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Koliaki C, Dalamaga M, Kakounis K, Liatis S. Metabolically Healthy Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Navigating the Controversies in Disease Development and Progression. Curr Obes Rep 2025; 14:46. [PMID: 40387999 DOI: 10.1007/s13679-025-00637-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/05/2025] [Indexed: 05/20/2025]
Abstract
PURPOSE OF REVIEW The natural course of metabolic dysfunction-associated steatotic liver disease (MASLD) in the population with metabolically healthy obesity (MHO) has not been adequately explored. In the present narrative review, we summarize the evidence regarding the association between MHO and MASLD prevalence, incidence and progression. RECENT FINDINGS Cross-sectional, population-based, cohort studies have shown an increased prevalence of hepatic steatosis and fibrosis in subjects with MHO compared with metabolically healthy non-obese individuals (MHNO). In large-scale longitudinal cohort studies among metabolically healthy subjects, increasing body mass index (BMI) has been found to be independently associated with an increased incidence of MASLD and progressive hepatic fibrosis over a mean follow-up period of 2.2-7.7 years. With regard to advanced MASLD, the prevalence of steatohepatitis and clinically significant liver fibrosis is lower in MHO compared with subjects with metabolically unhealthy obesity (MUO). The presence of MASLD has been proposed as a strong risk factor for metabolic health deterioration in MHO. Furthermore, subjects with MHO and MASLD display an elevated 10-year cardiovascular risk and a three-fold increased risk of incident diabetes compared with MHO without MASLD. MASLD may also predict the failure to convert from MUO to MHO after a weight loss intervention.
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Affiliation(s)
- Chrysi Koliaki
- First Propaedeutic Department of Internal Medicine and Diabetes Center, Medical School, Laiko General Hospital, National Kapodistrian University of Athens, 17 Agiou Thoma Street, Athens, 11527, Greece.
| | - Maria Dalamaga
- Department of Biologic Chemistry, Medical School, National Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Kakounis
- Department of Gastroenterology, Hippokration General Hospital of Athens, Athens, Greece
| | - Stavros Liatis
- First Propaedeutic Department of Internal Medicine and Diabetes Center, Medical School, Laiko General Hospital, National Kapodistrian University of Athens, 17 Agiou Thoma Street, Athens, 11527, Greece
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Askeland A, Rasmussen RW, Gjela M, Frøkjær JB, Højlund K, Mellergaard M, Handberg A. Non-invasive liver fibrosis markers are increased in obese individuals with non-alcoholic fatty liver disease and the metabolic syndrome. Sci Rep 2025; 15:10652. [PMID: 40148373 PMCID: PMC11950363 DOI: 10.1038/s41598-025-85508-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 01/03/2025] [Indexed: 03/29/2025] Open
Abstract
The need for early non-invasive diagnostic tools for chronic liver fibrosis is growing, particularly in individuals with obesity, non-alcoholic fatty liver disease (NAFLD), and the metabolic syndrome (MetS) since prevalence of these conditions is increasing. This case-control study compared non-invasive liver fibrosis markers in obesity with NAFLD and MetS (NAFLD-MetS, n = 33), in obese (n = 28) and lean (n = 27) control groups. We used MRI (T1 relaxation times (T1) and liver stiffness), circulating biomarkers (CK18, PIIINP, and TIMP1), and algorithms (FIB-4 index, Forns score, FNI, and MACK3 score) to assess their potential in predicting liver fibrosis risk. We found that T1 (892 ± 81 ms vs. 818 ± 64 ms, p < 0.001), FNI (15 ± 12% vs. 9 ± 7%, p = 0.018), CK18 (166 ± 110 U/L vs. 113 ± 41 U/L, p = 0.019), and MACK3 (0.18 ± 0.15 vs. 0.05 ± 0.04, p < 0.001) were higher in the NAFLD-MetS group compared with the obese control group. Moreover, correlations were found between CK18 and FNI (r = 0.69, p < 0.001), CK18 and T1 (r = 0.41, p < 0.001), FNI and T1 (r = 0.33, p = 0.006), MACK3 and FNI (r = 0.79, p < 0.001), and MACK3 and T1 (r = 0.50, p < 0.001). We show that liver fibrosis markers are increased in obese individuals with NAFLD and MetS without clinical signs of liver fibrosis. More studies are needed to validate the use of these non-invasive biomarkers for early identification of liver fibrosis risk.
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Affiliation(s)
- Anders Askeland
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | | | - Mimoza Gjela
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Jens Brøndum Frøkjær
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Kurt Højlund
- Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark
| | - Maiken Mellergaard
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Aase Handberg
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
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Van Woerkom A, Harney DJ, Nagarajan SR, Hakeem-Sanni MF, Lin J, Hooke M, Pulpitel T, Cooney GJ, Larance M, Saunders DN, Brandon AE, Hoy AJ. Hepatic lipid droplet-associated proteome changes distinguish dietary-induced fatty liver from glucose tolerance in male mice. Am J Physiol Endocrinol Metab 2024; 326:E842-E855. [PMID: 38656127 PMCID: PMC11376491 DOI: 10.1152/ajpendo.00013.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 04/12/2024] [Accepted: 04/15/2024] [Indexed: 04/26/2024]
Abstract
Fatty liver is characterized by the expansion of lipid droplets (LDs) and is associated with the development of many metabolic diseases. We assessed the morphology of hepatic LDs and performed quantitative proteomics in lean, glucose-tolerant mice compared with high-fat diet (HFD) fed mice that displayed hepatic steatosis and glucose intolerance as well as high-starch diet (HStD) fed mice who exhibited similar levels of hepatic steatosis but remained glucose tolerant. Both HFD- and HStD-fed mice had more and larger LDs than Chow-fed animals. We observed striking differences in liver LD proteomes of HFD- and HStD-fed mice compared with Chow-fed mice, with fewer differences between HFD and HStD. Taking advantage of our diet strategy, we identified a fatty liver LD proteome consisting of proteins common in HFD- and HStD-fed mice, as well as a proteome associated with glucose tolerance that included proteins shared in Chow and HStD but not HFD-fed mice. Notably, glucose intolerance was associated with changes in the ratio of adipose triglyceride lipase to perilipin 5 in the LD proteome, suggesting dysregulation of neutral lipid homeostasis in glucose-intolerant fatty liver. We conclude that our novel dietary approach uncouples ectopic lipid burden from insulin resistance-associated changes in the hepatic lipid droplet proteome.NEW & NOTEWORTHY This study identified a fatty liver lipid droplet proteome and one associated with glucose tolerance. Notably, glucose intolerance was linked with changes in the ratio of adipose triglyceride lipase to perilipin 5 that is indicative of dysregulation of neutral lipid homeostasis.
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Affiliation(s)
- Andries Van Woerkom
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Dylan J Harney
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
- Faculty of Science, School of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Shilpa R Nagarajan
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Mariam F Hakeem-Sanni
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Jinfeng Lin
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Matthew Hooke
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Tamara Pulpitel
- Faculty of Science, School of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Gregory J Cooney
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Mark Larance
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Darren N Saunders
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Amanda E Brandon
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
- Faculty of Science, School of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Andrew J Hoy
- Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
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Cernea S. NAFLD Fibrosis Progression and Type 2 Diabetes: The Hepatic-Metabolic Interplay. Life (Basel) 2024; 14:272. [PMID: 38398781 PMCID: PMC10890557 DOI: 10.3390/life14020272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/13/2024] [Accepted: 02/14/2024] [Indexed: 02/25/2024] Open
Abstract
The bidirectional relationship between type 2 diabetes and (non-alcoholic fatty liver disease) NAFLD is indicated by the higher prevalence and worse disease course of one condition in the presence of the other, but also by apparent beneficial effects observed in one, when the other is improved. This is partly explained by their belonging to a multisystemic disease that includes components of the metabolic syndrome and shared pathogenetic mechanisms. Throughout the progression of NAFLD to more advanced stages, complex systemic and local metabolic derangements are involved. During fibrogenesis, a significant metabolic reprogramming occurs in the hepatic stellate cells, hepatocytes, and immune cells, engaging carbohydrate and lipid pathways to support the high-energy-requiring processes. The natural history of NAFLD evolves in a variable and dynamic manner, probably due to the interaction of a variable number of modifiable (diet, physical exercise, microbiota composition, etc.) and non-modifiable (genetics, age, ethnicity, etc.) risk factors that may intervene concomitantly, or subsequently/intermittently in time. This may influence the risk (and rate) of fibrosis progression/regression. The recognition and control of the factors that determine a rapid progression of fibrosis (or its regression) are critical, as the fibrosis stages are associated with the risk of liver-related and all-cause mortality.
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Affiliation(s)
- Simona Cernea
- Department M3, Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu Mureş, Romania; or
- Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, 540136 Târgu Mureş, Romania
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Engin A. The Definition and Prevalence of Obesity and Metabolic Syndrome: Correlative Clinical Evaluation Based on Phenotypes. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:1-25. [PMID: 39287847 DOI: 10.1007/978-3-031-63657-8_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Increase in the prevalence of obesity has become a major worldwide health problem in adults as well as among children and adolescents. In the last four decades, studies have revealed that the significant increase in the prevalence of obesity has become a pandemic. Obesity is the result of complex interactions between biological, genetic, environmental, and behavioral factors. Indeed, almost all of the children suffering from obesity in early childhood face with being overweight or obese in adolescence. Different phenotypes have different risk factors in the clinical evaluation of obesity. Individuals suffering from metabolically unhealthy obesity (MUO) are at an excess risk of developing cardiovascular diseases (CVDs), several cancer types, and metabolic syndrome (MetS), whereas the metabolically healthy obesity (MHO) phenotype has a high risk of all-cause mortality and cardiometabolic events but not MetS. While most obese individuals have the MUO phenotype, the frequency of the MHO phenotype is at most 10-20%. Over time, approximately three-quarters of obese individuals transform from MHO to MUO. Total adiposity and truncal subcutaneous fat accumulation during adolescence are positively and independently associated with atherosclerosis in adulthood. Obesity, in general, causes a large reduction in life expectancy. However, the mortality rate of morbid obesity is greater among younger than older adults. Insulin resistance (IR) develops with the central accumulation of body fat. MHO patients are insulin-sensitive like healthy normal-weight individuals and have lower visceral fat content and cardiovascular consequences than do the majority of MUO patients. MetS includes clustering of abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. The average incidence of MetS is 3%, with a 1.5-fold increase in the risk of death from all causes in these patients. If lifestyle modifications, dietary habits, and pharmacotherapy do not provide any benefit, then bariatric surgery is recommended to reduce weight and improve comorbid diseases. However, obesity treatment should be continuous in obese patients by monitoring the accompanying diseases and their consequences. In addition to sodium-glucose co-transporter-2 (SGLT2) inhibitors, the long-acting glucagon-like peptide-1 (GLP-1) receptor agonist reduces the mean body weight. However, caloric restriction provides more favorable improvement in body composition than does treatment with the GLP-1 receptor (GLP1R) agonist alone. Combination therapy with orlistat and phentermine are the US Food and Drug Administration (FDA)-approved anti-obesity drugs. Recombinant leptin and synthetic melanocortin-4-receptor agonists are used in rarely occurring, monogenic obesity, which is due to loss of function in the leptin-melanocortin pathway.
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Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
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Moreira RO, Valerio CM, Villela-Nogueira CA, Cercato C, Gerchman F, Lottenberg AMP, Godoy-Matos AF, Oliveira RDA, Brandão Mello CE, Álvares-da-Silva MR, Leite NC, Cotrim HP, Parisi ER, Silva GF, Miranda PAC, Halpern B, Pinto Oliveira C. Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso). ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023; 67:e230123. [PMID: 38048417 DOI: 10.20945/2359-4292-2023-0123] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/06/2023]
Abstract
INTRODUCTION Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. MATERIAL AND METHODS A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. RESULTS Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. CONCLUSION A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.
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Affiliation(s)
- Rodrigo Oliveira Moreira
- Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rio de Janeiro, RJ, Brasil,
- Faculdade de Medicina de Valença,Centro Universitário de Valença, Valença, RJ, Brasil
- Faculdade de Medicina, Centro Universitário Presidente Antônio Carlos, Juiz de Fora, MG, Brasil
| | - Cynthia Melissa Valerio
- Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rio de Janeiro, RJ, Brasil
| | - Cristiane Alves Villela-Nogueira
- Departamento de Clínica Médica, Faculdade de Medicina e Serviço de Hepatologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Cintia Cercato
- Grupo de Obesidade, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brasil
- Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Fernando Gerchman
- Programa de Pós-graduação em Ciências Médicas (Endocrinologia), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Divisão de Endocrinologia e Metabolismo, Hospital das Clínicas de Porto Alegre, Porto Alegre, RS, Brasil
| | - Ana Maria Pita Lottenberg
- Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
- Hospital Israelita Albert Einstein, São Paulo, SP, Brasil
| | | | | | - Carlos Eduardo Brandão Mello
- Departamento de Clínica Médica e da Disciplina de Gastroenterologia Clínica e Cirúrgica, Escola de Medicina e Cirurgia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Departamento de Clínica Médica e Serviço de Hepatologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Mãrio Reis Álvares-da-Silva
- Serviço de Gastroenterologia, Hospital das Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
| | - Nathalie Carvalho Leite
- Serviço de Clínica Médica e Serviço de Hepatologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | | | - Edison Roberto Parisi
- Disciplina de Gastroenterologia e Hepatologia, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - Giovanni Faria Silva
- Departamento de Clínica Médica da Faculdade de Medicina de Botucatu, Botucatu, SP, Brasil
| | | | - Bruno Halpern
- Grupo de Obesidade, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Claudia Pinto Oliveira
- Laboratório de Investigação Médica (LIM07), Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
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Xiao P, Cheng H, Zhao X, Hou D, Mi J. Longitudinal association of serum 25-hydroxyvitamin D levels with metabolically healthy body size transition in children and adolescents: A prospective cohort study with 2 years of follow-up. Diabetes Metab Syndr 2023; 17:102904. [PMID: 37951097 DOI: 10.1016/j.dsx.2023.102904] [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: 08/10/2023] [Revised: 10/28/2023] [Accepted: 11/01/2023] [Indexed: 11/13/2023]
Abstract
BACKGROUND AND AIMS Although the associations of vitamin D with obesity and metabolic abnormalities have been reported, the role of vitamin D in the transition of obesity phenotype remains unclear but is highly desired since it is crucial to identify potential methods for obesity management. Therefore, we aimed to investigate the relationship between vitamin D and the risk for metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO) in metabolically healthy children with 2 years of follow-up. METHODS Data were collected from a population-based cohort consisting of 6424 metabolically healthy children aged 6-16 years at baseline. Metabolic abnormalities including hypertension, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), hyperglycemia, and hyperuricemia were assessed both at baseline and follow-up. Baseline serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured as exposure. The obesity phenotype transition was evaluated by weight status with the combination of metabolic health status from baseline to follow-up. RESULTS During a 2-year follow-up, 889 (13.8 %) incident MUO cases occurred. For participants with obesity, each 10 nmol/L increment in 25(OH)D concentrations was associated with a 21 % (95%CI: 13 %∼43 %) and a 7 % (95%CI: 1 %∼14 %) decreased risk in high TG and hyperuricemia, respectively. A 51 % (95%CI: 22 %∼69 %) lower risk of MUO was observed in participants with sufficient vitamin D levels (≥50 nmol/L) compared to those with vitamin D deficiency (<30 nmol/L). Besides, among children who were MHO at baseline, those with sufficient vitamin D levels (≥50 nmol/L) were more likely to transition to metabolically healthy normal weight (MHNW) than vitamin D deficient individuals (<30 nmol/L). CONCLUSIONS Vitamin D may prevent the development of MUO and help increase the transition from MHO to MHNW. The findings highlight that vitamin D might be an effective nutrient for obesity management.
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Affiliation(s)
- Pei Xiao
- Center for Non-communicable Disease Management, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Hong Cheng
- Department of Epidemiology, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Xiaoyuan Zhao
- Department of Epidemiology, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Dongqing Hou
- Child Health Big Data Research Center, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Jie Mi
- Center for Non-communicable Disease Management, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
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Ding Y, Deng Q, Yang M, Niu H, Wang Z, Xia S. Clinical Classification of Obesity and Implications for Metabolic Dysfunction-Associated Fatty Liver Disease and Treatment. Diabetes Metab Syndr Obes 2023; 16:3303-3329. [PMID: 37905232 PMCID: PMC10613411 DOI: 10.2147/dmso.s431251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 10/10/2023] [Indexed: 11/02/2023] Open
Abstract
Obesity,and metabolic dysfunction-associated fatty liver disease (MAFLD) have reached epidemic proportions globally. Obesity and MAFLD frequently coexist and act synergistically to increase the risk of adverse clinical outcomes (both hepatic and extrahepatic). Type 2 diabetes mellitus (T2DM) is the most important risk factor for rapid progression of steatohepatitis and advanced fibrosis. Conversely, the later stages of MAFLD are associated with an increased risk of T2DM incident. According to the proposed criteria, MAFLD is diagnosed in patients with liver steatosis and in at least one in three: overweight or obese, T2DM, or signs of metabolic dysregulation if they are of normal weight. However, the clinical classification and correlation between obesity and MAFLD is more complex than expected. In addition, treatment for obesity and MAFLD are associated with a reduced risk of T2DM, suggesting that liver-based treatments could reduce the risk of developing T2DM. This review describes the clinical classification of obesity and MAFLD, discusses the clinical features of various types of obesity and MAFLD, emphasizes the role of visceral obesity and insulin resistance (IR) in the development of MAFLD,and summarizes the existing treatments for obesity and MAFLD that reduce the risk of developing T2DM.
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Affiliation(s)
- Yuping Ding
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Quanjun Deng
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Mei Yang
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Haiyan Niu
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Zuoyu Wang
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
| | - Shihai Xia
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China
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No JS, Buckholz A, Han C, Matthews S, Fortune B, Krisko T, Newberry C, Kumar S. Identifying High-Risk Patients With Nonalcoholic Fatty Liver Disease: An Opportunity for Intervention Within the Primary Care Setting. J Clin Gastroenterol 2023; 57:956-961. [PMID: 36731002 DOI: 10.1097/mcg.0000000000001784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 09/18/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND/OBJECTIVE Patients with metabolic syndrome (MetS) are likely to have nonalcoholic fatty liver disease (NAFLD), which can progress to advanced fibrosis. Early recognition of those at highest risk may ameliorate outcomes. Noninvasive liver fibrosis assessment through validated scoring systems such as the fibrosis-4 (FIB-4) index is helpful to identify these high-risk patients, with the process ideally beginning in the primary care setting. The primary objective of this study was to determine rates of disease recognition and initial management of patients with NAFLD and advanced fibrosis in a diverse primary care setting. The secondary objective was to define demographic and clinical predictors of NAFLD identification and management in this population. METHODS Medical charts from patients seen at three university-based primary care practices in New York City from January 2016 to December 2019 were reviewed. Inclusion criteria consisted of: age 18 years and above, persistent alanine transaminase (ALT) elevation (2 values ≥40 IU/mL ≥6 mo apart), and body mass index ≥30 kg/m 2 . Patients with viral hepatitis or alcohol misuse were excluded. Patients were defined as likely having NAFLD if they met 2 of the following criteria indicating MetS: systolic blood pressure >135 mm Hg or diastolic blood pressure >85 mm Hg or active treatment for hypertension; high-density lipoprotein <40 g/dL; triglycerides >150 mg/dL or active treatment for hyperlipidemia; or hemoglobin A1c ≥5.7% or active treatment for insulin resistance. The primary study endpoints were the frequency of providers' recognition of NAFLD and referral to specialist and/or for imaging based on visit diagnosis codes or chart documentation. The secondary endpoints were frequency of detecting those with NAFLD and advanced fibrosis utilizing previously defined FIB-4 index cutoffs as well as predictors of disease recognition and management. Analysis was completed using descriptive statistics and logistical regression modeling. RESULTS A total of 295 patients were identified as having persistently elevated ALT, a body mass index ≥30 kg/m 2 , and MetS consistent with likely NAFLD diagnosis. In patients meeting these criteria, ALT elevation was documented by primary care providers in 129 patients (43.7%), NAFLD was noted in chart documentation in 76 patients (25.8%), and a NAFLD ICD-10 diagnosis was assigned to 7 patients (2.4%). 50 patients (16.9%) were referred for ultrasound. Among 51 patients (17.2%) at high risk for advanced fibrosis based on FIB-4 >3.25, 23 patients (45.1%) had NAFLD recognized by their provider and 3 (5.9%) were referred to a specialist. On logistic regression, female gender, dyslipidemia, and private insurance were predictors of disease identification by the primary care physician. CONCLUSION ALT elevation and NAFLD are under recognized among patients with MetS in the primary care setting. Importantly, while 17.2% of patients with likely NAFLD in our cohort were high risk for advanced fibrosis, less than half of this group had a NAFLD diagnosis recognized by their primary care provider and only three were referred to a liver specialist. Further investigation of disease recognition and management algorithms in the primary care setting are necessary to enhance NAFLD detection, implement clinical care pathways, and reduce disease progression and complications.
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Affiliation(s)
| | - Adam Buckholz
- Weill Cornell Medicine, Department of Gastroenterology and Hepatology, New York, NY
| | | | - Steven Matthews
- Weill Cornell Medicine, Department of Gastroenterology and Hepatology, New York, NY
| | | | - Tibor Krisko
- Weill Cornell Medicine, Department of Gastroenterology and Hepatology, New York, NY
| | - Carolyn Newberry
- Weill Cornell Medicine, Department of Gastroenterology and Hepatology, New York, NY
| | - Sonal Kumar
- Weill Cornell Medicine, Department of Gastroenterology and Hepatology, New York, NY
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10
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Adams LA. Metabolic Health and Outcomes in Fatty Liver: Does a Name Change Matter? Clin Gastroenterol Hepatol 2023; 21:2481-2482. [PMID: 36462756 DOI: 10.1016/j.cgh.2022.11.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 11/17/2022] [Indexed: 12/02/2022]
Affiliation(s)
- Leon A Adams
- Medical School, The University of Western Australia, Perth, Western Australia, Australia; Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
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11
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Abstract
PURPOSE OF REVIEW This review aims to detail the current global research state of metabolically healthy obesogenesis with regard to metabolic factors, disease prevalence, comparisons to unhealthy obesity, and targeted interventions to reverse or delay progression from metabolically healthy to unhealthy obesity. RECENT FINDINGS As a long-term condition with increased risk of cardiovascular, metabolic, and all-cause mortality risks, obesity threatens public health on a national level. The recent discovery of metabolically healthy obesity (MHO), a transitional condition during which obese persons carry comparatively lower health risks, has added to confusion about the true effect of visceral fat and subsequent long-term health risks. In this context, the evaluation of fat loss interventions, such as bariatric surgery, lifestyle changes (diet/exercise), and hormonal therapies require re-evaluation in light of evidence that progression to high-risk stages of obesity relies on metabolic status and that strategies to protect the metabolism may be useful in the prevention of metabolically unhealthy obesity. Typical calorie-based exercise and diet interventions have failed to reduce the prevalence of unhealthy obesity. Holistic lifestyle, psychological, hormonal, and pharmacological interventions for MHO, on the other hand, may at least prevent progression to metabolically unhealthy obesity.
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Affiliation(s)
- Bryan J Mathis
- International Medical Center, University of Tsukuba Hospital, Tsukuba, Ibaraki, 305-8576, Japan.
| | - Kiyoji Tanaka
- Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yuji Hiramatsu
- International Medical Center, University of Tsukuba Hospital, Tsukuba, Ibaraki, 305-8576, Japan
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12
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Fouad Y, Zheng MH. Metabolically Healthy Obese MAFLD: Are They Truly Healthy? Clin Gastroenterol Hepatol 2023; 21:857-858. [PMID: 35643417 DOI: 10.1016/j.cgh.2022.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 05/09/2022] [Indexed: 02/07/2023]
Affiliation(s)
- Yasser Fouad
- Department of Endemic Medicine and Gastroenterology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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13
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Han SK, Baik SK, Kim MY. Non-alcoholic fatty liver disease: Definition and subtypes. Clin Mol Hepatol 2023; 29:S5-S16. [PMID: 36577427 PMCID: PMC10029964 DOI: 10.3350/cmh.2022.0424] [Citation(s) in RCA: 100] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/21/2022] [Accepted: 12/24/2022] [Indexed: 12/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, with a global prevalence of approximately 30%. However, the prevalence of NAFLD has been variously reported depending on the comorbidities. The rising prevalence of obesity in both the adult and pediatric populations is projected to consequently continue increasing NAFLD prevalence. It is a major cause of chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma (HCC). NAFLD has a variety of clinical phenotypes and heterogeneity due to the complexity of pathogenesis and clinical conditions of its occurrence, resulting in various clinical prognoses. In this article, we briefly described the basic definition of NAFLD and classified the subtypes based on current knowledge in this field.
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Affiliation(s)
- Seul Ki Han
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
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14
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Lv H, Jiang Y, Zhu G, Liu S, Wang D, Wang J, Zhao K, Liu J. Liver fibrosis is closely related to metabolic factors in metabolic associated fatty liver disease with hepatitis B virus infection. Sci Rep 2023; 13:1388. [PMID: 36697471 PMCID: PMC9877001 DOI: 10.1038/s41598-023-28351-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/17/2023] [Indexed: 01/26/2023] Open
Abstract
This case-control study aimed to identify the clinical characteristics and explore the risk factors for liver fibrosis in metabolic associated fatty liver disease (MAFLD) patients with hepatitis B virus (HBV) infection. The patients were grouped into MAFLD + HBV and MAFLD (without HBV infection). Propensity score matching (PSM) was used to match baseline features between the groups. We included 401 patients with biopsy-proven MAFLD, 179 of whom had HBV infection. A total of 83 pairs were successfully matched via PSM, and steatosis scores and ballooning in the MAFLD + HBV group were lower than those in the MAFLD group, while the inflammation scores and liver fibrosis stages were higher. After adjusted for confounding factors, HBV infection was associated with a higher risk of significant liver fibrosis in patients with MAFLD [odds ratio (OR): 3.140, P = 0.003]. Overall, 43.58% (78/179) of patients in the MAFLD + HBV group had significant liver fibrosis. Further multivariate regression analysis, hypertension (OR: 2.640; P = 0.031), type 2 diabetes (OR: 4.939; P = 0.035), and elevated glutamyl-transferase levels (OR: 3.980; P = 0.001) were risk factors for liver fibrosis in the MAFLD + HBV group. This suggests metabolic rather than viral factors are more closely associated with liver fibrosis in MAFLD patients with HBV infection.
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Affiliation(s)
- Haifeng Lv
- Department of Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China
| | - Yanming Jiang
- Department of Hepatology, The Affiliated Hospital of Hangzhou Normal University, No. 126 Wenzhou Road, Gongshu District, Hangzhou, 310015, Zhejiang, China
| | - Geli Zhu
- Department of Hepatology, The Affiliated Hospital of Hangzhou Normal University, No. 126 Wenzhou Road, Gongshu District, Hangzhou, 310015, Zhejiang, China
| | - Shiyi Liu
- Zhejiang Chinese Medical University, Hangzhou, 310035, Zhejiang, China
| | - Dian Wang
- School of Clinical Medicine, Hangzhou Normal University, Hangzhou, 310015, Zhejiang, China
| | - Jie Wang
- Department of Hepatology, The Affiliated Hospital of Hangzhou Normal University, No. 126 Wenzhou Road, Gongshu District, Hangzhou, 310015, Zhejiang, China
| | - Ke Zhao
- School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China
| | - Jing Liu
- Department of Hepatology, The Affiliated Hospital of Hangzhou Normal University, No. 126 Wenzhou Road, Gongshu District, Hangzhou, 310015, Zhejiang, China.
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15
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Jam SA, Moloudpour B, Najafi F, Darbandi M, Pasdar Y. Metabolic obesity phenotypes and chronic kidney disease: a cross-sectional study from the RaNCD cohort study. BMC Nephrol 2022; 23:233. [PMID: 35778682 PMCID: PMC9248132 DOI: 10.1186/s12882-022-02858-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 06/21/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Investigating the effect of metabolic disorders on chronic kidney disease (CKD) in the presence or the absence of obesity is of great importance. This study aimed to examine the independent and joint relationships of obesity and metabolic syndrome (MetS) with CKD. METHODS : The present study was performed on 9,762 participants from the baseline phase of the Ravansar non- communicable diseases (RaNCD) study. Thereafter, the CKD was estimated by glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. All the included participants were categorized into the following four phenotypes: metabolically healthy non-overweight/obesity (MHNO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically healthy overweight/obesity (MHO), and metabolically unhealthy overweight/obesity (MUO). Finally, Logistic regression analysis was used to estimate the odds ratio (ORs). RESULTS The mean age of the included participants was 47.33 ± 8.27 years old, %48.16 (4,701) of whom were men. As well, 1,058(10.84%) participants had CKD (eGFR less than 60 ml/min/1.73m2). The overweight/obesity was not significantly associated with odds of CKD. The odds of CKD in male subjects with MetS was 1.48 times higher than non-MetS ones (95% CI: 1.10, 2.01). After adjusting the confounders, the odds of CKD were 1.54 times (95% CI: 1.12, 2.11) higher in the MUNO and 2.22 times (95% CI: 1.44, 3.41) higher in the MUO compared to MHNO phenotype in male subjects. The odds of CKD in the MUNO and MUO was 1.31 times (95% CI: 1.10, 1.60) and 1.23 times (95% CI: 1.01, 1.54) higher than MHNO phenotype in female subjects, respectively. CONCLUSION The odds of CKD were higher in MUNO and MUO phenotypes. Therefore, lifestyle modification is recommended to control normal weight and healthy metabolism.
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Affiliation(s)
- Samira Arbabi Jam
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Behrooz Moloudpour
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farid Najafi
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Cardiovascular Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mitra Darbandi
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yahya Pasdar
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Cardiovascular Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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16
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Huh JH, Kim KJ, Kim SU, Cha BS, Lee BW. Obesity is an important determinant of severity in newly defined metabolic dysfunction-associated fatty liver disease. Hepatobiliary Pancreat Dis Int 2022; 21:241-247. [PMID: 35365418 DOI: 10.1016/j.hbpd.2022.03.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 03/04/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND The recently proposed definition of metabolic dysfunction-associated fatty liver disease (MAFLD) is based on the co-existence of hepatic steatosis with other metabolic disorders, including obesity and metabolic risk abnormalities such as hyperglycemia, high blood pressure and dyslipidemia. This study aimed to assess MAFLD severity according to the presence of metabolic abnormalities and obesity. METHODS Using transient elastography, hepatic steatosis and fibrosis severity were assessed by measuring the controlled attenuation parameter and liver stiffness measurement. A total of 1163 patients with MAFLD were categorized into the following four groups according to metabolic risk abnormalities and obesity presence: non-obese without metabolic risk abnormality group (Group 1; reference group); non-obese with metabolic risk abnormality group (Group 2); obese without metabolic risk abnormality group (Group 3); and obese with metabolic risk abnormality group (Group 4). A multiple logistic regression analysis was performed to determine severe hepatic steatosis and fibrosis risk in each group in both unadjusted and adjusted models. RESULTS In the adjusted model, the odds ratios (ORs) [95% confidence interval (CI)] for severe hepatic steatosis in Groups 2, 3, and 4 were 1.07 (0.61-1.88), 2.43 (1.44-4.08), and 4.07 (2.56-6.48), respectively (Ptrend < 0.001). For liver fibrosis, compared with Group 1, Group 2 showed no significant increases in OR, whereas Groups 3 and 4 (obese groups) showed significant increases (OR = 4.70, 95% CI: 1.24-17.82 and OR = 6.43, 95% CI: 1.88-22.02, respectively). CONCLUSIONS Obesity, rather than metabolic abnormality, is the principal determinant of severe hepatic steatosis and fibrosis in patients with MAFLD.
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Affiliation(s)
- Ji Hye Huh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang 14068, Korea
| | - Kwang Joon Kim
- Division of Geriatrics, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Seung Up Kim
- Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Bong-Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
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17
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Mun H, So ES. Prevalence of liver cirrhosis based on the metabolic health and weight criteria: Report from the Korea National Health and Nutrition Examination Survey (KNHANES) data analysis. Ann Hepatol 2022:100721. [PMID: 35504573 DOI: 10.1016/j.aohep.2022.100721] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/18/2022] [Accepted: 04/24/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Recent studies have proposed two distinctive types of obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO), based on various physiological factors. This study sought to explore the relationship between the metabolic obesity types and the incidence of liver cirrhosis (LC) in a large nationally-representative population. METHODS Data on 27,629 adults with MHO or MUHO, were analyzed from the Korea National Health and Nutrition Examination Survey (KNHANES) obtained from 2015 through 2019. Four categories of metabolic health and weight (MHW) were generated for analysis: (1) MHO, (2) MUHO, (3) Metabolically unhealthy normal weight (MUHNW), and (4) Metabolically healthy normal weight (MHNW). Statistical analyzes were performed with univariate and multivariate logistic regression. RESULTS The prevalence of LC did not show statistically significant differences among the MHW categories: 0.5% in MHO, 0.4% in MUHO, 0.2% in MHNW, and 0.3% in MUHNW. The unadjusted analysis showed a significant association between self-reported LC and MUHO, but this association was not evident in the adjusted analysis. In the adjusted analysis of the prevalence of laboratory LC, a significant association emerged in the MUHO group, followed in descending order of magnitude by the MHO and MUHNW groups. A favorable fasting blood glucose level was the only factor associated with increased prevalence of reported LC in MUHO. CONCLUSIONS The study demonstrated a difference in the prevalence of LC between MHO and MUHO. Our study concludes that the MHO phenotype is a transient status with regard to metabolic abnormalities, and caution is necessary when evaluating MHO.
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Affiliation(s)
- Hyukjin Mun
- School of Nursing, Hanyang University, Seoul, Republic of Korea
| | - Eun Sun So
- College of Nursing, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Republic of Korea.
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18
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Hamzeh B, Pasdar Y, Moradi S, Darbandi M, Rahmani N, Shakiba E, Najafi F. Metabolically healthy versus unhealthy obese phenotypes in relation to hypertension incidence; a prospective cohort study. BMC Cardiovasc Disord 2022; 22:106. [PMID: 35287586 PMCID: PMC8922873 DOI: 10.1186/s12872-022-02553-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 03/09/2022] [Indexed: 11/10/2022] Open
Abstract
Background Although obesity increases the risk of hypertension, the effect of obesity based on metabolic status on the incidence of hypertension is not known. This study aimed to determine the association between obesity phenotypes including metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) and the risk of hypertension incidence. Methods We conducted a prospective cohort study on 6747 adults aged 35–65 from Ravansar non-communicable diseases (RaNCD) study. Obesity was defined as body mass index above 30 kg/m2 and metabolically unhealthy was considered at least two metabolic disorders based on the International Diabetes Federation criteria. Obesity phenotypes were categorized into four groups including MUO, MHO, metabolically unhealthy non obesity (MUNO), and metabolically healthy non obesity (MHNO). Cox proportional hazards regression models were applied to analyze associations with hypertension incidence. Results The MHO (HR: 1.37; 95% CI: 1.03–1.86) and MUO phenotypes (HR: 2.44; 95% CI: 1.81–3.29) were associated with higher hypertension risk compared to MHNO. In addition, MUNO phenotype was significantly associated with risk of hypertension incidence (HR: 1.65; 95% CI: 1.29–2.14). Conclusions Both metabolically healthy and unhealthy obesity increased the risk of hypertension incidence. However, the increase in metabolically unhealthy phenotype was higher.
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Affiliation(s)
- Behrooz Hamzeh
- Health Education and Promotion, Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yahya Pasdar
- Department of Nutrition Sciences, Research Center for Environmental Determinants of Health (RCEDH), Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shima Moradi
- Department of Nutrition Sciences, Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Mitra Darbandi
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Negin Rahmani
- Julius Maximillian University of Wuerzburg, Wuerzburg, Germany
| | - Ebrahim Shakiba
- Social Development and Health Promotion Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farid Najafi
- Epidemiology, School of Public Health, Communing Developmental and Health Promotion Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
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19
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Cho IY, Chang Y, Sung E, Kang JH, Shin H, Wild SH, Byrne CD, Ryu S. Weight Change and the Development of Nonalcoholic Fatty Liver Disease in Metabolically Healthy Overweight Individuals. Clin Gastroenterol Hepatol 2022; 20:e583-e599. [PMID: 33930552 DOI: 10.1016/j.cgh.2021.04.037] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/09/2021] [Accepted: 04/19/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The study sought to investigate the effect of weight change on hepatic steatosis (HS) incidence with or without liver fibrosis in metabolically healthy overweight or obese individuals. METHODS A cohort of 14,779 metabolically healthy men and women who were overweight or obese (body mass index ≥23 kg/m2) and free from HS and an intermediate or high probability of fibrosis at baseline were followed for a median of 5.2 years. Metabolic health was defined as freedom from the components of metabolic syndrome and a homeostatic model assessment of insulin resistance <2.5. Weight changes were calculated as differences from baseline at the next subsequent visit. The outcome was HS incidence, with or without liver fibrosis, as assessed by liver ultrasound and 2 noninvasive fibrosis scores. RESULTS During 76,794.6 person-years of follow-up, 3539 cases of HS incidence were identified. The multivariable adjusted hazard ratios (95% confidence intervals) for HS incidence by weight change group, <-5.0%, -5.0%-1.0%, 1.0%-5.0%, and >5.0%, relative to the no weight change group (-0.9% to 0.9%) were 0.52 (0.44-0.60), 0.83 (0.75-0.92), 1.21 (1.10-1.33), and 1.51 (1.36-1.69), respectively. Clinically relevant weight loss of >5% was also associated with a lowered risk of HS with intermediate or high probability of advanced fibrosis. In mediation analyses, associations remained significant, although adjustment for metabolic risk factors was attenuating. DISCUSSION Clinically relevant weight loss was associated with a reduced risk of developing nonalcoholic fatty liver disease with or without intermediate or high probability of advanced fibrosis in metabolically healthy overweight or obese individuals.
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Affiliation(s)
- In Young Cho
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea
| | - Eunju Sung
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Jae-Heon Kang
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hocheol Shin
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sarah H Wild
- Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.
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20
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Kouvari M, Chrysohoou C, Skoumas J, Pitsavos C, Panagiotakos DB, Mantzoros CS. The presence of NAFLD influences the transition of metabolically healthy to metabolically unhealthy obesity and the ten-year cardiovascular disease risk: A population-based cohort study. Metabolism 2022; 128:154893. [PMID: 34600906 DOI: 10.1016/j.metabol.2021.154893] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 09/24/2021] [Accepted: 09/26/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND/OBJECTIVES We evaluated the role of the presence of non-alcoholic fatty liver disease (NAFLD) at baseline in the transition from metabolically healthy to metabolically unhealthy obesity (MHO to MUO) ten years later. METHODS A prospective cohort study (ATTICA study, Greece) was performed between 2002 and 2012 studying a sample from the greater metropolitan Athens area. In total, 1514 (49·8%) men and 1528 (50.2%) women (aged >18 years old) free-of-CVD were included. Healthy metabolic status was defined as absence of all NCEP ATP III (2005) metabolic syndrome components. NAFLD was defined according to validated liver steatosis indices. Follow-up CVD assessment (2011-2012) was achieved in n = 2020 participants (n = 317 cases). RESULTS NAFLD prevalence among MHO participants ranged from 29% to 39% according to the specific NAFLD score used. MHO participants who developed metabolically unhealthy status had about two times higher odds to have NAFLD at baseline compared with their metabolically healthy normal weight counterparts whereas stable MHO was not associated significantly with NAFLD. Moreover, MHO status accompanied by NAFLD was associated with increased CVD risk (Hazard Ratio = 2.90 95% Confidence Interval (1.35, 5.40)) in comparison to their non-NAFLD MHO counterparts. Further analysis revealed that in the obese, NAFLD indices and not simply visceral adiposity increased significantly the ability of metabolic status (using standard definition) to predict long-term CVD incidence. CONCLUSIONS Considering NAFLD, even when assessed using validated indices only, in the clinical assessment of apparently healthy obese individuals predicts who is to develop MUO and contributes independently and more accurately to defining future cardiometabolic risk.
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Affiliation(s)
- Matina Kouvari
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; Faculty of Health, University of Canberra, Australia
| | - Christina Chrysohoou
- First Cardiology Clinic, School of Medicine, University of Athens, Greece, Greece
| | - John Skoumas
- First Cardiology Clinic, School of Medicine, University of Athens, Greece, Greece
| | - Christos Pitsavos
- First Cardiology Clinic, School of Medicine, University of Athens, Greece, Greece
| | - Demosthenes B Panagiotakos
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; Faculty of Health, University of Canberra, Australia.
| | - Christos S Mantzoros
- Department of Medicine, Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Wu Q, Xia MF, Gao X. Metabolically healthy obesity: Is it really healthy for type 2 diabetes mellitus? World J Diabetes 2022; 13:70-84. [PMID: 35211245 PMCID: PMC8855137 DOI: 10.4239/wjd.v13.i2.70] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/27/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
Metabolically healthy obese (MHO) individuals are reported to have a lower risk of developing cardiovascular diseases in comparison with individuals with metabolic syndrome. However, the association between MHO and type 2 diabetes (T2DM) is still controversial. Some studies indicated that MHO is a favorable phenotype for T2DM, but more studies showed that MHO individuals have an increased risk of developing T2DM compared with metabolically healthy normal-weight individuals, especially among those who would acquire metabolically unhealthy obesity. This has been supported by finding insulin resistance and low-grade inflammatory responses in MHO individuals with a tendency for impaired beta-cell dysfunction. Studies also showed that liver fat accumulation increased the risk of incidence of T2DM in MHO. Here, we reviewed current literature on the relationship between MHO and T2DM, discussed the determinants for the development of diabetes in MHO, and summarized the measures for the prevention of T2DM in MHO.
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Affiliation(s)
- Qi Wu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai 200032, China
| | - Ming-Feng Xia
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai 200032, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai 200032, China
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Tutunchi H, Naeini F, Ebrahimi-Mameghani M, Najafipour F, Mobasseri M, Ostadrahimi A. Metabolically healthy and unhealthy obesity and the progression of liver fibrosis: A cross-sectional study. Clin Res Hepatol Gastroenterol 2021; 45:101754. [PMID: 34303827 DOI: 10.1016/j.clinre.2021.101754] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND The development of liver fibrosis is the most important predictor of adverse outcomes in patients with non-alcoholic fatty liver disease (NAFLD). Little is known regarding the risk factors for the progression of NAFLD to liver fibrosis. The present cross-sectional study aimed to examine the association of liver fibrosis with metabolically healthy and unhealthy obesity among patients with NAFLD. METHODS The severity of fatty liver was examined using ultrasonography. We used the NAFLD fibrosis score to determine the severity of liver fibrosis. Anthropometric indices, physical activity, and body composition were assessed. Blood samples were collected to determine serum metabolic parameters. Participants without any component of metabolic syndrome and homeostasis model assessment of insulin resistance (HOMA-IR) <2.5 were considered as metabolically healthy. To examine the association of liver fibrosis with metabolically healthy and unhealthy obesity, multivariable-adjusted odds ratios (ORs) were applied. RESULTS The current study included a total of 246 patients with NAFLD and low probability of fibrosis. 46.3% of subjects were metabolically healthy and 53.7% were metabolically unhealthy. Among metabolically healthy subjects, multivariable-adjusted ORs (CIs) for worsening of NAFLD fibrosis score comparing body mass indexes (BMIs) 23.0-24.9, 25-29.9, and ≥30 with a BMI=18.5-22.9 kg/m2 were 1.28 (1.09-1.56), 1.99 (1.49-2.63), and 3.96 (2.89-4.71), respectively. The corresponding ORs (95% CIs) among metabolically unhealthy subjects were 1.39 (1.32-1.64), 2.27 (1.98-2.49), and 4.11 (3.12-4.93), respectively. Moreover, in both healthy and unhealthy individuals, higher percentages of body fat and waist circumference were significantly associated with worsening of NAFLD fibrosis score. CONCLUSION Excess body fat contributes to the progression of liver fibrosis regardless of metabolic health status.
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Affiliation(s)
- Helda Tutunchi
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran university of medical science, Tehran, Iran
| | - Mehrangiz Ebrahimi-Mameghani
- Social Determinant of Health Research Center, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzad Najafipour
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Mobasseri
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Ostadrahimi
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Serbis A, Giapros V, Paschou SA, Siomou E. Children with metabolically healthy obesity have a worse metabolic profile compared to normal-weight peers: a cross-sectional study. Endocrine 2021; 73:580-587. [PMID: 34023981 DOI: 10.1007/s12020-021-02762-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/10/2021] [Indexed: 12/25/2022]
Abstract
PURPOSE A phenotype of metabolically healthy obesity (MHO) has been described in youth with obesity, but data are still scarce in this age group. The aim of the current study was to describe and compare clinical and laboratory parameters related to obesity among three different groups of youth, namely youth with normal weight (NW), with MHO, and with metabolically unhealthy obesity (MUO). METHODS One hundred and three youngsters with obesity were divided according to 2018 consensus-based criteria into those with MHO [n = 49, age (±SD): 10.9 ± 2.9 years] and those with MUO [n = 54, 11.5 ± 2.7 years] and were compared to age-, sex- and Tanner-matched NW [n = 69, 11.3 ± 2.9 years]. Several obesity-related parameters were investigated for all three groups of children. Comparisons were made by analysis of variance (ANOVA) followed by the Fisher's PLSD test. RESULTS Youth with MHO had lower systolic (p < 0.001) and diastolic (p < 0.01) blood pressure z-score and triglycerides (p < 0.01), but higher HDL-C (p < 0.001), total cholesterol (p < 0.05), and apo-A1 (p < 0.05) compared to those with MUO. Compared to controls, both children with MHO and MUO showed higher fasting insulin (p < 0.05), HOMA-IR (p < 0.05), and QUICKI (p < 0.001). Similarly, both groups had higher hsCRP, fibrinogen, uric acid, and leptin compared to controls (for all, p < 0.001), while their adiponectin was lower (p < 0.05). Visfatin was higher in children with MUO compared to controls (p < 0.01), and it showed a trend to be lower in children with MHO compared to those with MUO (p = 0.1). CONCLUSION This study provides evidence that children identified as having MHO by the consensus-based criteria had better metabolic profiles than youth with MUO, but worse than NW. Further research is needed in pediatric populations both regarding MHO criteria and the nature of the MHO phenotype per se.
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Affiliation(s)
- Anastasios Serbis
- Child Health Department, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece.
| | - Vasilieios Giapros
- Child Health Department, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Stavroula A Paschou
- Division of Endocrinology, Diabetes and Metabolism, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Ekaterini Siomou
- Child Health Department, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
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Long working hours are associated with a higher risk of non-alcoholic fatty liver disease: A large population-based Korean cohort study. PLoS One 2021; 16:e0255118. [PMID: 34297733 PMCID: PMC8301658 DOI: 10.1371/journal.pone.0255118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 07/09/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease, may progress to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. But only a few cross-sectional studies have reported an association of NAFLD with working hours. This cohort study further examined the association between working hours and the development of NAFLD. METHODS We included 79,048 Korean adults without NAFLD at baseline who underwent a comprehensive health examination and categorized weekly working hours into 35-40, 41-52, 53-60, and >60 hours. NAFLD was defined as the presence of fatty liver, in the absence of excessive alcohol use, as observed by ultrasound. RESULTS During a median follow-up of 6.6 years, 15,095 participants developed new-onset NAFLD (incidence rate, 5.55 per 100 person-years). After adjustment for confounders, the hazard ratios (95% confidence interval) for the development of NAFLD in 41-52, 53-60, and >60 working hours compared with that in 35-40 working hours were 1.07 (1.02-1.13), 1.06 (1.00-1.13), and 1.13 (1.05-1.23), respectively. Furthermore, the association remained significant after confounders were treated as time-varying covariates. CONCLUSION In this large-scale cohort, long working hours, especially >60 working hours a week, were independently associated with incident NAFLD. Our findings indicate that long working hours are a risk factor for NAFLD.
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25
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Jung DH, Lee YJ, Park B. Joint Effect of Hepatic Steatosis and Alanine Aminotransferase Within the Normal Range on Incident Ischemic Heart Disease: A Prospective Study in Koreans. Clin Interv Aging 2021; 16:513-523. [PMID: 33790546 PMCID: PMC7997416 DOI: 10.2147/cia.s301741] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 03/08/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose Hepatic steatosis has been associated with some cardiovascular risks. Increased alanine aminotransferase (ALT) was suggested to be linked to endothelial dysfunction. We prospectively investigated the joint effect of hepatic steatosis and elevated ALT within the normal range on incident ischemic heart disease (IHD) risk as an extrahepatic complication. Patients and Methods We assessed 16,541 participants without diabetes using data from a health risk assessment study (HERAS) and Korean Health Insurance Review and Assessment (HIRA) data. We defined elevated ALT within the normal range as 30-40 IU/L in men and 23-40 IU/L in women, according to previous Korean epidemiological data. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional hazards regression models over a 50-month period after the baseline survey. Results During the follow-up period, 368 (2.2%) participants developed IHD. Compared to the group with no hepatic steatosis and controlled ALT, the HRs for IHD were 1.68 (95% CI, 1.16-2.42) in the group with hepatic steatosis and elevated ALT after adjusting for confounding variables. Conclusion Hepatic steatosis and elevated ALT levels within the normal range may jointly affect the development of IHD among nondiabetic adults. This indicates that lifestyle advice and vascular health management should be recommended among individuals with hepatic steatosis and elevated ALT, even if it falls within the normal range.
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Affiliation(s)
- Dong-Hyuk Jung
- Department of Family Medicine, Yongin Severance Hospital, Yongin-si, Gyeonggi-do, 16995, Republic of Korea.,Department of Health Promotion Centre, Yongin Severance Hospital, Yongin-si, Gyeonggi-do, 16995, Republic of Korea
| | - Yong Jae Lee
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.,Department of Family Medicine, Gangnam Severance Hospital, Seoul, 06273, Republic of Korea
| | - Byoungjin Park
- Department of Family Medicine, Yongin Severance Hospital, Yongin-si, Gyeonggi-do, 16995, Republic of Korea
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Abstract
UNLABELLED Abstract. AIMS The longitudinal relationship between depression and the risk of non-alcoholic fatty liver disease is uncertain. We examined: (a) the association between depressive symptoms and incident hepatic steatosis (HS), both with and without liver fibrosis; and (b) the influence of obesity on this association. METHODS A cohort of 142 005 Korean adults with neither HS nor excessive alcohol consumption at baseline were followed for up to 8.9 years. The validated Center for Epidemiologic Studies-Depression score (CES-D) was assessed at baseline, and subjects were categorised as non-depressed (a CES-D < 8, reference) or depression (CES-D ⩾ 16). HS was diagnosed by ultrasonography. Liver fibrosis was assessed by the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS During a median follow-up of 4.0 years, 27 810 people with incident HS and 134 with incident HS plus high FIB-4 were identified. Compared with the non-depressed category, the aHR (95% CIs) for incident HS was 1.24 (1.15-1.34) for CES-D ⩾ 16 among obese individuals, and 1.00 (0.95-1.05) for CES-D ⩾ 16 among non-obese individuals (p for interaction with obesity <0.001). The aHR (95% CIs) for developing HS plus high FIB-4 was 3.41 (1.33-8.74) for CES-D ⩾ 16 among obese individuals, and 1.22 (0.60-2.47) for CES-D ⩾ 16 among non-obese individuals (p for interaction = 0.201). CONCLUSIONS Depression was associated with an increased risk of incident HS and HS plus high probability of advanced fibrosis, especially among obese individuals.
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Lee YS, Hwang LC, Hsu HY, Tsou MT. The Association Between Different Obesity Phenotypes and Liver Fibrosis Scores in Elderly Individuals with Fatty Liver in Taiwan. Diabetes Metab Syndr Obes 2021; 14:1473-1483. [PMID: 33833538 PMCID: PMC8019606 DOI: 10.2147/dmso.s302207] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 03/11/2021] [Indexed: 04/14/2023] Open
Abstract
PURPOSE To examine the association between different phenotypes of obesity or metabolic syndromes and liver fibrosis score in a Taiwanese elderly population with fatty liver. PATIENTS AND METHODS This cross-sectional study included 1817 participants aged ≥65 years with fatty liver diagnosed by sonography. We used ethnicity-specific criteria for body mass index and metabolic syndrome, and to define obesity phenotypes as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Correlated fibrosis severity was calculated using the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 (FIB-4). Fibrosis severity was divided into two categories according to NFS (no-to-mild fibrosis and advanced fibrosis, defined as NFS ≤ 0.676 and >0.676, respectively) and FIB-4 score (no-to-mild fibrosis and advanced fibrosis, defined as FIB-4 score ≤2.67 and >2.67, respectively). RESULTS Compared with that in the MHNO group, the associated risk (odds ratio [OR], 95% confidence interval [CI]) of advanced fibrosis by NFS was 2.43 (1.50-3.93), 2.35 (1.25-4.41), and 6.11 (3.90-9.59), whereas that of advanced fibrosis by FIB-4 score was 1.34 (0.83-2.18), 2.37 (1.36-4.13), and 1.38 (0.82-2.31) in the MUNO, MHO, and MUO groups, respectively. CONCLUSION Both metabolic syndrome and obesity were positively associated with more advanced fibrosis according to NFS. The detrimental effect of obesity appears to be more than metabolic abnormalities per se in the elderly with more advanced fibrosis severity according to the FIB-4 score.
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Affiliation(s)
- Yu-Shan Lee
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Lee-Ching Hwang
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
| | - Hsin-Yin Hsu
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Meng-Ting Tsou
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan
- Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
- Correspondence: Meng-Ting Tsou Department of Family Medicine, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei City, 10449, Taiwan, R.O.C.Tel +886 2 2543 3535 (Ext. 2131 or 2132)Fax +886 2 2543 3642 Email
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Yamamura S, Eslam M, Kawaguchi T, Tsutsumi T, Nakano D, Yoshinaga S, Takahashi H, Anzai K, George J, Torimura T. MAFLD identifies patients with significant hepatic fibrosis better than NAFLD. Liver Int 2020; 40:3018-3030. [PMID: 32997882 DOI: 10.1111/liv.14675] [Citation(s) in RCA: 311] [Impact Index Per Article: 62.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 09/15/2020] [Accepted: 09/18/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Diagnostic criteria for metabolic associated fatty liver disease (MAFLD) have been proposed, but not validated. We aimed to compare the diagnostic accuracy of the MAFLD definition vs the existing NAFLD criteria to identify patients with significant fibrosis and to characterize the impact of mild alcohol intake. METHODS We enrolled 765 Japanese patients with fatty liver (median age 54 years). MAFLD and NAFLD were diagnosed in 79.6% and 70.7% of patients respectively. Significant fibrosis was defined by FIB-4 index ≥1.3 and liver stiffness ≥6.6 kPa using shear wave elastography. Mild alcohol intake was defined as <20 g/day. Factors associated with significant fibrosis were analysed by logistic regression and decision-tree analyses. RESULTS Liver stiffness was higher in MAFLD compared to NAFLD (7.7 vs 6.8 kPa, P = .0010). In logistic regression, MAFLD (OR 4.401; 95% CI 2.144-10.629; P < .0001), alcohol intake (OR 1.761; 95% CI 1.081-2.853; P = .0234), and NAFLD (OR 1.721; 95%CI 1.009-2.951; P = .0463) were independently associated with significant fibrosis. By decision-tree analysis, MAFLD, but not NAFLD or alcohol consumption was the initial classifier for significant fibrosis. The sensitivity for detecting significant fibrosis was higher for MAFLD than NAFLD (93.9% vs 73.0%). In patients with MAFLD, even mild alcohol intake was associated with an increase in the prevalence of significant fibrosis (25.0% vs 15.5%; P = .0181). CONCLUSIONS The MAFLD definition better identifies a group with fatty liver and significant fibrosis evaluated by non-invasive tests. Moreover, in patients with MAFLD, even mild alcohol consumption is associated with worsening of hepatic fibrosis measures.
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Affiliation(s)
- Sakura Yamamura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Shinobu Yoshinaga
- Medical Examination Section, Medical Examination Part Facilities, Public Utility Foundation Saga Prefectural Health Promotion Foundation, Saga, Japan
| | - Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
| | - Keizo Anzai
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Frey S, Patouraux S, Debs T, Gugenheim J, Anty R, Iannelli A. Prevalence of NASH/NAFLD in people with obesity who are currently classified as metabolically healthy. Surg Obes Relat Dis 2020; 16:2050-2057. [PMID: 32788075 DOI: 10.1016/j.soard.2020.07.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 06/28/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND While metabolic health in obesity may confer a protective status, recent studies indicate that nonalcoholic fatty liver disease (NAFLD) or even nonalcoholic steatohepatitis (NASH) may exist in this category of individuals. Although cardiovascular and diabetic risks have been well described, the risk of NAFLD and NASH among this population requires further investigation. OBJECTIVE Our goal was to compare the prevalence of steatosis, NAFLD, and NASH between individuals with metabolically healthy obesity (MHO) and individuals with metabolically abnormal obesity (MAO) and to identify preoperative risk factors for these conditions in a prospective cohort with morbid obesity scheduled for bariatric surgery. SETTINGS Tertiary referral university hospital in France. METHODS The prospective cohort included 837 bariatric patients who also had an intraoperative liver biopsy between 2002 and 2015. Obese individuals fulfilling none of the criteria in the strict definition of metabolic syndrome were considered metabolically healthy. Preoperative blood samples and liver pathology examinations were reviewed. Steatosis, NAFLD, and NASH were carefully identified allowing comparison of prevalence and risk factors between the 2 cohorts. RESULTS In total, 149 patients (17.8%) had MHO and the remaining 688 (82.2%) had MAO. The cohort with MHO was significantly younger, had a significantly lower glycosylated hemoglobin, a lower homeostasis model assessment of insulin resistance, and increased C-reactive protein. In individuals with MHO, 44 patients (29.5%) had at least moderate steatosis (>33% macrovesicular steatosis) and 5.4% had NASH. Using logistic regression, waist circumference was positively associated with NASH, whereas body mass index and alanine aminotransferase were significantly associated with severe steatosis (>66%). CONCLUSION Our study indicates that obese individuals without metabolic syndrome may develop subclinical liver involvement. Therefore, the occurrence of NAFLD and NASH in this population needs further investigation.
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Affiliation(s)
- Sébastien Frey
- Université Côte d'Azur, Nice, France; Department of Digestive surgery and liver transplantation, Archet 2 Hospital, University Hospital of Nice, Nice, France
| | - Stéphanie Patouraux
- Université Côte d'Azur, Nice, France; Department of Pathology, Pasteur Hospital, University Hospital of Nice, Nice, France
| | - Tarek Debs
- Department of Digestive surgery and liver transplantation, Archet 2 Hospital, University Hospital of Nice, Nice, France
| | - Jean Gugenheim
- Université Côte d'Azur, Nice, France; Department of Digestive surgery and liver transplantation, Archet 2 Hospital, University Hospital of Nice, Nice, France; Inserm, U1065, Team 8 "Hepatic complications of obesity and alcohol," Nice, France
| | - Rodolphe Anty
- Université Côte d'Azur, Nice, France; Inserm, U1065, Team 8 "Hepatic complications of obesity and alcohol," Nice, France; Department of Hepathology, Archet 2 Hospital, University Hospital of Nice, Nice, France
| | - Antonio Iannelli
- Université Côte d'Azur, Nice, France; Department of Digestive surgery and liver transplantation, Archet 2 Hospital, University Hospital of Nice, Nice, France; Department of Hepathology, Archet 2 Hospital, University Hospital of Nice, Nice, France.
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Lonardo A, Mantovani A, Lugari S, Targher G. Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity. Ann Hepatol 2020; 19:359-366. [PMID: 32349939 DOI: 10.1016/j.aohep.2020.03.001] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 03/02/2020] [Accepted: 03/02/2020] [Indexed: 02/06/2023]
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise in many countries, paralleling the epidemic of obesity worldwide. In the last years, the concept of metabolically healthy obesity [MHO, generally defined as obesity without metabolic syndrome (MetS)] has raised considerable scientific interest. MHO is a complex phenotype with risks intermediate between metabolically healthy individuals with normal-weight (NWMH) and patients who are obese and metabolically unhealthy (MUO, i.e. obesity with MetS). In this review we aimed to examine the association and pathophysiological link of NAFLD with MHO and MUO. Compared to NWMH individuals, patients with obesity, regardless of the presence of MetS features, are at higher risk of all-cause mortality and cardiovascular events. Moreover, MHO patients have a greater risk of NAFLD development and progression compared to NWMH individuals. However, this risk is generally lower than that of MUO patients, suggesting a stronger adverse effect of coexisting MetS disorders than obesity per se on the severity of NAFLD. Nevertheless, since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time) and NAFLD itself may predict the transition from MHO to MUO, we believe that any effort should be made to identify NAFLD in all obese individuals, although they appear to be "metabolically healthy". Future research is needed to better understand the role of NAFLD and other pathogenic factors potentially involved in the transition from MHO to MUO and to elucidate how this transition may affect the presence and severity of NAFLD.
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Affiliation(s)
- Amedeo Lonardo
- Operating Unit of Metabolic Syndrome, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy.
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, University of Verona, Verona, Italy
| | | | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, University of Verona, Verona, Italy
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Narankiewicz D, Ruiz-Nava J, Buonaiuto V, Ruiz-Moreno MI, López-Carmona MD, Pérez-Belmonte LM, Gómez-Huelgas R, Bernal-López MR. Utility of Liver Function Tests and Fatty Liver Index to Categorize Metabolic Phenotypes in a Mediterranean Population. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17103518. [PMID: 32443453 PMCID: PMC7277926 DOI: 10.3390/ijerph17103518] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 05/11/2020] [Accepted: 05/14/2020] [Indexed: 12/21/2022]
Abstract
The aim of this study was to analyze the utility of liver function tests (LFT) and fatty liver index (FLI), a surrogate marker of non-alcoholic fatty liver disease, in the categorization of metabolic phenotypes in a Mediterranean population. A cross-sectional study was performed on a random representative sample of 2233 adults assigned to a health center in Málaga, Spain. The metabolic phenotypes were determined based on body mass index (BMI) categorization and the presence or absence of two or more cardiometabolic abnormalities (high blood pressure, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, pre-diabetes) or type 2 diabetes. No difference was observed between metabolically healthy and metabolically abnormal phenotypes on LFT. The mean FLI of the population was 41.1 ± 28.6. FLI was significantly higher (p < 0.001) in the metabolically abnormal phenotypes in all BMI categories. The proportion of individuals with pathological FLI (≥60) was significantly higher in the metabolically abnormal overweight and obese phenotypes (p < 0.001). On a multivariate model adjusted for sex, age, and waist circumference, a significant correlation was found between pathological FLI and metabolically abnormal phenotypes in the overweight and obese BMI categories. Area under the curve (AUC) of FLI as a biomarker was 0.76, 0.74, and 0.72 for the metabolically abnormal normal-weight, overweight, and obese groups, respectively. Liver biochemistry is poorly correlated with metabolic phenotypes. Conversely, a good correlation between FLI, as a marker of non-alcoholic fatty liver disease (NAFLD), and metabolically abnormal phenotypes in all BMI ranges was found. Our study suggests that FLI may be a useful marker for characterizing metabolically abnormal phenotypes in individuals who are overweight or obese.
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Affiliation(s)
- Dariusz Narankiewicz
- Preventive Medicine Department, Virgen de la Victoria University Hospital, 29010 Malaga, Spain;
| | - Josefina Ruiz-Nava
- Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (J.R.-N.); (V.B.); (M.I.R.-M.); (M.D.L.-C.); (L.M.P.-B.)
| | - Veronica Buonaiuto
- Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (J.R.-N.); (V.B.); (M.I.R.-M.); (M.D.L.-C.); (L.M.P.-B.)
| | - María Isabel Ruiz-Moreno
- Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (J.R.-N.); (V.B.); (M.I.R.-M.); (M.D.L.-C.); (L.M.P.-B.)
| | - María Dolores López-Carmona
- Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (J.R.-N.); (V.B.); (M.I.R.-M.); (M.D.L.-C.); (L.M.P.-B.)
| | - Luis Miguel Pérez-Belmonte
- Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (J.R.-N.); (V.B.); (M.I.R.-M.); (M.D.L.-C.); (L.M.P.-B.)
| | - Ricardo Gómez-Huelgas
- Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (J.R.-N.); (V.B.); (M.I.R.-M.); (M.D.L.-C.); (L.M.P.-B.)
- Ciber Fisiopatología de la Obesidad y Nutrición. Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (R.G.-H.); (M.R.B.-L.); Tel.: +34-951-291-169 (R.G.-H.); 34-951-290-346 (M.R.B.-L.); Fax: +34-951-290-006 (R.G.-H.); +34-951-290-302 (M.R.B.-L.)
| | - María Rosa Bernal-López
- Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (J.R.-N.); (V.B.); (M.I.R.-M.); (M.D.L.-C.); (L.M.P.-B.)
- Ciber Fisiopatología de la Obesidad y Nutrición. Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (R.G.-H.); (M.R.B.-L.); Tel.: +34-951-291-169 (R.G.-H.); 34-951-290-346 (M.R.B.-L.); Fax: +34-951-290-006 (R.G.-H.); +34-951-290-302 (M.R.B.-L.)
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Tarantino G, Citro V, Conforti P, Balsano C, Capone D. Is There a Link between Basal Metabolic Rate, Spleen Volume and Hepatic Growth Factor Levels in Patients with Obesity-Related NAFLD? J Clin Med 2019; 8:1510. [PMID: 31547124 PMCID: PMC6832562 DOI: 10.3390/jcm8101510] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/10/2019] [Accepted: 09/16/2019] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Recent pieces of research point to a link between basal metabolic rate (BMR) and non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS). The spleen in obese patients is associated with the cardiovascular system. Enlargement of the spleen is suggestive of nonalcoholic steatohepatitis (NASH). Patients with NASH present an increase in growth factor (HGF) as well as those with advanced heart failure. Interleukin-16 and interleukin-12p40 levels were found to correlate significantly with BMI, and waist circumference. AIM We tried to find a relationship between BMR, spleen length and HGF. METHODS We analysed retrospective data from 80 obese patients with NAFLD. We evaluated indices of indirect calorimetry by the bioimpendance analysis; carotid intima-media thickness (IMT), spleen length (SLD) and HS by ultrasonography; serum HGF, IL-16, IL-12p40 and IL-6 concentrations by a magnetic bead-based multiplex immunoassays and the severity of NAFLD by BARD score > 2. RESULTS HGF levels of the obese were higher than those of controls, p < 0.001. At linear regression, BMR was foreseen by spleen length (p < 0.001), which was predicted by HGF (p = 0.04). BMR was predicted by IL-16 (p = 0.005), which predicted HGF, p = 0.034. Only fat mass, among other factors, predicted early atherosclerosis, p = 0.017; IL-12p40 did not predict IMT, HGF and BMR (p = 0.57, 0.09 and 0.59, respectively). The BARD score > 2 was negatively predicted by BMR and FFM (p =0.032 and 0.031, respectively), at the logistic regression. Interesting findings at the extended regression (mediation effect) were: IL-16 was likely causal in predicting BMR by HGF levels; HGF was influential in predicting BMR by SLD level. HS was predicted by SLD in males (p = 0.014), of advanced age (p < 0.001) and by BMR (p < 0.001). IL-6 concentrations, but not BMR were influential in the prediction of HS by SLD. CONCLUSION These data reinforce the concept that the immune system is a sensor of the metabolic state, showing a link between HGF levels and BMR, which is mediated by IL-16 (cytokine inducing a cascade of inflammatory factors), and ascertaining the influential effect of the spleen, as main immune organ.
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Affiliation(s)
- Giovanni Tarantino
- Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Napoli NA, Italy.
| | - Vincenzo Citro
- Department of General Medicine, "Umberto I" Hospital, Nocera Inferiore (Sa), 84014 Nocera Inferiore SA, Italy.
| | - Paolo Conforti
- "Federico II" University Medical School of Naples, 80131 Napoli NA, Italy.
| | - Clara Balsano
- Department of Clinical Medicine, Life, Health & Environmental Sciences-MESVA, University of L'Aquila, 67100 L'Aquila AQ, Italy.
| | - Domenico Capone
- Care Department of Public Health and Drug-Use, Section of Medical Pharmacology and Toxicology, "Federico II" University, 80131 Naples NA, Italy.
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