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Yu L, Que T, Zhou Y, Liu Z. Dose-response relationship of serum ferritin and dietary iron intake with metabolic syndrome and non-alcoholic fatty liver disease incidence: a systematic review and meta-analysis. Front Nutr 2024; 11:1437681. [PMID: 39410926 PMCID: PMC11476413 DOI: 10.3389/fnut.2024.1437681] [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: 05/24/2024] [Accepted: 09/09/2024] [Indexed: 10/19/2024] Open
Abstract
Aim This study aims to assess the dose-response impact of iron load on systemic and hepatic metabolic disorders including metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). Methods Serum ferritin (SF) and dietary iron intake were selected to represent the indicators of iron load in the general population. PubMed, EMBASE and Web of Science databases were searched for epidemiological studies assessing the impact of SF/dietary iron intake on MetS/NAFLD occurrence. All literature was published before September 1st, 2023 with no language restrictions. Results Fifteen and 11 papers were collected with a focus on connections between SF and MetS/NAFLD, respectively. Eight papers focusing on dietary iron and MetS were included in the following meta-analysis. For the impact of SF on MetS, the pooled odds ratio (OR) of MetS was 1.88 (95% CI: 1.58-2.24) for the highest versus lowest SF categories. In males, the OR was 1.15 (95% CI: 1.10-1.21) per incremental increase in SF of 50 μg/L, while for females, each 50 μg/L increase in SF was associated with a 1.50-fold higher risk of MetS (95% CI: 1.15-1.94). For connections between SF and NAFLD, we found higher SF levels were observed in NAFLD patients compared to the control group [standardized mean difference (SMD) 0.71; 95% CI: 0.27-1.15], NASH patients against control group (SMD1.05; 95% CI:0.44-1.66), NASH patients against the NAFLD group (SMD 0.6; 95% CI: 0.31-1.00), each 50 μg/L increase in SF was associated with a 1.08-fold higher risk of NAFLD (95% CI: 1.07-1.10). For the impact of dietary iron on MetS, Pooled OR of MetS was 1.34 (95% CI: 1.10-1.63) for the highest versus lowest dietary iron categories. Conclusion Elevated SF levels is a linear relation between the incidence of MetS/NAFLD. In addition, there is a positive association between dietary iron intake and metabolic syndrome. The association between serum ferritin and metabolic syndrome may be confounded by body mass index and C-reactive protein levels.
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Affiliation(s)
- Lu Yu
- School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Shulan (Hangzhou) Hospital, Hangzhou, China
| | - Ting Que
- Birth Defects Prevention and Control Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Yifeng Zhou
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Zhengtao Liu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Shulan (Hangzhou) Hospital, Hangzhou, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, School of Medicine, Chinese Academy of Medical Sciences, First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Zhu N, Wang X, Zhu H, Zheng Y. Blood cell parameters and risk of nonalcoholic fatty liver disease: a comprehensive Mendelian randomization study. BMC Med Genomics 2024; 17:102. [PMID: 38654378 DOI: 10.1186/s12920-024-01879-7] [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: 11/28/2023] [Accepted: 04/16/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to explore the potential correlation between whole blood cell indices and NAFLD risk using Mendelian randomization (MR). METHODS We analyzed data from 4,198 participants in the 2017-2018 National Health and Nutrition Examination Survey to investigate the link between blood cell indicators and NAFLD. Using various methods like weighted quantile sum and multivariate logistic regression, we assessed the association. Additionally, two-sample Mendelian randomization were employed to infer causality for 36 blood cell indicators and NAFLD. RESULTS Multivariate logistic regression identified 10 NAFLD risk factors. Weighted quantile sum revealed a positive correlation (p = 6.03e-07) between total blood cell indices and NAFLD, with hemoglobin and lymphocyte counts as key contributors. Restricted cubic spline analysis found five indicators with significant nonlinear correlations to NAFLD. Mendelian randomization showed a notable association between reticulocyte counts and NAFLD using the inverse-variance weighted method. CONCLUSIONS Hematological markers pose an independent NAFLD risk, with a positive causal link found for reticulocyte count. These results emphasize the importance of monitoring NAFLD and investigating specific underlying mechanisms further.
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Affiliation(s)
- Nan Zhu
- Department of Internal Medicine, Hebei Medical University, 050017, Shijiazhuang, Hebei Province, China
- Department of Internal Medicine, The First Hospital of Qinhuangdao, 066000, Qinhuangdao, Hebei Province, China
| | - Xiaoliang Wang
- Department of Cardiology, The First Hospital of Qinhuangdao, 066000, Qinhuangdao, Hebei Province, China
| | - Huiting Zhu
- Department of Internal Medicine, The First Hospital of Qinhuangdao, 066000, Qinhuangdao, Hebei Province, China
| | - Yue Zheng
- Department of Internal Medicine, Hebei Medical University, 050017, Shijiazhuang, Hebei Province, China.
- Department of Gastroenterology, The First Hospital of Qinhuangdao, 066000, Qinhuangdao, Hebei Province, China.
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Bao B, Xu S, Sun P, Zheng L. Neutrophil to albumin ratio: a biomarker in non-alcoholic fatty liver disease and with liver fibrosis. Front Nutr 2024; 11:1368459. [PMID: 38650638 PMCID: PMC11033504 DOI: 10.3389/fnut.2024.1368459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 03/27/2024] [Indexed: 04/25/2024] Open
Abstract
Objective Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) and its potential to progress to liver fibrosis, it is crucial to identify the presence of NAFLD in patients to guide their subsequent management. However, the current availability of non-invasive biomarkers for NAFLD remains limited. Therefore, further investigation is needed to identify and develop non-invasive biomarkers for NAFLD. Methods A retrospective analysis was conducted on 11,883 patients admitted to the Healthcare Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2016 to December 2019 and divided into NAFLD and non-NAFLD groups. Anthropometric and laboratory examination data were collected. The correlations between variables and NAFLD were evaluated using the student's t-test or Mann-Whitney U test and binary logistic regression analysis. The predictive ability of these variables for NAFLD was assessed using the areas under the curves (AUCs) of receiver operating characteristics. Results Among the included patients, 3,872 (32.58%) were diagnosed with NAFLD, with 386 (9.97%) individuals having liver fibrosis. Patients with NAFLD exhibited a higher proportion of males, elevated body mass index (BMI), and increased likelihood of hypertension, diabetes mellitus, and atherosclerosis. Logistic regression analysis identified the neutrophil to albumin ratio (NAR) as the most promising novel inflammation biomarkers, with the highest AUC value of 0.701, a cut-off value of 0.797, sensitivity of 69.40%, and specificity of 66.00% in identifying the risk of NAFLD. Moreover, NAR demonstrated superior predictive value in identifying NAFLD patients at risk of liver fibrosis, with an AUC value of 0.795, sensitivity of 71.30%, and specificity of 73.60% when NAR reached 1.285. Conclusion These findings highlight that the novel inflammatory biomarker, NAR, is a convenient and easily accessible non-invasive predictor for NAFLD and NAFLD with liver fibrosis.
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Affiliation(s)
- Banghe Bao
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuang Xu
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Peng Sun
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liduan Zheng
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Ito Y, Yoshioka K, Hayashi K, Shimizu Y, Fujimoto R, Yamane R, Yoshizaki M, Kajikawa G, Mizutani T, Goto H. Prevalence of Non-alcoholic Fatty Liver Disease Detected by Computed Tomography in the General Population Compared with Ultrasonography. Intern Med 2024; 63:159-167. [PMID: 37225482 PMCID: PMC10864065 DOI: 10.2169/internalmedicine.1861-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 04/09/2023] [Indexed: 05/26/2023] Open
Abstract
Objective To assess the prevalence and clinical correlates of non-alcoholic fatty liver disease (NAFLD) identified by computed tomography (CT) in the general population compared with ultrasonography (US). Methods Four hundred and fifty-eight subjects who received health checkups at Meijo Hospital in 2021 and underwent CT within a year of US in the past decade were analyzed. The mean age was 52.3±10.1 years old, and 304 were men. Results NAFLD was diagnosed in 20.3% by CT and in 40.4% by the US. The NAFLD prevalence in men was considerably greater in subjects 40-59 years old than in those ≤39 years old and in those ≥60 years old by both CT and US. The NAFLD prevalence in women was substantially higher in the subjects 50-59 years old than in those ≤49 years old or those ≥60 years old on US, while no significant differences were observed on CT. The abdominal circumference, hemoglobin value, high-density lipoprotein cholesterol level, albumin level, and diabetes mellitus were independent predictors of NAFLD diagnosed by CT. The body mass index, abdominal circumference, and triglyceride level were independent predictors of NAFLD diagnosed by the US. Conclusion NAFLD was found in 20.3% of CT cases and 40.4% of US cases among recipients of health checkups. An "inverted U curve" in which the NAFLD prevalence rose with age and dropped in late adulthood was reported. NAFLD was associated with obesity, the lipid profile, diabetes mellitus, hemoglobin values, and albumin levels. Our research is the first in the world to compare the NAFLD prevalence in the general population simultaneously by CT and US.
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Affiliation(s)
- Yuki Ito
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Kentaro Yoshioka
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Yuko Shimizu
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Ryo Fujimoto
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Ryosuke Yamane
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Michiyo Yoshizaki
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Go Kajikawa
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Taro Mizutani
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
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Jiang Y, Zhuang X, Zhang J, Li M, Du S, Tian J, Yuan Y, Ji G, Hu C. Clinical characterization and proteomic profiling of lean nonalcoholic fatty liver disease. Front Endocrinol (Lausanne) 2023; 14:1171397. [PMID: 38034020 PMCID: PMC10687542 DOI: 10.3389/fendo.2023.1171397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 07/06/2023] [Indexed: 12/02/2023] Open
Abstract
INTRODUCTION Obesity has been historically associated with nonalcoholic fatty liver disease (NAFLD), but it can also occur in lean individuals. However, limited data is available on this special group. To investigate the clinical and proteomic characteristics of lean subjects with NAFLD, and to identify potential clinical variables and plasma proteins for diagnosing NAFLD in lean individuals, we collected clinical data from a large cohort of 2,236 subjects. METHODS Diagnosis of NAFLD relied on detecting pronounced hepatic steatosis through abdominal ultrasonography. Participants were categorized into four groups based on body mass index: overweight NAFLD, overweight control, lean NAFLD, and lean control. Plasma proteomic profiling was performed on samples from 20 subjects in each group. The lean NAFLD group was compared to both lean healthy and obese NAFLD groups across all data. RESULTS AND DISCUSSION The results indicated that the lean NAFLD group exhibited intermediate metabolic profiles, falling between those of the lean healthy and overweight NAFLD groups. Proteomic profiling of plasma in lean subjects with or without NAFLD revealed 45 statistically significant changes in proteins, of which 37 showed high diagnostic value (AUC > 0.7) for lean NAFLD. These potential biomarkers primarily involved lipid metabolism, the immune and complement systems, and platelet degranulation. Furthermore, AFM, GSN, CFH, HGFAC, MMP2, and MMP9 have been previously associated with NAFLD or NAFLD-related factors such as liver damage, insulin resistance, metabolic syndromes, and extracellular homeostasis. Overall, lean individuals with NAFLD exhibit distinct clinical profiles compared to overweight individuals with NAFLD. Despite having worse metabolic profiles than their healthy counterparts, lean NAFLD patients generally experience milder systemic metabolic disturbances compared to obese NAFLD patients. Additionally, the plasma proteomic profile is significantly altered in lean NAFLD, highlighting the potential of differentially expressed proteins as valuable biomarkers or therapeutic targets for diagnosing and treating NAFLD in this population.
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Affiliation(s)
- Yuanye Jiang
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoyu Zhuang
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiaqi Zhang
- Department of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Meng Li
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shengnan Du
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiyun Tian
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yifu Yuan
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Cheng Hu
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Chen H, Li X, Meng F, Ai W, Lin Q, Cai K. A decision tree network with semi-supervised entropy learning strategy for spectroscopy aided detection of blood hemoglobin. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2023; 291:122354. [PMID: 36640527 DOI: 10.1016/j.saa.2023.122354] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 12/22/2022] [Accepted: 01/08/2023] [Indexed: 06/17/2023]
Abstract
Non-invasive techniques for rapid blood testing are gaining traction in global healthcare as they optimize medical screening, diagnosis and clinical decisions. Fourier transform infrared (FT-IR) spectroscopy is one of the most common technologies that can be used for non-destructive aided medical detection. Typically, after acquiring the Fourier transform infrared spectrum, spectral data preprocessing and feature extraction and quantitative analysis of several indicators of blood samples can be accomplished, in combination with chemometric method studies. At present, blood hemoglobin (HGB) concentration is one of the most valuable information for the clinical diagnosis of patient's health status. FT-IR spectroscopy is employed as a green technique aided medical test of blood HGB. Then the acquired HGB concentration data is switched to the spectral feature data by the studies of advanced chemometric method, in help for hiding the sensitive medical information to protect the privacy of patients. The decision tree network architecture is proposed for feature extraction of FT-IR data in order to find the small set of wavenumbers that are able to quantify HGB. A semi-supervised learning strategy is designed for tuning the number of network neuron nodes, in the way of searching for the maximum entropy increment. Each neuron is optimized by the growing of a semi-supervised decision tree, to accurately identify the informative FT-IR wavenumbers. The features extracted by the semi-supervised learning decision tree network guarantees the FT-IR aided detection model has high efficiency and high prediction accuracy. A model of quantifying the HGB concentration shows that the proposed decision tree network with semi-supervised entropy learning strategy outperforms the usual methods of full spectrum partial least square model and the fully connected neural network model in prediction accuracy. The framework is expected to support the FT-IR spectral technology for aided detection of medical and clinical data.
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Affiliation(s)
- Huazhou Chen
- College of Science, Guilin University of Technology, Guilin 541004, China; Center for Data Analysis and Algorithm Technology, Guilin University of Technology, Guilin 541004, China
| | - Xiaorong Li
- Department of Radiology, General Hospital of Southern Theater Command, PLA, Guangzhou 510010, China
| | - Fangxiu Meng
- College of Science, Guilin University of Technology, Guilin 541004, China
| | - Wu Ai
- College of Science, Guilin University of Technology, Guilin 541004, China; Center for Data Analysis and Algorithm Technology, Guilin University of Technology, Guilin 541004, China
| | - Qinyong Lin
- College of Automation, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China
| | - Ken Cai
- College of Automation, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China.
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Ragab HM, Ezzat WM, Hassan EM, El Maksoud NA, Afify M, Abd El-Maksoud MDE, Elaziz WA. Significance of MiRNA-34a and MiRNA-192 as a risk factor for nonalcoholic fatty liver disease. J Genet Eng Biotechnol 2023; 21:13. [PMID: 36757530 PMCID: PMC9911573 DOI: 10.1186/s43141-023-00467-z] [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: 09/04/2022] [Accepted: 01/14/2023] [Indexed: 02/10/2023]
Abstract
BACKGROUND AND AIMS NAFLD is one of the fast-growing health problems that affects up to 25% of people worldwide. Numerous miRNAs have been clarified as important regulators of liver pathophysiology, including NAFLD. Thus, we investigated the expression of the MiRNA-34a and MiRNA-192 as diagnostic markers for NAFLD. PATIENTS AND METHODS Blood samples were collected from NAFLD cases and healthy controls. The expression profile of both studied miRNAs was detected via real-time PCR analysis. RESULTS The present study showed that both studied miRNAs were upregulated in NAFLD patients compared to controls. Interestingly, miRNA-34a and MiRNA-192 are upregulated in NAFLD patients with early fibrosis compared to controls [with a fold change of 4.02 ± 11.49 (P = 0.05) and 18.43 ± 47.8 (P = 0.017), respectively]. However, miRNA-34a is downregulated in NAFLD patients with advanced fibrosis compared to controls, with fold expression of 0.65 ± 1.17 (P = 0.831). The area under the receiver operating characteristics (AUROC) for miRNA-34a and miRNA-192 were 0.790 and 0.643, respectively; furthermore, the sensitivities and specificities were 76.7%, 100% for miRNA-34a and 63.3%, and 93.3% for miRNA-192 (P < 0.05). Additionally, MiRNA34a was positively correlated with hypertension and fasting blood sugar, and it also was negatively correlated with hemoglobin level and total leucocyte count (P < 0.05). CONCLUSION The results obtained indicated that both studied miRNAs could potentially be used as diagnostic biomarkers for the early stage of liver fibrosis in NAFLD cases. Also, miRNA-34a was positively correlated with metabolic disorders associated with NAFLD such as hypertension and diabetes. However, their expression showed no association with advanced fibrosis. Thus, larger cohorts are necessitated to certify the utility of serum MiRNA-34a and MiRNA-192 in monitoring the deterioration of NAFLD.
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Affiliation(s)
- Halla M. Ragab
- grid.419725.c0000 0001 2151 8157Biochemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, Egypt
| | - Wafaa M. Ezzat
- grid.419725.c0000 0001 2151 8157Internal Medicine Department, National Research Centre, Dokki, Giza, Egypt
| | - Eman Mahmoud Hassan
- grid.419725.c0000 0001 2151 8157Clinical and Chemical Pathology Department, National Research Centre, Dokki, Giza, Egypt
| | - Nabila Abd El Maksoud
- grid.419725.c0000 0001 2151 8157Biochemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, Egypt
| | - Mie Afify
- grid.419725.c0000 0001 2151 8157Biochemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, Egypt
| | - Mohamed D. E. Abd El-Maksoud
- grid.419725.c0000 0001 2151 8157Biochemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, Egypt
| | - Wafaa Abd Elaziz
- grid.419725.c0000 0001 2151 8157Biochemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, Egypt
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A Physiologically Based Pharmacokinetic Model to Predict the Impact of Metabolic Changes Associated with Metabolic Associated Fatty Liver Disease on Drug Exposure. Int J Mol Sci 2022; 23:ijms231911751. [PMID: 36233052 PMCID: PMC9570165 DOI: 10.3390/ijms231911751] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/09/2022] [Accepted: 09/26/2022] [Indexed: 11/17/2022] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease, with an estimated prevalence of between 20 and 30% worldwide. Observational data supported by in vitro and pre-clinical animal models of MAFLD suggest meaningful differences in drug disposition in MAFLD patients. This study aimed to build a physiologically based pharmacokinetic (PBPK) model reflecting observed changes in physiological and molecular parameters relevant to drug disposition that are associated with MAFLD. A comprehensive literature review and meta-analysis was conducted to identify all studies describing in vivo physiological changes along with in vitro and pre-clinical model changes in CYP 1A2, 2C9, 2C19, 2D6 and 3A4 protein abundance associated with MAFLD. A MAFLD population profile was constructed in Simcyp (version 19.1) by adapting demographic and physiological covariates from the Sim-Healthy population profile based on a meta-analysis of observed data from the published literature. Simulations demonstrated that single dose and steady state area under the plasma concentration time curve (AUC) for caffeine, clozapine, omeprazole, metoprolol, dextromethorphan and midazolam, but not s-warfarin or rosiglitazone, were increased by >20% in the MAFLD population compared to the healthy control population. These findings indicate that MAFLD patients are likely to be experience meaningfully higher exposure to drugs that are primarily metabolized by CYP 1A2, 2C19, 2D6 and 3A4, but not CYP2C9. Closer monitoring of MAFLD patients using drugs primarily cleared by CYP 1A2, 2C19 and 3A4 is warranted as reduced metabolic activity and increased drug exposure are likely to result in an increased incidence of toxicity in this population.
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May M, Barlow D, Ibrahim R, Houseknecht KL. Mechanisms Underlying Antipsychotic-Induced NAFLD and Iron Dysregulation: A Multi-Omic Approach. Biomedicines 2022; 10:biomedicines10061225. [PMID: 35740245 PMCID: PMC9220331 DOI: 10.3390/biomedicines10061225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 05/18/2022] [Accepted: 05/19/2022] [Indexed: 02/06/2023] Open
Abstract
Atypical antipsychotic (AA) medications are widely prescribed for the treatment of psychiatric disorders, including schizophrenia, bipolar disorder and treatment-resistant depression. AA are associated with myriad metabolic and endocrine side effects, including systemic inflammation, weight gain, dyslipidemia and insulin resistance, all of which are associated with increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is highly prevalent in patients with mental illness, and AA have been shown to increase incidence of NAFLD pre-clinically and clinically. However, the underlying mechanisms have not been described. We mined multi-omic datasets from preclinical murine models of sub-chronic risperidone or olanzapine treatment, in vitro exposure of human cells to risperidone and psychiatric patients following onset of aripiprazole therapy focused on pathways associated with the pathophysiology of NAFLD, including iron accumulation, systemic inflammation and dyslipidemia. We identified numerous differentially expressed traits affecting these pathways conserved across study systems and AA medications. We used these findings to propose mechanisms for AA-associated development of NAFLD and dysregulated iron homeostasis.
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Affiliation(s)
- Meghan May
- Correspondence: (M.M.); (K.L.H.); Tel.: +1-207-602-2872 (K.L.H.)
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Distinctive clinical and genetic features of lean vs overweight fatty liver disease using the UK Biobank. Hepatol Int 2022; 16:325-336. [PMID: 35178663 DOI: 10.1007/s12072-022-10304-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Lean NAFLD may differ from NAFLD found in overweight or obese patients. We used the UK biobank to conduct a cross-sectional study that examined features that distinguish lean NAFLD from overweight or obese NAFLD. METHODS MRI-PDFF data were used to identify patients with NAFLD, with NAFLD defined as PDFF ≥ 5%. BMI patient cohorts were identified, with lean defined as a BMI < 25, and overweight or obese defined as a BMI ≥ 25. Variables of interest to fatty liver disease, including single nucleotide polymorphisms, were chosen from the UK biobank data portal. Logistic regression was used to generate models predictive of NAFLD in each cohort. RESULTS 1007 patients had NAFLD, and of these, 871 had BMI ≥ 25, and 136 BMI < 25. Factors associated with NAFLD in patients with BMI < 25 included male sex, white blood cell count, red blood cell count, triglycerides, ALT, creatinine, visceral adipose tissue, rs58542926 T, and rs738409 G. In contrast, factors associated with NAFLD in patients with BMI ≥ 25 included male sex, waist circumference, HDL cholesterol, triglycerides, serum glucose, ALT, creatinine, urate, visceral adipose tissue, rs1260326 T, rs1044498 C, rs58542926 T, and rs738409 G. For lean patients, our generated prediction score had an AUC of 0.92, sensitivity of 0.90 and specificity of 0.81. For overweight or obese patients, the prediction score had an AUC of 0.86, sensitivity of 0.87 and specificity of 0.70. CONCLUSIONS Our analysis suggests that lean and overweight or obese NAFLD are distinct entities. We have developed a risk score incorporating both clinical and genetic factors that accurately classify lean patients with NAFLD, with the potential to serve as a tool for screening purposes.
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Ma H, Liu XF, Qi XQ, Huang YH, Sun XX, Zhou L, Wu HP. Evaluation of Left Ventricular Diastolic Function by 2-D Speckle Tracking Echocardiography in Patients with Connective Tissue Disease-Associated Pulmonary Artery Hypertension. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:910-918. [PMID: 33483161 DOI: 10.1016/j.ultrasmedbio.2020.09.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 08/06/2020] [Accepted: 09/14/2020] [Indexed: 06/12/2023]
Abstract
The purpose of this study was to evaluate the role of 2-D speckle tracking imaging in assessing left ventricular diastolic function in patients with connective tissue disease (CTD). A total of 98 CTD patients and 32 healthy controls were prospectively recruited. Early (E) and late (A) diastolic velocities of the transmitral flow were measured by pulsed Doppler echocardiography. Peak early diastolic myocardial velocity (E') was calculated on tissue Doppler echocardiography. The longitudinal strain rate (SR) was calculated as the average of three apical views, while circumferential and radial SRs were measured in three short-axis views. Pulmonary arterial hypertension (PAH) was defined as systolic pulmonary arterial pressure (sPAP) >36 mm Hg. Compared with the control group, CTD patients exhibited significant impairment of left ventricular diastolic function, manifested as lower global SR during early diastole (SRe) in the longitudinal deformation and higher E/SRe in both longitudinal and radial deformation. CTD-PAH patients had significantly lower SRe and higher E/SRe values in both the longitudinal and radial deformation compared with the patients with CTD without PAH. Pearson's correlation analysis revealed that sPAP levels correlated positively with E/E', longitudinal E/SRe, circumferential E/SRe and radial SRe, and it correlated negatively with septal E' and radial E/SRe. Receiver operating characteristic curve analysis suggested that E/E', longitudinal E/SRe and radial SRe could be used to predict PAH. The present study indicates that 2-D speckle tracking imaging is a useful method for evaluation of left ventricular diastolic function, and these derived parameters can serve as good predictors of PAH, but it may not be superior to the commonly used E/E' in CTD patients.
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Affiliation(s)
- Hong Ma
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xian-Fang Liu
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiao-Qing Qi
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ying-Heng Huang
- Department of Rheumatology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiao-Xuan Sun
- Department of Rheumatology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lei Zhou
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Hong-Ping Wu
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
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12
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He S, Gu H, Yang J, Su Q, Li X, Qin L. Hemoglobin concentration is associated with the incidence of metabolic syndrome. BMC Endocr Disord 2021; 21:53. [PMID: 33740939 PMCID: PMC7980652 DOI: 10.1186/s12902-021-00719-4] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 03/10/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND An association between hemoglobin and metabolic syndrome (MetS) has been reported. However, the relationships between hemoglobin and individual MetS components remain unclear. Therefore, we investigated these associations at baseline and at the 3-year follow-up. METHODS We enrolled 9960 middle-aged and elderly subjects (6726 women and 3234 men) and performed a 3-year follow-up cohort study. All subjects completed a questionnaire and underwent anthropometric measurements and laboratory tests. Logistic regression models were developed to assess the association between hemoglobin and MetS and its components. RESULTS MetS was present in 45.1% of women and 41.4% of men at baseline. The hemoglobin concentration was positively correlated with SBP, DBP, TGs, WC, FPG, insulin, HOMA-IR, BMI and uric acid (p < 0.05). The mean hemoglobin concentration was higher in subjects with hypertension, high TGs, abdominal obesity or elevated FPG (p < 0.01). At follow-up, elevated hemoglobin correlated with an increased incidence and ORs for MetS, high TGs, low HDL-c, hyperuricemia and NAFLD but not abdominal obesity, BP or FPG in women. Increased hemoglobin corresponded with an increased incidence and ORs for MetS, abdominal obesity, low HDL-c, hyperuricemia and NAFLD but not BP, high TGs or FPG in men. CONCLUSIONS Hemoglobin may play a role in predicting new-onset MetS in both women and men. Hemoglobin was notably correlated with future risk of high TGs, low HDL-c, hyperuricemia, and NAFLD among women and abdominal obesity, low HDL-c, hyperuricemia, and NAFLD among men.
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Affiliation(s)
- Sunyue He
- Department of Endocrinology, Xinhua Hospital Chongming Branch, School of Medicine, Shanghai Jiaotong University, 25 Nanmen Road, Shanghai, 202150, China
| | - Hongxia Gu
- Department of Endocrinology, Xinhua Hospital Chongming Branch, School of Medicine, Shanghai Jiaotong University, 25 Nanmen Road, Shanghai, 202150, China
| | - Jie Yang
- Department of Endocrinology, Xinhua Hospital Chongming Branch, School of Medicine, Shanghai Jiaotong University, 25 Nanmen Road, Shanghai, 202150, China
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China
| | - Xiaoyong Li
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.
| | - Li Qin
- Department of Endocrinology, Xinhua Hospital Chongming Branch, School of Medicine, Shanghai Jiaotong University, 25 Nanmen Road, Shanghai, 202150, China.
- Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.
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Hao X, Ma C, Xiang T, Ou L, Zeng Q. Associations Among Methylene Tetrahydrofolate Reductase rs1801133 C677T Gene Variant, Food Groups, and Non-alcoholic Fatty Liver Disease Risk in the Chinese Population. Front Genet 2021; 12:568398. [PMID: 33679874 PMCID: PMC7930608 DOI: 10.3389/fgene.2021.568398] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 01/22/2021] [Indexed: 12/20/2022] Open
Abstract
Objectives To investigate the associations among the methylene tetrahydrofolate reductase rs1801133 C677T gene variant, food groups, and the risk of non-alcoholic fatty liver disease in the Chinese population. Methods A study of gene polymorphism was conducted using the polymerase chain reaction method. A total of 4,049 adults participated in the study, and all underwent physical examination and genotyping. Participants filled out a dietary questionnaire to enable us to assess the frequency and quantity of food consumption. Results The important variables identified as risk factors of non-alcoholic fatty liver disease were age, smoking, sex, body mass index, hyperlipidemia, diabetes, and methylene tetrahydrofolate reductase genotype (T – allele carriers). The homocysteine content was higher in the non-alcoholic fatty liver disease group than in the control group, and was higher in the T- allele than C- allele carriers. The homocysteine content was the highest in the T- allele carriers. Additionally, certain food groups such as milk and beans were associated with a lower risk of non-alcoholic fatty liver disease. Food groups such as meat, were associated with a higher risk of non-alcoholic fatty liver disease. Fresh fruit and vegetables, salted and smoked foods, desserts, cereals, fish, and eggs were not associated with the risk of non-alcoholic fatty liver disease. However, the influence of salted and smoked foods on non-alcoholic fatty liver disease was different in the C-allele and T-allele carriers of methylene tetrahydrofolate reductase (CT + TT vs. CC, OR = 1.196, P = 0.041 for 1–4 times food per week, OR = 1.580, P = 0.004 for 5–7 times per week). Similarly, salted and smoked foods were also a risk factor for the development of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease. Conclusion This study found that the T-allele of the C677T variant of methylene tetrahydrofolate reductase was a risk factor for non-alcoholic fatty liver disease among Chinese people. These results can likely aid the development of novel approaches for managing non-alcoholic fatty liver disease risk.
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Affiliation(s)
- Xiaoyan Hao
- Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Cong Ma
- Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Tianyuan Xiang
- Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Lei Ou
- Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Qiang Zeng
- Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
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Composite BMI and Waist-to-Height Ratio Index for Risk Assessment of Non-alcoholic Fatty Liver Disease in Adult Populations. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.103607] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: As obesity becomes more prevalent, non-alcoholic fatty liver disease (NAFLD) is also becoming a major worldwide health problem and the most common cause of chronic liver disease. A new obesity classification method based on a composite index which includes both the body mass index (BMI) and the waist-to-height ratio (WHtR) was recently proposed. However, the usefulness of this approach to assess the risk of NAFLD is unclear. Methods: This is a cross-sectional study of 1,276 adult individuals in Dalian, China. The Mann Whitney U test, χ2 test and t-test were used to compare differences between groups. Binary logistic regression analysis was used to identify independent risk factors. Based on BMI and WHtR tertiles, individuals were divided into five new groups. Spearman correlation and receiver operating characteristic curve (ROC) analyses were performed to compare the NAFLD risk factors among groups based on BMI alone, WHtR alone, or the combination of both indexes. Results: BMI, waistline circumference (WC), WHtR, alanine aminotransferase (ALT), weight, triglycerides (TG), γ-glutamyl transpeptidase (GGT), serum uric acid (SUA), red blood cell (RBC) counts, hemoglobin levels (HGB), fasting blood glucose (FBG) and aspartate aminotransferase (AST) levels were identified as high risk factors for NAFLD (all AUC > 0.7). Logistic regression analysis suggested that BMI and WHtR were independent predictors of the appearance of NAFLD (the ORs for BMI and WHtR were 1.595 and 4.060E-11, respectively; all P < 0.001). The combination of BMI and WHtR tertiles significantly improved the correlation coefficient and Area under the receiver operating characteristic curve (AUC) for NAFLD risk factors in subjects classified as overweight or obese when compared with either BMI or WHtR alone. Conclusions: BMI, WC, WHtR, ALT, weight, TG, GGT, SUA, RBC, HGB, FBG, AST were high risk factors for NAFLD. The composite BMI and WHtR index improved body fat classification and the ability to detect individuals with NAFLD risk, offering a more precise method for the early identification of high- and low-risk NAFLD patients.
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15
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Zhong F, Guan L, Lin H, Zhao M, Qin Y, Li Q, Yuan Z, Yang G, Gao L, Zhao J. Red Blood Cell Count: An Unrecognized Risk Factor for Nonalcoholic Fatty Liver Disease. Front Endocrinol (Lausanne) 2021; 12:760981. [PMID: 34950103 PMCID: PMC8688742 DOI: 10.3389/fendo.2021.760981] [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: 08/19/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is becoming a global public health challenge. A convenient NAFLD indicator will greatly facilitate risk appraisal and prevention. As a readily available and inexpensive hematological index in routine clinical examinations, red blood cells (RBCs) are gaining increasing attention in many diseases, such as metabolic syndrome, but their association with NAFLD is unknown. METHODS This health management cohort study included 27,112 subjects (17,383 non-NAFLD and 9,729 NAFLD) with up to 5 years of follow-up (median 2.8 years). NAFLD was diagnosed by ultrasonography. NAFLD severity was categorized as mild, moderate, or severe. The generalized estimation equation (GEE), an extension of generalized linear models that allows for analysis of repeated measurements, was used to analyze the association between RBC count and NAFLD. RESULTS Overall, 4,332 of 17,383 (24.9%) subjects without NAFLD at baseline developed NAFLD. Incident NAFLD risk was positively associated with RBC count. After adjustment for hemoglobin and other confounders, the risk of incident NAFLD was 21%, 32%, and 51% higher in the second, third, and fourth RBC count quartiles, respectively, than in the lowest quartile. In 1,798 of 9,476 (19.0%) subjects with NAFLD at baseline, the severity of NAFLD increased. NAFLD progression risk increased progressively as RBC count increased (P for trend < 0.001). Every one-unit (1012 cells/L) increase in RBC count was associated with a 53% [OR 1.53 (95% CI 1.32-1.77)] increased risk for NAFLD progression. CONCLUSIONS Elevated RBC count was independently associated with a high risk of NAFLD incidence and progression. This finding revealed a convenient NAFLD risk indicator.
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Affiliation(s)
- Fang Zhong
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, China
- Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
| | - Liying Guan
- Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Haiyan Lin
- Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Meng Zhao
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, China
- Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yiming Qin
- College of Chemical Engineering and Materials Science, Shandong Normal University, Jinan, China
| | - Qihang Li
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, China
- Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
| | - Zhongshang Yuan
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, China
| | - Guang Yang
- Beijing Institute of Pharmacology and Toxicology, Beijing, China
| | - Ling Gao
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, China
- Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jiajun Zhao
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, China
- Shandong Institute of Endocrine and Metabolic Disease, Jinan, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- *Correspondence: Jiajun Zhao,
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16
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Kohsari M, Moradinazar M, Rahimi Z, Najafi F, Pasdar Y, Moradi A, Shakiba E. Association between RBC Indices, Anemia, and Obesity-Related Diseases Affected by Body Mass Index in Iranian Kurdish Population: Results from a Cohort Study in Western Iran. Int J Endocrinol 2021; 2021:9965728. [PMID: 34527049 PMCID: PMC8437600 DOI: 10.1155/2021/9965728] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 08/27/2021] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE The relationship between RBC indices and metabolic diseases remains unclear. The association between anemia and obesity is also controversial. The present study aimed to investigate the relationship between RBC indices and metabolic diseases caused by obesity and evaluate the effect of body mass index (BMI) on RBC indices on the Ravansar cohort data. METHOD For the purpose of this study, 9826 participants aged 35-65 years (5158 females and 4668 males) were recruited in the analyses. A quadratic prediction fit plot investigated the association between RBC indices with BMI and lipid profile. The odds ratio of obesity-related diseases in each quartile category of RBC indices and anemia was estimated using multivariable logistic regression models. RESULTS Subjects in the fourth quartiles of RBC count, hematocrit (HCT), hemoglobin (HGB), and red cell distribution width (RDW) had a higher risk for obesity-related diseases compared to the first quartiles. However, individuals with the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in fourth quartiles had lower ORs of obesity-related diseases. While BMI reduced the effect of RBC count, HCT, HGB, and RDW on the incidence risk of obesity-related disease, it increased the impact of MCV, MCH, and MCHC. There was a negative association between BMI and RBC indices except for RDW. The BMI effect on RBC indices was different in normal and obese individuals. BMI in mild anemia lowered the risk of metabolic diseases, but it increased the risk of metabolic diseases for moderate anemia. CONCLUSION A higher risk of obesity-related diseases was observed in the fourth quartiles of RBC count, HCT, HGB, and RDW compared to the first quartiles. However, the incidence risk was lower for MCV, MCH, and MCHC. BMI plays an anemia-type dependent role in the relationship. Consideration should be given to the type of anemia in the relationship between BMI and anemia.
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Affiliation(s)
- Maryam Kohsari
- Behavioral Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehdi Moradinazar
- Behavioral Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zohreh Rahimi
- Behavioral Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farid Najafi
- Behavioral Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yahya Pasdar
- Behavioral Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Atefeh Moradi
- Behavioral Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ebrahim Shakiba
- Behavioral Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
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17
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Zhang J, Cao J, Xu H, Dong G, Huang K, Wu W, Ye J, Fu J. Ferritin as a key risk factor for nonalcoholic fatty liver disease in children with obesity. J Clin Lab Anal 2020; 35:e23602. [PMID: 33249617 PMCID: PMC7891541 DOI: 10.1002/jcla.23602] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 08/31/2020] [Accepted: 09/11/2020] [Indexed: 02/06/2023] Open
Abstract
Background The association between serum ferritin and nonalcoholic fatty liver disease (NAFLD) in children with obesity is not clear. This study was designed to investigate whether serum ferritin can be an independent predictor for NAFLD. Methods According to the hepatic ultrasound results, a total of 347 children with obesity were enrolled in this study. Among them, 95 patients with NAFLD and 95 without NAFLD were matched for gender, age, blood pressure and body mass index, the odds ratios (OR) and 95% confidence intervals (CI) for the association of ferritin and the risk of NAFLD were analyzed. Results After propensity score matching, ferritin values of the patients with NAFLD were significantly higher than those without NAFLD group. Alanine aminotransferase and ferritin were strongly associated with NAFLD in multivariate stepwise logistic regression analysis. The medium and high levels of ferritin increased risk of NAFLD, and the adjusted ORs were 3.298 (95% CI:1.326‐8.204), 7.322 (95% CI:2.725‐19.574) across the ferritin concentration tertiles after adjustment for confounders. Ferritin was shown to be the best predictor for NAFLD with sensitivity and specificity of 60.0% and 77.9%, respectively, area under the curve was 0.733. Conclusion The results show that serum ferritin can usefully be considered as a predictor of NAFLD in children with obesity.
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Affiliation(s)
- Junfeng Zhang
- Department of Clinical Laboratory, School of Medicine, The Children's Hospital, Zhejiang University, Zhejiang, China.,National Clinical Research Center for Child Health, Hangzhou, China
| | - Jiajia Cao
- Department of Clinical Laboratory, School of Medicine, The Children's Hospital, Zhejiang University, Zhejiang, China.,National Clinical Research Center for Child Health, Hangzhou, China
| | - Hui Xu
- Department of Clinical Laboratory, School of Medicine, The Children's Hospital, Zhejiang University, Zhejiang, China.,National Clinical Research Center for Child Health, Hangzhou, China
| | - Guanping Dong
- National Clinical Research Center for Child Health, Hangzhou, China.,Department of Endocrinology, School of Medicine, The Children's Hospital, Zhejiang University, Zhejiang, China
| | - Ke Huang
- National Clinical Research Center for Child Health, Hangzhou, China.,Department of Endocrinology, School of Medicine, The Children's Hospital, Zhejiang University, Zhejiang, China
| | - Wei Wu
- National Clinical Research Center for Child Health, Hangzhou, China.,Department of Endocrinology, School of Medicine, The Children's Hospital, Zhejiang University, Zhejiang, China
| | - Jingjing Ye
- National Clinical Research Center for Child Health, Hangzhou, China.,Department of Ultrasound, School of Medicine, The Children's Hospital, Zhejiang University, Zhejiang, China
| | - Junfen Fu
- National Clinical Research Center for Child Health, Hangzhou, China.,Department of Endocrinology, School of Medicine, The Children's Hospital, Zhejiang University, Zhejiang, China
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Ding Q, Zhou Y, Zhang S, Liang M. Association between hemoglobin levels and non-alcoholic fatty liver disease in patients with young-onset type 2 diabetes mellitus. Endocr J 2020; 67:1139-1146. [PMID: 32684526 DOI: 10.1507/endocrj.ej20-0071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
This retrospective study aimed to investigate the relationship between hemoglobin (Hb) levels and non-alcoholic fatty liver disease (NAFLD) in patients with young-onset type 2 diabetes mellitus (T2DM). Data were collected for 296 patients with young-onset T2DM admitted to the first Affiliated Hospital of Guangxi Medical University from May 2017 to January 2020. Subjects were divided into NAFLD (n = 186) and non-NAFLD groups (n = 110). Patients with NAFLD had significantly higher Hb levels (p = 0.001). According to logistic regression analysis, Hb levels were significantly correlated with NAFLD after adjusting for confounding factors [odds ratio (OR) = 1.024, 95% confidence interval = 1.003-1.046, p = 0.028]. Subjects were also grouped according to Hb quartiles. After adjusting for sex and body mass index (BMI), the OR (95%CI) for NAFLD significantly increased with increasing Hb levels (p for trend = 0.009). Patients were also divided into lean (BMI <25 kg/m2, n = 139) and overweight/obese groups (BMI ≥25 kg/m2, n = 157), with adjusted ORs (95%CI) for the highest quartiles of 1.797 (0.559-5.776) and 6.009 (1.328-27.181), respectively. Further quartile classification of Hb according to sex showed adjusted OR (95%CI) for the highest compared with the lowest quartile of 2.796 (1.148-6.814) for males and 2.945 (0.482-17.997) for females. In conclusion, high Hb levels were associated with the presence of NAFLD in patients with young-onset T2DM, especially in males and overweight/obese patients.
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Affiliation(s)
- Qinpei Ding
- Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Yubo Zhou
- Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Shu Zhang
- Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Min Liang
- Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
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Choe AR, Ryu DR, Kim HY, Lee HA, Lim J, Kim JS, Lee JK, Kim TH, Yoo K. Noninvasive indices for predicting nonalcoholic fatty liver disease in patients with chronic kidney disease. BMC Nephrol 2020; 21:50. [PMID: 32066395 PMCID: PMC7027038 DOI: 10.1186/s12882-020-01718-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 02/10/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Data on clinical characteristics of nonalcoholic fatty liver disease (NAFLD) in patients with chronic kidney disease (CKD) are scarce. We investigated the clinical features and risk factors of NAFLD using noninvasive serum markers in CKD patients and attempted the temporal validation of a predictive model for CKD based on NAFLD. METHODS This retrospective cross-sectional study was conducted in a single tertiary center. We enrolled 819 CKD patients and evaluated the predictive performance of relevant clinical and laboratory markers for the presence of NAFLD in both derivation (data from 2011 to 2014, n = 567) and validation (data from 2015 to 2016, n = 252) groups. RESULTS In the derivation group, NAFLD was observed in 89 patients (15.7%; mean body mass index (BMI), 24.6 kg/m2; median estimated glomerular filtration rate (eGFR), 28.0 ml/min). BMI, hemoglobin, serum alanine aminotransferase, eGFR, and triglyceride-glucose index were used to derive a prediction model for the presence of NAFLD. Using the cutoff value of 0.146, the area under the receiver operating characteristic curve (AUROC) for the prediction of NAFLD was 0.850. In the validation group, NAFLD was observed in 51 patients (20.2%; mean BMI, 25.4 kg/m2; median eGFR, 36.0 ml/min). Using the same prediction model and cutoff value, the AUROC was 0.842. NAFLD prevalence in CKD patients was comparable to that in the general population, increasing over time. CONCLUSIONS Our model using BMI, renal function, triglyceride-glucose index, serum alanine aminotransferase, and hemoglobin accurately predicted the presence of NAFLD in CKD patients.
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Affiliation(s)
- A Reum Choe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Dong-Ryeol Ryu
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Hwi Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea
| | - Jiyoung Lim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Jin Sil Kim
- Department of Radiology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Jeong Kyong Lee
- Department of Radiology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Tae Hun Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Kwon Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
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Non-alcoholic fatty liver disease in lean individuals. JHEP Rep 2019; 1:329-341. [PMID: 32039383 PMCID: PMC7001558 DOI: 10.1016/j.jhepr.2019.08.002] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 08/15/2019] [Accepted: 08/16/2019] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, encompassing a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis, which can progress to cirrhosis. It has recently been recognised that NAFLD also occurs in individuals who are not obese, especially in Asian populations. In these patients, NAFLD manifests at lower overall body mass index thresholds in the presence of increased visceral adipose tissue. Currently, the principles of clinical management are similar to those in obese individuals, although, in specific regions and clinical situations, unique aetiologies of NAFLD must be treated specifically.
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Pang K, Zhu Z, Zhu S, Han L. A high dose of conjugated linoleic acid increases fatty liver and insulin resistance in lactating mice. PLoS One 2019; 14:e0214903. [PMID: 31390361 PMCID: PMC6685630 DOI: 10.1371/journal.pone.0214903] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 07/12/2019] [Indexed: 12/11/2022] Open
Abstract
This study aimed to evaluate the effects of a high dose of conjugated linoleic acid (CLA) on lactating mice. In one experiment, Kunming mice were separated into four groups (n = 6 per group); the control (CON) group received 3.0% linoleic acid (LA) oil, the L-CLA group received a mixture of 2.0% LA and 1.0% CLA, the M-CLA group received a mixture of 1.0% LA and a 2.0% CLA, and the H-CLA group received 3.0% CLA. Feeding proceeded from day 4 to day 10 of lactation. In a second experiment, a CON group received 3.0% LA, and an H-CLA group received 3.0% CLA. Plasma parameters were analyzed for all groups, and insulin tolerance tests (ITTs) were conducted. CLA treatment did not affect dam weight but significantly decreased the food intake of dams during lactation. Furthermore, CLA decreased the weight of pups on day 10 of lactation; this effect was attributed to lower milk fat of dams in the CLA group than in those of the other groups. Relative to mice in the CON group, the mice in the H-CLA group displayed increased liver weight and liver triglyceride (TG) content as well as higher TG content and γ-glutamyl transferase (γ-GT) activity in the plasma. Moreover, high-dose CLA resulted in insulin resistance, possibly affecting the red blood cell (RBC) and hemoglobin (HCB) levels in the plasma. In conclusion, lactating mice receiving a high dose of CLA exhibited fatty liver, insulin resistance, and impaired lactation performance.
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Affiliation(s)
- Kun Pang
- College of Animal Science and Veterinary Medicine, Xinyang Agriculture and Forestry University, Xinyang, China
| | - Zhongke Zhu
- College of Animal Science and Veterinary Medicine, Xinyang Agriculture and Forestry University, Xinyang, China
| | - Songbo Zhu
- Zhengzhou Academy of Agriculture and Forestry Sciences, Zhengzhou, China
| | - Liqiang Han
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
- * E-mail:
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22
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Wang AY, Dhaliwal J, Mouzaki M. Lean non-alcoholic fatty liver disease. Clin Nutr 2018; 38:975-981. [PMID: 30466956 DOI: 10.1016/j.clnu.2018.08.008] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 07/26/2018] [Accepted: 08/09/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD), with its increasing prevalence and association with various co-morbidities, such as diabetes, cardiovascular disease and metabolic syndrome, is a growing concern. Previously thought to predominantly affect obese individuals, NAFLD has been shown to occur in non-obese subjects. This subset of individuals, known to have 'lean NAFLD' or 'non-obese NAFLD', is also growing increasingly prevalent. We summarize the clinical manifestations, pathophysiology and management of lean NAFLD in both adult and pediatric populations. METHODS Two reviewers performed an independent, formal review and analysis of the literature (PubMed and EMBASE search until April 2018). RESULTS AND CONCLUSIONS Patients with lean NAFLD share metabolic features of insulin resistance and dyslipidemia, similar to obese patients with NAFLD. Genetic predisposition, dietary and environmental factors may play a role in the pathogenesis of lean NAFLD. Genetic and metabolic conditions should be considered as well. Currently, there are no formal recommendations for the treatment of adult or pediatric lean NAFLD; however, lifestyle changes aimed at improving overall fitness are likely to have a favorable impact.
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Affiliation(s)
- Alice Yuxin Wang
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Jasbir Dhaliwal
- Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Marialena Mouzaki
- Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH, USA.
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Bernhardt P, Kratzer W, Schmidberger J, Graeter T, Gruener B. Laboratory parameters in lean NAFLD: comparison of subjects with lean NAFLD with obese subjects without hepatic steatosis. BMC Res Notes 2018; 11:101. [PMID: 29409538 PMCID: PMC5801753 DOI: 10.1186/s13104-018-3212-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 01/31/2018] [Indexed: 12/13/2022] Open
Abstract
Objective Search for meaningful laboratory and anthropometric parameters in lean non-alcoholic fatty liver disease (lean NAFLD) in the general population. Out of 2445 subjects in a random population sample, we compared those who had a body mass index (BMI) < 25 and a fatty liver [lean NAFLD (LN), n = 5] with obese subjects who had a BMI > 30 but no fatty liver [non-NAFLD (NN), n = 27] in a follow-up examination. Ultrasonic, anthropometric and laboratory parameters were collected. Results There were significant differences (p < 0.05) between the LN and the NN groups with respect to serum ferritin (199.2 ± 72.1 LN vs 106.0 ± 89.6 NN), haemoglobin (14.9 ± 0.8 LN vs 13.5 ± 1.2 NN), haematocrit (0.438 ± 0.019 LN vs 0.407 ± 0.035 NN) and Mean corpuscular haemoglobin concentration (34 ± 0.6 LN vs 33.2 ± 0.8 NN). Significantly lower values of soluble transferrin receptor were measured in the LN group (2.8 ± 0.4 LN vs 3.8 ± 1.5 NN). In both groups, the measured HOMA-IR index (homeostatic model assessment of insulin resistance index) (2.3; normal range ≤ 1) was abnormal. Mean cholesterol (6.2 ± 1.4 LN and 5.6 ± 1.1 NN) and low-density lipoprotein levels (3.8 ± 1.0 LN 3.4 ± 0.9 NN) were above the upper limit of normal in both groups, as was the mean triglycerides level in the LN group (2.6 ± 2.0). In summary, there are differences in parameters of iron and fat metabolism between subjects with LN and overweight subjects without fatty liver infiltration. Electronic supplementary material The online version of this article (10.1186/s13104-018-3212-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Philipp Bernhardt
- Department of Internal Medicine I, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany
| | - Wolfgang Kratzer
- Department of Internal Medicine I, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
| | - Julian Schmidberger
- Department of Internal Medicine I, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany
| | - Tilmann Graeter
- Department of Diagnostic and Interventional Radiology, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany
| | - Beate Gruener
- Department of Internal Medicine III, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany
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24
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Wu K, Cheng Y, Li T, Ma Z, Liu J, Zhang Q, Cheng H. The utility of HbA1c combined with haematocrit for early screening of gestational diabetes mellitus. Diabetol Metab Syndr 2018. [PMID: 29541163 PMCID: PMC5844109 DOI: 10.1186/s13098-018-0314-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
AIMS To evaluate the utility of glycated haemoglobin A1c (HbA1c) alone and in combination with haematocrit (HCT) for screening gestational diabetes mellitus (GDM) between 12-16 gestational weeks. METHODS This prospective study was carried out in the Obstetrics and Gynaecology Hospital of Fudan University from November 2014 to February 2015. In total, 690 pregnant women between 20 and 35 years old were included in this study. All subjects received a routine blood examination for HbA1c and HCT at 12-16 gestational weeks (gw) and a 75-g oral glucose tolerance test at 24-28 gw. Threshold values for the diagnosis of GDM were a plasma glucose concentration of 5.1 mmol/L after fasting, 10.0 mmol/L at 60 min, and 8.5 mmol/L at 120 min. Receiver operating characteristic curves were used to evaluate the diagnostic performance of HbA1c with or without HCT. RESULTS One hundred seven women were diagnosis with GDM at 24-28 gw. An HbA1c cutoff value < 4.55% at 12-16 gw showed adequate sensitivity to exclude GDM (85.0%) but low specificity (17.3%), while an HbA1c cutoff value ≥ 5.25% presented adequate specificity (96.6%) but low sensitivity (13.3%) in diagnosing GDM. The area under the receiver operating characteristic curve for HbA1c (12-16 gw) detection of GDM was 0.563 (95% confidence interval [CI], 0.50-0.625). When combined HbA1c with HCT ( > 38.8%) for the screening of GDM, the area under the receiver operating characteristic curve was 0.604 (95% [CI] 0.509, 0.701). CONCLUSIONS Whether the adoption of HbA1c as a screening test for GDM would benefit pregnant women remains to be determined. However, combining HbA1c with HCT for the screening of GDM may be a useful tool to predict GDM.
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Affiliation(s)
- Kui Wu
- Obstetrics and Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai, 200090 People’s Republic of China
| | - Yan Cheng
- Obstetrics and Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai, 200090 People’s Republic of China
| | - Tingting Li
- Obstetrics and Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai, 200090 People’s Republic of China
| | - Ziwen Ma
- Obstetrics and Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai, 200090 People’s Republic of China
| | - Junxiu Liu
- Obstetrics and Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai, 200090 People’s Republic of China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011 China
| | - Qingying Zhang
- Obstetrics and Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai, 200090 People’s Republic of China
| | - Haidong Cheng
- Obstetrics and Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai, 200090 People’s Republic of China
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Du SX, Lu LL, Geng N, Victor DW, Chen LZ, Wang C, Yue HY, Xin YN, Xuan SY, Jin WW. Association of serum ferritin with non-alcoholic fatty liver disease: a meta-analysis. Lipids Health Dis 2017; 16:228. [PMID: 29197393 PMCID: PMC5712169 DOI: 10.1186/s12944-017-0613-4] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 11/12/2017] [Indexed: 02/06/2023] Open
Abstract
Background A growing number of studies reported the connection between the level of serum ferritin (SFL) and non-alcoholic fatty liver disease (NAFLD). However, such connection was still disputable. The aim of our meta-analysis was to estimate SFL between the groups as below: patients with NAFLD against control group; non-alcoholic steatohepatitis (NASH) patients against control group; non-alcoholic fatty liver (NAFL) patients against a control group and NASH patients vs NAFL patients. Methods We screened the studies in PubMed, EMBASE, the Cochrane Database and the Cochrane Central register controlled trials from the beginning to July 10, 2016 to find the studies indicated the connection between SFL and NAFLD (NAFL and/or NASH). Fourteen published studies which evaluate the SFL in NAFLD patients were selected. Results Higher SFL was noticed in NAFLD patients against control group (standardized mean difference [SMD] 1.01; 95% CI 0.89, 1.13), NASH patients against control group (SMD 1.21; 95% CI 1.00, 1.42), NAFL patients against control group (SMD 0.51; 95% CI 0.24, 0.79) and NASH patients against NAFL patients (SMD 0.63; 95% CI 0.52, 0.75). These results remained unaltered actually after the elimination of studies which were focused on paediatric or adolescent populations. Higher SFL was presented in NAFLD patients against the control group (SMD 1.08; 95% CI 0.95, 1.20) in adults and NASH patients against NAFL patients in adults (SMD 0.74; 95% CI 0.62, 0.87). The connection between SFL and NASH against NAFL group in paediatric or adolescent populations was observed inconsistently (SMD 0.10; 95% CI -0.18, 0.38). Conclusions The level of SFL was elevated in patients with NAFLD (NAFL and/or NASH) compared with the controls. Compared with NAFL, The level of SFL was increased in NASH. The result remained unaltered actually after the elimination of studies focused on paediatric or adolescent populations.
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Affiliation(s)
- Shui-Xian Du
- Medical College of Qingdao University, Qingdao, 266071, China.,Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong Province, 266011, China
| | - Lin-Lin Lu
- Digestive Disease Key Laboratory of Qingdao, Qingdao, 266071, China.,Central Laboratories, Qingdao Municipal Hospital, Qingdao, 266071, China
| | - Ning Geng
- Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong Province, 266011, China
| | - David W Victor
- Hepatology & Transplant Medicine, Department of Medicine, Houston Methodist Hospital, Houston, USA
| | - Li-Zhen Chen
- Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong Province, 266011, China.,College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266003, China
| | - Cong Wang
- Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong Province, 266011, China.,Department of Gastroenterology, Dalian Medical University, Qingdao, 266011, China
| | - Hai-Yan Yue
- Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong Province, 266011, China.,Department of Gastroenterology, Dalian Medical University, Qingdao, 266011, China
| | - Yong-Ning Xin
- Medical College of Qingdao University, Qingdao, 266071, China. .,Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong Province, 266011, China. .,Digestive Disease Key Laboratory of Qingdao, Qingdao, 266071, China.
| | - Shi-Ying Xuan
- Medical College of Qingdao University, Qingdao, 266071, China. .,Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong Province, 266011, China. .,Digestive Disease Key Laboratory of Qingdao, Qingdao, 266071, China.
| | - Wen-Wen Jin
- Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong Province, 266011, China
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Wang HL, Zhang H, Wu SL, Liao GC, Fang AP, Zhu MF, Zhu HL. Red blood cell count has an independent contribution to the prediction of ultrasonography-diagnosed fatty liver disease. PLoS One 2017; 12:e0172027. [PMID: 28187211 PMCID: PMC5302451 DOI: 10.1371/journal.pone.0172027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 01/30/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND & AIMS Red blood cell (RBC) indices have been demonstrated to be associated with fatty liver disease (FLD) and metabolic syndrome. However, controversy exists regarding the relationship of RBC indices with FLD to date and few has focused on RBC count. This study aimed to explore the association between RBC count and risk of FLD in Southern Chinese adults. METHODS A hospital-based cross-sectional study was performed in two hospital health examination centers, including information on ultrasonography-diagnosed FLD, anthropometric indices and biochemical measurements. Covariance analysis was used to evaluate group differences. After quintile classification of RBC counts, logistic regression analysis was conducted to evaluate the odds ratios (ORs) of FLD. RESULTS This study consisted of 8618 subjects (4137 men and 4481 women) aged between 20 and 89 years. FLD cases had higher RBC counts than non-FLD cases in both genders (P<0.001). The prevalence rates of FLD increased with the RBC quintiles in both genders (all P trend<0.001), and were higher in men than women. Binary logistic regression analysis showed positive association between RBC count and FLD, and the OR (95% confidence interval (CI)) were 2.56 (2.06-3.18) in men and 3.69 (2.74-4.98) in women, respectively, when comparing Q5 with Q1. Stratified analyses showed similar trends among subjects with and without FLD risk factors. Gender independent results were similar to gender dependent results. CONCLUSIONS Elevated RBC count is independently associated with high risk of FLD, suggesting that the RBC count may be a potential risk predictor for FLD.
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Affiliation(s)
- Hai-lin Wang
- Faculty of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, The People’s Republic of China
| | - Hui Zhang
- Health Examination Centre, Shenzhen Luohu People’s Hospital, Shenzhen, Guangdong Province, The People’s Republic of China
| | - Shang-ling Wu
- Faculty of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, The People’s Republic of China
| | - Gong-cheng Liao
- Faculty of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, The People’s Republic of China
| | - Ai-ping Fang
- Faculty of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, The People’s Republic of China
| | - Ming-fan Zhu
- Health Examination Centre, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, The People’s Republic of China
| | - Hui-lian Zhu
- Faculty of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, The People’s Republic of China
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Nuño-Lámbarri N, Barbero-Becerra VJ, Uribe M, Chávez-Tapia NC. Mitochondrial Molecular Pathophysiology of Nonalcoholic Fatty Liver Disease: A Proteomics Approach. Int J Mol Sci 2016; 17:281. [PMID: 26999105 PMCID: PMC4813145 DOI: 10.3390/ijms17030281] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 02/19/2016] [Accepted: 02/19/2016] [Indexed: 12/14/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition that can progress to nonalcoholic steatohepatitis, cirrhosis and cancer. It is considered an emerging health problem due to malnourishment or a high-fat diet (HFD) intake, which is observed worldwide. It is well known that the hepatocytes’ apoptosis phenomenon is one of the most important features of NAFLD. Thus, this review focuses on revealing, through a proteomics approach, the complex network of protein interactions that promote fibrosis, liver cell stress, and apoptosis. According to different types of in vitro and murine models, it has been found that oxidative/nitrative protein stress leads to mitochondrial dysfunction, which plays a major role in stimulating NAFLD damage. Human studies have revealed the importance of novel biomarkers, such as retinol-binding protein 4, lumican, transgelin 2 and hemoglobin, which have a significant role in the disease. The post-genome era has brought proteomics technology, which allows the determination of molecular pathogenesis in NAFLD. This has led to the search for biomarkers which improve early diagnosis and optimal treatment and which may effectively prevent fatal consequences such as cirrhosis or cancer.
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Affiliation(s)
- Natalia Nuño-Lámbarri
- Traslational Research Unit, Médica Sur Clinic & Foundation, Mexico City 14050, Mexico.
| | | | - Misael Uribe
- Obesity and Digestive Diseases Unit, Médica Sur Clinic & Foundation, Mexico City 14050, Mexico.
| | - Norberto C Chávez-Tapia
- Traslational Research Unit, Médica Sur Clinic & Foundation, Mexico City 14050, Mexico.
- Obesity and Digestive Diseases Unit, Médica Sur Clinic & Foundation, Mexico City 14050, Mexico.
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Hashimoto Y, Tanaka M, Kimura T, Kitagawa N, Hamaguchi M, Asano M, Yamazaki M, Oda Y, Toda H, Nakamura N, Fukui M. Hemoglobin concentration and incident metabolic syndrome: a population-based large-scale cohort study. Endocrine 2015; 50:390-6. [PMID: 25863486 DOI: 10.1007/s12020-015-0587-9] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 03/27/2015] [Indexed: 02/06/2023]
Abstract
Previous cross-sectional studies revealed an association between hemoglobin concentration and a prevalence of metabolic syndrome (MetS). However, the association between hemoglobin concentration and incident MetS remains to be elucidated. Thus, the aim of this study was to investigate the association between hemoglobin concentration and incident MetS. We enrolled 2695 subjects (1454 men and 1241 women) and performed 8-year follow-up cohort study. MetS was diagnosed, according to the joint interim statement, when a subject had three or more of the following components: hypertension; hyperglycemia; hypertriglyceridemia; low high-density lipoprotein cholesterol; and abdominal obesity. Logistic regression analyses were performed to assess the impact of hemoglobin concentration on incident MetS by adjusting for age, body mass index, lifestyle factors, including smoking status, habit of alcohol and habit of exercise, systolic blood pressure, fasting plasma glucose, triglycerides, high-density lipoprotein cholesterol, creatinine, and uric acid. The highest (≥157 g/L) and third (151-156 g/L) hemoglobin concentration quartiles were associated with the increased risk of incident MetS compared to the lowest (<145 g/L) hemoglobin concentration quartile after adjusting for covariates in men (multivariate odds ratio (OR) 2.24, 95% CI 1.34-3.85, P = 0.0021 and multivariate OR 2.03, 95% CI 1.21-3.45, P = 0.0070). On the other hand, there was no association between hemoglobin concentration and incident MetS in women. Hemoglobin concentration was a novel risk marker for incident MetS in men.
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Affiliation(s)
- Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Muhei Tanaka
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Toshihiro Kimura
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Noriyuki Kitagawa
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Mai Asano
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Masahiro Yamazaki
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Yohei Oda
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hitoshi Toda
- Department of Internal Medicine, Oike Clinic, Kyoto, Japan
| | - Naoto Nakamura
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
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Ma H, Xie RA, Gao LJ, Zhang JP, Wu WC, Wang H. Prediction of Left Ventricular Filling Pressure by 3-Dimensional Speckle-Tracking Echocardiography in Patients With Coronary Artery Disease. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2015; 34:1809-1818. [PMID: 26333567 DOI: 10.7863/ultra.15.14.11010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Accepted: 01/12/2015] [Indexed: 06/05/2023]
Abstract
OBJECTIVES The purpose of this study was to investigate the diagnostic value of 3-dimensional (3D) speckle-tracking echocardiography for estimating left ventricular filling pressure in patients with coronary artery disease (CAD) and a preserved left ventricular ejection fraction. METHODS Altogether, 84 patients with CAD and 30 age- and sex-matched healthy control participants in sinus rhythm were recruited prospectively. All participants underwent conventional and 3D speckle-tracking echocardiography. Global strain values were automatically calculated by 3D speckle-tracking analysis. The left ventricular end-diastolic pressure (LVEDP) was determined invasively by left heart catheterization. Echocardiography and cardiac catheterization were performed within 24 hours. RESULTS Compared with the controls, patients with CAD showed lower global longitudinal strain, global circumferential strain, global area strain, and global radial strain. Patients with CAD who had an elevated LVEDP had much lower levels of all 4 3D-speckle-tracking echocardiographic variables. Pearson correlation analysis revealed that the LVEDP correlated positively with the early transmitral flow velocity/early diastolic myocardial velocity (E/E') ratio, global longitudinal strain, global circumferential strain, and global area strain. It correlated negatively with global radial strain. Receiver operating characteristic curve analysis revealed that these 3D speckle-tracking echocardiographic indices could effectively predict elevated left ventricular filling pressure (LVEDP >15 mm Hg) in patients with CAD (areas under the curve: global longitudinal strain, 0.78; global radial strain, 0.77; global circumferential strain, 0.75; and global area strain, 0.74). These parameters, however, showed no advantages over the commonly used E/E' ratio (area under the curve, 0.84). CONCLUSIONS Three-dimensional speckle-tracking echocardiography was a practical technique for predicting elevated left ventricular filling pressure, but it might not be superior to the commonly used E/E' ratio in patients with CAD who have a normal left ventricular ejection fraction.
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Affiliation(s)
- Hong Ma
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (H.M., L.-J.G., J.P.Z., W.-C.W., H.W.); and Department of Cardiology, Peking University Shougang Hospital, Beijing, China (R.-A.X.)
| | - Rong-Ai Xie
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (H.M., L.-J.G., J.P.Z., W.-C.W., H.W.); and Department of Cardiology, Peking University Shougang Hospital, Beijing, China (R.-A.X.)
| | - Li-Jian Gao
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (H.M., L.-J.G., J.P.Z., W.-C.W., H.W.); and Department of Cardiology, Peking University Shougang Hospital, Beijing, China (R.-A.X.)
| | - Jin-Ping Zhang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (H.M., L.-J.G., J.P.Z., W.-C.W., H.W.); and Department of Cardiology, Peking University Shougang Hospital, Beijing, China (R.-A.X.)
| | - Wei-Chun Wu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (H.M., L.-J.G., J.P.Z., W.-C.W., H.W.); and Department of Cardiology, Peking University Shougang Hospital, Beijing, China (R.-A.X.).
| | - Hao Wang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (H.M., L.-J.G., J.P.Z., W.-C.W., H.W.); and Department of Cardiology, Peking University Shougang Hospital, Beijing, China (R.-A.X.).
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Hb and dyslipidaemia as predicting markers of serum alanine aminotransferase elevation in Chinese adolescents. Public Health Nutr 2015; 19:1067-73. [PMID: 26328752 DOI: 10.1017/s1368980015002293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Fe is an essential element for erythropoiesis and Hb synthesis. High Hb levels affect the blood's viscosity and are associated with cardiovascular dysfunction. The aim of the present study was to examine relationships of Hb and cardiometabolic abnormalities with the risk of alanine aminotransferase (ALT) elevation in adolescents. DESIGN A population-based, cross-sectional study. SETTING National Nutrition and Health Survey in Taiwan (2010-2011, adolescents). SUBJECTS Healthy adolescents aged 13-18 years. RESULTS In total, 1941 adolescents (963 boys and 978 girls) were entered in the study. The mean age was 15·3 (sd 0·1) years (boys, 15·3 (sd 0·1) years; girls, 15·2 (sd 0·1) years). ALT tertile cut-off points for boys were 11 and 16 U/l, and for girls were 9 and 12 U/l. Girls without dyslipidaemia and presenting in the highest quartile (Q1) of Hb (>13·6 g/dl) were 1·89 and 3·76 times more likely to have raised serum ALT (9 and >12 U/l, respectively) than the reference (lowest quartile of Hb (Q1), 12 U/l) than the reference (Q1 of Hb, 15·4 g/dl), who were 7·40 times more likely to have elevated serum ALT of >16 U/l than the reference (Q1 of Hb, <14·1 g/dl). CONCLUSIONS Our findings suggest that an increased Hb level is a predictor of elevated serum ALT in adolescent girls with dyslipidaemia. Our study also highlights the importance of further research to establish cut-off points for Hb and its utility in diagnosing and preventing the onset of dyslipidaemia in adolescents.
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Akyuz U, Yesil A, Yilmaz Y. Characterization of lean patients with nonalcoholic fatty liver disease: potential role of high hemoglobin levels. Scand J Gastroenterol 2015; 50:341-6. [PMID: 25540973 DOI: 10.3109/00365521.2014.983160] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Overweight and obesity are major risk factors for the development of nonalcoholic fatty liver disease (NAFLD). However, a minority of NAFLD patients have a body mass index (BMI) <25 kg/m(2) (lean NAFLD). We sought to investigate whether significant differences exist between lean NAFLD and more common forms of NAFLD associated with overweight/obesity. PATIENTS AND METHODS A total of 483 consecutive patients with biopsy-proven NAFLD were enrolled. Lean NAFLD was defined as having a BMI <25 kg/m(2). We identified 37 patients with lean NAFLD (7.6%). RESULTS Compared with NAFLD patients with overweight/obesity, lean NAFLD patients were younger, had lower blood pressure values, higher levels of hemoglobin, a lower prevalence of the metabolic syndrome, and less severe hepatic fibrosis. In NAFLD patients with overweight/obesity, diabetes was the only independent predictor of nonalcoholic steatohepatitis (NASH). In lean NAFLD, the only variable independently associated with NASH was hemoglobin. Alanine aminotransferase and diabetes were independent predictors of fibrosis ≥2 in NAFLD patients with overweight/obesity, whereas hemoglobin was the only independent predictor of fibrosis ≥2 in lean NAFLD. CONCLUSION In summary, lean NAFLD patients are younger and show less severe hepatic fibrosis. However, such subjects have higher hemoglobin levels, which seem to predict the histological severity.
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Affiliation(s)
- Umit Akyuz
- Department of Gastroenterology, Medical Faculty, Yeditepe University , Istanbul , Turkey
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Xu Q, Li Y, Shang YF, Wang HL, Yao MX. miRNA-103: Molecular link between insulin resistance and nonalcoholic fatty liver disease. World J Gastroenterol 2015; 21:511-516. [PMID: 25593466 PMCID: PMC4292282 DOI: 10.3748/wjg.v21.i2.511] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Revised: 07/04/2014] [Accepted: 07/30/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the associations between miRNA-103 (miR-103) and insulin resistance and nonalcoholic fatty liver disease (NAFLD).
METHODS: Serum samples were collected from 50 NAFLD patients who were overweight or obese (NAFLD group) and from 30 healthy subjects who served as controls (normal control group). Quantitative polymerase chain reaction was used to detect expression of miR-103. Fasting plasma glucose, fasting insulin, and triglyceride (TG) levels were measured. Homeostasis model assessment was used to evaluate basal insulin resistance (HOMA-IR). Patient height and weight were measured to calculate body mass index (BMI).
RESULTS: Compared with the normal control group, higher serum levels of miR-103 were expressed in the NAFLD group (8.18 ± 0.73 vs 4.23 ± 0.81, P = 0.000). When P = 0.01 (bilateral), miR-103 was positively correlated with HOMA-IR (r = 0.881), TG (r = 0.774) and BMI (r = 0.878), respectively. miR-103, TG and BMI were all independent factors for HOMA-IR (β = 0.438/0.657/0.251, P = 0.000/0.007/0.001). miR-103, TG, BMI and HOMA-IR were all risk factors for NAFLD (odds ratio = 2.411/16.196/1.574/19.11, P = 0.009/0.022/0.01/0.014).
CONCLUSION: miR-103 is involved in insulin resistance and NAFLD, and may be a molecular link between insulin resistance and NAFLD and a therapeutic target for these disorders.
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Feng RN, Du SS, Wang C, Li YC, Liu LY, Guo FC, Sun CH. Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population. World J Gastroenterol 2014; 20:17932-17940. [PMID: 25548491 PMCID: PMC4273143 DOI: 10.3748/wjg.v20.i47.17932] [Citation(s) in RCA: 161] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2014] [Revised: 06/12/2014] [Accepted: 07/11/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To study the prevalence and clinical biochemical, blood cell and metabolic features of lean-non-alcoholic fatty liver disease (lean-NAFLD) and its association with other diseases. METHODS Demographic, biochemical and blood examinations were conducted in all the subjects in this study. We classified the subjects into four groups according to their weight and NAFLD status: lean-control, lean-NAFLD [body mass index (BMI) < 24 kg/m(2)], overweight-obese control and overweight-obese NAFLD. One-way analysis of variance (ANOVA) was used to compare the means of continuous variables (age, BMI, blood pressure, glucose, lipid, insulin, liver enzymes and blood cell counts) and the χ (2) test was used to compare the differences in frequency of categorical variables (sex, education, physical activity, smoking, alcohol consumption and prevalence of hypertension, hyperlipidemia, diabetes, metabolic syndrome central obesity and obesity). Both univariate and multivariate logistic regression models were adopted to calculate odds ratios (ORs) and predict hyperlipidemia, hypertension, diabetes and metabolic syndrome when we respectively set all controls, lean-control and overweight-obese-control as references. In multivariate logistic regression models, we adjusted potential confounding factors, including age, sex, smoking, alcohol consumption and physical activity. RESULTS The prevalence of NAFLD was very high in China. NAFLD patients were older, had a higher BMI, waist circumference, blood pressure, fasting blood glucose, insulin, blood lipid, liver enzymes and uric acid than the controls. Although lean-NAFLD patients had lower BMI and waist circumstance, they had significantly higher visceral adiposity index than overweight-obese controls. Lean-NAFLD patients had comparable triglyceride, cholesterin and low-density lipoprotein cholesterin to overweight-obese NAFLD patients. In blood cell examination, both lean and overweight-obese NAFLD was companied by higher white blood cell count, red blood cell count, hemoglobin and hematocrit value. All NAFLD patients were at risk of hyperlipidemia, hypertension, diabetes and metabolic syndrome (MetS). Lean-NAFLD was more strongly associated with diabetes (OR = 2.47, 95%CI: 1.14-5.35), hypertension (OR = 1.72, 95%CI: 1.00-2.96) and MetS (OR = 3.19, 95%CI: 1.17-4.05) than overweight-obese-NAFLD (only OR for MetS was meaningful: OR = 1.89, 95%CI: 1.29-2.77). NAFLD patients were more likely to have central obesity (OR = 1.97, 95%CI: 1.38-2.80), especially in lean groups (OR = 2.17, 95%CI: 1.17-4.05). CONCLUSION Lean-NAFLD has unique results in demographic, biochemical and blood examinations, and adds significant risk for diabetes, hypertension and MetS in lean individuals.
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