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Sasaki N, Ueno Y, Ozono R, Nakano Y, Higashi Y. Insulin resistance in adipose tissue and fatty liver, but not fat mass, are involved in worsening glycaemic status: The Hiroshima study on glucose metabolism and cardiovascular diseases. Diabetes Obes Metab 2025; 27:3025-3035. [PMID: 40045548 DOI: 10.1111/dom.16307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 02/12/2025] [Accepted: 02/20/2025] [Indexed: 05/04/2025]
Abstract
AIMS Insulin resistance in adipose tissue causes dysregulation of various adipokine levels and ectopic fat accumulation in other organs, such as the liver. This study investigated the effects of insulin resistance in adipose tissue and concomitant fatty liver on each stage of impaired glucose metabolism compared with visceral fat mass. MATERIALS AND METHODS This observational study included 3644 individuals who underwent two 75-g oral glucose tolerance tests at baseline and follow-up. Adipose insulin resistance index (Adipo-IR), lipid accumulation product (LAP) and fatty liver index (FLI) were used as indicators of insulin resistance in the adipose tissue, visceral fat mass and fatty liver, respectively. RESULTS Over a mean 2.9-year follow-up period, 463 (32.4%) individuals progressed from normoglycaemia to prediabetes, and 198 (10.6%) developed type 2 diabetes from prediabetes. Comparing the highest-to-lowest quartiles, baseline levels and changes in Adipo-IR were associated with an increased odds of progression from normoglycaemia to prediabetes (odds ratio [OR], 2.22; 95% CI, 1.36-3.65, OR, 2.70; 95% CI, 1.83-3.98, respectively) and from prediabetes to the onset of type 2 diabetes (OR, 2.02; 95% CI, 1.04-3.92, OR, 3.09; 95% CI, 1.84-4.19, respectively), after adjusting for possible confounders. Changes in FLI were associated with progression from prediabetes to type 2 diabetes. LAP did not affect the progression of impaired glucose metabolism. CONCLUSIONS Adipose tissue insulin resistance, rather than fat mass, is crucial in all stages of deterioration of glycaemic status. Fatty liver plays a decisive role in the eventual development of type 2 diabetes.
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Affiliation(s)
- Nobuo Sasaki
- Health Management and Promotion Center, Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan
- Department of Regenerative Medicine, Division of Radiation Medical Science, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yoshitaka Ueno
- Health Management and Promotion Center, Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan
| | - Ryoji Ozono
- Department of General Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
| | - Yukiko Nakano
- Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
| | - Yukihito Higashi
- Department of Regenerative Medicine, Division of Radiation Medical Science, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
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Kim J, Ito T, Arai T, Atsukawa M, Kawanaka M, Toyoda H, Honda T, Yu ML, Yoon EL, Jun DW, Cha K, Nguyen MH. Modified FIB-4 Index in Type 2 Diabetes Mellitus with Steatosis: A Non-Linear Predictive Model for Advanced Hepatic Fibrosis. Diagnostics (Basel) 2024; 14:2500. [PMID: 39594165 PMCID: PMC11592587 DOI: 10.3390/diagnostics14222500] [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: 10/10/2024] [Revised: 11/04/2024] [Accepted: 11/05/2024] [Indexed: 11/28/2024] Open
Abstract
Background: The Fibrosis-4 (FIB-4) index is widely recommended as a first-tier method for screening advanced hepatic fibrosis; however, its diagnostic performance is known to be suboptimal in patients with Type 2 diabetes mellitus (T2DM). We aim to propose a modified FIB-4, using the parameters of the existing FIB-4, tailored specifically for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A total of 1503 patients who underwent liver biopsy were divided into T2DM (n = 517) and non-T2DM (n = 986) groups. The model was developed using multiple regression analysis in the derivation cohort and validated in the validation cohort. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic (AUC) curves. Results: Among the 1503 individuals, those with T2DM were older, more likely to be male, and had a higher prevalence of advanced hepatic fibrosis (≥F3) compared to non-T2DM individuals. Independent risk factors for advanced fibrosis in T2DM included age, AST, AST/ALT ratio, albumin, triglycerides, and platelet count. The optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index) demonstrated superior diagnostic accuracy (AUC 0.771) compared to the FIB-4 (AUC 0.735, p = 0.012). The model showed a higher negative predictive value than the original FIB-4 across all age groups in the diabetic group. Conclusions: The newly optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index), incorporating a non-linear predictive model, improves diagnostic performance (AUC) and the negative predictive value in MASLD with T2DM.
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Affiliation(s)
- Jonghyun Kim
- Research Institute for Convergence of Basic Science, Department of Applied Statistics, College of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea;
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Hospital, Nagoya 466-8560, Japan; (T.I.); (T.H.)
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (T.A.); (M.A.)
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (T.A.); (M.A.)
| | - Miwa Kawanaka
- Department of General Internal Medicine, Kawasaki Medical School General Medical Center, Okayama 700-8505, Japan;
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki 503-8502, Japan;
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Hospital, Nagoya 466-8560, Japan; (T.I.); (T.H.)
| | - Ming-Lung Yu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Eileen L. Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Republic of Korea;
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Republic of Korea;
| | - Kyungjoon Cha
- Research Institute for Convergence of Basic Science, Department of Applied Statistics, College of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea;
- Department of Mathematics, College of Natural Sciences, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA 94304, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA 94304, USA
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3
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Bale G, Clarembeau F, Stärkel P, Dahlqvist G, Horsmans Y, Lanthier N. Patients with chronic liver diseases are at risk for diabetes even before development of cirrhosis. Clin Res Hepatol Gastroenterol 2024; 48:102428. [PMID: 39048075 DOI: 10.1016/j.clinre.2024.102428] [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: 06/11/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND AND AIMS The prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is higher in patients with cirrhosis, compared to control patients without liver disease. The exact mechanism for this is unknown but could include liver inflammation. In this study we investigate whether cirrhosis is the primum movens of IR or if impaired insulin sensitivity is already present in non-cirrhotic patients with chronic liver diseases. METHODS Patients were recruited and divided into three groups: control (CTL), chronic liver disease without cirrhosis (CLD) and cirrhosis (CIR). In patients not taking pharmacological treatment for T2DM, IR was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). The proportion of patients with T2DM as well as HOMA-IR levels among different disease etiologies were recorded and compared. RESULTS 532 patients were included in our study. Median glycemia and insulinemia and therefore HOMA-IR values were significantly different between the three cohorts (p-value <0.001): IR levels in CLD subjects lie between those seen in CTL and CIR subjects. The proportion of diabetic patients in the two case categories also differs (p-value = 0.027): one quarter of CLD subjects and one third of CIR patients suffer from T2DM. Finally, HOMA-IR levels vary according to disease etiology (p-value <0.001): metabolic steatosis and chronic viral hepatitis C are at greater risk than alcohol and other disease causes. CONCLUSION CLD is already a predisposing factor to T2DM, regardless of the presence of CIR. CIR is a factor which elicits additional increase in insulin levels. Metabolic steatosis and hepatitis C are associated with more severe IR.
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Affiliation(s)
- Georgia Bale
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Frédéric Clarembeau
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium; Laboratory of Hepatology and Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
| | - Peter Stärkel
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium; Laboratory of Hepatology and Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
| | - Géraldine Dahlqvist
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Yves Horsmans
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium; Laboratory of Hepatology and Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
| | - Nicolas Lanthier
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium; Laboratory of Hepatology and Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium.
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Li M, Zhang J, Li Z, Xu Z, Qian S, Tay LJ, Zhang Z, Yang F, Huang Y. The role and mechanism of SUMO modification in liver disease. Biomed Pharmacother 2024; 177:116898. [PMID: 38878635 DOI: 10.1016/j.biopha.2024.116898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 07/28/2024] Open
Abstract
Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO) modification is a highly conserved post-translational modification of proteins. They are widely expressed in a variety of tissues, including the heart, liver, kidney and lung. SUMOylation of protein plays a key role in the occurrence and development of liver disease. Therefore, this study reviewed the effects of SUMO protein on non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases to provide novel strategies for targeted treatment of liver disease.
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Affiliation(s)
- Mengxue Li
- Anhui Provincial laboratory of inflammatory and immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China
| | - Jingrong Zhang
- Anhui Provincial laboratory of inflammatory and immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China
| | - Zihao Li
- Anhui Provincial laboratory of inflammatory and immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China
| | - Zhou Xu
- Anhui Provincial laboratory of inflammatory and immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China
| | - Shishun Qian
- Anhui Provincial laboratory of inflammatory and immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China
| | - Lynn Jia Tay
- School of International Education, Anhui Medical University, Hefei 230032, China
| | - Ziwen Zhang
- Anhui Provincial laboratory of inflammatory and immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China
| | - Furong Yang
- Anhui Provincial laboratory of inflammatory and immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China.
| | - Yan Huang
- Anhui Provincial laboratory of inflammatory and immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China; School of International Education, Anhui Medical University, Hefei 230032, China.
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Gignac T, Trépanier G, Pradeau M, Morissette A, Agrinier AL, Larose É, Marois J, Pilon G, Gagnon C, Vohl MC, Marette A, Carreau AM. Metabolic-associated fatty liver disease is characterized by a post-oral glucose load hyperinsulinemia in individuals with mild metabolic alterations. Am J Physiol Endocrinol Metab 2024; 326:E616-E625. [PMID: 38477665 DOI: 10.1152/ajpendo.00294.2023] [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: 09/07/2023] [Revised: 03/07/2024] [Accepted: 03/11/2024] [Indexed: 03/14/2024]
Abstract
Metabolic-associated fatty liver disease (MAFLD) has been identified as risk factor of incident type 2 diabetes (T2D), but the underlying postprandial mechanisms remain unclear. We compared the glucose metabolism, insulin resistance, insulin secretion, and insulin clearance post-oral glucose tolerance test (OGTT) between individuals with and without MAFLD. We included 50 individuals with a body mass index (BMI) between 25 and 40 kg/m2 and ≥1 metabolic alteration: increased fasting triglycerides or insulin, plasma glucose 5.5-6.9 mmol/L, or glycated hemoglobin 5.7-5.9%. Participants were grouped according to MAFLD status, defined as hepatic fat fraction (HFF) ≥5% on MRI. We used oral minimal model on a frequently sampled 3 h 75 g-OGTT to estimate insulin sensitivity, insulin secretion, and pancreatic β-cell function. Fifty percent of participants had MAFLD. Median age (IQR) [57 (45-65) vs. 57 (44-63) yr] and sex (60% vs. 56% female) were comparable between groups. Post-OGTT glucose concentrations did not differ between groups, whereas post-OGTT insulin concentrations were higher in the MAFLD group (P < 0.03). Individuals with MAFLD exhibited lower insulin clearance, insulin sensitivity, and first-phase pancreatic β-cell function. In all individuals, increased insulin incremental area under the curve and decreased insulin clearance were associated with HFF after adjusting for age, sex, and BMI (P < 0.02). Among individuals with metabolic alterations, the presence of MAFLD was characterized mainly by post-OGTT hyperinsulinemia and reduced insulin clearance while exhibiting lower first phase β-cell function and insulin sensitivity. This suggests that MAFLD is linked with impaired insulin metabolism that may precede T2D.NEW & NOTEWORTHY Using an oral glucose tolerance test, we found hyperinsulinemia, lower insulin sensitivity, lower insulin clearance, and lower first-phase pancreatic β-cell function in individuals with MAFLD. This may explain part of the increased risk of incident type 2 diabetes in this population. These data also highlight implications of hyperinsulinemia and impaired insulin clearance in the progression of MAFLD to type 2 diabetes.
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Affiliation(s)
- Théo Gignac
- Axe Endocrinologie et Néphrologie, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
- Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
| | - Gabrielle Trépanier
- Axe Endocrinologie et Néphrologie, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
- Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
| | - Marion Pradeau
- Axe Endocrinologie et Néphrologie, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
- Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
| | - Arianne Morissette
- Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
- Centre Nutrition, santé et société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, Quebec, Canada
- Axe Obésité, Diabète de type 2 et Métabolisme, Centre de recherche de l'IUCPQ-Université Laval, Québec, Quebec, Canada
| | - Anne-Laure Agrinier
- Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
- Centre Nutrition, santé et société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, Quebec, Canada
- Axe Obésité, Diabète de type 2 et Métabolisme, Centre de recherche de l'IUCPQ-Université Laval, Québec, Quebec, Canada
| | - Éric Larose
- Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
- Axe Obésité, Diabète de type 2 et Métabolisme, Centre de recherche de l'IUCPQ-Université Laval, Québec, Quebec, Canada
| | - Julie Marois
- Centre Nutrition, santé et société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, Quebec, Canada
| | - Geneviève Pilon
- Centre Nutrition, santé et société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, Quebec, Canada
- Axe Obésité, Diabète de type 2 et Métabolisme, Centre de recherche de l'IUCPQ-Université Laval, Québec, Quebec, Canada
| | - Claudia Gagnon
- Axe Endocrinologie et Néphrologie, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
- Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
- Centre Nutrition, santé et société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, Quebec, Canada
- Axe Obésité, Diabète de type 2 et Métabolisme, Centre de recherche de l'IUCPQ-Université Laval, Québec, Quebec, Canada
| | - Marie-Claude Vohl
- Centre Nutrition, santé et société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, Quebec, Canada
- École de nutrition, Faculté des sciences de l'agriculture et de l'alimentation, Université Laval, Québec, Quebec, Canada
| | - André Marette
- Centre Nutrition, santé et société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, Quebec, Canada
- Axe Obésité, Diabète de type 2 et Métabolisme, Centre de recherche de l'IUCPQ-Université Laval, Québec, Quebec, Canada
| | - Anne-Marie Carreau
- Axe Endocrinologie et Néphrologie, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
- Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
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Rasoulizadeh Z, Namazi A, Sohouli MH, Rohani P, Hekmatdoost A, Hosseinzadeh M. Association between Baltic sea diet and healthy Nordic diet index with risk of non-alcoholic fatty liver disease: a case-control study. Sci Rep 2024; 14:9537. [PMID: 38664485 PMCID: PMC11045829 DOI: 10.1038/s41598-024-60400-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 04/23/2024] [Indexed: 04/28/2024] Open
Abstract
Recent evidence shows the beneficial effects of Baltic Sea diet score (BSDS) and healthy Nordic diet index (HNDI) on chronic diseases, however, there is no evidence to investigate them on the risk of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to investigate the associations between BSDS and HNDI with the risk of NAFLD. In this case-control study, 552 people in good health and 340 people with NAFLD over the age of 18 took part. The evaluation of BSDS and HNDI employed a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Binary logistic regression was used to determine how OBS and NAFLD are related. The mean BSDS and HNDI were 16.00 ± 2.49 and 11.99 ± 2.61, respectively. The final model's confounder adjustment revealed that greater HNDI adherence scores gave protection against the occurrence of NAFLD (odds ratio [OR]: 0.42; 95% confidence interval [CI] 0.18-0.98; P for trend = 0.043). In addition, those with the highest BSDS scores had significantly lower risks of developing NAFLD compared to subjects with the lowest scores (OR = 0.48, 95% CI 0.32-0.89; p for trend = 0.003). Our findings showed that following a healthy Nordic diet can significantly prevent the risk of developing NAFLD, and suggest that the highly nutritious components of the Nordic diet are beneficial for the prevention of NAFLD.
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Affiliation(s)
- Zahra Rasoulizadeh
- School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Abolfazl Namazi
- Department of Internal Medicine, Hazrat-E Rasool General Hospital, Iran University Of Medical Sciences, Tehran, Iran
| | - Mohammad Hassan Sohouli
- Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, No 7, West Arghavan St, Farahzadi Blvd, PO Box 19395-4741, Tehran, 1981619573, Iran.
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Pejman Rohani
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdieh Hosseinzadeh
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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7
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Nogueira JP, Cusi K. Role of Insulin Resistance in the Development of Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: From Bench to Patient Care. Diabetes Spectr 2024; 37:20-28. [PMID: 38385099 PMCID: PMC10877218 DOI: 10.2337/dsi23-0013] [Citation(s) in RCA: 38] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/23/2024]
Abstract
Insulin resistance is implicated in both the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and its progression from steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma, which is known to be more common in people with type 2 diabetes. This article reviews the role of insulin resistance in the metabolic dysfunction observed in obesity, type 2 diabetes, atherogenic dyslipidemia, and hypertension and how it is a driver of the natural history of NAFLD by promoting glucotoxicity and lipotoxicity. The authors also review the genetic and environmental factors that stimulate steatohepatitis and fibrosis progression and their relationship with cardiovascular disease and summarize guidelines supporting the treatment of NAFLD with diabetes medications that reduce insulin resistance, such as pioglitazone or glucagon-like peptide 1 receptor agonists.
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Affiliation(s)
- Juan Patricio Nogueira
- Universidad del Pacifico, Asunción, Paraguay
- Centro de Investigación en Endocrinología, Nutrición y Metabolismo, Facultad de Ciencias de la Salud, Universidad Nacional de Formosa, Formosa, Argentina
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
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Jiang W, Jin Q, Li C, Xun Y. A Plasma Exosomal Metabolic Profiling of Nonalcoholic Fatty Liver Disease Patients Complicated with Impaired Fasting Glucose. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2024; 35:125-135. [PMID: 38454244 PMCID: PMC10895878 DOI: 10.5152/tjg.2024.22739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 03/03/2023] [Indexed: 03/09/2024]
Abstract
BACKGROUND/AIMS Nonalcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Detection of circulating exosomes together with metabolomic analysis of their cargo would provide early signals for metabolic derangements and complications associated with nonalcoholic fatty liver disease. Therefore, this study profiled exosomal metabolome of patients with nonalcoholic fatty liver disease and impaired fasting glucose. MATERIALS AND METHODS Plasma exosomes were extracted from nonalcoholic fatty liver disease patients with or without impaired fasting glucose through differential ultracentrifugation. Their metabolite profiles were examined by ultrahigh-performance liquid chrom atography-quadrupole time-of-flight mass spectrometry. Pathway analysis was carried out on platform MetaboAnalyst 4.0. RESULTS Thirty-nine patients were enrolled, including nonalcoholic fatty liver disease-alone group (n = 26) and age-and gender-comparable nonalcoholic fatty liver disease plus impaired fasting glucose group (n = 13). Although less than and different from their plasma counterparts, a total of 10 significantly differential exosomal metabolites were identified. Nonalcoholic fatty liver disease plus impaired fasting glucose group had higher concentrations of linoleic acid, palmitamide, stearamide, and oleamide, as well as a lower concentration of phosphatidylethanolamine [20:5(5Z,8Z,11Z,14Z,17Z)/20:5(5Z,8Z,11Z,14Z,17Z)]. Pathway analysis showed an obviously changed metabolism of linoleic acid. CONCLUSION Metabolomic analysis of plasma exosomes revealed a distinct change in fatty acids and related pathways in nonalcoholic fatty liver disease patients with impaired fasting glucose. These preliminary results provide a metabolomic snapshot and basis for further investigation of exosome biology for these patients.
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Affiliation(s)
- Weiyun Jiang
- Department of Liver Disease, Hangzhou Sixth People’s Hospital/Xixi Hospital of Hangzhou Afflicted to Zhejiang University, Hangzhou, China
| | - Qiaofei Jin
- Department of Liver Disease, Hangzhou Sixth People’s Hospital/Xixi Hospital of Hangzhou Afflicted to Zhejiang University, Hangzhou, China
| | - Chunqing Li
- Department of Liver Disease, Hangzhou Sixth People’s Hospital/Xixi Hospital of Hangzhou Afflicted to Zhejiang University, Hangzhou, China
| | - Yunhao Xun
- Department of Liver Disease, Hangzhou Sixth People’s Hospital/Xixi Hospital of Hangzhou Afflicted to Zhejiang University, Hangzhou, China
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Saleh SAK, Santos HO, Găman MA, Cerqueira HS, Zaher EA, Alromaih WR, Arafat NS, Adi AR, Adly HM, Alyoubi R, Alyahyawi N, Kord-Varkaneh H. Effects of intermittent fasting regimens on glycemic, hepatic, anthropometric, and clinical markers in patients with non-alcoholic fatty liver disease: Systematic review and meta-analysis of randomized controlled trials. Clin Nutr ESPEN 2024; 59:70-80. [PMID: 38220409 DOI: 10.1016/j.clnesp.2023.11.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 11/08/2023] [Accepted: 11/08/2023] [Indexed: 01/16/2024]
Abstract
OBJECTIVES Intermittent fasting (IF) regimens have been hypothesized to influence several markers of cardiometabolic and liver function. The objective of our meta-analysis was to investigate the impact of IF regimens on cardiometabolic and liver markers in subjects diagnosed with non-alcoholic fatty liver disease (NAFLD). METHODS We searched several online databases (PubMed/Medline, Web of Science, Scopus and Embase) in order to identify suitable publications for inclusion in the meta-analysis. Results were expressed as weighted mean differences (WMD). RESULTS From 12343 articles identified in different databases, a total of 7 RCT arms were entered into the quantitative synthesis. The manuscripts were published between 2019 and 2023. IF regimens (the 5:2 diet, 16/8 time-restricting feeding, and alternate day fasting) varied from 2 months to 3 months. IF regimens reduced steatosis scores (WMD: -33.22 CAP dB/m, 95 % CI: -50.72 to -15.72), anthropometric characteristics of obesity (WMD: -0.77 kg/m2, 95 % CI: -1.38 to -0.17 for body mass index; WMD: -3.16 kg, 95 % CI: -4.71 to -1.61 for body weight; WMD: -1.90 kg, 95 % CI: -3.51 to -0.29 for waist circumference), as well as ALT (WMD: -9.10 U/L, 95 % CI: -12.45 to -5.75), triglyceride (WMD: -20.83 mg/dl, 95 % CI: -39.01 to -2.66), total cholesterol (WMD: -7.80 mg/dl, 95 % CI: -15.18), HbA1c (WMD: -0.14 %, 95 % CI: -0.20 to -0.08) and HOMA-IR (WMD: -1.21, 95 % CI: -2.08 to -0.34) levels versus controls. Nevertheless, no between-group differences were detected for other biomarkers, e.g., fasting blood glucose, insulin, AST, HDL-C or LDL-C values, and fibrosis scores. CONCLUSION IF regimens can improve some markers of cardiometabolic and liver function in patients with NAFLD. However, the available evidence to support the benefits of IF regimens is limited and derived from a small number of studies, thus further research is needed to clarify the impact of IF on the cardiometabolic health of NAFLD patients.
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Affiliation(s)
- Saleh A K Saleh
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; Oncology Diagnostic Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Heitor O Santos
- School of Medicine, Federal University of Uberlandia (UFU), Uberlandia 38408-100, Brazil
| | - Mihnea-Alexandru Găman
- Faculty of Medicine, Carol Davila, University of Medicine and Pharmacy, Bucharest, Romania; Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Henrique S Cerqueira
- School of Medicine, University of São Paulo (USP), Ribeirão Preto 14049-900, Brazil
| | - Eman Abbas Zaher
- Department of Family Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Wafa Romaih Alromaih
- Department of Family Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Norah Saud Arafat
- Department of Family Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
| | | | - Heba M Adly
- Department of Community Medicine and Pilgrims Healthcare, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Reem Alyoubi
- Department of Pediatrics, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Naseem Alyahyawi
- Department of Pediatrics, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Hamed Kord-Varkaneh
- Department of Nutrition and Food Hygiene, Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
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Basheer M, Boulos M, Basheer A, Loai A, Nimer A. Olive Oil's Attenuating Effects on Lipotoxicity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:869-882. [PMID: 39287875 DOI: 10.1007/978-3-031-63657-8_29] [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
Dietary fatty acids play a role in the pathogenesis of obesity-associated nonalcoholic fatty liver disease. Lipotoxicity in obesity mediates insulin resistance, endothelial dysfunction, atherosclerosis, and gut microbiota dysbiosis. Cardiovascular complications are the main cause of morbidity and mortality in obese, insulin-resistant, and type 2 diabetes mellitus patients.Interventions targeting lipotoxicity are the main issue in preventing its multiple insults. Lifestyle modifications including healthy eating and regular exercise are the primary recommendations. Treatments also include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation, fibrogenesis, and cirrhosis.Diet and nutrition have been linked to insulin resistance, an increased risk of developing type 2 diabetes, and impaired postprandial lipid metabolism. Low-fat diets are associated with higher survival. The Mediterranean diet includes an abundance of olive oil. Extra-virgin olive oil is the main source of monounsaturated fatty acids in Mediterranean diets. An olive oil-rich diet decreases triglyceride accumulation in the liver, improves postprandial triglyceride levels, improves glucose and insulin secretions, and upregulates GLUT-2 expression in the liver. The exact molecular mechanisms of olive oil's effects are unknown, but decreasing NF-kB activation, decreasing LDL oxidation, and improving insulin resistance by reducing the production of inflammatory cytokines (TNF-α and IL-6) and upregulating kinases and JNK-mediated phosphorylation of IRS-1 are possible principal mechanisms. Olive oil phenolic compounds also modulate gut microbiota diversity, which also affects lipotoxicity.In this review, we document lipotoxicity in obesity manifestations and the beneficial health effects of the Mediterranean diet derived from monounsaturated fatty acids, mainly from olive oil.
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Affiliation(s)
- Maamoun Basheer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Mariana Boulos
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Areej Basheer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
- Nutrition and Diet Services, Hillel Yaffe, Hadera, Israel
| | - Arraf Loai
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Assy Nimer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel.
- Faculty of Medicine at Galilee, Bar-Ilan University, Safed, Israel.
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Yang RX, Fan JG. Metabolic comorbidities, endocrine—Diabetes, polycystic ovarian syndrome, thyroid dysfunction. METABOLIC STEATOTIC LIVER DISEASE 2024:123-136. [DOI: 10.1016/b978-0-323-99649-5.00004-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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12
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Kong L, Ye C, Wang Y, Dou C, Zheng J, Wang S, Lin H, Zhao Z, Li M, Xu Y, Chen Y, Lu J, Xu M, Wang W, Ning G, Bi Y, Wang T. Diabesity phenotype in relation to the incidence and resolution of nonalcoholic fatty liver disease: A prospective cohort study. J Diabetes 2024; 16:e13459. [PMID: 37584361 PMCID: PMC10809295 DOI: 10.1111/1753-0407.13459] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 07/06/2023] [Accepted: 07/30/2023] [Indexed: 08/17/2023] Open
Abstract
BACKGROUND Diabesity is a term used to emphasize the dual epidemic and the combined detrimental effects of diabetes and obesity. We aimed to investigate the associations of diabesity with the incidence and resolution of nonalcoholic fatty liver disease (NAFLD). METHODS This prospective cohort study included 5549 participants with a median follow-up of 4.3 years (2010-2015). Diabesity was defined as six categories by the combinations of glucose tolerance status (normal glucose tolerance [NGT], prediabetes, and diabetes) diagnosed by fasting and oral glucose tolerance test 2-h glucose and hemoglobin A1c and general or abdominal obesity status. We examined the odds ratios (ORs) for the incidence and resolution of NAFLD associated with diabesity categories, respectively. RESULTS For NAFLD incidence, compared with the diabesity category of NGT with nonobesity, the categories of either glucose intolerance or general obesity were associated with higher risks of NAFLD, of which the categories with obesity, regardless of glucose intolerance status, exhibited greater risks (ORs ranged from 3.19 to 4.49) than the categories of nonobesity. For NAFLD resolution, the categories of prediabetes or diabetes with obesity were associated with decreased likelihoods of a resolution of NAFLD (ORs ranged from 0.40 to 0.58). These association patterns were consistent across various definitions of diabesity by glucose tolerance status diagnosed by different combinations of glycemic parameters and general or abdominal obesity. CONCLUSIONS The diabesity association pattern with NAFLD incidence was mainly determined by obesity, while that with NAFLD resolution was driven by the combined phenotype of glucose intolerance and obesity.
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Affiliation(s)
- Lijie Kong
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Chaojie Ye
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yiying Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Chun Dou
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Jie Zheng
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Shuangyuan Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Hong Lin
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Zhiyun Zhao
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Mian Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yuhong Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Guang Ning
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Tiange Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
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Song Y, Yang H, Kim J, Lee Y, Kim SH, Do IG, Park CY. Gemigliptin, a DPP4 inhibitor, ameliorates nonalcoholic steatohepatitis through AMP-activated protein kinase-independent and ULK1-mediated autophagy. Mol Metab 2023; 78:101806. [PMID: 37739179 PMCID: PMC10542016 DOI: 10.1016/j.molmet.2023.101806] [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: 06/25/2023] [Revised: 08/16/2023] [Accepted: 09/11/2023] [Indexed: 09/24/2023] Open
Abstract
OBJECTIVE Abnormal autophagic function and activated inflammasomes are typical features in the liver of patients with non-alcoholic steatohepatitis (NASH). Here, we explored whether gemigliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor for treatment of type 2 diabetes, can induce autophagy and regulate inflammasome activation as a potential NASH treatment independent of its anti-diabetic effect. METHODS Expression analysis was performed using human liver samples obtained from 18 subjects who underwent hepatectomy. We explored the function and mechanism of gemigliptin using a methionine- and choline-deficient diet (MCD)-induced NASH mouse model and HepG2 cells cultured in MCD-mimicking medium. RESULTS Autophagy was suppressed by marked decreases in the expression of ULK1 and LC3II/LC3I ratio in human NAFLD/NASH patients, a NASH mouse model, and HepG2 cells cultured with MCD-mimicking media. Surprisingly, we found that the expression of p-AMPK decreased in liver tissues from patients with steatosis but was restored in NASH patients. The expression of p-AMPK in the NASH mouse model was similar to that of the control group. Hence, these results indicate that autophagy was reduced in NASH via an AMPK-independent pathway. However, gemigliptin treatment attenuated lipid accumulation, inflammation, and fibrosis in the liver of MCD diet-fed mice with restoration of ULK1 expression and autophagy induction. In vitro, gemigliptin alleviated inflammasome activation through induction of ULK1-dependent autophagy. Furthermore, gemigliptin treatment upregulated ULK1 expression and activated AMPK even after siRNA-mediated knockdown of AMPKα1/2 and ULK1, respectively. CONCLUSIONS Collectively, these results suggest that gemigliptin ameliorated NASH via AMPK-independent, ULK1-mediated effects on autophagy.
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Affiliation(s)
- Youngmi Song
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hyekyung Yang
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Juhee Kim
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yoonjin Lee
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung-Ho Kim
- LG Chem Life Sciences, Gangseo-gu, Seoul, South Korea
| | - In-Gu Do
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Cheol-Young Park
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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Colosimo S, Mitra SK, Chaudhury T, Marchesini G. Insulin resistance and metabolic flexibility as drivers of liver and cardiac disease in T2DM. Diabetes Res Clin Pract 2023; 206:111016. [PMID: 37979728 DOI: 10.1016/j.diabres.2023.111016] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/15/2023] [Accepted: 11/13/2023] [Indexed: 11/20/2023]
Abstract
Metabolic flexibility refers to the ability of tissues to adapt their use of energy sources according to substrate availability and energy demands. This review aims to disentangle the emerging mechanisms through which altered metabolic flexibility and insulin resistance promote NAFLD and heart disease progression. Insulin resistance and metabolic inflexibility are central drivers of hepatic and cardiac diseases in individuals with type 2 diabetes. Both play a critical role in the complex interaction between glucose and lipid metabolism. Disruption of metabolic flexibility results in hyperglycemia and abnormal lipid metabolism, leading to increased accumulation of fat in the liver, contributing to the development and progression of NAFLD. Similarly, insulin resistance affects cardiac glucose metabolism, leading to altered utilization of energy substrates and impaired cardiac function, and influence cardiac lipid metabolism, further exacerbating the progression of heart failure. Regular physical activity promotes metabolic flexibility by increasing energy expenditure and enabling efficient switching between different energy substrates. On the contrary, weight loss achieved through calorie restriction ameliorates insulin sensitivity without improving flexibility. Strategies that mimic the effects of physical exercise, such as pharmacological interventions or targeted lifestyle modifications, show promise in effectively treating both diabetes and NAFLD, finally reducing the risk of advanced liver disease.
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Affiliation(s)
- Santo Colosimo
- School of Nutrition Science, University of Milan, Milan, Italy
| | - Sandip Kumar Mitra
- Diabetes and Endocrinology Unit, Apollo Gleneagles Hospital, Kolkata, West Bengal, India
| | - Tirthankar Chaudhury
- Diabetes and Endocrinology Unit, Apollo Gleneagles Hospital, Kolkata, West Bengal, India
| | - Giulio Marchesini
- IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.
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15
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Malucelli M, Strobel R, Ivantes C, Sakamoto D, Luís Duarte M, Lucia Alves Pedroso M. Histological findings and NAFLD/NASH Status in liver biopsies of patients subjected to bariatric surgery. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023; 68:e220138. [PMID: 37948562 PMCID: PMC10916797 DOI: 10.20945/2359-4292-2022-0138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 04/11/2023] [Indexed: 11/12/2023]
Abstract
Objective To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.
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Affiliation(s)
- Marielle Malucelli
- Departamento de Pós-graduação em Medicina Interna, Universidade Federal do Paraná, Curitiba, PR, Brasil,
| | - Rodrigo Strobel
- Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brasil
| | | | | | - Márcio Luís Duarte
- Departamento de Radiologia, Universidade de Ribeirão Preto Campus Guarujá, Guarujá, SP, Brasil
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Adhikari P, Oli K, Shrestha S. Diabetes Mellitus among Patients with Non-alcoholic Fatty Liver Disease Visiting the Outpatient Department of Internal Medicine in a Tertiary Care Centre. JNMA J Nepal Med Assoc 2023; 61:871-873. [PMID: 38289738 PMCID: PMC10725226 DOI: 10.31729/jnma.8324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Indexed: 02/01/2024] Open
Abstract
Introduction Diabetes mellitus is a chronic metabolic illness which is mainly associated with reduced physical activity and obesity. Diabetes mellitus and non-alcoholic fatty liver disease may coexist and synergistically lead to poor clinical outcomes. The aim of the study was to find out the prevalence of diabetes mellitus among patients with non-alcoholic fatty liver disease in a tertiary care centre. Methods A descriptive cross-sectional study was conducted among patients with non-alcoholic fatty liver disease in the outpatient department of Internal Medicine of a tertiary care centre between 1st January 2022 and 29th June 2023. Convenience sampling was done. A convenience sampling technique was used. The point estimate was calculated at a 95% Confidence Interval. Results Among 150 patients with non-alcoholic fatty liver disease, diabetes mellitus was seen among 18 (12%) (6.80-17.20, 95% Confidence Interval). Diabetes mellitus was more prevalent in males 12 (66.67%) in patients with non-alcoholic fatty liver disease. Conclusions The prevalence of diabetes mellitus among patients with non-alcoholic fatty liver disease was found to be lower as compared to similarly reported research studies. Keywords diabetes mellitus; fatty liver; non-alcoholic fatty liver disease; prevalence.
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Affiliation(s)
- Prabin Adhikari
- Department of Internal Medicine, Nepal Medical College and Teaching Hospital, Jorpati, Kathmandu, Nepal
| | - Kaushal Oli
- Nepal Medical College and Teaching Hospital, Jorpati, Kathmandu, Nepal
| | - Saloni Shrestha
- Nepal Medical College and Teaching Hospital, Jorpati, Kathmandu, Nepal
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Cho Y, Chang Y, Ryu S, Kim C, Wild SH, Byrne CD. History of Gestational Diabetes and Incident Nonalcoholic Fatty Liver Disease: The Kangbuk Samsung Health Study. Am J Gastroenterol 2023; 118:1980-1988. [PMID: 36940424 DOI: 10.14309/ajg.0000000000002250] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 03/15/2023] [Indexed: 03/22/2023]
Abstract
INTRODUCTION We examined the relationship between a previous history of gestational diabetes mellitus (pGDM) and risk of incident nonalcoholic fatty liver disease (NAFLD) and investigated the effect of insulin resistance or development of diabetes as mediators of any association. METHODS We performed a retrospective cohort study of 64,397 Korean parous women without NAFLD. The presence of and the severity of NAFLD at baseline and follow-up were assessed using liver ultrasonography. Cox proportional hazards models were used to determine adjusted hazard ratios for incident NAFLD according to a self-reported GDM history, adjusting for confounders as time-dependent variables. Mediation analyses were performed to examine whether diabetes or insulin resistance may mediate the association between pGDM and incident NAFLD. RESULTS During a median follow-up of 3.7 years, 6,032 women developed incident NAFLD (of whom 343 had moderate-to-severe NAFLD). Multivariable adjusted hazard ratios (95% confidence intervals) comparing women with time-dependent pGDM with the reference group (no pGDM) were 1.46 (1.33-1.59) and 1.75 (1.25-2.44) for incident overall NAFLD and moderate-to-severe NAFLD, respectively. These associations remained significant in analyses restricted to women with normal fasting glucose <100 mg/dL or that excluded women with prevalent diabetes at baseline or incident diabetes during follow-up. Diabetes and insulin resistance (Homeostatic Model Assessment for Insulin Resistance) each mediated <10% of the association between pGDM and overall NAFLD development. DISCUSSION A previous history of GDM is an independent risk factor for NAFLD development. Insulin resistance, measured by the Homeostatic Model Assessment for Insulin Resistance, and development of diabetes each explained only <10% of the association between GDM and incident NAFLD.
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Affiliation(s)
- Yoosun Cho
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea
| | - Seungho Ryu
- Center for Cohort Studies, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea
| | - Chanmin Kim
- Department of Statistics, Sungkyunkwan University, Seoul, South Korea
| | - Sarah H Wild
- Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- National Institute for Health and Care Research etc Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
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Golabi P, Paik JM, Kumar A, Al Shabeeb R, Eberly KE, Cusi K, GunduRao N, Younossi ZM. Nonalcoholic fatty liver disease (NAFLD) and associated mortality in individuals with type 2 diabetes, pre-diabetes, metabolically unhealthy, and metabolically healthy individuals in the United States. Metabolism 2023:155642. [PMID: 37380016 DOI: 10.1016/j.metabol.2023.155642] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 06/12/2023] [Accepted: 06/22/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND The prevalence of nonalcoholic fatty liver disease (NAFLD) is high among subjects with type 2 diabetes (T2D). However, the prevalence and outcomes of NAFLD among individuals with pre-diabetes (PreD) and metabolically healthy and metabolically unhealthy individuals without T2D are not known. Our aim was to assess prevalence and mortality of NAFLD among these four groups. METHODS The Third National Health and Nutrition Examination Survey (NHANES) III (1988-1994) with mortality data (follow up to 2019) via linkage to the National Death Index was utilized. NAFLD was defined by ultrasound and absence of other liver diseases and excess alcohol use. Pre-D was defined as fasting plasma glucose values of 100-125 mg/dL and/or HbA1c level between 5.7 %-6.4 % in the absence of established diagnosis of T2D. Metabolically healthy (MH) was defined if all of the following criteria were absent: waist circumference of ≥102 cm (men) or ≥ 88 cm (women) or BMI of ≥30; blood pressure (BP) ≥ 130/85 mmHg or using BP-lowering medication; triglyceride level ≥ 150 mg/dL or using lipid-lowering medication; lipoprotein cholesterol level of <40 mg/dL (men) or < 50 mg/dL (women); homeostasis model assessment of insulin resistance (HOMA-IR) score ≥ 2.5; C-reactive protein (CRP) level of >2 mg/L; Pre-D and T2D. Metabolically unhealthy (MU) individuals were defined as the presence of any component of metabolic syndrome but not having Pre-D and T2D. Competing risk analyses of cause-specific mortality were performed. FINDINGS 11,231 adults (20-74y) were included: mean age 43.4 years; 43.9 % male; 75.4 % white, 10.8 % Black, and 5.4 % Mexican American, 18.9 % NAFLD, 7.8 % T2D; 24.7 % PreD; 44.3 % MU; and 23.3 % in MH individuals. In multivariable adjusted logistic model, as compared to MH individuals, the highest risk of having NAFLD were in T2D individuals (Odd Ratio [OR] = 10.88 [95 % confidence interval: 7.33-16.16]), followed by Pre-D (OR = 4.19 [3.02-5.81]), and MU (OR = 3.36 [2.39-4.71]). During a median follow up of 26.7 years (21.2-28.7 years), 3982 died. NAFLD subjects had significantly higher age-adjusted mortality than non-NAFLD (32.7 % vs. 28.7 %, p < .001). Among subjects with NAFLD, the highest age-standardized cumulative mortality was observed among those with T2D (41.3 %), followed by with Pre-D (35.1 %), MU subjects (30.0 %), and MH subjects (21.9 %) (pairwise p-values<.04 vs. ND with MH). Multivariable adjusted cox models showed that NAFLD with T2D had a higher risk of all-causes and cardiac-specific deaths (Hazard Ratio [HR] = 4.71 [2.23-9.96] and HR = 20.01 [3.00-133.61]), followed by NAFLD with Pre-D (HR = 2.91 [1.41-6.02] and HR = 10.35 [1.57-68.08]) and metabolically unhealthy NAFLD (HR = 2.59 [1.26-5.33] and HR = 6.74 [0.99-46.03]) compared to metabolically healthy NAFLD. In addition to older age, independent predictors of mortality among NAFLD with T2D included high CRP, CVD, CKD, high FIB-4, and active smoking. Similarly, among NAFLD with PreD, high CRP, CKD, CVD, hypertension, and active smoking were associated with mortality. Finally, CVD and active smoking were predictors of mortality among metabolically unhealthy NAFLD, and active smoking was the only mortality risk among metabolically healthy NAFLD subjects. INTERPRETATION Metabolic abnormality impacts both prevalence and outcomes of subjects with NAFLD.
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Affiliation(s)
- Pegah Golabi
- Department of Medicine, Center for Liver Disease, Inova Fairfax Medical Campus, Falls Church, VA, United States; Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, United States
| | - James M Paik
- Department of Medicine, Center for Liver Disease, Inova Fairfax Medical Campus, Falls Church, VA, United States; Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, United States
| | - Ameeta Kumar
- Department of Medicine, Center for Liver Disease, Inova Fairfax Medical Campus, Falls Church, VA, United States
| | - Reem Al Shabeeb
- Department of Medicine, Center for Liver Disease, Inova Fairfax Medical Campus, Falls Church, VA, United States
| | - Kathrine E Eberly
- Department of Medicine, Center for Liver Disease, Inova Fairfax Medical Campus, Falls Church, VA, United States
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, United States
| | - Nagashree GunduRao
- Department of Medicine, Center for Liver Disease, Inova Fairfax Medical Campus, Falls Church, VA, United States; Inova Medicine, Inova Health System, Falls Church, VA, United States
| | - Zobair M Younossi
- Department of Medicine, Center for Liver Disease, Inova Fairfax Medical Campus, Falls Church, VA, United States; Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, United States; Inova Medicine, Inova Health System, Falls Church, VA, United States.
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19
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Morales-Romero J, Ortíz-León MC, Hernández-Gutiérrez H, Bahena-Cerón RA, Miranda-Reza A, Marín-Carmona JA, Rodríguez-Romero E, Mora SI, García-Román J, Peréz-Carreón JI, Rivadeneyra-Domínguez E, Riande-Juárez G, García-Román R. [Risk factors for metabolic dysfunction-associated fatty liver disease in the Hispanic-Mexican population.]. Rev Esp Salud Publica 2023; 97:e202306053. [PMID: 37387209 PMCID: PMC10540909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 05/20/2023] [Indexed: 07/01/2023] Open
Abstract
OBJECTIVE Metabolic dysfunction-associated fatty liver disease (MAFLD) is a poor attended disease, which has gained attention due the elevated number of cases in countries as Mexico, where the incidence is the number 4th globally. MAFLD develops in obese or overweighted individuals and is characterized by triglycerides accumulation in the liver, this condition can develop to hepatocellular carcinoma. It has been observed that MAFLD depends on the genetics and lifestyle. Due to the high prevalence of this disease among Hispanic population, we focused on this study in the characteristics and prevalence of MAFLD in Mexican patients. METHODS In this study were included 572 overweighted and obese patients, who underwent a screening analysis using the fatty liver index (IHG), clinical parameters were analysed, demographic and comorbidities. Frequency of variables were obtained, and the data were analysed by Chi-square test or Fisher test, odd ratio (OR) and binary logistic regression. RESULTS A MALFD prevalence of 37% were obtained, where the history of familiar obesity, paracetamol usage, carbohydrate and fat intake are shown to be risk factors. It was found that high blood pressure, central obesity and hypertriglyceridemia were also associated to the MAFLD development. On the other hand, physical exercise was a protector factor. CONCLUSIONS Our results show the necessity to study the MAFLD causalities in Mexican patients, focused on the paracetamol intake.
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Affiliation(s)
- Jaime Morales-Romero
- Instituto de Salud Pública, Universidad Veracruzana.Universidad VeracruzanaXalapa (Veracruz)Mexico
| | | | | | - Roberto A. Bahena-Cerón
- Facultad de Química Farmacéutica Biológica, Universidad Veracruzana.Universidad VeracruzanaXalapa (Veracruz)Mexico
| | - Aidé Miranda-Reza
- Facultad de Estadística e Informática, Universidad Veracruzana.Universidad VeracruzanaXalapa (Veracruz)Mexico
| | - José A. Marín-Carmona
- Facultad de Biología, Universidad Veracruzana.Universidad VeracruzanaXalapa (Veracruz)Mexico
| | - Edit Rodríguez-Romero
- Instituto de Salud Pública, Universidad Veracruzana.Universidad VeracruzanaXalapa (Veracruz)Mexico
| | - Silvia I. Mora
- Unidad de Procedimientos Preparativos y de Acceso a Servicios de Proteómica (UPASPro), Instituto de Investigaciones Biomédicas UNAM.Instituto de Investigaciones Biomédicas UNAMCiudad de México.Mexico
| | - Jonathan García-Román
- Facultad de Medicina-Región Poza Rica-Tuxpan, Universidad Veracruzana.Universidad VeracruzanaPoza Rica (Veracruz)Mexico
| | - Julio I. Peréz-Carreón
- Laboratorio de Bioquímica y Estructura de Proteínas, Instituto Nacional de Medicina Genómica.Instituto Nacional de Medicina GenómicaCiudad de México.Mexico
| | | | - Gabriel Riande-Juárez
- Instituto de Salud Pública, Universidad Veracruzana.Universidad VeracruzanaXalapa (Veracruz)Mexico
| | - Rebeca García-Román
- Instituto de Salud Pública, Universidad Veracruzana.Universidad VeracruzanaXalapa (Veracruz)Mexico
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20
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Castera L, Cusi K. Diabetes and cirrhosis: Current concepts on diagnosis and management. Hepatology 2023; 77:2128-2146. [PMID: 36631005 DOI: 10.1097/hep.0000000000000263] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 10/03/2022] [Indexed: 01/13/2023]
Abstract
Type 2 diabetes mellitus is often associated with cirrhosis as comorbidities, acute illness, medications, and other conditions profoundly alter glucose metabolism. Both conditions are closely related in NAFLD, the leading cause of chronic liver disease, and given its rising burden worldwide, management of type 2 diabetes mellitus in cirrhosis will be an increasingly common dilemma. Having diabetes increases cirrhosis-related complications, including HCC as well as overall mortality. In the absence of effective treatments for cirrhosis, patients with type 2 diabetes mellitus should be systematically screened as early as possible for NAFLD-related fibrosis/cirrhosis using noninvasive tools, starting with a FIB-4 index followed by transient elastography, if available. In people with cirrhosis, an early diagnosis of diabetes is critical for an optimal management strategy (ie, nutritional goals, and glycemic targets). Diagnosis of diabetes may be missed if based on A1C in patients with cirrhosis and impaired liver function (Child-Pugh B-C) as anemia may turn the test unreliable. Clinicians must also become aware of their high risk of hypoglycemia, especially in decompensated cirrhosis where insulin is the only therapy. Care should be within multidisciplinary teams (nutritionists, obesity management teams, endocrinologists, hepatologists, and others) and take advantage of novel glucose-monitoring devices. Clinicians should become familiar with the safety and efficacy of diabetes medications for patients with advanced fibrosis and compensated cirrhosis. Management is conditioned by whether the patient has either compensated or decompensated cirrhosis. This review gives an update on the complex relationship between cirrhosis and type 2 diabetes mellitus, with a focus on its diagnosis and treatment, and highlights knowledge gaps and future directions.
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Affiliation(s)
- Laurent Castera
- Departement of Hepatology, Hospital Beaujon, Assistance Publique-Hôpitaux de Paris, INSERM UMR 1149, Université Paris Cité, Clichy, France
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, The University of Florida, Gainesville, Florida, USA
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21
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Yaribeygi H, Maleki M, Jamialahmadi T, Moallem SA, Sahebkar A. Hepatic benefits of sodium-glucose cotransporter 2 inhibitors in liver disorders. EXCLI JOURNAL 2023; 22:403-414. [PMID: 37346806 PMCID: PMC10279968 DOI: 10.17179/excli2023-6022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 04/18/2023] [Indexed: 06/23/2023]
Abstract
Diabetic patients are at higher risk of liver dysfunction compared with the normal population. Thus, using hypoglycemic agents to improve liver efficiency is important in these patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are newly developed antidiabetic drugs with potent glucose-lowering effects. However, recent limited evidence suggests that they have extra-glycemic benefits and may be able to exert protective effects on the liver. Hence, these drugs could serve as promising pharmacological agents with multiple benefits against different hepatic disorders. In this review, the current knowledge about the possible effects of SGLT2 inhibitors on different forms of liver complications and possible underlying mechanisms are discussed.
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Affiliation(s)
- Habib Yaribeygi
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran
| | - Mina Maleki
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tannaz Jamialahmadi
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Adel Moallem
- Department of Pharmacology and Toxicology, College of Pharmacy, Al-Zahraa University for Women, Karbala, Iraq
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Medicine, The University of Western Australia, Perth, Australia
- Department of Biotechnology, Mashhad University of Medical Sciences, Mashhad, Iran
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22
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Kosmalski M, Śliwińska A, Drzewoski J. Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus—The Chicken or the Egg Dilemma. Biomedicines 2023; 11:biomedicines11041097. [PMID: 37189715 DOI: 10.3390/biomedicines11041097] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/28/2023] [Accepted: 03/28/2023] [Indexed: 04/08/2023] Open
Abstract
In clinical practice, we often deal with patients who suffer from non-alcoholic fatty liver disease (NAFLD) concurrent with type 2 diabetes mellitus (T2DM). The etiopathogenesis of NAFLD is mainly connected with insulin resistance (IR) and obesity. Similarly, the latter patients are in the process of developing T2DM. However, the mechanisms of NAFLD and T2DM coexistence have not been fully elucidated. Considering that both diseases and their complications are of epidemic proportions and significantly affect the length and quality of life, we aimed to answer which of these diseases appears first and thereby highlight the need for their diagnosis and treatment. To address this question, we present and discuss the epidemiological data, diagnoses, complications and pathomechanisms of these two coexisting metabolic diseases. This question is difficult to answer due to the lack of a uniform procedure for NAFLD diagnosis and the asymptomatic nature of both diseases, especially at their beginning stages. To conclude, most researchers suggest that NAFLD appears as the first disease and starts the sequence of circumstances leading ultimately to the development of T2DM. However, there are also data suggesting that T2DM develops before NAFLD. Despite the fact that we cannot definitively answer this question, it is very important to bring the attention of clinicians and researchers to the coexistence of NAFLD and T2DM in order to prevent their consequences.
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Affiliation(s)
- Marcin Kosmalski
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Agnieszka Śliwińska
- Department of Nucleic Acids Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland
| | - Józef Drzewoski
- Central Teaching Hospital of Medical University of Lodz, 92-213 Lodz, Poland
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23
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Xin Kwok AL, Balasooriya H, Ng K. Efficacy of ellagic acid and ellagitannins on diabetes mellitus: A meta-analysis of preclinical and clinical trials. FOOD BIOSCI 2023. [DOI: 10.1016/j.fbio.2023.102573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2023]
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Villela Nogueira CA, Leite NC. Nonalcoholic Fatty Liver in the Pathogenesis of Diabetes. THE DIABETES TEXTBOOK 2023:261-270. [DOI: 10.1007/978-3-031-25519-9_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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25
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Li R, Kong D, Ye Z, Zong G, Hu K, Xu W, Fang P, Zhang L, Zhou Y, Zhang K, Xue Y. Correlation of multiple lipid and lipoprotein ratios with nonalcoholic fatty liver disease in patients with newly diagnosed type 2 diabetic mellitus: A retrospective study. Front Endocrinol (Lausanne) 2023; 14:1127134. [PMID: 36875464 PMCID: PMC9982122 DOI: 10.3389/fendo.2023.1127134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/03/2023] [Indexed: 02/19/2023] Open
Abstract
BACKGROUND AND OBJECTIVE The diagnostic value of lipid and lipoprotein ratios for NAFLD in newly diagnosed T2DM remains unclear. This study aimed to investigate the relationships between lipid and lipoprotein ratios and the risk of NAFLD in subjects with newly diagnosed T2DM. METHODS A total of 371 newly diagnosed T2DM patients with NAFLD and 360 newly diagnosed T2DM without NAFLD were enrolled in the study. Demographics variables, clinical history and serum biochemical indicators of the subjects were collected. Six lipid and lipoprotein ratios, including triglycerides to high-density lipoprotein-cholesterol (TG/HDL-C) ratio, cholesterol to HDL-C (TC/HDL-C) ratio, free fatty acid to HDL-C (FFA/HDL-C) ratio, uric acid to HDL-C (UA/HDL-C) ratio, low-density lipoprotein-cholesterol to HDL-C (LDL-C/HDL-C) ratio, apolipoprotein B to apolipoprotein A1 (APOB/A1) ratio, were calculated. We compared the differences in lipid and lipoprotein ratios between NAFLD group and non-NAFLD group, and further analyzed the correlation and diagnostic value of these ratios with the risk of NAFLD in the newly diagnosed T2DM patients. RESULTS The proportion of NAFLD in patients with newly diagnosed T2DM increased progressively over the range Q1 to Q4 of six lipid ratios, including the TG/HDL-C ratio, TC/HDL-C ratio, FFA/HDL-C ratio, UA/HDL-C ratio, LDL-C/HDL-C ratio, and APOB/A1 ratio. After adjusting for multiple confounders, TG/HDL-C, TC/HDL-C, UA/HDL-C, LDL-C/HDL-C and APOB/A1 were all strongly correlated with the risk of NAFLD in patients with newly diagnosed T2DM. In patients with newly-onset T2DM, the TG/HDL-C ratio was the most powerful indicator for the diagnosis of NAFLD among all six indicators, with an area under the curve (AUC) of 0.732 (95% CI 0.696-0.769). In addition, TG/HDL-C ratio>1.405, with a sensitivity of 73.8% and specificity of 60.1%, had a good diagnostic ability for NAFLD in patients with newly diagnosed T2DM. CONCLUSIONS The TG/HDL-C ratio may be an effective marker to help identify the risk of NAFLD in patients with newly diagnosed T2DM.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Ying Xue
- *Correspondence: Ying Xue, ; Keqin Zhang,
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26
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He W, Huang C, Wang L, Su W, Wang S, Huang P, Zhang X, Huang Y, Zhao Y, Lin M, Shi X, Li X. The correlation between triiodothyronine and the severity of liver fibrosis. BMC Endocr Disord 2022; 22:313. [PMID: 36503486 PMCID: PMC9743744 DOI: 10.1186/s12902-022-01228-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 11/23/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The severity of liver fibrosis is an important predictor of death in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, there is still no definite conclusion on the relationship between triiodothyronine (T3) and the severity of liver fibrosis. Thus, the aim of this study was to analyze the correlation between T3 level and the severity of liver fibrosis. METHODS We performed a cross-sectional study of 2072 T2DM patients with normal thyroid function from January 2017 to January 2020. NAFLD fibrosis score (NFS), Fibrosis index based on the 4 factors (FIB-4) and BARD score (BARD) were used to assess the severity of fibrosis in T2DM patients, and linear regression analyses were used to determine the factors independently associated with liver fibrosis. Further experiments were performed to assess the impact of low T3 on fibrosis progression in mice model and explore possible mechanisms. RESULTS Free triiodothyronine (fT3) levels had significantly inverse correlations with NFS and FIB-4, and BARD in T2DM patients (P < 0.05). In multiple linear regression analyses, decreased fT3 level was an independent risk factor for the severity of liver fibrosis of T2DM patients (P < 0.01). Findings from in-vivo experiment using mice model proved that hypothyroidism mice had more severe of liver fibrosis than those mice with normal thyroid function. We also found that T3 could inhibit the profibrotic TREM2+CD9+ macrophage, which had been identified an important player in the progression of liver fibrosis. CONCLUSION The findings from this study proved an inverse correlation between T3 level and the severity of liver fibrosis, and lower fT3 level within the normal range was an independent risk factor for severe liver fibrosis.
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Affiliation(s)
- Weiwei He
- School of Medicine, Xiamen University, Xiamen, China
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Caoxin Huang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Liying Wang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Weijuan Su
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Shunhua Wang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Peiying Huang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Xiaofang Zhang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Yinxiang Huang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Yan Zhao
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Mingzhu Lin
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Xiulin Shi
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China.
- Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, No.55 Zhenhai Road, 361003, Xaimen, China.
| | - Xuejun Li
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China.
- Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, No.55 Zhenhai Road, 361003, Xaimen, China.
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Kalavalapalli S, Leiva EG, Lomonaco R, Chi X, Shrestha S, Dillard R, Budd J, Romero JP, Li C, Bril F, Samraj G, Pennington J, Townsend P, Orlando F, Shetty S, Mansour L, Silva-Sombra LR, Bedossa P, Malaty J, Barb D, Gurka MJ, Cusi K. Adipose Tissue Insulin Resistance Predicts the Severity of Liver Fibrosis in Patients with Type 2 Diabetes and NAFLD. J Clin Endocrinol Metab 2022; 108:1192-1201. [PMID: 36378995 DOI: 10.1210/clinem/dgac660] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022]
Abstract
CONTEXT While T2D is a risk factor for liver fibrosis in NAFLD, the specific contribution of insulin resistance (IR) relative to other factors is unknown. OBJECTIVE Assess the impact on liver fibrosis in NAFLD of adipose tissue (Adipo-IR) and liver (HOMA-IR) IR in people with T2D and NAFLD. DESIGN Participants were screened by elastography in the outpatient clinics for hepatic steatosis and fibrosis, including routine metabolites, cytokeratin-18 (marker of hepatocyte apoptosis/steatohepatitis), and HOMA-IR/Adipo-IR. SETTING University ambulatory care practice. PARTICIPANTS 483 participants with T2D. INTERVENTION Screening for steatosis and fibrosis with elastography. MAIN OUTCOME MEASURES Liver steatosis (CAP) and fibrosis (LSM) and measurements of IR (Adipo-IR, HOMA-IR) and fibrosis (cytokeratin-18). RESULTS Clinically significant liver fibrosis (stage F ≥ 2= LSM ≥8.0 kPa) was found in 11%, having more features of the metabolic syndrome, lower adiponectin, and higher AST, ALT, liver fat and cytokeratin-18 (p < 0.05-0.01). In multivariable analysis including just clinical variables (model 1), obesity (BMI) had the strongest association with fibrosis (OR: 2.56, CI:1.87-3.50; p < 0.01). When metabolic measurements and cytokeratin-18 were included (model 2), only BMI, AST and liver fat remained significant. When fibrosis stage was adjusted for BMI, AST, and steatosis (model 3), only adipo-IR remained strongly associated with fibrosis (OR: 1.51, CI:1.05-2.16; p = 0.03), but not BMI, hepatic IR or steatosis. CONCLUSIONS These findings pinpoint to the central role of dysfunctional, insulin-resistant adipose tissue to advanced fibrosis in T2D, beyond simply BMI or steatosis. The clinical implication is that targeting adipose tissue should be the priority of treatment in NAFLD.
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Affiliation(s)
- Srilaxmi Kalavalapalli
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Eddison Godinez Leiva
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Xiaofei Chi
- Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | - Sulav Shrestha
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Rachel Dillard
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Jeffery Budd
- Division of General Internal Medicine, University of Florida, Gainesville, FL, USA
| | | | - Christina Li
- Division of General Internal Medicine, University of Florida, Gainesville, FL, USA
| | - Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - George Samraj
- Department of Family Medicine, University of Florida, Gainesville, FL, USA
| | - John Pennington
- Department of Family Medicine, University of Florida, Gainesville, FL, USA
| | - Petra Townsend
- Department of Family Medicine, University of Florida, Gainesville, FL, USA
| | - Frank Orlando
- Department of Family Medicine, University of Florida, Gainesville, FL, USA
| | - Shwetha Shetty
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Lydia Mansour
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | | | - Pierre Bedossa
- Publique-Hôpitaux de Paris, Beaujon Hospital, Pathology Department and University Paris-Diderot, Paris, France
| | - John Malaty
- Department of Family Medicine, University of Florida, Gainesville, FL, USA
| | - Diana Barb
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Matthew J Gurka
- Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
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Succurro E, Marini MA, Fiorentino TV, Perticone M, Sciacqua A, Andreozzi F, Sesti G. Sex-specific differences in prevalence of nonalcoholic fatty liver disease in subjects with prediabetes and type 2 diabetes. Diabetes Res Clin Pract 2022; 190:110027. [PMID: 35917992 DOI: 10.1016/j.diabres.2022.110027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 07/26/2022] [Accepted: 07/28/2022] [Indexed: 12/18/2022]
Abstract
AIMS To characterize the prevalence of NAFLD among subjects with NGT, prediabetes and type 2 diabetes (T2DM) by sex in adults with one or more cardio-metabolic risk factors, and to assess whether cardio-metabolic factors explained sex-related differences in NAFLD prevalence. METHODS The study sample encompasses 742 individuals with NGT, 553 with prediabetes, and 431 with T2DM. RESULTS Women with prediabetes and T2DM exhibited greater relative differences in waist circumference, HOMA-IR, hsCRP, and lipid profile than prediabetic and diabetic men when compared with their NGT counterparts. Formal tests for glucose tolerance status × sex interaction were statistically significant for waist circumference (P = 0.008), HOMA-IR (P = 0.03), total cholesterol (P = 0.003), LDL (P = 0.001), HDL (P = 0.006), triglycerides (P < 0.0001), and hsCRP (P < 0.05). In a logistic regression analysis, prediabetic and diabetic women exhibited a higher OR for NAFLD than their male counterparts with test for glucose tolerance status × sex interaction being statistically significant. CONCLUSIONS Prediabetic and diabetic women have higher OR of having NAFLD than men. Deterioration of glucose homeostasis in women is associated with a greater worsening in metabolic risk factors than men, which may explain the stronger impact of prediabetes and T2DM on NAFLD in women.
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Affiliation(s)
- Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro 88100, Italy
| | | | - Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro 88100, Italy
| | - Maria Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro 88100, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro 88100, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro 88100, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome 00189, Italy.
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Kolluru K, Giri A, Kumar S, Acharya S, Agrawal S, Wanjari A, Gaidhane SA. Association of Metabolic-Associated Fatty Liver Disease With Various Anthropometric Parameters in Pre-diabetes in Comparison With Diabetes and Control: A Single Tertiary Care Center Study. Cureus 2022; 14:e27130. [PMID: 36004015 PMCID: PMC9392852 DOI: 10.7759/cureus.27130] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 07/21/2022] [Indexed: 11/17/2022] Open
Abstract
Introduction Individuals with pre-diabetes and metabolic-associated fatty liver disease (MAFLD) have an increased risk of developing diabetes mellitus (type-2) when compared with individuals with pre-diabetes without MAFLD. Patients with any of the components of metabolic syndrome should be screened for the risk of MAFLD, as all its components are well correlated with the degree of liver fat content. In this research article, we have highlighted the association of MAFLD with various anthropometric parameters in pre-diabetes as compared to diabetes and normal individual. Methods In this cross-sectional study a total of 356 patients more than 18 years of age who meet the criteria for diabetes and pre-diabetes according to WHO, were enrolled. Anthropometric indices like body mass index (BMI), waist-hip ratio, waist to height ratio, and neck circumference were recorded. Patients underwent ultrasonography of liver and blood investigations like lipid profile, and liver function tests. Results The prevalence of MAFLD observed in this study was 44.1% in diabetics and 22% in pre-diabetics, compared to 9.2% in healthy controls. The ROC analyses showed that MAFLD predict pre-diabetes using the waist-hip ratio was higher in women compared to men (0.750 and 0.693 respectively). In men, the waist-hip ratio was followed by 0.648 for Neck Circumference, 0.646 for BMI, and 0.635 for waist-to-height ratio respectively, whereas the ROC analyses in women showed that other than waist-hip ratio, no other anthropometric index that had consistently higher AUC value. Conclusion Though there was an association between high BMI, waist-hip ratio, waist to height ratio, and neck circumference with MAFLD in pre-diabetes, it was not strongly associated as in the diabetic group.
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Bao S, Wang X, Ma Q, Wei C, Nan J, Ao W. Mongolian medicine in treating type 2 diabetes mellitus combined with nonalcoholic fatty liver disease via FXR/LXR-mediated P2X7R/NLRP3/NF-κB pathway activation. CHINESE HERBAL MEDICINES 2022; 14:367-375. [PMID: 36118003 PMCID: PMC9476729 DOI: 10.1016/j.chmed.2022.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 02/17/2022] [Accepted: 06/15/2022] [Indexed: 11/20/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are the most problematic metabolic diseases in the world. NAFLD encompasses a spectrum of severity, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis, increasing the risk of cirrhosis and hepatocellular carcinoma. Importantly, NAFLD is closely linked to obesity and tightly interrelated with insulin resistance and T2DM. T2DM and NAFLD (T2DM-NAFLD) are called as the Xike Rixijing Disease and Tonglaga Indigestion Disease respectively, in Mongolian medicine. Xike Rixijing Disease maybe develop into Tonglaga Indigestion Disease. Forturnately many Mongolian medicines show efficient treatment of T2DM-NAFLD, such as Agriophyllum squarrosum, Haliyasu (dried powder of camel placenta), Digeda-4 (herbs of Lomatogonium carinthiacum, rhizomata of Coptis chinensis, ripe fruits of Gardenia jasminoides, herbs of Dianthus superbus), Guangmingyan Siwei Decoction Powder (Halite, ripe fruits of Terminalia chebula, rhizomata of Zingiber officinale, fruit clusters of Piper longum), Tonglaga-5 (ripe fruits of Punica granatum, barks of Cinnamomum cassia, ripe fruits of Amomum kravanh, fruit clusters of Piper longum, flowers of Carthamus tinctorius), Tegexidegeqi (rhizomata of Inula helenium, ripe fruits of Gardenia jasminoides, rhizomata of Platycodon grandiflorum, rhizomata of Coptis chinensis, heartwood of Caesalpinia sappan), Ligan Shiliu Bawei San (ripe fruits of Punica granatum, barks of Cinnamomum cassia, ripe fruits of Amomum kravanh, fruit clusters of Piper longum, flowers of Carthamus tinctorius, ripe fruits of Amomum tsao-ko, rhizomata of Zingiber officinale), etc. Principles of Mongolian medicine in treating diseases: by balancing “three essences or roots” and “seven elements”, strengthening liver and kidney function, transporting nutrients to enhance physical strength and disease resistance, and combined with drugs for comprehensive conditioning treatment. However, their molecular mechanisms remain unclear. In this review, we prospect that Mongolian medicines might be a promising treatment for T2DM-NAFLD by activating P2X7R/NLRP3/NF-κB inflammatory pathway via lipid-sensitive nuclear receptors (i.e., FXR and LXR).
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Affiliation(s)
- Shuyin Bao
- Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao 028000, China
- Jilin Key Laboratory for Traditional Chinese Korean Medicine, College of Pharmacy, Yanbian University, Yanji 133002, China
| | - Xiuzhi Wang
- Department of Medicines and Foods, Tongliao Vocational College, Tongliao 028000, China
| | - Qianqian Ma
- Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao 028000, China
| | - Chengxi Wei
- Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao 028000, China
- Corresponding authors.
| | - Jixing Nan
- Jilin Key Laboratory for Traditional Chinese Korean Medicine, College of Pharmacy, Yanbian University, Yanji 133002, China
- Corresponding authors.
| | - Wuliji Ao
- Research and development center, Inner Mongolia Research Institute of Traditional Mongolian Medicine Engineering Technology, Tongliao 028000, China
- Mongolian Medicine R&D National Local Union Engineering Research Center, Inner Mongolia Minzu University, Tongliao 028000, China
- Corresponding authors.
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Exploring the Path of Mediterranean Diet, Non-Alcoholic Fatty Liver Disease (NAFLD) and Inflammation towards 10-Year Cardiovascular Disease (CVD) Risk: The ATTICA Study 10-Year Follow-Up (2002-2012). Nutrients 2022; 14:nu14122367. [PMID: 35745097 PMCID: PMC9229573 DOI: 10.3390/nu14122367] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/03/2022] [Accepted: 06/05/2022] [Indexed: 01/27/2023] Open
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease, affecting ~30% of the population and increasing CVD. This study aimed to explore the direct, indirect and combined effects of Mediterranean diet, NAFLD and inflammation on the 10-year CVD risk in a healthy adult population. Methods: Using baseline and 10-year follow-up data from the ATTICA study, adherence to Mediterranean diet was measured using MedDietScore, and presence of NAFLD at baseline was assessed using the fatty liver index (FLI). Participants’ 10-year CVD outcomes were recorded and C-reactive protein (CRP) was used as a surrogate marker for inflammation. The direct and indirect roles of these factors were explored using logistic regression models and the pathways between them were analysed using a structural equation model (SEM). Results: NAFLD prevalence was 22.9% and its presence was 17% less likely for every unit increase in MedDietScore. NAFLD presence at baseline was associated with increased 10-year CVD incidence (39.4% vs. 14.5%, p = 0.002), but when adjusted for MedDietScore, NAFLD was not an independent predictor of 10-year CVD risk. MedDietScore was an independent protective factor of 10-year CVD risk (OR = 0.989, 95% CI: 0.847, 0.935), when adjusted for NAFLD at baseline, age, gender, sedentary lifestyle and other confounders. Further exploration using SEM showed that MedDietScore was associated with CVD risk directly even when inflammation as CRP was introduced as a potential mediator. Conclusion: FLI as a proxy measure of NAFLD is a strong predictor of 10-year CVD risk, and this prognostic relationship seems to be moderated by the level of adherence to Mediterranean diet. Adherence to Mediterranean diet remained an independent and direct CVD risk factor irrespective of NAFLD status and CRP.
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Tang Y, Wei ZM, Li N, Sun LL, Jin ZY, Wu Z, Sun H. Quantitative analysis of the risk of type 2 diabetes and fatty liver in non-obese individuals by computed tomography. Abdom Radiol (NY) 2022; 47:2099-2105. [PMID: 35389075 DOI: 10.1007/s00261-022-03506-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/19/2022] [Accepted: 03/21/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE To explore the risk of fatty liver and type 2 diabetes with quantitative parameters of abdominal computed tomography (CT) in a non-obese population. METHODS A retrospective analysis of abdominal CT and hospitalization records of inpatients admitted from May 2019 to May 2021 were divided into a non-obese control group (n = 143 cases) and a non-obese diabetes group (n = 105 cases). The measured abdominal CT parameters included body width, liver and spleen CT values, and the ratio of the liver CT value to the spleen CT value (L/S ratio). Logistic regression was used to analyze the risk factors for diabetes in non-obese individuals. RESULTS Three variables including body width (P < 0.001), liver CT value (P = 0.013), and L/S ratio (P = 0.002) were significantly correlated with the presence of diabetes in non-obese individuals. CONCLUSION Body width, liver CT value, and L/S ratio can be used to indicate the risk of type 2 diabetes in non-obese individuals.
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Affiliation(s)
- Yi Tang
- Department of Endocrinology, Fushun Central Hospital, Fushun, 113006, Liaoning Province, China
| | - Ze-Min Wei
- Department of Endocrinology, Fushun Central Hospital, Fushun, 113006, Liaoning Province, China
| | - Ning Li
- Department of Radiology, Fushun Central Hospital, Fushun, 113006, Liaoning Province, China
| | - Lin-Lin Sun
- Department of Endocrinology, Fushun Central Hospital, Fushun, 113006, Liaoning Province, China
| | - Zheng-Yu Jin
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Zhe Wu
- Department of Radiology, Fushun Central Hospital, Fushun, 113006, Liaoning Province, China.
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Hao Sun
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
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Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022; 28:528-562. [PMID: 35569886 DOI: 10.1016/j.eprac.2022.03.010] [Citation(s) in RCA: 537] [Impact Index Per Article: 179.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/11/2022] [Accepted: 03/11/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders. METHODS The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RECOMMENDATION SUMMARY This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base. CONCLUSION NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.
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Affiliation(s)
- Kenneth Cusi
- Guideine and Algorithm Task Forces Co-Chair, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida
| | - Scott Isaacs
- Guideline and Algorithm Task Forces Co-Chair, Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia
| | - Diana Barb
- University of Florida, Gainesville, Florida
| | - Rita Basu
- Division of Endocrinology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Sonia Caprio
- Yale University School of Medicine, New Haven, Connecticut
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - Jeffrey I Mechanick
- The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health at Mount Sinai Heart, Icahn School of Medicine at Mount Sinai
| | | | - Karl Nadolsky
- Michigan State University College of Human Medicine, Grand Rapids, Michigan
| | - Mary E Rinella
- AASLD Representative, University of Pritzker School of Medicine, Chicago, Illinois
| | - Miriam B Vos
- Center for Clinical and Translational Research, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Zobair Younossi
- AASLD Representative, Inova Medicine, Inova Health System, Falls Church, Virginia
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Ji Y, Liang Y, Mak JC, Ip MS. Obstructive sleep apnea, intermittent hypoxia and non-alcoholic fatty liver disease. Sleep Med 2022; 95:16-28. [DOI: 10.1016/j.sleep.2022.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 04/10/2022] [Accepted: 04/11/2022] [Indexed: 12/15/2022]
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Lee DH, Sung SU, Lee YK, Lim IH, Jang H, Joo SK, Park JH, Chang MS, So YH, Kim W. A sequential approach using the age-adjusted fibrosis-4 index and vibration-controlled transient elastography to detect advanced fibrosis in Korean patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2022; 55:994-1007. [PMID: 35005800 DOI: 10.1111/apt.16766] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/02/2021] [Accepted: 12/24/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Vibration-controlled transient elastography (VCTE) has shown good diagnostic performance in predicting fibrosis stages in patients with non-alcoholic fatty liver disease (NAFLD). However, an optimal diagnostic approach to detect advanced fibrosis in patients with NAFLD has not been established. APPROACH AND RESULTS We prospectively collected data from 539 subjects who underwent liver biopsy at a single centre between January 2014 and December 2019. Diagnostic performance was estimated using the area under the receiver-operating characteristic curve (AUROC). Several models combining the fibrosis 4 index (FIB-4) score and liver stiffness measurement (LSM) were analysed to reduce the need for unnecessary liver biopsies. We observed significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4) in 173 (32.1%), 74 (13.7%) and 46 subjects (8.5%), respectively. The AUROCs (95% CI) for LSMs to diagnose ≥F2, ≥F3 and F4 were 0.82 (0.78-0.85), 0.92 (0.89-0.94) and 0.95 (0.93-0.97), respectively. Optimal LSM cut-off values were 6.7 (≥F2), 8.3 (≥F3) and 9.8 (F4) kPa. LSMs were affected by waist circumference, serum albumin and fibrosis stage (R2 = 0.315). Abdominal obesity, elevated transaminase, diabetes mellitus and high IQR/Median were associated with the discordance of ≥2 fibrosis stages between LSMs and histologic data. The sequential use of the age-adjusted FIB-4 and LSMs yielded the least uncertainty (5.3%) in classifying disease severity with the highest diagnostic accuracy (81%) among a variety of non-invasive test combinations. CONCLUSIONS The sequential approach of age-adjusted FIB-4 and VCTE could represent a practical diagnostic strategy to detect advanced fibrosis in NAFLD (ClinicalTrials.gov #NCT02206841).
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Affiliation(s)
- Dong Hyeon Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Se Un Sung
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yun Kyu Lee
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ik Hyeon Lim
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Heejoon Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Sae Kyoung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Jeong Hwan Park
- Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Mee Soo Chang
- Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Young Ho So
- Department of Radiology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
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Kim PH, Cho YA, Yoon HM, Bak B, Lee JS, Jung AY, Oh SH, Kim KM. Accuracy of attenuation imaging in the assessment of pediatric hepatic steatosis: correlation with the controlled attenuation parameter. Ultrasonography 2022; 41:761-769. [PMID: 35765803 PMCID: PMC9532206 DOI: 10.14366/usg.21246] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 03/05/2022] [Indexed: 11/03/2022] Open
Abstract
PURPOSE This study evaluated the accuracy of attenuation imaging (ATI) for the assessment of hepatic steatosis in pediatric patients, in comparison with the FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP). METHODS Consecutive pediatric patients referred for evaluation of obesity who underwent both ATI and FibroScan between February 2020 and September 2021 were included. The correlation between attenuation coefficient (AC) and CAP values was assessed using the Spearman test. The AC cutoff value for discriminating hepatic steatosis corresponding to a CAP value of 241 dB/m was calculated. Multivariable linear regression analysis was performed to estimate the strength of the association between AC and CAP. The diagnostic accuracy of AC cutoffs was estimated using the imperfect gold-standard methodology based on a two-level Bayesian latent class model. RESULTS Seventy patients (median age, 12.5 years; interquartile range, 11.0 to 14.0 years; male:female, 58:12) were included. AC and CAP showed a moderate-to-good correlation (ρ =0.646, P<0.001). Multivariable regression analysis affirmed the significant association between AC and CAP (P<0.001). The correlation was not evident in patients with a body mass index ≥30 kg/m2 (ρ=-0.202, P=0.551). Linear regression revealed that an AC cutoff of 0.66 dB/cm/MHz corresponded to a CAP of 241 dB/m (sensitivity, 0.93; 95% confidence interval [CI], 0.85 to 0.98 and specificity, 0.87; 95% CI, 0.56 to 1.00). CONCLUSION ATI showed an acceptable correlation with CAP values in a pediatric population, especially in patients with a body mass index <30 kg/m2. An AC cutoff of 0.66 dB/cm/MHz, corresponding to a CAP of 241 dB/m, can accurately diagnose hepatic steatosis.
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Affiliation(s)
- Pyeong Hwa Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Ah Cho
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Mang Yoon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Boram Bak
- University of Ulsan Foundation for Industry Cooperation, Ulsan, Korea
| | - Jin Seong Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ah Young Jung
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seak Hee Oh
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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The Coexistence of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. J Clin Med 2022; 11:jcm11051375. [PMID: 35268466 PMCID: PMC8910939 DOI: 10.3390/jcm11051375] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/28/2022] [Accepted: 03/01/2022] [Indexed: 12/12/2022] Open
Abstract
The incidence of nonalcoholic fatty liver disease (NAFLD) is growing worldwide. Epidemiological data suggest a strong relationship between NAFLD and T2DM. This is associated with common risk factors and pathogenesis, where obesity, insulin resistance and dyslipidemia play pivotal roles. Expanding knowledge on the coexistence of NAFLD and T2DM could not only protect against liver damage and glucotoxicity, but may also theoretically prevent the subsequent occurrence of other diseases, such as cancer and cardiovascular disorders, as well as influence morbidity and mortality rates. In everyday clinical practice, underestimation of this problem is still observed. NAFLD is not looked for in T2DM patients; on the contrary, diagnosis for glucose metabolism disturbances is usually not performed in patients with NAFLD. However, simple and cost-effective methods of detection of fatty liver in T2DM patients are still needed, especially in outpatient settings. The treatment of NAFLD, especially where it coexists with T2DM, consists mainly of lifestyle modification. It is also suggested that some drugs, including hypoglycemic agents, may be used to treat NAFLD. Therefore, the aim of this review is to detail current knowledge of NAFLD and T2DM comorbidity, its prevalence, common pathogenesis, diagnostic procedures, complications and treatment, with special attention to outpatient clinics.
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Li H, Xu QY, Xie Y, Luo JJ, Cao HX, Pan Q. Effects of chronic HBV infection on lipid metabolism in non-alcoholic fatty liver disease: A lipidomic analysis. Ann Hepatol 2022; 24:100316. [PMID: 33515803 DOI: 10.1016/j.aohep.2021.100316] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/04/2021] [Accepted: 01/06/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Chronic hepatitis B virus (HBV) infection exerts an impact on lipid metabolism, but its interaction with dysmetabolism-based non-alcoholic fatty liver disease (NAFLD) remains uncertain. The purpose of the study was to investigate the effects of HBV infection on lipid metabolism, hepatic steatosis and related impairments of NAFLD patients. METHODS Biopsy-proven Chinese NAFLD patients with (NAFLD-HBV group, n = 21) or without chronic HBV infection (NAFLD group, n = 41) were enrolled in the case-control study. Their serum lipidomics was subjected to individual investigation by ultra-performance liquid chromatography-tandem mass spectrometry. Steatosis, activity, and fibrosis (SAF) scoring revealed the NAFLD-specific pathological characteristics. RESULTS Chronic HBV infection was associated with global alteration of serum lipidomics in NAFLD patients. Upregulation of phosphatidylcholine (PCs), choline plasmalogen (PC-Os) and downregulation of free fatty acids (FFAs), lysophosphatidylcholine (LPCs) dominated the HBV-related lipidomic characteristics. Compared to those of NAFLD group, the levels of serum hepatoxic lipids (FFA16:0, FFA16: 1, FFA18:1, FFA18:2) were significantly lowered in the NAFLD-HBV group. These low-level FFAs demonstrated correlation to statistical improvements in aspartate aminotransferase activity (FFA16:0, r = 0.33; FFA16:1, r = 0.37; FFA18:1, r = 0.32; FFA18:2, r = 0.42), hepatocyte steatosis (FFA16: 1, r = 0.39; FFA18:1, r = 0.39; FFA18:2, r = 0.32), and ballooning (FFA16:0, r = 0.30; FFA16:1, r = 0.45; FFA18:1, r = 0.36; FFA18:2, r = 0.30) (all P < 0.05). CONCLUSION Chronic HBV infection may impact on the serum lipidomics and steatosis-related pathological characteristics of NAFLD.
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Affiliation(s)
- Han Li
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Qing-Yang Xu
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Yang Xie
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Ji-Jun Luo
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Hai-Xia Cao
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
| | - Qin Pan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
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The effects of metformin, pioglitazone, exenatide and exercise on fatty liver in obese diabetic rats: the role of IRS-1 and SOCS-3 molecules. Inflammopharmacology 2022; 30:243-250. [DOI: 10.1007/s10787-021-00916-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 12/23/2021] [Indexed: 12/12/2022]
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Zambon Azevedo V, Silaghi CA, Maurel T, Silaghi H, Ratziu V, Pais R. Impact of Sarcopenia on the Severity of the Liver Damage in Patients With Non-alcoholic Fatty Liver Disease. Front Nutr 2022; 8:774030. [PMID: 35111794 PMCID: PMC8802760 DOI: 10.3389/fnut.2021.774030] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
An extensive body of the literature shows a strong interrelationship between the pathogenic pathways of non-alcoholic fatty liver disease (NAFLD) and sarcopenia through the muscle-liver-adipose tissue axis. NAFLD is one of the leading causes of chronic liver diseases (CLD) affecting more than one-quarter of the general population worldwide. The disease severity spectrum ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and its complications: end-stage chronic liver disease and hepatocellular carcinoma. Sarcopenia, defined as a progressive loss of the skeletal muscle mass, reduces physical performances, is associated with metabolic dysfunction and, possibly, has a causative role in NAFLD pathogenesis. Muscle mass is a key determinant of the whole-body insulin-mediated glucose metabolism and impacts fatty liver oxidation and energy homeostasis. These mechanisms drive the accumulation of ectopic fat both in the liver (steatosis, fatty liver) and in the muscle (myosteatosis). Myosteatosis rather than the muscle mass per se, seems to be closely associated with the severity of the liver injury. Sarcopenic obesity is a recently described entity which associates both sarcopenia and obesity and may trigger worse clinical outcomes including hepatic fibrosis progression and musculoskeletal disabilities. Furthermore, the muscle-liver-adipose tissue axis has a pivotal role in changes of the body composition, resulting in a distinct clinical phenotype that enables the identification of the "sarcopenic NAFLD phenotype." This review aims to bring some light into the complex relationship between sarcopenia and NAFLD and critically discuss the key mechanisms linking NAFLD to sarcopenia, as well as some of the clinical consequences associated with the coexistence of these two entities: the impact of body composition phenotypes on muscle morphology, the concept of sarcopenic obesity, the relationship between sarcopenia and the severity of the liver damage and finally, the future directions and the existing gaps in the knowledge.
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Affiliation(s)
- Vittoria Zambon Azevedo
- Doctoral School Physiology, Physiopathology and Therapeutics 394, Sorbonne Université, Paris, France
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
| | - Cristina Alina Silaghi
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Thomas Maurel
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
| | - Horatiu Silaghi
- Department of Surgery V, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Vlad Ratziu
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
| | - Raluca Pais
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS 938, Paris, France
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Hazem RM, Ibrahim AZ, Ali DA, Moustafa YM. Dapagliflozin improves steatohepatitis in diabetic rats via inhibition of oxidative stress and inflammation. Int Immunopharmacol 2022; 104:108503. [PMID: 34998036 DOI: 10.1016/j.intimp.2021.108503] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/19/2021] [Accepted: 12/26/2021] [Indexed: 12/11/2022]
Abstract
Type-2 diabetes mellitus and NAFLD are considered as one of the greatest worldwide metabolic disorders with growing incidence. It was found that patients with T2DM have two-fold increase to develop NAFLD. Evidence that some antidiabetic agents improve NAFLD/NASH in patients with T2DM is evolving. However, there are no certain pharmacologic therapies. The current study aimed to investigate the underlying mechanisms for the hepatoprotective effect of dapagliflozin against steatohepatitis in diabetic rats. Type-2 diabetes was induced by HFD followed by a single dose of STZ (30 mg/kg I.P). Fifty rats were randomly divided into 5 groups: Group1; normal control, Group 2; diabetic control, Groups (3-5); diabetic rats received daily dapagliflozin (0.75, 1.5, 3 mg/kg, p.o.) respectively for 6 weeks. At the end of the experiment, blood glucose level and serum insulin were measured. Hepatic tissue homogenization was performed for measuring inflammatory and oxidative stress markers. In addition, histopathological investigation of the hepatic tissue was done. Diabetic rats exhibited remarkable increase in liver weight and liver enzymes, along with histopathological changes, significant elevation in MDA, IL-1 β, TGFβ levels and, NF-κB, alpha-SMA expressions. Dapagliflozin treatment decreased liver weight, liver enzymes, together with marked improvement in histopathological changes. Furthermore, dapagliflozin increased antioxidant enzymes, GSH levels. Interestingly, Dapagliflozin reduced IL-1 β, TGFβ levels and, NF-κB, alpha-SMA expressions. Present data show that dapagliflozin represent a viable approach to protect the liver against diabetes-encouraged steatohepatitis through inhibiting oxidative stress, inflammation and fibrosis progression thus conserving liver function.
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Affiliation(s)
- Reem M Hazem
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Ahmed Z Ibrahim
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Dina A Ali
- Department of clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
| | - Yasser M Moustafa
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Badr University, Cairo 11829, Egypt
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Woldu MA, Minzi O, Engidawork E. Dyslipidemia and associated cardiovascular risk factors in HIV-positive and HIV-negative patients visiting ambulatory clinics: A hospital-based study. JRSM Cardiovasc Dis 2022; 11:20480040221114651. [PMID: 35898404 PMCID: PMC9309774 DOI: 10.1177/20480040221114651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 06/29/2022] [Accepted: 07/03/2022] [Indexed: 11/23/2022] Open
Abstract
Background Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD),
accounting for more than half of all instances of coronary artery disease
globally (CAD). Purpose The purpose of this study was to determine lipid-related cardiovascular risks
in HIV-positive and HIV-negative individuals by evaluating lipid profiles,
ratios, and other related parameters. Methods A hospital-based study was carried out from January 2019 to February 2021 in
both HIV + and HIV- ambulatory patients. Results High TG (p = .003), high TC (p = .025), and low HDL (p < .001) were all
associated with a two-fold increased risk of CVD in people aged 45 and up.
Due to higher TG (p < .001) and lower HDL (p < .001), males were found
to have a higher risk of atherogenic dyslipidemia. A twofold increase in the
likelihood of higher TG levels has been associated with smoking (p = .032)
and alcohol intake (p = .022). A twofold increase in a high TC/HDL ratio and
an elevated TG/HDL ratio was observed with an increase in waist-to-height
ratio (p = .030) and a high level of FBS (126 mg/dl) and/or validated
diabetes (p = .017), respectively. In HIV + participants, central obesity
(p < .001), diabetes (p < .001), and high blood pressure (p < .001)
were all less common than in HIV- participants. Conclusions Dyslipidemia is linked to advanced age, male gender, diabetes, smoking,
alcohol consumption, and increased waist circumference, all of which could
lead to an increased risk of CVD, according to the study. The study also
revealed that the risks are less common in HIV + people than in HIV-negative
ambulatory patients.
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Affiliation(s)
- Minyahil A Woldu
- Department of Clinical Pharmacy and Pharmacology, Muhimbili University of Health and Allied Sciences (www.muhas.ac.tz), Dar Es Salaam, Tanzania.,Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University (www.aad.edu.et), Addis Ababa, Ethiopia
| | - Omary Minzi
- Department of Clinical Pharmacy and Pharmacology, Muhimbili University of Health and Allied Sciences (www.muhas.ac.tz), Dar Es Salaam, Tanzania
| | - Ephrem Engidawork
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University (www.aad.edu.et), Addis Ababa, Ethiopia
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Gluvic Z, Tomasevic R, Bojovic K, Obradovic M, Isenovic ER. Non-alcoholic fatty liver disease: a multidisciplinary clinical practice approach—the institutional adaptation to existing Clinical Practice Guidelines. EMERGENCY AND CRITICAL CARE MEDICINE 2021; 2:12-22. [DOI: 10.1097/ec9.0000000000000016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 08/16/2021] [Indexed: 10/13/2023]
Abstract
Abstract
Non-alcoholic fatty liver disease (NAFLD) is among the most frequently encountered chronic liver diseases in everyday clinical practice. It is considered the hepatic manifestation of metabolic syndrome. Today, liver biopsy is still the gold standard for NAFLD confirmation and assessing NAFLD's possible progression to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Because of the high prevalence of NAFLD and potential associated risks of invasive diagnostic procedures, it is of great interest to recruit the patients for liver biopsy. However, as the presence of liver fibrosis determines the further clinical course, liver biopsy is expectedly reserved for those with increased fibrosis risk. The quality of liver biopsy recruitment and patient monitoring could be significantly improved by using non-invasive tools to assess liver fibrosis presence and interactive collaboration between general practitioners, gastroenterologists, and endocrinologists. As a result, the quality of liver biopsy recruitment and patients monitoring could be significantly improved. Here, we proposed clinical practice guidelines that could be implemented for everyday clinical practice in NAFLD patients.
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Affiliation(s)
- Zoran Gluvic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ratko Tomasevic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ksenija Bojovic
- Clinical Centre of Serbia, Clinic of Infectious and Tropical Diseases, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences – National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Esma R. Isenovic
- Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences – National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia
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Barb D, Repetto EM, Stokes ME, Shankar SS, Cusi K. Type 2 diabetes mellitus increases the risk of hepatic fibrosis in individuals with obesity and nonalcoholic fatty liver disease. Obesity (Silver Spring) 2021; 29:1950-1960. [PMID: 34553836 PMCID: PMC9290591 DOI: 10.1002/oby.23263] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 06/18/2021] [Accepted: 07/09/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE This study assessed the impact of diabetes mellitus (DM) on nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) with advanced fibrosis prevalence in adults with overweight or obesity in the United States. METHODS Participants (National Health and Nutrition Examination Survey [NHANES] 2015-2016 database) included 834 middle-aged patients with DM (21.7%) and 3,007 without DM (78.3%). NAFLD was defined by Fatty Liver Index (FLI) ≥ 60 or United States FLI (USFLI) ≥ 30. Moderate-to-high and high risk of advanced fibrosis was defined by fibrosis-4 index (FIB-4) ≥ 1.67 and ≥ 2.67, respectively, and NAFLD fibrosis scores > 0.676 also indicated a high risk. RESULTS NAFLD prevalence increased with BMI. Steatosis was higher in individuals with overweight with DM versus without DM (USFLI ≥ 30: 48.3% vs. 17.4%; p < 0.01) and in individuals with obesity with DM versus without DM (USFLI ≥ 30: 79.9% vs. 57.6%; p < 0.01). DM significantly increased the proportion of individuals at moderate-to-high risk of fibrosis (FIB-4 ≥ 1.67: 31.8% vs. 20.1%; p < 0.05). In the high risk of advanced fibrosis group (FIB-4 ≥ 2.67), the risk almost doubled (3.8% vs. 7.1%). Among individuals with obesity, DM increased the proportion of adults with moderate and high risk of fibrosis by 1.8- and 2.5-fold, respectively (p < 0.01 and p = 0.39, respectively, vs. without DM). CONCLUSIONS In this US cohort, DM modestly impacted steatosis, which was primarily obesity-driven. DM added a significant risk of fibrosis to individuals with overweight or obesity, suggesting that screening is imperative in adults with DM.
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Affiliation(s)
- Diana Barb
- Division of Endocrinology, Diabetes and MetabolismUniversity of FloridaGainesvilleFloridaUSA
| | | | | | - Sudha S. Shankar
- Early Clinical DevelopmentAstraZeneca plcGaithersburgMarylandUSA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and MetabolismUniversity of FloridaGainesvilleFloridaUSA
- Division of Endocrinology, Diabetes and MetabolismMalcom Randall Veterans Affairs Medical CenterGainesvilleFloridaUSA
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A weight regain of 1.5 kg or more and lack of exercise are associated with nonalcoholic fatty liver disease recurrence in men. Sci Rep 2021; 11:19992. [PMID: 34620897 PMCID: PMC8497533 DOI: 10.1038/s41598-021-99036-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 09/13/2021] [Indexed: 12/16/2022] Open
Abstract
The importance of maintaining the remission of nonalcoholic fatty liver disease (NAFLD) has been overlooked. Here we aimed to clarify factors causing NAFLD recurrence. In this retrospective cohort study over 10.8 ± 5.4 years, we investigated 1260 male health check-up participants diagnosed with NAFLD who achieved remission. The data were compared between the maintained remission and recurrence group. Among all participants, 618 (49.0%) showed NAFLD recurrence at the last visit. Participants in the maintained remission group continued to lose weight (72.7 ± 9.1, 68.7 ± 8.5 and 68.2 ± 8.9 kg), whereas those in the recurrence group lost and regained weight (72.9 ± 9.9, 69.7 ± 9.3 and 73.0 ± 10.4 kg). Receiver operating characteristic curve analysis showed a weight regain of + 1.5 kg as the cutoff value for recurrence. The proportion of regular exercisers at the last visit was 34.6% in the maintained remission group and 24.5% in the recurrence group (p < 0.0001). Multivariable analysis revealed the amount of weight regain (in 1 kg increments; adjusted odds ratio, 1.29; 95% confidence interval, 1.24–1.34) and regular exercise at the last visit (adjusted odds ratio, 0.67; 95% confidence interval, 0.55–0.89) were independently associated with recurrence. These findings demonstrate a weight regain of 1.5 kg or more and lack of exercise were associated with NAFLD recurrence.
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Daniel T, Ben-Shachar M, Drori E, Hamad S, Permyakova A, Ben-Cnaan E, Tam J, Kerem Z, Rosenzweig T. Grape pomace reduces the severity of non-alcoholic hepatic steatosis and the development of steatohepatitis by improving insulin sensitivity and reducing ectopic fat deposition in mice. J Nutr Biochem 2021; 98:108867. [PMID: 34571189 DOI: 10.1016/j.jnutbio.2021.108867] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 07/08/2021] [Accepted: 09/12/2021] [Indexed: 12/17/2022]
Abstract
While non-alcoholic fatty liver disease (NAFLD) represents the common cause of chronic liver disease, specific therapies are currently unavailable. The wine industry produces millions of tons of residue (pomace), which contains high levels of bioactive phytochemicals. The aim of this study was to clarify the potential benefits of grape pomace for the treatment of NAFLD at different levels of severity, and to clarify the mechanism of action. C57Bl/6 mice were given high fat diet (HFD) or western diet (WD) as models of obesity and hepatic steatosis or steatohepatitis, respectively, with or without pomace supplementation (50-250 mg/day). Pomace inhibited food intake, and reduced serum leptin and body weight gain. Ectopic fat deposition was reduced, while white adipose tissue mass was preserved. In addition, pomace improved glucose tolerance and insulin sensitivity, prevented the development of adipose tissue inflammation, and reduced hepatic steatosis. Higher expression of genes involved in fatty acids transport and oxidation was observed in adipose tissue, while lipogenic genes were attenuated in the liver of pomace-treated mice. In WD-fed mice, pomace reduced the severity of hepatic steatosis and inflammation and improved blood lipid profile, but was ineffective in reversing hepatic damage of advanced NASH. In conclusion, pomace improved insulin sensitivity and reduced ectopic fat deposition, leading to a healthier metabolic profile. Pomace may hold the potential as a supplement with beneficial health outcomes for the prevention and treatment of hepatic steatosis and other obesity-related pathologies.
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Affiliation(s)
- Tehila Daniel
- Departments of Molecular Biology and Nutrition Sciences, Ariel University, Ariel, Israel
| | - Michaella Ben-Shachar
- Departments of Molecular Biology and Nutrition Sciences, Ariel University, Ariel, Israel
| | - Elyashiv Drori
- Agriculture and Oenology Research Department, Eastern Regional R&D Center, Ariel, Israel; Department of Chemical Engineering, Biotechnology and Materials, Ariel University, Ariel, Israel
| | - Sharleen Hamad
- Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Anna Permyakova
- Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Elad Ben-Cnaan
- Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Joseph Tam
- Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Zohar Kerem
- Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Tovit Rosenzweig
- Departments of Molecular Biology and Nutrition Sciences, Ariel University, Ariel, Israel.
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Liu L, Wang Y, Zhang J, Wang C, Li Y, Dai W, Piao C, Liu J, Yu H, Li X, Wang Y, Liu J. Probiotics in treating with alcoholic liver disease and nonalcoholic fatty liver disease. FOOD REVIEWS INTERNATIONAL 2021. [DOI: 10.1080/87559129.2021.1967380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Lingchong Liu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- College of Life Science, Changchun Sci-Tech University, Changchun, China
| | - Yu Wang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
| | - Jing Zhang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
| | - Chao Wang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
| | - Youbao Li
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Weichang Dai
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Chunhong Piao
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Junmei Liu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Hansong Yu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Xia Li
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Yuhua Wang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
| | - Jingsheng Liu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China
- Department of Food Science and Engineering, National Processing Laboratory for Soybean Industry and Technology, Changchun, China
- Department of Food Science and Engineering, National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, China
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Jesrani G, Gupta M, Kaur J, Kaur N, Lehl SS, Singh R. One-Hour Postload Plasma Glucose in Obese Indian Adults with Nonalcoholic Fatty Liver Disease: An Observational Study from North India. Indian J Endocrinol Metab 2021; 25:450-455. [PMID: 35300452 PMCID: PMC8923315 DOI: 10.4103/ijem.ijem_357_21] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/23/2021] [Accepted: 10/18/2021] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Metabolic perturbations and hyperglycemia are increasingly identified as causal factors for nonalcoholic fatty liver disease (NAFLD). Insulin resistance, an indirect marker for initiation of NAFLD can be promptly diagnosed with standard oral glucose tolerance test (OGTT). One-hour postOGTT plasma glucose measurement can have a significant impact on early identification of dysglycemia with NAFLD and may be superior to fasting and 2-hour plasma glucose. OBJECTIVE To assess 1-hour post OGTT plasma glucose levels and presence of NAFLD in obese adults. MATERIALS AND METHODS In this observational study, we included 101 consecutive obese (body mass index >25 kg/m2) participants of age 20-50 years without known illness of diabetes mellitus. Their anthropometric and laboratory characteristics were recorded and a standard OGTT was performed. Plasma glucose (PG) levels were measured during fasting, 1-hour (1-hour-PPG), and 2-hour (2-hour-PPG) intervals. All participants underwent ultrasound of the abdomen by a single, experienced observer for fatty liver (FL) grade assessment. Comparison of the PG and FL was done by the Chi-square test and a P value <0.05 was considered statistically significant with a 95% confidence interval. Data analysis was done using SPSS version 24.0 (IBM® SPSS Statistics Inc., Chicago, Illinois, USA). RESULTS The result demonstrated that 53 adults had 1-hour-PPG values above the cutoff (≥155 mg/dl), whereas only 20 individuals had raised PG at 2 hours (≥140 mg/dl). All study subjects (100%) had an evidence of FL disease on ultrasound scan. Among these, 33 had grade I and 68 participants had grade II or III FL. About 41.6% of individuals had deranged 1-hour-PPG levels and higher FL grades as compared to 11.9% individuals with raised 2-hour-PPG values and FL of same grades. The relationship between 1-hour-PPG and FL grades was also statistically significant (P value <0.05). CONCLUSIONS 1-hour-PPG levels were more deranged in obese adults without diabetes, and had more consistent and significant relationship with higher FL grades than the 2-hour-PPG levels.
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Affiliation(s)
- Gautam Jesrani
- Department of General Medicine, Government Medical College and Hospital, Sector 32, Chandigarh, India
| | - Monica Gupta
- Department of General Medicine, Government Medical College and Hospital, Sector 32, Chandigarh, India
| | - Jasbinder Kaur
- Department of Biochemistry, Government Medical College and Hospital, Sector 32, Chandigarh, India
| | - Narinder Kaur
- Department of Radio-Diagnosis, Government Medical College and Hospital, Sector 32, Chandigarh, India
| | - Sarabmeet S. Lehl
- Department of General Medicine, Government Medical College and Hospital, Sector 32, Chandigarh, India
| | - Ram Singh
- Department of General Medicine, Government Medical College and Hospital, Sector 32, Chandigarh, India
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Sousa L, Guarda M, Meneses MJ, Macedo MP, Vicente Miranda H. Insulin-degrading enzyme: an ally against metabolic and neurodegenerative diseases. J Pathol 2021; 255:346-361. [PMID: 34396529 DOI: 10.1002/path.5777] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/01/2021] [Accepted: 08/09/2021] [Indexed: 11/11/2022]
Abstract
Insulin-degrading enzyme (IDE) function goes far beyond its known proteolytic role as a regulator of insulin levels. IDE has a wide substrate promiscuity, degrading several proteins such as amyloid-β peptide, glucagon, islet amyloid polypeptide (IAPP) and insulin-like growth factors, that have diverse physiological and pathophysiological functions. Importantly, IDE plays other non-proteolytical functions such as a chaperone/dead-end chaperone, an E1-ubiquitin activating enzyme, and a proteasome modulator. It also responds as a heat shock protein, regulating cellular proteostasis. Notably, amyloidogenic proteins such as IAPP, amyloid-β and α-synuclein have been reported as substrates for IDE chaperone activity. This is of utmost importance as failure of IDE may result in increased protein aggregation, a key hallmark in the pathogenesis of beta cells in type 2 diabetes mellitus and of neurons in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this review, we focus on the biochemical and biophysical properties of IDE and the regulation of its physiological functions. We further raise the hypothesis that IDE plays a central role in the pathological context of dysmetabolic and neurodegenerative diseases and discuss its potential as a therapeutic target. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Luís Sousa
- CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal
| | - Mariana Guarda
- CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal
| | - Maria João Meneses
- CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal.,APDP-Diabetes Portugal Education and Research Center (APDP-ERC), Lisbon, Portugal
| | - M Paula Macedo
- CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal.,APDP-Diabetes Portugal Education and Research Center (APDP-ERC), Lisbon, Portugal.,Departamento de Ciências Médicas, Instituto de Biomedicina - iBiMED, Universidade de Aveiro, Aveiro, Portugal
| | - Hugo Vicente Miranda
- CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal
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Mediterranean dietary pattern and non-alcoholic fatty liver diseases: a case-control study. J Nutr Sci 2021; 10:e55. [PMID: 34367629 PMCID: PMC8327389 DOI: 10.1017/jns.2021.43] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 06/18/2021] [Indexed: 12/17/2022] Open
Abstract
The Mediterranean (MED) diet was associated with a reduced risk of chronic disease, but the epidemiological studies reported inconsistent findings related to the MED diet and non-alcoholic fatty liver disease (NAFLD) risk. This age and the gender-matched case-control study were conducted among 247 adult patients. The MED diet score was obtained based on the Trichopoulou model. Multivariate logistic regression was used to examine the association between the MED diet and NAFLD risk. NAFLD prevalence in people with low, moderate and high adherence to the MED diet was 33, 13⋅1 and 4⋅6 %, respectively. The increasing intake of the MED diet was significantly related to the increment intake of nuts and fruits, vegetables, monounsaturated fatty acid/polyunsaturated fatty acid ratio, legumes, cereals and fish. However, total energy consumption, low-fat dairy and meats intake were reduced (P for all < 0⋅05). Following control for age, the person in the highest of the MED diet tertile compared with the lowest, the odds of NAFLD decreased (OR: 0⋅40, 95 % CI: 0⋅17-0⋅95). This relation became a little stronger after further adjusting for sex, diabetes, physical activity and supplement intake (OR: 0⋅36, 95 % CI: 0⋅15-0⋅89). However, this association disappeared after adjusting for body mass index, waist and hip circumference (OR: 0⋅70, 95 % CI: 0⋅25-1⋅97). High adherence to the MED diet was associated with a 64 % reduction in NAFLD odds before some anthropometric variable adjustments. However, further prospective studies are required, particularly in BMI-stratified models.
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