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Hu S, Chen W, Tan X, Zhang Y, Wang J, Huang L, Duan J. Early Identification of Metabolic Syndrome in Adults of Jiaxing, China: Utilizing a Multifactor Logistic Regression Model. Diabetes Metab Syndr Obes 2024; 17:3087-3102. [PMID: 39193547 PMCID: PMC11348986 DOI: 10.2147/dmso.s468718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 08/12/2024] [Indexed: 08/29/2024] Open
Abstract
Purpose The purpose of this study is to develop and validate a clinical prediction model for diagnosing Metabolic Syndrome (MetS) based on indicators associated with its occurrence. Patients and Methods This study included a total of 26,637 individuals who underwent health examinations at the Jiaxing First Hospital Health Examination Center from January 19, 2022, to December 31, 2022. They were randomly divided into training (n = 18645) and validation (n = 7992) sets in a 7:3 ratio. Firstly, the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was employed for variable selection. Subsequently, a multifactor Logistic regression analysis was conducted to establish the predictive model, accompanied by nomograms. Thirdly, model validation was performed using Receiver Operating Characteristic (ROC) curves, Harrell's concordance index (C-index), calibration plots, and Decision Curve Analysis (DCA), followed by internal validation. Results In this study, six predictive indicators were selected, including Body Mass Index, Triglycerides, Blood Pressure, High-Density Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Fasting Blood Glucose. The model demonstrated excellent predictive performance, with an AUC of 0.978 (0.976-0.980) for the training set and 0.977 (0.974-0.980) for the validation set in the nomogram. Calibration curves indicated that the model possessed good calibration ability (Training set: Emax 0.081, Eavg 0.005, P = 0.580; Validation set: Emax 0.062, Eavg 0.007, P = 0.829). Furthermore, decision curve analysis suggested that applying the nomogram for diagnosis is more beneficial when the threshold probability of MetS is less than 89%, compared to either treating-all or treating-none at all. Conclusion We developed and validated a nomogram based on MetS risk factors, which can effectively predict the occurrence of MetS. The proposed nomogram demonstrates significant discriminative ability and clinical applicability. It can be utilized to identify variables and risk factors for diagnosing MetS at an early stage.
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Affiliation(s)
- Shiyu Hu
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
- Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China
| | - Wenyu Chen
- Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China
| | - Xiaoli Tan
- Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China
| | - Ye Zhang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
- Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China
| | - Jiaye Wang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
- Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China
| | - Lifang Huang
- Health Management Center, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China
| | - Jianwen Duan
- Department of Hepatobiliary Surgery, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of China
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Kyhl LK, Nordestgaard BG, Tybjærg-Hansen A, Nielsen SF. High fat in blood and body and increased risk of clinically diagnosed non-alcoholic fatty liver disease in 105,981 individuals. Atherosclerosis 2023; 376:1-10. [PMID: 37253311 DOI: 10.1016/j.atherosclerosis.2023.05.015] [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: 11/29/2022] [Revised: 05/17/2023] [Accepted: 05/17/2023] [Indexed: 06/01/2023]
Abstract
BACKGROUND AND AIMS High caloric diets rich in fat and carbohydrates lead to increased fat accumulation in adipose tissue and blood. This may lead to increased risk of non-alcoholic fatty liver disease. We hypothesized that baseline high nonfasting plasma triglycerides, body mass index (BMI), and waist circumference, individually and combined, associate with increased risk of clinically diagnosed non-alcoholic fatty liver disease during follow-up. METHODS Cohort of 105,981 white Danish individuals recruited in 2003-2015 with end of follow-up on December 13th, 2018. Mean follow-up was 9.2 years during which time 418 were clinically diagnosed at hospitals with non-alcoholic fatty liver disease. RESULTS Risk of clinically diagnosed non-alcoholic fatty liver disease increased with higher plasma triglycerides, higher BMI, and with higher waist circumference, continuously and stepwise using multivariable adjusted hazard ratios and cumulative incidences. Combining clinical categories of plasma triglycerides with BMI or waist circumference categories, illustrated an almost additive risk with increasing categories. Compared with plasma triglycerides of <1 mmol/L and BMI <25 kg/m2, the multivariable adjusted hazard ratio was 5.2(95% confidence interval: 1.3-21.6) for individuals with both plasma triglycerides of ≥5 mmol/L and BMI ≥35 kg/m2. The corresponding hazard ratio for individuals with plasma triglycerides ≥5 mmol/L and waist circumference was >88 cm for women and >102 cm for men was 4.8(2.3-9.7). Triglyceride results were more pronounced in women versus men. CONCLUSIONS High fat in blood and body measured by plasma triglycerides, BMI, and waist circumference, individually and especially combined, are associated with up to a 5-fold increased risk of clinically diagnosed non-alcoholic fatty liver disease.
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Affiliation(s)
- Lærke Kristine Kyhl
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Børge Grønne Nordestgaard
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Anne Tybjærg-Hansen
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Sune Fallgaard Nielsen
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
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Shaaban HH, Alzaim I, El-Mallah A, Aly RG, El-Yazbi AF, Wahid A. Metformin, pioglitazone, dapagliflozin and their combinations ameliorate manifestations associated with NAFLD in rats via anti-inflammatory, anti-fibrotic, anti-oxidant and anti-apoptotic mechanisms. Life Sci 2022; 308:120956. [PMID: 36103959 DOI: 10.1016/j.lfs.2022.120956] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 09/07/2022] [Accepted: 09/09/2022] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an important health threat that is strongly linked to components of metabolic syndrome, particularly the low-grade inflammatory changes. Significantly, several of the available anti-diabetic drug classes demonstrate a considerable anti-inflammatory effect, and hence might be of benefit for NAFLD patients. In this study, we used a rat model of diet-induced NAFLD to examine the potential effect of metformin, pioglitazone, dapagliflozin and their combinations on NAFLD manifestations. Rats were fed an atherogenic diet containing 1.25 % cholesterol, 0.5 % cholic acid and 60 % cocoa butter for 6 weeks causing a number of metabolic and hepatic alterations including insulin resistance, dyslipidemia, systemic inflammation, increased hepatic oxidative stress and lipid peroxidation, hepatic steatosis, lobular inflammation, as well as increased markers of liver inflammation and hepatocyte apoptosis. Drug treatment, which started at the third week of NAFLD induction and continued for three weeks, not only ameliorated the observed metabolic impairment, but also functional and structural manifestations of NAFLD. Specifically, anti-diabetic drug treatment reversed markers of systemic and hepatic inflammation, oxidative stress, hepatic fibrosis, and hepatocyte apoptosis. Our findings propose that anti-diabetic drugs with a potential anti-inflammatory effect can ameliorate the manifestations of NAFLD, and thus may provide a therapeutic option for such a condition that is closely associated with metabolic diseases. The detailed pharmacology of these classes in aspects linked to the observed impact on NAFLD requires to be further investigated and translated into clinical studies for tailored therapy specifically targeting NAFLD.
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Affiliation(s)
- Hager H Shaaban
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Egypt.
| | - Ibrahim Alzaim
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine the American University of Beirut, Beirut, Lebanon; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Ahmed El-Mallah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Egypt
| | - Rania G Aly
- Department of Pathology, Faculty of Medicine, Alexandria University, Egypt
| | - Ahmed F El-Yazbi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Egypt; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Faculty of Pharmacy, Al-Alamein International University, Alamein, Egypt.
| | - Ahmed Wahid
- Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
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Mahabaleshwarkar R, Liu TL, McKillop IH, Spencer M. The Association Between Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease Diagnosis Varies by Race. Metab Syndr Relat Disord 2022; 20:286-294. [PMID: 35319282 DOI: 10.1089/met.2021.0108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
Objectives: This study investigated how the association between metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) diagnosis varies between non-Hispanic African American and white patients. Methods: A retrospective cohort study was performed using electronic medical records from an integrated health care system (2010-2018). Adults with records for all MetS measurements (body mass index, lipids, blood pressure, and blood glucose) in 2011, who did not have a NAFLD diagnosis before their last MetS measurement, were included. Results: The study cohort consisted of 139,336 patients (age 56.1 ± 15.2 years, 57.9% female, 79.4% non-Hispanic white). The rate of NAFLD diagnosis was higher in MetS patients compared with non-MetS patients [adjusted hazards ratio (AHR) = 1.99, 95% CI = 1.91-2.09] with a significant interaction by race (AHR = 2.05, 95% CI = 1.95-2.15 in non-Hispanic whites vs. AHR = 1.76, 95% CI = 1.58-1.96 non-Hispanic African Americans, P = 0.017). Secondary analyses revealed that the relative NAFLD diagnosis rate was higher in non-Hispanic whites with MetS compared with non-Hispanic African Americans with MetS among females and patients 18-39 years of age and 40-59 years, but not among males and those ≥60 years of age. Conclusions: Non-Hispanic white patients with MetS, particularly females and those <60 years of age, may be at increased risk of NAFLD compared with non-Hispanic African American MetS patients and may benefit from extra attention regarding NAFLD screening.
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Affiliation(s)
- Rohan Mahabaleshwarkar
- Center for Outcomes Research and Evaluation, Atrium Health, Charlotte, North Carolina, USA
| | - Tsai-Ling Liu
- Center for Outcomes Research and Evaluation, Atrium Health, Charlotte, North Carolina, USA
| | - Iain H McKillop
- Department of Surgery, Atrium Health, Charlotte, North Carolina, USA
| | - Melanie Spencer
- Center for Outcomes Research and Evaluation, Atrium Health, Charlotte, North Carolina, USA
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Peng CH, Ker YB, Li HH, Tsou SH, Lin CL, Huang CN. Abelmoschus esculentus subfractions ameliorate hepatic lipogenesis and lipid uptake via regulating dipeptidyl peptidase-4—With improving insulin resistance. PLoS One 2022; 17:e0265444. [PMID: 35290413 PMCID: PMC8923473 DOI: 10.1371/journal.pone.0265444] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 03/01/2022] [Indexed: 01/18/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is recognized as the liver component of metabolic syndrome. The regulation of hepatic lipid should be emphasized to prevent accompanying illness. As AMP-activated protein kinase (AMPK) and sterol regulatory element binding protein (SREBP) regulate lipid metabolism, CD36 and fatty acid synthase (FAS) promote lipid uptake and lipogenesis respectively, while acetyl-CoA carboxylase (ACC) is an indicator of negative feedback. The increase of IRS-1 phosphorylation at the residue ser307 (p-ser307-IRS-1) and decrease of p-ser473-Akt (p-Akt) are viewed as the insulin resistance markers, and our previous reports suggested dipeptidyl peptidase-4 (DPP-4) mediates insulin resistance, the crucial factor of metabolic syndrome. Abelmoschus esculentus (AE) fruit is well-known for its antidiabetic utility. We had isolated several AE subfractions by successive steps, and found that F1 and F2 were especially valid in suppressing DPP-4 signaling. Since little is known if AE works on NAFLD, now we first attempt to investigate whether AE is useful to attenuate hepatic lipogenesis and lipid uptake in liver cells, along with improving the metabolic targets. We demonstrated that AE subfractions attenuated the hepatic lipid accumulation induced by free fatty acids. Treatment of AE alleviated FAS and returned the level of p-ser79-ACC (p-ACC). Although F1 was more effective on AMPK, F2 seemed more stable to attenuate SREBP-1. Moreover, as fatty acids stimulated the expression of CD36, F2 showed a superior effect to down-regulate the lipid uptake. Both AE subfractions reduced the generation of ROS, decreased the level of p-ser307-IRS-1, and restored the expression of p-Akt. Moreover, treatment of DPP-4 inhibitor linagliptin revealed that, AE could prevent the hepatic lipogenesis, oxidative burden, and the related insulin resistance via downregulating DPP-4. In conclusion, the present investigation revealed that AE, especially F2, is potential to be developed as adjuvant to prevent NAFLD.
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Affiliation(s)
- Chiung-Huei Peng
- Division of Basic Medical Science, Hungkuang University, Taichung, Taiwan
| | - Yaw-Bee Ker
- Department of Food Science and Technology, Hungkuang University, Taichung, Taiwan
| | - Hsin-Hua Li
- General Education Center, National Taiwan University of Sport, Taichung, Taiwan
- Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan
| | - Sing-Hua Tsou
- Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan
| | - Chih-Li Lin
- Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
- * E-mail: (C-LL); (C-NH)
| | - Chien-Ning Huang
- Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan
- Department of Internal Medicine, Chung-Shan Medical University Hospital, Taichung, Taiwan
- * E-mail: (C-LL); (C-NH)
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Yao CC, Tong YX, Jiang H, Yang DR, Zhang XJ, Zhang P, Su L, Zhao YY, Chen ZW. Native polypeptide vglycin prevents nonalcoholic fatty liver disease in mice by activating the AMPK pathway. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104110] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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Zou ZY, Wong VWS, Fan JG. Epidemiology of nonalcoholic fatty liver disease in non-obese populations: Meta-analytic assessment of its prevalence, genetic, metabolic, and histological profiles. J Dig Dis 2020; 21:372-384. [PMID: 32369237 DOI: 10.1111/1751-2980.12871] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 04/10/2020] [Accepted: 04/28/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE As a subgroup of nonalcoholic fatty liver disease (NAFLD), patients with non-obese NAFLD may also have an increased risk of adverse hepatic and metabolic outcomes. We aimed to estimate the prevalence and incidence of non-obese NAFLD and to describe its clinical characteristics in this systematic review and meta-analysis. METHODS We performed a systematic search of 1235 citations published up to Mar 2020. Meta-analyses, stratified analyses and meta-regression were all performed. RESULTS Of the 46 studies included, 28 cross-sectional and longitudinal studies of 155 846 non-obese participants reported a pooled NAFLD prevalence of 14.5% (95% confidence interval [CI] 12.3%-17.1%). A multivariate meta-regression analysis showed the trend that the prevalence varied by their geographical location. Further stratified analyses showed that NAFLD was relatively prevalent among people aged ≥45 years (16.2%; 95% CI 10.8-23.4) and those in South America (25.7%; 95% CI 24.4-27.0). The PNPLA3 rs738409 gene polymorphism was more frequently observed in non-obese NAFLD than in both obese NAFLD and non-obese controls, while the metabolic profiles of non-obese NAFLD were less severe than those of the obese NAFLD group. Patients with non-obese NAFLD had 4.81-fold and 5.43-fold higher risk of diabetes mellitus and metabolic syndrome, respectively, than the non-obese controls. CONCLUSIONS Non-obese NAFLD is common, particularly in South America and among people aged ≥45 years. Metabolic diseases and PNPLA3 rs738409 gene polymorphism are more frequent in the non-obese NAFLD group than in non-obese controls.
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Affiliation(s)
- Zi Yuan Zou
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jian Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China
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Kotzé-Hörstmann LM, Sadie-Van Gijsen H. Modulation of Glucose Metabolism by Leaf Tea Constituents: A Systematic Review of Recent Clinical and Pre-clinical Findings. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:2973-3005. [PMID: 32105058 DOI: 10.1021/acs.jafc.9b07852] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Leaf teas are widely used as a purported treatment for dysregulated glucose homeostasis. The objective of this study was to systematically evaluate the clinical and cellular-metabolic evidence, published between January 2013 and May 2019, and indexed on PubMed, ScienceDirect, and Web of Science, supporting the use of leaf teas for this purpose. Fourteen randomized controlled trials (RCTs) (13 on Camellia sinensis teas) were included, with mixed results, and providing scant mechanistic information. In contrast, 74 animal and cell culture studies focusing on the pancreas, liver, muscle, and adipose tissue yielded mostly positive results and highlighted enhanced insulin signaling as a recurring target associated with the effects of teas on glucose metabolism. We conclude that more studies, including RCTs and pre-clinical studies examining teas from a wider variety of species beyond C. sinensis, are required to establish a stronger evidence base on the use of leaf teas to normalize glucose metabolism.
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Affiliation(s)
- Liske M Kotzé-Hörstmann
- Centre for Cardio-metabolic Research in Africa (CARMA), Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University Tygerberg Campus, Parow 7505, South Africa
| | - Hanél Sadie-Van Gijsen
- Centre for Cardio-metabolic Research in Africa (CARMA), Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University Tygerberg Campus, Parow 7505, South Africa
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The severity of coronary artery disease was not associated with non-alcoholic fatty liver disease in a series of 264 non-diabetic patients who underwent coronary angiography. ACTA ACUST UNITED AC 2019; 56:167-172. [PMID: 29561732 DOI: 10.2478/rjim-2018-0009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND It is now suggested an association between non-alcoholic fatty liver disease (NAFLD) and the occurrence of coronary artery disease even in non-diabetic patients. We will determine the rate of NAFLD and its main determinants in non-diabetic patients undergoing coronary angiography. METHODS This cross-sectional study was accomplished on 264 patients who were candidates for coronary angiography during the year 2016. Coronary angiography has been done to depict the presence or absence of coronary involvement, and the severity of coronary artery disease by determining the number of vessels involved and also the SYNTAX score. During 48 hours after coronary angiography, the patients underwent abdominal ultrasonography for detection of NAFLD. RESULTS The overall prevalence of NAFLD in the patients was 72.3%. The prevalence of NAFLD in those with and without coronary involvement was 71.9% and 73.1% respectively, with no notable difference (p = 0.837). The mean SYNTAX score in the patients with and without NAFLD was 22.32 ± 11.10 and 21.75 ± 10.71 respectively with no difference (p = 0.702). According to the multivariable regression models, the presence of NAFLD could not predict the likelihood of coronary artery disease (OR = 0.879, p = 0.669) or its severity assessed by the SYNTAX score (beta = 0.046, p = 0.456). NAFLD grade was also not a determinant for coronary artery disease (OR = 1.139, p = 0.178) or its severity (beta = 0.058, p = 0.165). CONCLUSION It seems that the presence and grade of NAFLD may not be correlated with atherosclerotic involvement of coronary arteries and its severity in non-diabetic patients. Future large studies and trials could elucidate the independent role of fatty liver in nondiabetic non-alcoholic patients.
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Newsome P, Francque S, Harrison S, Ratziu V, Van Gaal L, Calanna S, Hansen M, Linder M, Sanyal A. Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity. Aliment Pharmacol Ther 2019; 50:193-203. [PMID: 31246368 PMCID: PMC6617813 DOI: 10.1111/apt.15316] [Citation(s) in RCA: 125] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 01/19/2019] [Accepted: 05/01/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Obesity and type 2 diabetes are drivers of non-alcoholic fatty liver disease (NAFLD). Glucagon-like peptide-1 analogues effectively treat obesity and type 2 diabetes and may offer potential for NAFLD treatment. AIM To evaluate the effect of the glucagon-like peptide-1 analogue, semaglutide, on alanine aminotransferase (ALT) and high-sensitivity C-reactive protein (hsCRP) in subjects at risk of NAFLD. METHODS Data from a 104-week cardiovascular outcomes trial in type 2 diabetes (semaglutide 0.5 or 1.0 mg/week) and a 52-week weight management trial (semaglutide 0.05-0.4 mg/day) were analysed. Treatment ratios vs placebo were estimated for ALT (both trials) and hsCRP (weight management trial only) using a mixed model for repeated measurements, with or without adjustment for change in body weight. RESULTS Elevated baseline ALT (men >30 IU/L; women >19 IU/L) was present in 52% (499/957) of weight management trial subjects. In this group with elevated ALT, end-of-treatment ALT reductions were 6%-21% (P<0.05 for doses≥0.2 mg/day) and hsCRP reductions 25%-43% vs placebo (P < 0.05 for 0.2 and 0.4 mg/day). Normalisation of elevated baseline ALT occurred in 25%-46% of weight management trial subjects, vs 18% on placebo. Elevated baseline ALT was present in 41% (1325/3268) of cardiovascular outcomes trial subjects. In this group with elevated ALT, no significant ALT reduction was noted at end-of-treatment for 0.5 mg/week, while a 9% reduction vs placebo was seen for 1.0 mg/week (P = 0.0024). Treatment ratios for changes in ALT and hsCRP were not statistically significant after adjustment for weight change. CONCLUSIONS Semaglutide significantly reduced ALT and hsCRP in clinical trials in subjects with obesity and/or type 2 diabetes.
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Affiliation(s)
- Philip Newsome
- National Institute for Health Research Birmingham Biomedical Research Centre and Liver Unit at University Hospitals Birmingham NHS Foundation TrustBirminghamUK,Centre for Liver & Gastrointestinal Research, Institute of Immunology and ImmunotherapyUniversity of BirminghamBirminghamUK
| | - Sven Francque
- Department of Gastroenterology and HepatologyAntwerp University HospitalEdegem, AntwerpBelgium
| | | | - Vlad Ratziu
- ICAN – Institute for Cardiometabolism and NutritionHôpital Pitié Salpêtrière, Sorbonne UniversityParisFrance
| | - Luc Van Gaal
- Department of Endocrinology, Diabetology and MetabolismAntwerp University HospitalEdegem, AntwerpBelgium
| | | | | | | | - Arun Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal MedicineVirginia Commonwealth UniversityRichmondVirginia
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Häggström C, Jonsson H, Bjørge T, Nagel G, Manjer J, Ulmer H, Drake I, Ghaderi S, Lang A, Engeland A, Stattin P, Stocks T. Linear age‐course effects on the associations between body mass index, triglycerides, and female breast and male liver cancer risk: An internal replication study of 800,000 individuals. Int J Cancer 2019; 146:58-67. [DOI: 10.1002/ijc.32240] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 01/28/2019] [Accepted: 02/14/2019] [Indexed: 12/17/2022]
Affiliation(s)
- Christel Häggström
- Department of Biobank ResearchUmeå University Umeå Sweden
- Department of Surgical SciencesUppsala University Uppsala Sweden
- Department of Public Health and Clinical Medicine, Nutritional ResearchUmeå University Umeå Sweden
| | - Håkan Jonsson
- Department of Radiation SciencesUmeå University Umeå Sweden
| | - Tone Bjørge
- Department of Global Public Health and Primary CareUniversity of Bergen Bergen Norway
- Cancer Registry of Norway Oslo Norway
| | - Gabriele Nagel
- Institute of Epidemiology and Medical BiometryUlm University Ulm Germany
- Vorarlberg Cancer RegistryAgency for Preventive and Social Medicine Bregenz (aks) Austria
| | - Jonas Manjer
- Department of SurgerySkåne University Hospital, Lund University Malmö Sweden
| | - Hanno Ulmer
- Department of Medical Statistics, Informatics and Health EconomicsInnsbruck Medical University Innsbruck Austria
| | - Isabel Drake
- Department of Clinical Sciences in MalmöLund University Lund Sweden
| | - Sara Ghaderi
- Department of Global Public Health and Primary CareUniversity of Bergen Bergen Norway
| | - Alois Lang
- Vorarlberg Cancer RegistryAgency for Preventive and Social Medicine Bregenz (aks) Austria
| | - Anders Engeland
- Department of Global Public Health and Primary CareUniversity of Bergen Bergen Norway
- Norwegian Institute of Public Health Bergen/Oslo Norway
| | - Pär Stattin
- Department of Surgical SciencesUppsala University Uppsala Sweden
| | - Tanja Stocks
- Department of Clinical Sciences in LundLund University Lund Sweden
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Bernal-Reyes R, Castro-Narro G, Malé-Velázquez R, Carmona-Sánchez R, González-Huezo M, García-Juárez I, Chávez-Tapia N, Aguilar-Salinas C, Aiza-Haddad I, Ballesteros-Amozurrutia M, Bosques-Padilla F, Castillo-Barradas M, Chávez-Barrera J, Cisneros-Garza L, Flores-Calderón J, García-Compeán D, Gutiérrez-Grobe Y, Higuera de la Tijera M, Kershenobich-Stalnikowitz D, Ladrón de Guevara-Cetina L, Lizardi-Cervera J, López-Cossio J, Martínez-Vázquez S, Márquez-Guillén E, Méndez-Sánchez N, Moreno-Alcantar R, Poo-Ramírez J, Ramos-Martínez P, Rodríguez-Hernández H, Sánchez-Ávila J, Stoopen-Rometti M, Torre-Delgadillo A, Torres-Villalobos G, Trejo-Estrada R, Uribe-Esquivel M, Velarde-Ruiz Velasco J. The Mexican consensus on nonalcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2019.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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13
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Bernal-Reyes R, Castro-Narro G, Malé-Velázquez R, Carmona-Sánchez R, González-Huezo MS, García-Juárez I, Chávez-Tapia N, Aguilar-Salinas C, Aiza-Haddad I, Ballesteros-Amozurrutia MA, Bosques-Padilla F, Castillo-Barradas M, Chávez-Barrera JA, Cisneros-Garza L, Flores-Calderón J, García-Compeán D, Gutiérrez-Grobe Y, Higuera de la Tijera MF, Kershenobich-Stalnikowitz D, Ladrón de Guevara-Cetina L, Lizardi-Cervera J, López-Cossio JA, Martínez-Vázquez S, Márquez-Guillén E, Méndez-Sánchez N, Moreno-Alcantar R, Poo-Ramírez JL, Ramos-Martínez P, Rodríguez-Hernández H, Sánchez-Ávila JF, Stoopen-Rometti M, Torre-Delgadillo A, Torres-Villalobos G, Trejo-Estrada R, Uribe-Esquivel M, Velarde-Ruiz Velasco JA. The Mexican consensus on nonalcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2019; 84:69-99. [PMID: 30711302 DOI: 10.1016/j.rgmx.2018.11.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 11/06/2018] [Accepted: 11/20/2018] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Mexico is one of the countries whose population has several risk factors for the disease and its prevalence could surpass 50%. If immediate action is not taken to counteract what is now considered a national health problem, the medium-term panorama will be very bleak. This serious situation prompted the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología to produce the Mexican Consensus on Fatty Liver Disease. It is an up-to-date and detailed review of the epidemiology, pathophysiology, clinical forms, diagnosis, and treatment of the disease, whose aim is to provide the Mexican physician with a useful tool for the prevention and management of nonalcoholic fatty liver disease.
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Affiliation(s)
- R Bernal-Reyes
- Sociedad Española de Beneficencia, Pachuca, Hidalgo, México.
| | - G Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, México
| | | | - M S González-Huezo
- Servicio de Gastroenterología y Endoscopia GI, ISSSEMYM, Metepec, Estado de México, México
| | - I García-Juárez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - N Chávez-Tapia
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - C Aguilar-Salinas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - I Aiza-Haddad
- Clínica de enfermedades hepáticas, Hospital Ángeles Lómas, Ciudad de México, México
| | | | | | - M Castillo-Barradas
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico La Raza IMSS, Ciudad de México, México
| | - J A Chávez-Barrera
- Servicio de Gastroenterología Pediátrica, Hospital General, Centro Médico La Raza, IMSS, Ciudad de México, México
| | - L Cisneros-Garza
- Servicio de Gastroenterología, Hospital Universitario de la UANL, Monterrey, Nuevo León, México
| | - J Flores-Calderón
- Servicio de Gastroenterología, Hospital de Pediatría, Centro Médico Siglo XXI, IMSS, Ciudad de México, México
| | - D García-Compeán
- Servicio de Gastroenterología, Hospital Universitario de la UANL, Monterrey, Nuevo León, México
| | - Y Gutiérrez-Grobe
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | | | | | | | - J Lizardi-Cervera
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - J A López-Cossio
- Servicio de Gastroenterología y Endoscopia GI, ISSSEMYM, Metepec, Estado de México, México
| | - S Martínez-Vázquez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - E Márquez-Guillén
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - N Méndez-Sánchez
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - R Moreno-Alcantar
- Servicio de Gastroenterología, Hospital de Especialidades Centro Médico Siglo XXI, IMSS, Ciudad de México, México
| | - J L Poo-Ramírez
- Centro de Innovación y Educación Ejecutiva, Tec de Monterrey, Ciudad de México, México
| | | | - H Rodríguez-Hernández
- Unidad de Investigación Biomédica AMCCI, Hospital de Especialidades, Durango, México
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, México
| | - M Stoopen-Rometti
- Centro de Diagnóstico CT-Scanner Lomas Altas, Ciudad de México, México
| | - A Torre-Delgadillo
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - G Torres-Villalobos
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - M Uribe-Esquivel
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
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14
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Gerhard GS, Malenica I, Llaci L, Chu X, Petrick AT, Still CD, DiStefano JK. Differentially methylated loci in NAFLD cirrhosis are associated with key signaling pathways. Clin Epigenetics 2018; 10:93. [PMID: 30005700 PMCID: PMC6044005 DOI: 10.1186/s13148-018-0525-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 06/25/2018] [Indexed: 12/16/2022] Open
Abstract
Altered DNA methylation events contribute to the pathogenesis and progression of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Investigations of global DNA methylation patterns in liver biopsies representing severe NAFLD fibrosis have been limited. We used the HumanMethylation 450K BeadChip to analyze genome-wide methylation in patients with biopsy-proven grade 3/4 NAFLD fibrosis/cirrhosis (N = 14) and age- and sex-matched controls with normal histology (N = 15). We identified 208 CpG islands (CGIs), including 99 hypomethylated and 109 hypermethylated CGIs, showing statistically significant evidence (adjusted P value < 0.05) for differential methylation between cirrhotic and normal samples. Comparison of β values for each CGI to the read count of its corresponding gene obtained from RNA-sequencing analysis revealed negative correlation (adjusted P value < 0.05) for 34 transcripts. These findings provide supporting evidence for a role for CpG methylation in the pathogenesis of NAFLD-related cirrhosis, including confirmation of previously reported differentially methylated CGIs, and contribute new insight into the molecular mechanisms underlying the initiation and progression of liver fibrosis and cirrhosis.
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Affiliation(s)
- Glenn S Gerhard
- Temple University School of Medicine, Philadelphia, PA, 19140, USA
| | - Ivana Malenica
- Translational Genomics Research Institute, 445 N 5th St, Phoenix, AZ, 85004, USA
| | - Lorida Llaci
- Translational Genomics Research Institute, 445 N 5th St, Phoenix, AZ, 85004, USA
| | - Xin Chu
- Geisinger Obesity Institute, Danville, PA, 17822, USA
| | | | | | - Johanna K DiStefano
- Translational Genomics Research Institute, 445 N 5th St, Phoenix, AZ, 85004, USA.
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15
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Lallukka S, Sädevirta S, Kallio MT, Luukkonen PK, Zhou Y, Hakkarainen A, Lundbom N, Orho-Melander M, Yki-Järvinen H. Predictors of Liver Fat and Stiffness in Non-Alcoholic Fatty Liver Disease (NAFLD) - an 11-Year Prospective Study. Sci Rep 2017; 7:14561. [PMID: 29109528 PMCID: PMC5674024 DOI: 10.1038/s41598-017-14706-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 10/10/2017] [Indexed: 12/16/2022] Open
Abstract
Liver fat can be non-invasively measured by proton magnetic resonance spectroscopy (1H-MRS) and fibrosis estimated as stiffness using transient elastography (FibroScan). There are no longitudinal data on changes in liver fat in Europids or on predictors of liver stiffness using these methods. We determined liver fat (1H-MRS) and clinical characteristics including features of insulin resistance at baseline and after a median follow-up period of 11.3 (range 7.3-13.4) years in 97 Finnish subjects. Liver stiffness was measured at 11.3 years. Liver fat content decreased by 5% (p < 0.05) over time. Values at baseline and 11.3 years were closely interrelated (r = 0.81, p < 0.001). Baseline liver fat (OR 1.32; 95%CI: 1.15-1.50) and change in BMI (OR 1.67; 95%CI: 1.24-2.25) were independent predictors of liver fat at 11.3 years (AUROC 0.90; 95%CI: 0.83-0.96). Baseline liver fat (AUROC 0.84; 95%CI: 0.76-0.92) predicted liver fat at 11.3 years more accurately than routinely available parameters (AUROC 0.76; 95%CI: 0.65-0.86, p = 0.02). At 11.3 years, 29% of the subjects had increased liver stiffness. Baseline liver fat (OR 2.17; 95%CI: 1.05-4.46) was an independent predictor of increased liver stiffness. These data show that liver fat is more important than the associated metabolic abnormalities as the predictor of future liver fat and fibrosis.
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Affiliation(s)
- Susanna Lallukka
- Minerva Foundation Institute for Medical Research, Helsinki, Finland. .,Department of Medicine, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.
| | - Sanja Sädevirta
- Minerva Foundation Institute for Medical Research, Helsinki, Finland.,Department of Medicine, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland
| | - Markus T Kallio
- Minerva Foundation Institute for Medical Research, Helsinki, Finland.,Department of Medicine, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland
| | - Panu K Luukkonen
- Minerva Foundation Institute for Medical Research, Helsinki, Finland.,Department of Medicine, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland
| | - You Zhou
- Minerva Foundation Institute for Medical Research, Helsinki, Finland.,Systems Immunity University Research Institute and Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
| | - Antti Hakkarainen
- HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland
| | - Nina Lundbom
- HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland
| | - Marju Orho-Melander
- Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö, Sweden
| | - Hannele Yki-Järvinen
- Minerva Foundation Institute for Medical Research, Helsinki, Finland.,Department of Medicine, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland
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16
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Wang S, Wu C, Li X, Zhou Y, Zhang Q, Ma F, Wei J, Zhang X, Guo P. Syringaresinol-4- O- β-d-glucoside alters lipid and glucose metabolism in HepG2 cells and C2C12 myotubes. Acta Pharm Sin B 2017; 7:453-460. [PMID: 28752030 PMCID: PMC5518665 DOI: 10.1016/j.apsb.2017.04.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 03/29/2017] [Accepted: 04/10/2017] [Indexed: 12/21/2022] Open
Abstract
Syringaresinol-4-O-β-d-glucoside (SSG), a furofuran-type lignan, was found to modulate lipid and glucose metabolism through an activity screen of lipid accumulation and glucose consumption, and was therefore considered as a promising candidate for the prevention and treatment of metabolic disorder, especially in lipid and glucose metabolic homeostasis. In this study, the effects of SSG on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were further investigated. Treatment with SSG significantly inhibited lipid accumulation by oil red O staining and reduced the intracellular contents of total lipid, cholesterol and triglyceride in HepG2 cells. No effect was observed on cell viability in the MTT assay at concentrations of 0.1–10 μmol/L. SSG also increased glucose consumption by HepG2 cells and glucose uptake by C2C12 myotubes. Furthermore, real-time quantitative PCR revealed that the beneficial effects were associated with the down-regulation of sterol regulatory element-binding proteins-1c, -2 (SREBP-1c, -2), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC) and hydroxyl methylglutaryl CoA reductase (HMGR), and up-regulation of peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ). SSG also significantly elevated transcription activity of PPARγ tested by luciferase assay. These results suggest that SSG is an effective regulator of lipogenesis and glucose consumption and might be a candidate for further research in the prevention and treatment of lipid and glucose metabolic diseases.
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17
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Aller MA, Arias N, Peral I, García-Higarza S, Arias JL, Arias J. Embrionary way to create a fatty liver in portal hypertension. World J Gastrointest Pathophysiol 2017; 8:39-50. [PMID: 28573066 PMCID: PMC5437501 DOI: 10.4291/wjgp.v8.i2.39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 01/18/2017] [Accepted: 03/02/2017] [Indexed: 02/06/2023] Open
Abstract
Portal hypertension in the rat by triple partial portal vein ligation produces an array of splanchnic and systemic disorders, including hepatic steatosis. In the current review these alterations are considered components of a systemic inflammatory response that would develop through three overlapping phenotypes: The neurogenic, the immune and the endocrine. These three inflammatory phenotypes could resemble the functions expressed during embryonic development of mammals. In turn, the inflammatory phenotypes would be represented in the embryo by two functional axes, that is, a coelomic-amniotic axis and a trophoblastic yolk-sac or vitelline axis. In this sense, the inflammatory response developed after triple partial portal vein ligation in the rat would integrate both functional embryonic axes on the liver interstitial space of Disse. If so, this fact would favor the successive development of steatosis, steatohepatitis and fibrosis. Firstly, these recapitulated embryonic functions would produce the evolution of liver steatosis. In this way, this fat liver could represent a yolk-sac-like in portal hypertensive rats. After that, the systemic recapitulation of these embryonic functions in experimental prehepatic portal hypertension would consequently induce a gastrulation-like response in which a hepatic wound healing reaction or fibrosis occur. In conclusion, studying the mechanisms involved in embryonic development could provide key results for a better understanding of the nonalcoholic fatty liver disease etiopathogeny.
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18
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Cheng DD, He C, Ai HH, Huang Y, Lu NH. The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease. Front Microbiol 2017; 8:743. [PMID: 28539915 PMCID: PMC5423951 DOI: 10.3389/fmicb.2017.00743] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Accepted: 04/10/2017] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori (H. pylori) which colonizes the stomach can cause a wide array of gastric disorders, including chronic gastritis, peptic ulcer, and gastric cancer. Recently, accumulating evidence has implicated H. pylori infection in extragastrointestinal diseases such as cardiovascular diseases, neurological disorders, and metabolic diseases. At the same time, many scholars have noted the relationship between H. pylori infection and non-alcoholic fatty liver disease (NAFLD). Despite the positive association between H. pylori and NAFLD reported in some researches, there are opposite perspectives denying their relationship. Due to high prevalence, unclear etiology and difficult treatment of NAFLD, confirming the pathogenicity of H. pylori infection in NAFLD will undoubtedly provide insights for novel treatment strategies for NAFLD. This paper will review the relationship between H. pylori infection and NAFLD and the possible pathogenic mechanisms.
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Affiliation(s)
- Dan-Dan Cheng
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang UniversityNanchang, China
| | - Cong He
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang UniversityNanchang, China
| | - Hong-Hui Ai
- Department of Orthopaedics, The Yugan County People's HospitalYugan, China
| | - Ying Huang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang UniversityNanchang, China
| | - Nong-Hua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang UniversityNanchang, China
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19
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Associations between hemoglobin concentrations and the development of incidental metabolic syndrome or nonalcoholic fatty liver disease. Dig Liver Dis 2017; 49:57-62. [PMID: 27810399 DOI: 10.1016/j.dld.2016.10.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 09/30/2016] [Accepted: 10/04/2016] [Indexed: 02/07/2023]
Abstract
AIMS Hemoglobin (Hb) is known to be associated with both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). We evaluated the relationship between serum Hb levels and the development of MS or NAFLD. METHODS A retrospective cohort study was conducted. We recruited participants who underwent abdominal ultrasonography and blood samplings in both 2005 and 2010. RESULTS Graded independent relationships were observed between higher Hb levels and the incidence of MS and NAFLD. After adjusting for age, body mass index, and fasting glucose, high-density lipoprotein cholesterol and triglyceride levels, the risk of developing MS was significantly higher according to the Hb quartiles in men (P for trend=0.027). The adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the highest Hb quartile was 1.81 (1.06-3.10) for women and 1.43 (1.00-2.05) for men. The risk of developing NAFLD was also significantly higher according to the Hb quartiles in men (P for trend=0.03). The adjusted OR and 95% CI for the highest Hb quartile was 1.18 (0.73-1.91) in women and 1.76 (1.16-2.66) in men. CONCLUSIONS The risk of developing either MS or NAFLD was significantly associated with serum Hb levels in men. These findings have implications in the clinical availability of serum Hb as a predictor of MS and NAFLD.
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20
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Gliozzi M, Maiuolo J, Oppedisano F, Mollace V. The effect of bergamot polyphenolic fraction in patients with non alcoholic liver steato-hepatitis and metabolic syndrome. PHARMANUTRITION 2016. [DOI: 10.1016/j.phanu.2015.11.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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21
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Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev 2016; 17:510-9. [PMID: 27020692 DOI: 10.1111/obr.12407] [Citation(s) in RCA: 266] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 02/07/2016] [Accepted: 02/15/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The association between obesity and nonalcoholic fatty liver disease (NAFLD) has not been fully quantified, and the magnitude of NAFLD risk associated with obesity is still unclear. A meta-analysis of cohort studies was performed to elucidate the NAFLD risk associated with obesity. METHODS Pubmed, Web of Science and Embase were searched for cohort studies assessing NAFLD risk associated with obesity or increased body mass index (BMI). Relative risks (RRs) with 95% confidence intervals (95%CIs) were pooled using random-effects model of meta-analysis. RESULTS Twenty-one cohort studies including 13 prospective studies and 8 retrospective studies were finally included. There were a total of 381,655 participants in the meta-analysis. Compared with normal weight, obesity independently led to a 3.5-fold increased risk of developing NAFLD (RR = 3.53, 95%CI 2.48 to 5.03, P < 0.001). Meta-analysis also suggested an obvious dose-dependent relationship between BMI and NAFLD risk (per 1-unit increment in BMI: RR = 1.20, 95%CI 1.14 to 1.26, P < 0.001). Subgroup analyses further identified the robustness of the association above. No obvious risk of publication bias was observed. CONCLUSION Obese individuals have a 3.5-fold increased risk of developing NAFLD, and there is an obvious dose-dependent relationship between BMI and NAFLD risk. © 2016 World Obesity.
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Affiliation(s)
- L Li
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - D-W Liu
- Department of Urinary Surgery, Southwest Hospital Affiliated to Third Military Medical University, Chongqing, China
| | - H-Y Yan
- Department of Gastroenterology, 210 Hospital of PLA, Dalian, China
| | - Z-Y Wang
- Surgical Center, Zhucheng People's Hospital, Zhucheng, China
| | - S-H Zhao
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - B Wang
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China
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22
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Kanwar P, Kowdley KV. The Metabolic Syndrome and Its Influence on Nonalcoholic Steatohepatitis. Clin Liver Dis 2016; 20:225-43. [PMID: 27063266 DOI: 10.1016/j.cld.2015.10.002] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) and the metabolic syndrome (MetS) are highly prevalent in the Western population. Their pathogenesis is closely linked to insulin resistance, which serves as a therapeutic target for the management of these conditions. This review article reviews the research supporting the influence of MetS on NASH and includes studies supporting their similar epidemiology, pathogenesis, and treatment.
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Affiliation(s)
- Pushpjeet Kanwar
- Department of Gastroenterology and Hepatology, New York Methodist Hospital, 506, 6th Street, Brooklyn, NY 11215, USA
| | - Kris V Kowdley
- Department of Transplant Hepatology, Swedish Medical Center, 1101, Madison Street, Suite 200, Seattle, WA 98104, USA.
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23
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Abstract
The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is associated with the increasing global pandemic of obesity. These conditions cluster with type II diabetes mellitus and the metabolic syndrome to result in obesity-associated liver disease. The benefits of bariatric procedures on diabetes and the metabolic syndrome have been recognized for some time, and there is now mounting evidence to suggest that bariatric procedures improve liver histology and contribute to the beneficial resolution of NAFLD in obese patients. These beneficial effects derive from a number of weight-dependent and weight-independent mechanisms including surgical BRAVE actions (bile flow changes, restriction of stomach size, anatomical gastrointestinal rearrangement, vagal manipulation, enteric hormonal modulation) and subsequent effects such as reduced lipid intake, adipocytokine secretion, modulation of gut flora, improvements in insulin resistance and reduced inflammation. Here, we review the clinical investigations on bariatric procedures for NAFLD, in addition to the mounting mechanistic data supporting these findings. Elucidating the mechanisms by which bariatric procedures may resolve NAFLD can help enhance surgical approaches for metabolic hepatic dysfunction and also contribute toward developing the next generation of therapies aimed at reducing the burden of obesity-associated liver disease.
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24
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Gan L, Meng ZJ, Xiong RB, Guo JQ, Lu XC, Zheng ZW, Deng YP, Luo BD, Zou F, Li H. Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice. Acta Pharmacol Sin 2015; 36:597-605. [PMID: 25891086 DOI: 10.1038/aps.2015.11] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Accepted: 02/27/2015] [Indexed: 12/14/2022]
Abstract
AIM Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. In this study, we investigated the effects of EGCG on insulin resistance and insulin clearance in non-alcoholic fatty liver disease (NAFLD) mice. METHODS Mice were fed on a high-fat diet for 24 weeks. During the last 4 weeks, the mice were injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip). Glucose tolerance, insulin tolerance and insulin clearance were assessed. After the mice were euthanized, blood samples and tissue specimens were collected. Glucose-stimulated insulin secretion was examined in isolated pancreatic islets. The progression of NAFLD was evaluated histologically and by measuring lipid contents. Insulin-degrading enzyme (IDE) protein expression and enzyme activity were detected using Western blot and immunocapture activity assays, respectively. RESULTS The high-fat diet significantly increased the body weight and induced grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning) accompanied by severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in the model mice. Administration of EGCG dose-dependently ameliorated the hepatic morphology and function, reduced the body weight, and alleviated hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in NAFLD mice. Furthermore, EGCG dose-dependently enhanced insulin clearance and upregulated IDE protein expression and enzyme activity in the liver of NAFLD mice. CONCLUSION EGCG dose-dependently improves insulin resistance in NAFLD mice not only by reducing body weight but also through enhancing the insulin clearance by hepatic IDE. The results suggest that IDE be a potential drug target for the treatment of NAFLD.
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Paredes-Turrubiarte G, González-Chávez A, Pérez-Tamayo R, Salazar-Vázquez BY, Hernández VS, Garibay-Nieto N, Fragoso JM, Escobedo G. Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients. Clin Exp Med 2015; 16:193-202. [PMID: 25894568 DOI: 10.1007/s10238-015-0347-4] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 04/02/2015] [Indexed: 02/06/2023]
Abstract
Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index > 40 kg/m(2)), exhibiting different grades of NAFLD. Blood glucose, glycated hemoglobin, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, high- and low-density lipoproteins, parameters of liver function, TNF-α, and IL-10 were measured in each subject. The stage of NAFLD was estimated by abdominal ultrasound imaging. In comparison with morbidly obese subjects without steatosis, morbidly obese patients with NAFLD showed increased age (39.23 ± 9.80 years), HOMA-IR (6.74 ± 1.62), total cholesterol (219.7 ± 9.58 mg/dl), aspartate aminotransferase (36.25 ± 3.24 UI/l), gamma-glutamyl transpeptidase (37.12 ± 3.41 UI/l), and TNF-α (37.41 ± 1.72 pg/ml) as well as decreased serum levels of IL-10 (61.05 ± 2.43 pg/ml). Interestingly, the systemic levels of TNF-α increased, while IL-10 decreased in accordance with the severity of NAFLD, which supports a role for systemic inflammatory mediators in promoting steatosis progression. Further clinical prospective studies need to be addressed to elucidate the role of TNF-α and IL-10 in the development of NAFLD while also establishing their clinical utility in the assessment of morbidly obese patients at higher risk to develop severe steatosis.
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Affiliation(s)
| | - Antonio González-Chávez
- Department of Internal Medicine, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico, D.F., Mexico.
| | - Ruy Pérez-Tamayo
- Unit of Experimental Medicine, School of Medicine, National University of Mexico, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico, D.F., Mexico
| | - Beatriz Y Salazar-Vázquez
- Unit of Experimental Medicine, School of Medicine, National University of Mexico, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico, D.F., Mexico
| | - Vito S Hernández
- Departament of Physiology, School of Medicine, National University of Mexico, 04510, Mexico, D.F., Mexico
| | - Nayeli Garibay-Nieto
- Department of Human Genetics, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico, D.F., Mexico
| | - José Manuel Fragoso
- Department of Molecular Biology, National Institute of Cardiology "Ignacio Chávez", 14080, Mexico, D.F., Mexico
| | - Galileo Escobedo
- Unit of Experimental Medicine, School of Medicine, National University of Mexico, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico, D.F., Mexico.
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DiStefano JK, Kingsley C, Wood GC, Chu X, Argyropoulos G, Still CD, Doné SC, Legendre C, Tembe W, Gerhard GS. Genome-wide analysis of hepatic lipid content in extreme obesity. Acta Diabetol 2015; 52:373-82. [PMID: 25246029 PMCID: PMC4370808 DOI: 10.1007/s00592-014-0654-3] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Accepted: 09/08/2014] [Indexed: 12/11/2022]
Abstract
AIMS Individuals with type 2 diabetes have an increased risk of developing non-alcoholic fatty liver disease (NAFLD), and NAFLD patients are also at greater risk for developing type 2 diabetes. Although the relationship between type 2 diabetes and NAFLD is highly interconnected, the pathogenic mechanisms linking the two diseases are poorly understood. The goal of this study was to identify genetic determinants of hepatic lipid accumulation through association analysis using histological phenotypes in obese individuals. METHODS Using the Illumina HumanOmniExpress BeadChip assay, we genotyped 2,300 individuals on whom liver biopsy data were available. RESULTS We analyzed total bilirubin levels, which are linked to fatty liver in severe obesity, and observed the strongest evidence for association with rs4148325 in UGT1A (P < 5.0 × 10(-93)), replicating previous findings. We assessed hepatic fat level and found strong evidence for association with rs4823173, rs2896019, and rs2281135, all located in PNPLA3 and rs10401969 in SUGP1. Analysis of liver transcript levels of 20 genes residing at the SUGP1/NCAN locus identified a 1.6-fold change in the expression of the LPAR2 gene in fatty liver. We also observed suggestive evidence for association between low-grade fat accumulation and rs10859525 and rs1294908, located upstream from SOCS2 and RAMP3, respectively. SOCS2 was differentially expressed between fatty and normal liver. CONCLUSIONS These results replicate findings for several hepatic phenotypes in the setting of extreme obesity and implicate new loci that may play a role in the pathophysiology of hepatic lipid accumulation.
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Affiliation(s)
- Johanna K. DiStefano
- Diabetes, Cardiovascular and Metabolic Diseases Division, Translational Genomics Research Institute, 445 Fifth Street, Phoenix, AZ 85004
- Corresponding author: Please send all correspondence to: Johanna K. DiStefano, Ph.D., Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, AZ 85004, Tel: 602.343.8812, FAX: 602.343.8844,
| | - Christopher Kingsley
- Diabetes, Cardiovascular and Metabolic Diseases Division, Translational Genomics Research Institute, 445 Fifth Street, Phoenix, AZ 85004
| | - G. Craig Wood
- Geisinger Obesity Institute, Geisinger Clinic, 100 N. Academy Ave., Danville, PA 17822
| | - Xin Chu
- Geisinger Obesity Institute, Geisinger Clinic, 100 N. Academy Ave., Danville, PA 17822
| | - George Argyropoulos
- Geisinger Obesity Institute, Geisinger Clinic, 100 N. Academy Ave., Danville, PA 17822
| | - Christopher D. Still
- Geisinger Obesity Institute, Geisinger Clinic, 100 N. Academy Ave., Danville, PA 17822
| | - Stefania Cotta Doné
- Diabetes, Cardiovascular and Metabolic Diseases Division, Translational Genomics Research Institute, 445 Fifth Street, Phoenix, AZ 85004
| | - Christophe Legendre
- Diabetes, Cardiovascular and Metabolic Diseases Division, Translational Genomics Research Institute, 445 Fifth Street, Phoenix, AZ 85004
| | - Waibhav Tembe
- Diabetes, Cardiovascular and Metabolic Diseases Division, Translational Genomics Research Institute, 445 Fifth Street, Phoenix, AZ 85004
| | - Glenn S. Gerhard
- Geisinger Obesity Institute, Geisinger Clinic, 100 N. Academy Ave., Danville, PA 17822
- Department of Biochemistry and Molecular Biology, Institute for Personalized Medicine, Department of Pathology and Laboratory Medicine, Pennsylvania State University College of Medicine, Room C5750, 500 University Drive, MC - H171, Hershey, PA 17033
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Wang CC, Tseng TC, Kao JH. Hepatitis B virus infection and metabolic syndrome: fact or fiction? J Gastroenterol Hepatol 2015; 30:14-20. [PMID: 25092429 DOI: 10.1111/jgh.12700] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/12/2014] [Indexed: 12/12/2022]
Abstract
Although hepatitis C virus infection is known to be linked with insulin resistance, dyslipidemia, and hepatic steatosis, the relationship between hepatitis B virus (HBV) infection and metabolic factors remains unclear. HBV infection is a health problem worldwide, especially in endemic regions such as Asia and Africa. It induces liver decompensation, cirrhosis, hepatocellualr carcinoma, and premature mortality. The prevalence of metabolic syndrome continues to increase in parallel with the epidemic of obesity, which is closely associated with the development of diabetes, cardiovascular disease, or even cancer. The systemic review shows that chronic HBV infection protects against instead of promotes fatty liver. The mechanism is possibly due to a lower frequency of dyslipidemia profile in patients with chronic HBV infection. The association of HBV with metabolic syndrome, insulin resistance, and the risk of arteriosclerosis is still inconclusive. In addition, obesity, diabetes, and metabolic syndrome may accelerate the progression of liver disease in patients with chronic HBV infection and synergistically induce cirrhosis or even hepatocellualr carcinoma development.
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Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology and Hepatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
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Abstract
OBJECTIVES This study was designed to test the hypothesis that normal thyroid function is associated with non-alcoholic fatty liver disease (NAFLD) in euthyroid general subjects. METHODS A total of 739 euthyroid subjects were enrolled in this cross-sectional study. Using ultrasound, a diagnosis of NAFLD was made in subjects without a history of excessive alcohol consumption or liver diseases. Fasting serum samples were collected for determining thyroid function [thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels] and other biochemical parameters. RESULTS Among the enrolled subjects, 196 (26.5%) satisfied the diagnostic criteria for NAFLD. Subjects with NAFLD had significantly higher TSH levels and lower FT4 levels than those without NAFLD (p < 0.01 for both). NAFLD prevalence increased gradually with increasing quartiles of TSH levels and decreasing quartiles of FT4 levels. After adjustment for gender and age, TSH levels were found to correlate positively with body mass index (BMI), waist circumference (WC), and LDL-cholesterol levels (p < 0.05 for all) and negatively with HDL-cholesterol levels (p < 0.01). FT4 levels correlated negatively with both BMI and WC (p < 0.05 for both). Multiple logistic regression analysis showed that TSH and FT4 levels were independent risk factors for NAFLD [odds ratio (OR): 2.21, 95% confidence interval (CI): 1.21-4.02, p = 0.01, for TSH levels; OR: 0.39, 95% CI: 0.17-0.87, p = 0.02, for FT4 levels]. CONCLUSION Our findings suggest that serum FT4 and TSH levels, even those within the reference range, are associated with NAFLD in the general population, independent of known metabolic risk factors.
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Affiliation(s)
- Yang Tao
- Department of Clinical Laboratory, Affiliated People's Hospital of Jiangsu University , Zhenjiang , P. R. China and
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Tsunoda K, Kai Y, Uchida K, Kuchiki T, Nagamatsu T. Physical activity and risk of fatty liver in people with different levels of alcohol consumption: a prospective cohort study. BMJ Open 2014; 4:e005824. [PMID: 25095878 PMCID: PMC4127917 DOI: 10.1136/bmjopen-2014-005824] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Revised: 07/08/2014] [Accepted: 07/10/2014] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE To investigate whether physical activity affects the future incidence of fatty liver in people with never-moderate and heavy alcohol consumption. DESIGN Prospective cohort study. SETTING Health check-up programme at Meiji Yasuda Shinjuku Medical Center in Shinjuku Ward, Tokyo, Japan. POPULATION A total of 10,146 people aged 18 years or older without fatty liver enrolled through baseline surveys conducted from 2005 to 2007. They were grouped into never-moderate alcohol drinkers (n=7803) and heavy alcohol drinkers (n=2343) and followed until 2013. MAIN OUTCOME MEASURE Incident fatty liver diagnosed by ultrasound. RESULTS During a mean follow-up of 4.4 years (34,648 person-years), 1255 never-moderate alcohol drinkers developed fatty liver; 520 heavy alcohol drinkers developed fatty liver during a mean follow-up of 4.1 years (9596 person-years). For never-moderate alcohol drinkers, engaging in >3×/week of low-intensity (HR=0.82, 95% CI 0.71 to 0.96) and moderate-intensity (HR=0.56, 95% CI 0.39 to 0.81) physical activity significantly reduced incident fatty liver compared with those who engaged in physical activity <1×/week. For vigorous-intensity physical activity, frequencies of 2×/week (HR=0.57, 95% CI 0.38 to 0.86) and >3×/week (HR=0.55, 95% CI 0.38 to 0.79) were significantly associated with lower risk of incident fatty liver. In propensity-adjusted models, these significant associations still remained. By contrast, in heavy alcohol drinkers, there were no significant associations between the type or frequency of physical activity and incident fatty liver. CONCLUSIONS Physical activity had an independent protective effect on incident fatty liver only in the never-moderate alcohol drinkers, and the preventive effect increased with higher frequencies and intensities of physical activity.
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Affiliation(s)
- Kenji Tsunoda
- Physical Fitness Research Institute, Meiji Yasuda Life Foundation of Health and Welfare, Hachioji, Tokyo, Japan
| | - Yuko Kai
- Physical Fitness Research Institute, Meiji Yasuda Life Foundation of Health and Welfare, Hachioji, Tokyo, Japan
| | - Ken Uchida
- Meiji Yasuda Shinjuku Medical Center, Meiji Yasuda Life Foundation of Health and Welfare, Shinjuku, Tokyo, Japan
| | - Tsutomu Kuchiki
- Meiji Yasuda Wellness Development Office, Meiji Yasuda Life Foundation of Health and Welfare, Shinjuku, Tokyo, Japan
| | - Toshiya Nagamatsu
- Physical Fitness Research Institute, Meiji Yasuda Life Foundation of Health and Welfare, Hachioji, Tokyo, Japan
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the liver disease of this century, increasing in parallel with obesity, insulin resistance and the metabolic syndrome. NAFLD can be seen as a component of the metabolic syndrome, and as such, contributing as a risk factor for cardiovascular disease. In fact, these patients die more often from cardiovascular disease than from direct consequences of liver disease. In this review, we will summarize the data that link NAFLD as a central player in this dysmetabolism, as well as the evidence for appropriate therapy, in order to improve not only liver disease prognosis, but also the overall prognosis and risk of mortality, with particular focus on cardiovascular risk.
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Affiliation(s)
- Mariana Verdelho Machado
- Departamento de Gastrenterologia, Hospital Santa Maria, CHLN, Unidade de Nutrição e Metabolismo, Faculdade de Medicina de Lisboa, IMM, Lisbon, Portugal
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Celikbilek A, Celikbilek M, Okur A, Dogan S, Borekci E, Kozan M, Gursoy S. Non-alcoholic fatty liver disease in patients with migraine. Neurol Sci 2014; 35:1573-8. [PMID: 24756192 DOI: 10.1007/s10072-014-1798-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 04/09/2014] [Indexed: 12/13/2022]
Abstract
Evidence suggests that migraine is associated with metabolic syndrome, which is also implicated in non-alcoholic fatty liver disease (NAFLD). Reported for the first time, we aimed to investigate the relationship between migraine and NAFLD in patients with migraine. A total of 90 consecutive migraine patients were enrolled in this cross-sectional study. The diagnosis of migraine was determined according to the International Classification of Headache Disorders-II diagnostic criteria. The diagnosis of NAFLD was based on abdominal ultrasonography findings. Anthropometric indices and the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated, and serum insulin level measurements and other biochemical analyses were performed for each subject. The measurements of body mass index and waist circumference were significantly higher in migraine patients with NAFLD than in those without NAFLD (p < 0.001). Regarding the laboratory results, insulin (p = 0.024), alanine aminotransferase (p = 0.027), and triglyceride levels (p = 0.001) and the HOMA-IR (p = 0.039) were higher in migraineurs with NAFLD than in those without NAFLD. Among the headache characteristics, the presence of aura was higher, and disease and attack durations were significantly longer in migraineurs with NAFLD than in those without NAFLD (p = 0.005, p = 0.024, and p = 0.023; respectively). However, the headache characteristics did not correlate with either the hepatosteatosis grade or HOMA-IR in migraine patients (p > 0.05). Our results show that NAFLD may present in migraine patients with higher frequency of auras and longer disease and attack durations.
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Affiliation(s)
- Asuman Celikbilek
- Department of Neurology, Bozok University, School of Medicine, 66200, Yozgat, Turkey,
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Gerhard GS, Benotti P, Wood GC, Chu X, Argyropoulos G, Petrick A, Strodel WE, Gabrielsen JD, Ibele A, Still CD, Kingsley C, DiStefano J. Identification of novel clinical factors associated with hepatic fat accumulation in extreme obesity. J Obes 2014; 2014:368210. [PMID: 25610640 PMCID: PMC4290025 DOI: 10.1155/2014/368210] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Revised: 10/16/2014] [Accepted: 10/17/2014] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES The accumulation of lipids stored as excess triglycerides in the liver (steatosis) is highly prevalent in obesity and has been associated with several clinical characteristics, but most studies have been based on relatively small sample sizes using a limited set of variables. We sought to identify clinical factors associated with liver fat accumulation in a large cohort of patients with extreme obesity. METHODS We analyzed 2929 patients undergoing intraoperative liver biopsy during a primary bariatric surgery. Univariate and multivariate regression modeling was used to identify associations with over 200 clinical variables with the presence of any fat in the liver and with moderate to severe versus mild fat accumulation. RESULTS A total of 19 data elements were associated with the presence of liver fat and 11 with severity of liver fat including ALT and AST, plasma lipid, glucose, and iron metabolism variables, several medications and laboratory measures, and sleep apnea. The accuracy of a multiple logistic regression model for presence of liver fat was 81% and for severity of liver fat accumulation was 77%. CONCLUSIONS A limited set of clinical factors can be used to model hepatic fat accumulation with moderate accuracy and may provide potential mechanistic insights in the setting of extreme obesity.
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Affiliation(s)
- Glenn S. Gerhard
- Department of Medical Genetics and Molecular Biochemistry, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA
- *Glenn S. Gerhard:
| | - Peter Benotti
- Geisinger Obesity Research Institute, Danville, PA 17822, USA
| | - G. Craig Wood
- Geisinger Obesity Research Institute, Danville, PA 17822, USA
| | - Xin Chu
- Geisinger Obesity Research Institute, Danville, PA 17822, USA
| | | | - Anthony Petrick
- Geisinger Obesity Research Institute, Danville, PA 17822, USA
| | | | | | - Anna Ibele
- Geisinger Obesity Research Institute, Danville, PA 17822, USA
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Chakraborty S. Analysis of NHANES 1999-2002 data reveals noteworthy association of alcohol consumption with obesity. Ann Gastroenterol 2014; 27:250-257. [PMID: 24974978 PMCID: PMC4073022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Accepted: 01/09/2014] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND With the obesity pandemic sweeping the globe and alcohol use on the rise worldwide, there is growing interest in how the two might be linked epidemiologically. The aim of the study was to use data from the NHANES registry from 1999-2002 to analyze the association between obesity and alcohol use. METHODS Multivariate logistic regression was used to assess the relationship between alcohol use and obesity. Risk was assessed separately for men and women. RESULTS Of the 9,193 individuals (49% males), 26.8% of males and 33.6% of females were obese. About 17% of males and 12% of females were never drinkers (less than 12 drinks in their lifetime). After adjusting for age, race, marital status, highest level of education of the individual and spouse, country of origin, annual household income and duration of physical activity in the past 30 days, the odds of obesity were higher in never drinkers compared to ever drinkers in both men and women. Consumption of alcohol for more than 45 days, binge drinking (>5 drinks/day) for more than 90 days and being "ever binge drinker" were associated with significantly higher odds of obesity (in both genders) than those who drank for shorter duration or were "never binge drinkers". Consumption of alcohol more than the recommended limit for moderate drinking (3 drinks/day in females and 4 drinks/day in males) was associated with increased (OR 1.074, 95% CI 1.072-1.076) and decreased (OR 0.970, 95%CI 0.968-0.972) obesity in females and males respectively. CONCLUSION Frequent or heavy alcohol consumption is associated with greater odds of being obese.
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Affiliation(s)
- Subhankar Chakraborty
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA,
Correspondence to: Subhankar Chakraborty, MD, Ph.D., Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-2055, USA, Tel.: +19 7881 05992, e-mail:
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Fruci B, Giuliano S, Mazza A, Malaguarnera R, Belfiore A. Nonalcoholic Fatty liver: a possible new target for type 2 diabetes prevention and treatment. Int J Mol Sci 2013; 14:22933-66. [PMID: 24264040 PMCID: PMC3856099 DOI: 10.3390/ijms141122933] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 10/30/2013] [Accepted: 11/08/2013] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.
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Affiliation(s)
- Barbara Fruci
- Endocrinology, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro 88100, Italy.
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