsi A, Latsou D, Manesis E, Gatos I, Theotokas I, Zoumpoulis P, Rapti S, Tsitsopoulos E, Moshoyianni H, Manolakopoulos S, Pektasides D, Thanopoulou A. Noninvasive, Blood-Based Biomarkers as Screening Tools for Hepatic Fibrosis in People With Type 2 Diabetes. Clin Diabetes 2022; 40:327-338. [PMID: 35983425 PMCID: PMC9331611 DOI: 10.2337/cd21-0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is dramatically increasing in parallel with the pandemic of type 2 diabetes. Here, the authors aimed to assess the performance of the most commonly used noninvasive, blood-based biomarkers for liver fibrosis (FibroTest, NAFLD fibrosis score, BARD score, and FIB-4 Index) in subjects with type 2 diabetes. Liver stiffness measurement was estimated by two-dimensional shear wave elastography. Finally, the authors assessed the diagnostic role of ActiTest and NashTest 2 in liver fibrosis in the examined population.
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Affiliation(s)
- Angeliki Meritsi
- Diabetic Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitra Latsou
- Department of Social and Educational Policy, University of Peloponnese, Corinth, Greece
| | | | - Ilias Gatos
- Diagnostic Echotomography, SA, Kifissia, Athens, Greece
| | | | | | - Stamatia Rapti
- Laboratory of Molecular Genetics, Biomedicine, SA, Athens, Greece
| | | | | | - Spilios Manolakopoulos
- Liver and Gastrointestinal Unit, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Pektasides
- 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Thanopoulou
- Diabetic Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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29
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Rodriguez LA, Kanaya AM, Shiboski SC, Fernandez A, Herrington D, Ding J, Bradshaw PT. Does NAFLD mediate the relationship between obesity and type 2 diabetes risk? evidence from the multi-ethnic study of atherosclerosis (MESA). Ann Epidemiol 2021; 63:15-21. [PMID: 34293421 PMCID: PMC8500945 DOI: 10.1016/j.annepidem.2021.07.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE To estimate the effect of obesity on type 2 diabetes (T2DM) risk and evaluate to what extent non-alcoholic fatty liver disease (NAFLD) mediates this association. METHODS Data came from 4,522 adults ages 45-84 participating in the Multi-Ethnic Study of Atherosclerosis cohort. Baseline obesity was defined using established BMI categories. NAFLD was measured by CT scans at baseline and incident T2DM defined as fasting glucose ≥126 mg/dL or use of diabetes medications. RESULTS Over a median 9.1 years of follow-up between 2000 and 2012, 557 new cases of T2DM occurred. After adjusting for age, sex, race/ethnicity, education, diet and exercise, those with obesity had 4.5 times the risk of T2DM compared to normal weight (hazard ratio [HR] = 4.5, 95% confidence interval [CI]: 3.0, 5.9). The mediation analysis suggested that NAFLD accounted for ~36% (95% CI: 27, 44) of the effect (direct effect HR = 3.2, 95% CI: 2.3, 4.6; indirect effect through NAFLD, HR = 1.4, 95% CI: 1.3, 1.5). CONCLUSIONS These data suggest that the association between obesity and T2DM risk is partially explained by the presence of NAFLD. Future studies should evaluate if NAFLD could be an effective target to reduce the effect of obesity on T2DM.
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Affiliation(s)
- Luis A Rodriguez
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA; Kaiser Permanente Northern California, Division of Research, Oakland, CA.
| | - Alka M Kanaya
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA; University of California, San Francisco, Division of General Internal Medicine, San Francisco, CA
| | - Stephen C Shiboski
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA
| | - Alicia Fernandez
- University of California, San Francisco, Department of Medicine, San Francisco, CA
| | - David Herrington
- Wake Forest School of Medicine, Department of Internal Medicine, Winston-Salem, NC
| | - Jingzhong Ding
- Wake Forest School of Medicine, Sticht Center on Aging, Winston-Salem, NC
| | - Patrick T Bradshaw
- University of California, Berkeley, School of Public Health, Division of Epidemiology & Biostatistics, Berkeley, CA
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30
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Chung GE, Cho EJ, Yoon JW, Yoo JJ, Chang Y, Cho Y, Park SH, Han K, Shin DW, Yu SJ. Nonalcoholic fatty liver disease increases the risk of diabetes in young adults: A nationwide population-based study in Korea. Metabolism 2021; 123:154866. [PMID: 34411553 DOI: 10.1016/j.metabol.2021.154866] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 08/08/2021] [Accepted: 08/10/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of diabetes but has been rarely investigated in young adults. In this study, we investigated the relationship between NAFLD and incident diabetes risk in young adults using nationwide Korean population data. METHODS This population-based cohort study from the Korean National Health Insurance Service included adults aged 20 through 39 years who underwent a health examination from 2009 to 2012. NAFLD was defined as a fatty liver index (FLI) ≥60 in the absence of alcohol consumption of ≥30 g/day. Newly diagnosed diabetes during follow-up was identified using claims data. Cox regression was used to calculate the hazard ratio for incident diabetes after adjusting for classical confounders. FINDINGS Among the 5,254,786 participants, 9.3% had an FLI ≥60. During the median follow-up of 8.6 years, 91,885 cases of incident diabetes occurred. In multivariable analysis, the risk of incident diabetes was significantly higher in the NAFLD group than the control group (adjusted hazard ratio = 4.97, 95% confidence interval, 4.90-5.05). Stratified analyses showed higher associations in those who were ≥30 years, male, obese, smokers, alcohol consumers, and did not regularly exercise (all P < 0.001). CONCLUSIONS NAFLD is associated with a five-fold increased risk of incident diabetes in young adults. These results suggest an independent high risk for incident diabetes in young adults and underscore the importance of paying early attention to patients who develop NAFLD before middle age.
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Affiliation(s)
- Goh Eun Chung
- Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ji Won Yoon
- Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Jeong-Ju Yoo
- Department of Gastroenterology and Hepatology, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, Republic of Korea
| | - Young Chang
- Department of Gastroenterology and Hepatology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sang-Hyun Park
- Department of Biostatistics, College of Medicine, Soongsil University, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Biostatistics, College of Medicine, Soongsil University, Seoul, Republic of Korea
| | - Dong Wook Shin
- Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science, Republic of Korea; Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Digital Health, Samsung Advanced Institute for Health Science, Republic of Korea.
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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31
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Miyake T, Matsuura B, Furukawa S, Yoshida O, Hirooka M, Kumagi T, Ishihara T, Kanzaki S, Nakaguchi H, Miyazaki M, Nakamura Y, Yamamoto Y, Koizumi Y, Tokumoto Y, Takeshita E, Ikeda Y, Abe M, Kitai K, Hiasa Y. Nonalcoholic fatty liver disease is a risk factor for glucose intolerance onset in men regardless of alanine aminotransferase status. J Diabetes Investig 2021; 12:1890-1898. [PMID: 33742744 PMCID: PMC8504916 DOI: 10.1111/jdi.13548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 02/21/2021] [Accepted: 03/17/2021] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Fatty liver disease (FLD) is a surrogate condition for glucose intolerance development. FLD may involve normal or abnormal liver enzyme levels. Whether FLD is a risk factor for glucose intolerance, regardless of liver enzyme levels, remains unknown. We assessed relationships between the development of impaired fasting glucose (IFG) and FLD, liver enzyme abnormalities, and alcohol consumption. MATERIALS AND METHODS We retrospectively evaluated 8,664 participants with more than two annual health check-ups. Participants were classified according to sex, alcohol consumption, alanine aminotransferase (ALT) levels, and fatty liver status. RESULTS In univariate analyses, IFG onset among men was related to normal or high ALT levels with FLD in the nonalcoholic and alcoholic groups (P-trend < 0.01). In multivariate analyses, IFG onset among nonalcoholic men was associated with normal or high ALT levels with FLD, independent of potential confounding factors (P-trend < 0.01). However, IFG onset was non-independently associated with any condition among alcoholic men. In univariate analyses, IFG onset among women was related to normal or high ALT levels with FLD in the nonalcoholic group (P-trend < 0.01) and high ALT levels with FLD in the alcoholic group (P-trend < 0.05). In multivariate analyses, IFG onset was independently associated with only normal ALT levels in nonalcoholic FLD women. CONCLUSIONS Among nonalcoholic men and women, FLD was a risk factor for IFG onset, including normal ALT concentrations. Care is needed for individuals with nonalcoholic FLD, regardless of liver injury, possibly helping reduce glucose intolerance risk.
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Affiliation(s)
- Teruki Miyake
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Bunzo Matsuura
- Department of Lifestyle‐Related Medicine and EndocrinologyEhime University Graduate School of MedicineToonEhimeJapan
| | | | - Osamu Yoshida
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Masashi Hirooka
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Teru Kumagi
- Postgraduate Medical Education CenterEhime University Graduate School of MedicineToonEhimeJapan
| | - Toru Ishihara
- Ehime General Health Care AssociationMatsuyamaEhimeJapan
| | - Sayaka Kanzaki
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Hironobu Nakaguchi
- Department of Lifestyle‐Related Medicine and EndocrinologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Masumi Miyazaki
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Yoshiko Nakamura
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Yasunori Yamamoto
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Yohei Koizumi
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Yoshio Tokumoto
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Eiji Takeshita
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Yoshio Ikeda
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | - Masanori Abe
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
| | | | - Yoichi Hiasa
- Department of Gastroenterology and MetabologyEhime University Graduate School of MedicineToonEhimeJapan
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32
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Alam U. To Be, or Not To Be … a Biomarker? A Question to the FDA. Clin Ther 2021; 43:1438-1440. [PMID: 34535276 DOI: 10.1016/j.clinthera.2021.08.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 08/19/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Uazman Alam
- Department of Diabetes and Endocrinology Research, Institute of Life Course and Medical Sciences and the Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, United Kingdom
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33
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Lim S, Kim JW, Targher G. Links between metabolic syndrome and metabolic dysfunction-associated fatty liver disease. Trends Endocrinol Metab 2021; 32:500-514. [PMID: 33975804 DOI: 10.1016/j.tem.2021.04.008] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/15/2021] [Accepted: 04/15/2021] [Indexed: 02/08/2023]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition characterized by hepatic fat accumulation combined with underlying metabolic dysregulation. Having evolved from the previous term of nonalcoholic fatty liver disease (NAFLD), the term MAFLD more closely implicates the presence of overweight/obesity, type 2 diabetes, or metabolic dysregulation as essential pathogenic factors, leading to better identification of individuals with this metabolic liver disease. Low-grade inflammation, increased oxidative stress, mitochondrial dysfunction, and intestinal dysbiosis are also involved in its pathogenesis. MAFLD is not only associated with liver-related complications, but also with adverse cardiometabolic outcomes. Further studies are needed to assess whether the newly proposed definition of MAFLD is more accurate than the NAFLD in predicting the adverse liver-related and extrahepatic outcomes.
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Affiliation(s)
- Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Korea.
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Korea
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
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34
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Association of hepatic steatosis derived from ultrasound and quantitative MRI with prediabetes in the general population. Sci Rep 2021; 11:13276. [PMID: 34168217 PMCID: PMC8225774 DOI: 10.1038/s41598-021-92681-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 06/11/2021] [Indexed: 12/23/2022] Open
Abstract
The aim of our study was to investigate the association of hepatic steatosis derived from quantitative ultrasound and magnetic resonance imaging (MRI) with prediabetes in a large population-based study conducted in Northeast Germany. Hepatic steatosis was assessed through transabdominal ultrasound and quantitative MRI. For analysis we included 1622 subjects with MRI who participated in an oral glucose tolerance test and reported no known type 2 diabetes mellitus (T2DM). We classified participants as proposed by the American Diabetes Association: isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT), and undiagnosed T2DM. Regression models were adjusted for age, sex body mass index and alcohol consumption. We observed positive associations of hepatic steatosis with glycated hemoglobin, fasting glucose and insulin, 2-h glucose and insulin, as well as homeostasis model assessment-insulin resistance index. Similarly, individuals having hepatic steatosis as defined by MRI had a higher relative risk ratio (RR) to be in the prediabetes groups i-IFG (RR = 1.6; 95% confidence interval (CI) 1.2; 2.2), i-IGT (RR = 3.3, 95% CI 2.0; 5.6) and IFG + IGT (RR = 2.5, 95% CI 1.6; 3.9) or to have undiagnosed T2DM (RR = 4.8, 95% CI 2.6; 9.0). All associations were attenuated when defining hepatic steatosis by ultrasound. Hepatic steatosis is associated with prediabetes and undiagnosed T2DM in the general population. Quantitative liver MRI revealed stronger associations with prediabetes and undiagnosed T2DM compared to ultrasound, which indicates the higher sensitivity and specificity of MRI to determine hepatic steatosis.
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35
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Muzurović E, Mikhailidis DP, Mantzoros C. Non-alcoholic fatty liver disease, insulin resistance, metabolic syndrome and their association with vascular risk. Metabolism 2021; 119:154770. [PMID: 33864798 DOI: 10.1016/j.metabol.2021.154770] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/25/2021] [Accepted: 03/27/2021] [Indexed: 02/07/2023]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is rising. About 25% of adults worldwide are probably affected by NAFLD. Insulin resistance (IR) and fat accumulation in the liver are strongly related. The association between NAFLD, metabolic syndrome (MetS) and IR is established, but an independent impact of NAFLD on vascular risk and progression of cardiovascular (CV) disease (CVD) still needs to be confirmed. This narrative review considers the evidence regarding the link between NAFLD, IR and CVD risk. There is strong evidence for a "concomitantly rising incidence" of NAFLD, IR, MetS and CVD but there is no definitive evidence regarding whether NAFLD is, or is not, an independent and significant risk factor the development of CVD. There are also considerations that type 2 diabetes mellitus (T2DM) may be a common link between NAFLD/non-alcoholic steatohepatitis (NASH) and CVD. NAFLD may be associated with widespread abnormal peri-organ or intra-organ fat (APIFat) deposition (e.g. epicardial adipose tissue) which may further contribute to CV risk. It is clear that NAFLD patients have a greater CV risk (independent or not) which needs to be addressed in clinical practice.
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Affiliation(s)
- Emir Muzurović
- Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Ljubljanska bb, 81000 Podgorica, Montenegro; Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro.
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), Pond Street, London NW3 2QG, UK; Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Christos Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA 02115, USA
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Taylor R. Type 2 diabetes and remission: practical management guided by pathophysiology. J Intern Med 2021; 289:754-770. [PMID: 33289165 PMCID: PMC8247294 DOI: 10.1111/joim.13214] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 09/10/2020] [Accepted: 09/15/2020] [Indexed: 12/13/2022]
Abstract
The twin cycle hypothesis postulated that type 2 diabetes was a result of excess liver fat causing excess supply of fat to the pancreas with resulting dysfunction of both organs. If this was so, the condition should be able to be returned to normal by calorie restriction. The Counterpoint study tested this prediction in short-duration type 2 diabetes and showed that liver glucose handling returned to normal within 7 days and that beta-cell function returned close to normal over 8 weeks. Subsequent studies have demonstrated the durability of remission from type 2 diabetes. Remarkably, during the first 12 months of remission, the maximum functional beta-cell mass returns completely to normal and remains so for at least 24 months, consistent with regain of insulin secretory function of beta cells which had dedifferentiated in the face of chronic nutrient oversupply. The likelihood of achieving remission after 15% weight loss has been shown to be mainly determined by the duration of diabetes, with responders having better beta-cell function at baseline. Remission is independent of BMI, underscoring the personal fat threshold concept that type 2 diabetes develops when an individual acquires more fat than can be individually tolerated even at a BMI which in the nonobese range. Observations on people of South Asian or Afro-American ethnicity confirm that substantial weight loss achieves remission in the same way as in the largely White Europeans studied in detail. Diagnosis of type 2 diabetes can now be regarded as an urgent signal that weight loss must be achieved to avoid a progressive decline of health.
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Affiliation(s)
- Roy Taylor
- Magnetic Resonance CentreInstitute of Cellular MedicineNewcastle UniversityNewcastleUK
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37
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Park G, Jung S, Wellen KE, Jang C. The interaction between the gut microbiota and dietary carbohydrates in nonalcoholic fatty liver disease. Exp Mol Med 2021; 53:809-822. [PMID: 34017059 PMCID: PMC8178320 DOI: 10.1038/s12276-021-00614-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 03/24/2021] [Indexed: 02/04/2023] Open
Abstract
Imbalance between fat production and consumption causes various metabolic disorders. Nonalcoholic fatty liver disease (NAFLD), one such pathology, is characterized by abnormally increased fat synthesis and subsequent fat accumulation in hepatocytes1,2. While often comorbid with obesity and insulin resistance, this disease can also be found in lean individuals, suggesting specific metabolic dysfunction2. NAFLD has become one of the most prevalent liver diseases in adults worldwide, but its incidence in both children and adolescents has also markedly increased in developed nations3,4. Progression of this disease into nonalcoholic steatohepatitis (NASH), cirrhosis, liver failure, and hepatocellular carcinoma in combination with its widespread incidence thus makes NAFLD and its related pathologies a significant public health concern. Here, we review our understanding of the roles of dietary carbohydrates (glucose, fructose, and fibers) and the gut microbiota, which provides essential carbon sources for hepatic fat synthesis during the development of NAFLD.
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Affiliation(s)
- Grace Park
- Department of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA
| | - Sunhee Jung
- Department of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA
| | - Kathryn E Wellen
- Department of Cancer Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Cholsoon Jang
- Department of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA.
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Kouvari M, Boutari C, Chrysohoou C, Fragkopoulou E, Antonopoulou S, Tousoulis D, Pitsavos C, Panagiotakos DB, Mantzoros CS. Mediterranean diet is inversely associated with steatosis and fibrosis and decreases ten-year diabetes and cardiovascular risk in NAFLD subjects: Results from the ATTICA prospective cohort study. Clin Nutr 2021; 40:3314-3324. [PMID: 33234342 DOI: 10.1016/j.clnu.2020.10.058] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/26/2020] [Accepted: 10/30/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS We assessed the association of Mediterranean diet with NAFLD and their interaction in predicting ten-year diabetes onset and first fatal/non-fatal cardiovascular disease (CVD) incidence. METHODS The ATTICA prospective observational study in Athens, Greece included 1,514 men and 1,528 women (>18 years old) free-of-CVD at baseline. Liver steatosis and fibrosis indices were calculated. Mediterranean diet adherence was assessed through MedDietScore. At the ten-year follow-up visit, CVD evaluation was performed in an a priori specified subgroup of n = 2,020 participants and diabetes onset in n = 1,485 free-of-diabetes participants. RESULTS MedDietScore was inversely associated with steatosis and fibrosis; e.g. in the case of the TyG index the Odds Ratio (OR) of the 3rd vs. 1st MedDietScore tertile was = 0·53, [95% Confidence Interval (95% CI) (0·29, 0·95)] and the associations persisted in multi-adjusted models. NAFLD predicted incident diabetes prospectively over a ten year period [HR = 1·87, 95% CI (0·75, 4·61)] and the association remained significant only in subjects with low MedDietScore (below median) whereas diabetes onset among subjects with higher MedDietScore was not influenced by NAFLD. Similarly, NAFLD predicted CVD [Hazard Ratio (HR) = 3·01, 95%CI(2·28, 3·95)]; the effect remained significant only in subjects with MedDietScore below median [HR = 1·38, 95% CI (1·00, 1·93)] whereas it was essentially null [HR = 1·00,95% CI (0·38, 2·63)] among subjects with higher score. Mediation analysis revealed that adiponectin and adiponectin-to-leptin ratio were the strongest mediators. CONCLUSIONS We report an inverse association between Mediterranean diet and NAFLD. Mediterranean diet protected against diabetes and CVD prospectively among subjects with NAFLD.
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Affiliation(s)
- M Kouvari
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - C Boutari
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA
| | - C Chrysohoou
- First Cardiology Clinic, School of Medicine, University of Athens, Greece
| | - E Fragkopoulou
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - S Antonopoulou
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - D Tousoulis
- First Cardiology Clinic, School of Medicine, University of Athens, Greece
| | - C Pitsavos
- First Cardiology Clinic, School of Medicine, University of Athens, Greece
| | - D B Panagiotakos
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; Faculty of Health, University of Canberra, Australia
| | - C S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA; Department of Medicine, Boston VA Healthcare System, Harvard Medical School, Boston, MA, 02115, USA.
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Ni L, Yu D, Wu T, Jin F. Gender-specific association between non-alcoholic fatty liver disease and type 2 diabetes mellitus among a middle-aged and elderly Chinese population: An observational study. Medicine (Baltimore) 2021; 100:e24743. [PMID: 33578624 PMCID: PMC10545277 DOI: 10.1097/md.0000000000024743] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 11/21/2020] [Accepted: 01/21/2021] [Indexed: 12/15/2022] Open
Abstract
ABSTRACT Limited data are available regarding the association of non-alcoholic fatty liver disease (NAFLD) with the risk of type 2 diabetes mellitus (T2DM) in China. Therefore, the purpose of this study is to evaluate the gender-specific association between NAFLD and T2DM risk in a middle-aged and elderly Chinese population.This cross-sectional study was carried out in a group of 1492 Chinese adults (60.30% males) aged between 45 and 69 years old, in Hangzhou city, Zhejiang province who were attending their annual health check-up from June 2015 to December 2016 in the Medical Center for Physical Examination, Zhejiang Hospital. Face-to-face interviews were conducted using a written questionnaire. NAFLD was divided into none, mild, moderate/severe based on ultrasound examination. Logistic regression analyses were employed to determine the relationship between NAFLD and the risk of T2DM, with adjustment of potential confounding variables.Of the 1492 participants, 163 (10.92%) were diagnosed with T2DM. Educational level, smoking, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), triglycerides (TG), alanine aminotransferase (ALT), asparagine aminotransferase (AST)and the prevalence of T2DM were significantly higher in males than in females (P < .05). Besides, females had significantly higher levels of high density lipoprotein-cholesterol (HDL-C) (1.51 ± 0.37 vs 1.29 ± 0.42, P < .001) than males. Pearson bivariate correlation analysis indicated that FG was positively associated with weight, BMI, WC, WHR, SBP, DBP, TG, TC, ALT and AST in both males and females (P < .05). Besides, FG was inversely associated with HDL-C in females (P < .001). After adjusting for confounding variables, NAFLD was positively associated with the risk of T2DM, and the effect of NAFLD on T2DM was stronger in males (OR = 2.442, 95%CI: 1.003-3.757) than in females (OR = 1.814, 95%CI: 1.011-3.257).Our data showed that NAFLD was significantly associated with the risk of T2DM in middle-aged and elderly males than in females. Further prospective cohort studies are needed to determine the causal effect of NAFLD on T2DM.
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Affiliation(s)
| | - Dan Yu
- Department of Endocrinology, Zhejiang Hospital, Lingyin Road Number 12, Xihu District, Hangzhou, Zhejiang, the People's Republic of China
| | - Tianfeng Wu
- Department of Endocrinology, Zhejiang Hospital, Lingyin Road Number 12, Xihu District, Hangzhou, Zhejiang, the People's Republic of China
| | - Fubi Jin
- Department of Endocrinology, Zhejiang Hospital, Lingyin Road Number 12, Xihu District, Hangzhou, Zhejiang, the People's Republic of China
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Bardugo A, Bendor CD, Zucker I, Lutski M, Cukierman-Yaffe T, Derazne E, Mosenzon O, Tzur D, Beer Z, Pinhas-Hamiel O, Ben-Ami M, Fishman B, Ben-Ami Shor D, Raz I, Afek A, Gerstein HC, Häring HU, Tirosh A, Levi Z, Twig G. Adolescent Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Young Adulthood. J Clin Endocrinol Metab 2021; 106:e34-e44. [PMID: 33075820 DOI: 10.1210/clinem/dgaa753] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Indexed: 02/08/2023]
Abstract
CONTEXT The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. OBJECTIVE To assess type 2 diabetes risk among adolescents with NAFLD. DESIGN AND SETTING A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997-2011 and were followed until December 31, 2016. PARTICIPANTS A total of 1 025 796 normoglycemic adolescents were included. INTERVENTIONS Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. MAIN OUTCOME MEASURES Type 2 diabetes incidence. RESULTS During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47-4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). CONCLUSIONS Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.
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Affiliation(s)
- Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Cole D Bendor
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Miri Lutski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Zivan Beer
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Michal Ben-Ami
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Boris Fishman
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Internal Medicine D and Hypertension Unit, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Dana Ben-Ami Shor
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology, Tel-Aviv Medical Center, Tel Aviv, Israel
| | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | | | - Hans-Ulrich Häring
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research, Tübingen, Germany
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Zohar Levi
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Gastroenterology Department, Rabin Medical Center, Petach Tikva, Israel
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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Muzica CM, Sfarti C, Trifan A, Zenovia S, Cuciureanu T, Nastasa R, Huiban L, Cojocariu C, Singeap AM, Girleanu I, Chiriac S, Stanciu C. Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: A Bidirectional Relationship. Can J Gastroenterol Hepatol 2020; 2020:6638306. [PMID: 33425804 PMCID: PMC7781697 DOI: 10.1155/2020/6638306] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/15/2020] [Indexed: 02/08/2023] Open
Abstract
Worldwide, the leading cause of chronic liver disease is represented by nonalcoholic fatty liver disease (NAFLD) which has now become a global epidemic of the 21st century, affecting 1 in 4 adults, and which appears to be associated with the steadily increasing rates of metabolic syndrome and its components (obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia). NAFLD has been reported to be associated with extrahepatic manifestations such as cardiovascular disease, T2DM, chronic kidney disease, extrahepatic malignancies (e.g., colorectal cancer), endocrine diseases (e.g., hypothyroidism, polycystic ovarian syndrome, psoriasis, and osteoporosis), obstructive sleep apnea, and iron overload. The prevalence of NAFLD is very high, affecting 25-30% of the world population and encloses two steps: (1) nonalcoholic fatty liver (NAFL), which includes steatosis only, and (2) nonalcoholic steatohepatitis (NASH) defined by the presence of steatosis and inflammation with hepatocyte ballooning, with or without fibrosis which can progress to liver fibrosis, hepatocellular carcinoma, and liver transplantation. Current data define a more complex relationship between NAFLD and T2DM than was previously believed, underlining a bidirectional and mutual association between the two entities. This review aims to summarize the current literature regarding the incidence of T2DM among patients with NAFLD and also the prevalence of NAFLD in T2DM patients, highlighting the recent key studies. Clinicians should screen, diagnose, and treat T2DM in patients with NAFLD in order to avoid short- and long-term complications.
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Affiliation(s)
- Cristina M. Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Robert Nastasa
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Carol Stanciu
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
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Kogiso T, Sagawa T, Kodama K, Taniai M, Hashimoto E, Tokushige K. Development and course of diabetes according to genetic factors and diabetes treatment among patients with nonalcoholic fatty liver disease. Nutrition 2020; 83:111080. [PMID: 33348109 DOI: 10.1016/j.nut.2020.111080] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 11/06/2020] [Accepted: 11/06/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Many patients with nonalcoholic fatty liver disease (NAFLD) also have diabetes. However, the genetic factors associated with diabetes in NAFLD are unclear. In this study, we investigated the clinical course and risk factors of diabetes development. METHODS A total of 544 patients (275 men; 50.6%) with a median age of 53 y and biopsy-confirmed NAFLD enrolled in the study. Patatin-like phospholipase 3 and voltage-gated potassium channel KQT-like subfamily member 1 (KCNQ1) single nucleotide polymorphisms were identified in 287 cases. There were 272 patients without diabetes, and 64, 141, and 67 patients with diabetes not treated with an oral hypoglycemic agent, treated with an oral hypoglycemic agent, and treated with insulin, respectively. Changes in biochemical parameters and body weight over a 1-y period were determined in patients treated with incretin agents (n = 91), a sodium glucose cotransporter 2 inhibitor (n = 19), or both (n = 33). The prevalence and risk factors for diabetes development among patients with NAFLD were determined in nondiabetic patients. RESULTS Among patients with NAFLD, half of the patients had diabetes and the incidence was high in those with advanced fibrosis. Reduction in body weight was higher after sodium glucose cotransporter 2 inhibitor treatment (P = .050) and in KCNQ1 CC genotype patients (P < .05). Reduction in hemoglobin A1c level was significantly lower in patatin-like phospholipase 3 GG subjects (P < .05). De novo diabetes developed in 44 patients (10-y incidence: 17.9%), especially in obese (P = .046) and KCNQ1 CC genotype patients (P < .01). CONCLUSIONS Patient genetic background affected treatment response and incidence of diabetes in patients with NAFLD.
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Affiliation(s)
- Tomomi Kogiso
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
| | - Takaomi Sagawa
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
| | - Kazuhisa Kodama
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
| | - Makiko Taniai
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
| | | | - Katsutoshi Tokushige
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
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Vesa CM, Behl T, Nemeth S, Bratu OG, Diaconu CC, Moleriu RD, Negrut N, Zaha DC, Bustea C, Radu FI, Bungau S. Prediction of NAFLD occurrence in prediabetes patients. Exp Ther Med 2020; 20:190. [PMID: 33101480 DOI: 10.3892/etm.2020.9320] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 08/07/2020] [Indexed: 12/18/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a component of metabolic syndrome that significantly increases the cardiovascular risk of patients with glucose metabolism alterations. This study identified the prevalence of NAFLD, predictors of NAFLD and explored the link between insulin sensitivity, insulin resistance and leptinemia in 143 patients registered with prediabetes. Abdominal ultrasound was performed, and fasting insulin, postprandial insulin, leptin levels, common clinical/biochemical determinations were assessed. Certain variables that can predict NAFLD existence were determined and it was found that there is a high prevalence of NAFLD in patients with prediabetes. In univariate analysis, statistically significant associations (P<0.05) were found between waist circumference, systolic blood pressure, diastolic blood pressure, triglycerides, HDL-cholesterol, insulin sensitivity, β-cell function, leptin and NAFLD presence. The coefficients for the variables which obtain statistically significant association (P<0.05) are low, except for leptin which is the biochemical parameter that (in both univariate and multivariate analysis) is a strong predictor of NAFLD presence.
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Affiliation(s)
- Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, 140401 Punjab, India
| | - Sebestian Nemeth
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Ovidiu G Bratu
- Clinical Department 3, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Camelia C Diaconu
- Department 5, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Radu Dumitru Moleriu
- Department of Mathematics, Faculty of Mathematics and Computer Science, West University of Timisoara, 300223 Timisoara, Romania
| | - Nicoleta Negrut
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Dana C Zaha
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Cristiana Bustea
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Florentina Ionita Radu
- Department of Gastroenterology, Emergency University Central Military Hospital, 010825 Bucharest, Romania
| | - Simona Bungau
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
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Zhu X, Yan H, Chang X, Xia M, Zhang L, Wang L, Sun X, Yang X, Gao X, Bian H. Association between non-alcoholic fatty liver disease-associated hepatic fibrosis and bone mineral density in postmenopausal women with type 2 diabetes or impaired glucose regulation. BMJ Open Diabetes Res Care 2020; 8:e000999. [PMID: 32759166 PMCID: PMC7409963 DOI: 10.1136/bmjdrc-2019-000999] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 04/02/2020] [Accepted: 06/22/2020] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION To evaluate the association of non-alcoholic fatty liver disease (NAFLD)-associated hepatic fibrosis with bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM) or impaired glucose regulation (IGR). RESEARCH DESIGN AND METHODS Two cohorts including 46 subjects with biopsy-proven NAFLD and 445 subjects with proton magnetic resonance spectrum-proven NAFLD were enrolled in this study. All subjects were postmenopausal women with T2DM or IGR. BMD at the lumbar spine L1-L4 and hip was measured using dual-energy X-ray absorptiometry. NAFLD fibrosis stage and NAFLD fibrosis score were used to evaluate the severity of liver fibrosis. RESULTS In subjects with liver biopsy-proven NAFLD, BMD (T-score, Z-score and BMD value) in the advanced fibrosis group were significantly lower than that in the non-advanced fibrosis group (p<0.05). Fibrosis stage was negatively associated with T-score, Z-score and BMD value after adjusting for age, body mass index (BMI) and fasting plasma glucose (FPG). Additionally, fibrosis stage was independently associated with T-score, Z-score and BMD value after adjusting for age, BMI and FPG. These results were validated in a large cohort of 445 subjects. Additionally, bone metabolism-associated factors, including calcium and phosphate, were associated with liver fibrosis, indicating that bone metabolism may play a critical role in the association between liver fibrosis and BMD. Mechanically, parathyroid hormone and biomarkers of bone formation (osteocalcin and procollagen type 1 N-terminal propeptide) and bone resorption (procollagen type I carboxy terminal peptide β special sequence) were increased in subjects with advanced liver fibrosis than in subjects without advanced liver fibrosis, indicating that liver fibrosis decreased BMD probably via increasing bone turnover. CONCLUSIONS NAFLD-associated hepatic fibrosis was negatively associated with decreased BMD in postmenopausal women with T2DM or IGR. Liver fibrosis decreased BMD probably via increasing bone turnover. Severe liver fibrosis may represent high risk for osteoporosis in postmenopausal women with T2DM or IGR.
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Affiliation(s)
- Xiaopeng Zhu
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Hongmei Yan
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Xinxia Chang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Mingfeng Xia
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Linshan Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Liu Wang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Xiaoyang Sun
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Xinyu Yang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
| | - Hua Bian
- Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai, China
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Cigrovski Berkovic M, Virovic-Jukic L, Bilic-Curcic I, Mrzljak A. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management. World J Gastroenterol 2020; 26:2740-2757. [PMID: 32550751 PMCID: PMC7284186 DOI: 10.3748/wjg.v26.i21.2740] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/24/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Dubrava, Zagreb 10000, Croatia
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
| | - Lucija Virovic-Jukic
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
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Pittala S, Levy I, De S, Kumar Pandey S, Melnikov N, Hyman T, Shoshan-Barmatz V. The VDAC1-based R-Tf-D-LP4 Peptide as a Potential Treatment for Diabetes Mellitus. Cells 2020; 9:E481. [PMID: 32093016 PMCID: PMC7072803 DOI: 10.3390/cells9020481] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 02/10/2020] [Accepted: 02/14/2020] [Indexed: 12/12/2022] Open
Abstract
Diabetes mellitus is a metabolic disorder approaching epidemic proportions. Non-alcoholic fatty liver disease (NAFLD) regularly coexists with metabolic disorders, including type 2 diabetes, obesity, and cardiovascular disease. Recently, we demonstrated that the voltage-dependent anion channel 1 (VDAC1) is involved in NAFLD. VDAC1 is an outer mitochondria membrane protein that serves as a mitochondrial gatekeeper, controlling metabolic and energy homeostasis, as well as crosstalk between the mitochondria and the rest of the cell. It is also involved in mitochondria-mediated apoptosis. Here, we demonstrate that the VDAC1-based peptide, R-Tf-D-LP4, affects several parameters of a NAFLD mouse model in which administration of streptozotocin (STZ) and high-fat diet 32 (STZ/HFD-32) led to both type 2 diabetes (T2D) and NAFLD phenotypes. We focused on diabetes, showing that R-Tf-D-LP4 peptide treatment of STZ/HFD-32 fed mice restored the elevated blood glucose back to close to normal levels, and increased the number and average size of islets and their insulin content as compared to untreated controls. Similar results were obtained when staining the islets for glucose transporter type 2. In addition, the R-Tf-D-LP4 peptide decreased the elevated glucose levels in a mouse displaying obese, diabetic, and metabolic symptoms due to a mutation in the obese (ob) gene. To explore the cause of the peptide-induced improvement in the endocrine pancreas phenotype, we analyzed the expression levels of the proliferation marker, Ki-67, and found it to be increased in the islets of STZ/HFD-32 fed mice treated with the R-Tf-D-LP4 peptide. Moreover, peptide treatment of STZ/HFD-32 fed mice caused an increase in the expression of β-cell maturation and differentiation PDX1 transcription factor that enhances the expression of the insulin-encoding gene, and is essential for islet development, function, proliferation, and maintenance of glucose homeostasis in the pancreas. This increase occurred mainly in the β-cells, suggesting that the source of their increased number after R-Tf-D-LP4 peptide treatment was most likely due to β-cell proliferation. These results suggest that the VDAC1-based R-Tf-D-LP4 peptide has potential as a treatment for diabetes.
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Affiliation(s)
| | | | | | | | | | | | - Varda Shoshan-Barmatz
- Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; (S.P.); (I.L.); (S.D.); (S.K.P.); (N.M.); (T.H.)
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Kılınç S, Demirbaş T, Atay E, Ceran Ö, Atay Z. Elevated 1-h post-load plasma glucose levels in normal glucose tolerance children with obesity is associated with early carotid atherosclerosis. Obes Res Clin Pract 2020; 14:136-141. [PMID: 32061583 DOI: 10.1016/j.orcp.2020.02.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 02/03/2020] [Accepted: 02/05/2020] [Indexed: 10/25/2022]
Abstract
CONTEXT Evidence suggests that the 1-h post-load plasma glucose (1-h PG) ≥155mg/dL during an oral glucose tolerance test (OGTT) predicts development of type 2 diabetes (T2DM) and associated complications, among adults with normal glucose tolerance (NGT), but relevant data on children is scarce. OBJECTIVES To investigate whether NGT children with obesity whose 1-h PG is ≥155mg/dL have an increased carotid intima-media thickness (IMT) and exhibit non-alcoholic fatty liver disease (NAFLD) diagnosed by ultrasonography, as compared with NGT subjects with 1-h PG <155mg/dL and impaired glucose tolerance (IGT). METHODS Cardio-metabolic profile, OGTT, measurements of carotid IMT and liver ultrasonography were analyzed in 171 non-diabetic children with obesity. Subjects were divided into 3 groups: NGT subjects with a 1-h PG <155mg/dL, NGT subjects with a 1-h PG ≥155mg/dL, and IGT subjects. RESULTS As compared with NGT individuals with a 1-h PG <155mg/dL, NGT individuals with a 1-h PG ≥155mg/dL exhibited higher carotid IMT (0.75±0.15mm vs. 0.68±0.15mm; p<0.05). No significant differences were observed in carotid IMT between IGT and NGT subjects with a 1-h PG ≥155mg/dL (0.75±0.18mm vs 0.75±0.15mm; p>0.05). Of the three glycemic parameters, 1-h and 2-h PG, but not fasting glucose, were significantly correlated with carotid IMT. There were no significant differences for increased risk of having NAFLD between the three groups. CONCLUSIONS These data suggest that a value of 1-h PG ≥155mg/dL in children and adolescents with obesity is as important as IGT with respect to cardiovascular risks.
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Affiliation(s)
- Suna Kılınç
- Health Sciences University, Bagcılar Training and Research Hospital, Department of Pediatric Endocrinology, Turkey.
| | - Tuna Demirbaş
- Health Sciences University, Bagcılar Training and Research Hospital, Department of Radiology, Turkey.
| | - Enver Atay
- Medipol University Hospital, Department of Pediatrics, Turkey.
| | - Ömer Ceran
- Medipol University Hospital, Department of Pediatrics, Turkey.
| | - Zeynep Atay
- Medipol University Hospital, Department of Pediatric Endocrinology, Turkey.
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The predictive value of the hepatorenal index for detection of impaired glucose metabolism in patients with non-alcoholic fatty liver disease. Indian J Gastroenterol 2020; 39:50-59. [PMID: 32185691 DOI: 10.1007/s12664-019-01009-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 11/06/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND/PURPOSE Non-alcoholic fatty liver disease (NAFLD) patients are at increased risk of liver-related as well as cardiovascular mortality, including diabetes, coronary heart disease, and stroke, independently of traditional cardiovascular risk factors and metabolic syndrome. The aim of this study was to find out the predictive impact of hepatorenal index (HRI) in the detection of impaired glucose metabolism in asymptomatic NAFLD patients. METHODS B-mode ultrasound examinations were performed and ultrasound images from all 89 NAFLD patients aged 50.8 ± 10.1 years were analyzed by echogenicity analyzing software and HRI was acquired, and appropriate laboratory tests for liver, glucose, and lipid metabolism were undertaken. RESULTS The mean HRI was 1.345 ± 0.189. 23.59% of patients had mild NAFLD (HRI = 1.167 ± 0.041), 64.04% moderate (HRI = 1.401 ± 0.102), and 12.36% patients severe NAFLD (HRI = 1.802 ± 0.098). Impaired glucose metabolism was present in 48.31% of patients. A positive correlation was present between HRI and impaired glucose metabolism (r = 0.335, p = 0.001). The coefficients of determinations R2 for linear regression for HRI and glycated hemoglobin (HbA1c) and oral glucose tolerance test (GTT) were 0.05841 and 0.07498, respectively. The cutoff values for HRI in the detection of diabetes and prediabetes, and prediabetes only, were 1.4 and 1.38, respectively. In logistic regression, the β coefficients for oral GTT, HbA1c, or HRI were 0.62042 (p = 0.0002), 2.18036 (p = 0.0033), and 2.36986 (p = 0.012). The hazard ratio (HR) coefficients (exp [b]) for HRI, HbA1c, and oral GTT sorted according to their HR strength were 10.6958, 8.8494, and 1.8597, respectively. CONCLUSION Ultrasonographically acquired HRI has a significant predictive impact on the detection of prediabetes and diabetes in patients with NAFLD.
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Fuse K, Kadota A, Kondo K, Morino K, Fujiyoshi A, Hisamatsu T, Kadowaki S, Miyazawa I, Ugi S, Maegawa H, Miura K, Ueshima H. Liver fat accumulation assessed by computed tomography is an independent risk factor for diabetes mellitus in a population-based study: SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis). Diabetes Res Clin Pract 2020; 160:108002. [PMID: 31904446 DOI: 10.1016/j.diabres.2020.108002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 12/16/2019] [Accepted: 12/31/2019] [Indexed: 12/31/2022]
Abstract
AIMS Ectopic fat accumulation is related to insulin resistance and diabetes mellitus (DM). However, the effect of fatty liver on DM in non-obese individuals has not been clarified. We investigated whether liver fat accumulation assessed by computed tomography (CT) is associated with the incidence of DM. METHODS In a prospective population-based study, 640 Japanese men were followed up for 5 years. The liver to spleen (L/S) ratio of the CT attenuation value was used as the liver fat accumulation index. We calculated the odds ratio (OR) and 95% confidence interval (CI) for the DM incidence of per 1 standard deviation (SD) lower L/S and those of L/S < 1.0 compared with L/S ≥ 1.0, using logistic regression models. RESULTS Both per 1 SD lower L/S and L/S < 1.0 were significantly associated with a risk for DM incidence (1 SD lower L/S: OR = 1.57, 95%CI = 1.14-2.16; L/S < 1.0: OR = 2.27, 95%CI = 1.00-5.14). The relationship between L/S and incidence of DM was consistent in the obese and non-obese groups, with thresholds of BMI 25 kg/m2, waist circumference 85 cm, or visceral adipose tissue 100 cm2. CONCLUSIONS Liver fat accumulation assessed by CT was associated with the incidence of DM.
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Affiliation(s)
- Keiko Fuse
- Department of Medicine, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan; Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Aya Kadota
- Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan; Department of Public Health, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Keiko Kondo
- Department of Public Health, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Katsutaro Morino
- Department of Medicine, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Akira Fujiyoshi
- Department of Hygiene, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
| | - Takashi Hisamatsu
- Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
| | - Sayaka Kadowaki
- Department of Public Health, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Itsuko Miyazawa
- Department of Medicine, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Satoshi Ugi
- Department of Medicine, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Hiroshi Maegawa
- Department of Medicine, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Katsuyuki Miura
- Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan; Department of Public Health, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
| | - Hirotsugu Ueshima
- Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan; Department of Public Health, Shiga University of Medical Science, Seta, Tsukinowa, Otsu, Shiga 520-2192, Japan.
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Stamatikos AD, Davis JE, Shay NF, Ajuwon KM, Deyhim F, Banz WJ. Consuming Diet Supplemented with Either Red Wheat Bran or Soy Extract Changes Glucose and Insulin Levels in Female Obese Zucker Rats. INT J VITAM NUTR RES 2020; 90:23-32. [PMID: 30843770 DOI: 10.1024/0300-9831/a000547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Type 2 diabetes mellitus is characterized by the inability to regulate blood glucose levels due to insulin resistance, resulting in hyperglycemia and hyperinsulinemia. Research has shown that consuming soy and fiber may protect against type 2 diabetes mellitus. We performed a study to determine whether supplementing diet with soy extract (0.5% weight of diet) or fiber (as red wheat bran; 11.4% weight of diet) would decrease serum insulin and blood glucose levels in a pre-diabetic/metabolic syndrome animal model. In our study, female obese Zucker rats were fed either a control diet (n = 8) or control diet supplemented with either soy extract (n = 7) or red wheat bran (n = 8) for seven weeks. Compared to rats consuming control diet, rats fed treatment diets had significantly lower (p-value < 0.05) fasting serum insulin (control = 19.34±1.6; soy extract = 11.1±1.54; red wheat bran = 12.4±1.11) and homeostatic model assessment of insulin resistance values (control = 2.16±0.22; soy extract = 1.22±0.21; red wheat bran = 1.54±0.16). Non-fasted blood glucose was also significantly lower (p-value < 0.05) in rats fed treatment diets compared to rats consuming control diet at weeks four (control = 102.63±5.67; soy extract = 80.14±2.13; red wheat bran = 82.63±3.16), six (control = 129.5±10.83; soy extract = 89.14±2.48; red wheat bran = 98.13±3.54), and seven (control = 122.25±8.95; soy extract = 89.14±4.52; red wheat bran = 84.75±4.15). Daily intake of soy extract and red wheat bran may protect against type 2 diabetes mellitus by maintaining normal glucose homeostasis.
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Affiliation(s)
- Alexis D Stamatikos
- Department of Animal Science, Food and Nutrition, Southern Illinois University, Carbondale, IL 62901, USA
| | - Jeremy E Davis
- Department of Animal Science, Food and Nutrition, Southern Illinois University, Carbondale, IL 62901, USA
| | - Neil F Shay
- Department of Food Science and Technology, Oregon State University, Corvallis, OR 97331, USA
| | - Kolapo M Ajuwon
- Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA
| | - Farzad Deyhim
- Department of Human Sciences, Texas A&M University-Kingsville, Kingsville, TX 78363, USA
| | - William J Banz
- Department of Animal Science, Food and Nutrition, Southern Illinois University, Carbondale, IL 62901, USA
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