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Parker J, Moris JM, Goodman LC, Paidisetty VK, Vanegas V, Turner HA, Melgar D, Koh Y. A multifactorial lens on risk factors promoting the progression of Alzheimer's disease. Brain Res 2025; 1846:149262. [PMID: 39374837 DOI: 10.1016/j.brainres.2024.149262] [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: 03/10/2024] [Revised: 08/14/2024] [Accepted: 10/02/2024] [Indexed: 10/09/2024]
Abstract
The prevalence of Alzheimer's disease (AD) among adults has continued to increase over the last two decades, which has sparked a significant increase in research that focuses on the topic of "brain health." While AD is partially determined by a genetic predisposition, there are still numerous pathophysiological factors that require further research. This research requirement stems from the acknowledgment that AD is a multifactorial disease that to date, cannot be prevented. Therefore, addressing and understanding the potential AD risk factors is necessary to increase the quality of life of an aging population. To raise awareness of critical pathways that impact AD progression, this review manuscript describes AD etiologies, structural impairments, and biomolecular changes that can significantly increase the risk of AD. Among them, a special highlight is given to inflammasomes, which have been shown to bolster neuroinflammation. Alike, the role of brain-derived neurotrophic factor, an essential neuropeptide that promotes the preservation of cognition is presented. In addition, the functional role of neurovascular units to regulate brain health is highlighted and contrasted to inflammatory conditions, such as cellular senescence, vascular damage, and increased visceral adiposity, who all increase the risk of neuroinflammation. Altogether, a multifactorial interventional approach is warranted to reduce the risk of AD.
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Affiliation(s)
- Jenna Parker
- Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA
| | - Jose M Moris
- Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA
| | - Lily C Goodman
- School of Medicine, Creighton University, Phoenix, AZ, USA
| | - Vineet K Paidisetty
- Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA
| | - Vicente Vanegas
- Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA
| | - Haley A Turner
- Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Daniel Melgar
- Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA
| | - Yunsuk Koh
- Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA.
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2
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Bawiskar N, Acharya S, Kumar S. Fatty liver disease - non alcoholic to metabolic - A transition of concepts!! J Family Med Prim Care 2024; 13:2857-2862. [PMID: 39228650 PMCID: PMC11368329 DOI: 10.4103/jfmpc.jfmpc_1863_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 12/12/2021] [Accepted: 01/12/2022] [Indexed: 09/05/2024] Open
Abstract
Metabolic dysfunction associated fatty liver disease (MAFLD) was a concept suggested lately. Initially, the only criterion for the diagnosis of MAFLD was the absence of alcohol intake. With rising prevalence and studies assessing this condition, certain "positive criteria" were put forth. Experts from 22 countries proposed a simple yet comprehensive definition for the condition independent of other liver diseases. The presence of hepatic steatosis in addition to diabetes mellitus type 2, metabolic dysregulation, and obesity is generally observed. Criteria to define MAFLD-associated cirrhosis were also proposed. Reaching an agreement on MAFLD criteria will help define a protocol (for example: for International classification of Diseases (ICD) - coding), which will improve clinical care and advance the clinical and scientific field of liver research. As it is a condition that increases the risk of diabetes mellitus, chronic kidney disease (CKD), cirrhosis, hepatocellular carcinoma, and cardiac disorders it is important to recognize it at an early stage which makes it essential part of family medicine and primary care.
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Affiliation(s)
- Nipun Bawiskar
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
| | - Sourya Acharya
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
| | - Sunil Kumar
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
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Andreozzi F, Mancuso E, Mazza E, Mannino GC, Fiorentino TV, Arturi F, Succurro E, Perticone M, Sciacqua A, Montalcini T, Pujia A, Sesti G. One-hour post-load glucose levels are associated with hepatic steatosis assessed by transient elastography. Diabetes Obes Metab 2024; 26:682-689. [PMID: 37953652 DOI: 10.1111/dom.15358] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 10/11/2023] [Accepted: 10/19/2023] [Indexed: 11/14/2023]
Abstract
AIM To examine the association between 1-hour plasma glucose (PG) concentration and markers of non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). METHODS We performed TE in 107 metabolically well-characterized non-diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. RESULTS Controlled attenuation parameter correlated significantly with 1-hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2-hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high-density lipoprotein cholesterol (r = -0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1-hour PG (β = 0.274, P = 0.008) and fasting insulin levels (β = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1-hour PG was the sole predictor of CAP variation (β = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1-hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43-11.13; P = 0.008) than individuals with 1-hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1-hour PG and LS. CONCLUSION Our data confirm that 1-hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low-impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy.
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Affiliation(s)
- Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elettra Mancuso
- Department of Science of Health, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elisa Mazza
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Gaia Chiara Mannino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Franco Arturi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Maria Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Tiziana Montalcini
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
- Department of Clinical and Experimental Medicine, University Magna Greaecia of Catanzaro, Catanzaro, Italy
| | - Arturo Pujia
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
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Kim JH, Lyu YS, Kim MK, Kim SY, Baek KH, Song KH, Han K, Kwon HS. Repeated detection of non-alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults. Diabetes Obes Metab 2024; 26:180-190. [PMID: 37872007 DOI: 10.1111/dom.15304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/14/2023] [Accepted: 09/15/2023] [Indexed: 10/25/2023]
Abstract
AIM This study aimed to investigate the effects of repeated detection of non-alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults. MATERIALS AND METHODS In this nationwide population-based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20-39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0-4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points. RESULTS The multivariable-adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57-2.921), 3.45 (3.221-3.694), 4.588 (4.303-4.892) and 6.126 (5.77-6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores. CONCLUSIONS Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.
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Affiliation(s)
- Jin Hwa Kim
- Department of Endocrinology and Metabolism, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of Korea
| | - Young Sang Lyu
- Department of Endocrinology and Metabolism, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Yong Kim
- Department of Endocrinology and Metabolism, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of Korea
| | - Ki-Hyun Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Sandforth A, von Schwartzenberg RJ, Arreola EV, Hanson RL, Sancar G, Katzenstein S, Lange K, Preißl H, Dreher SI, Weigert C, Wagner R, Kantartzis K, Machann J, Schick F, Lehmann R, Peter A, Katsouli N, Ntziachristos V, Dannecker C, Fritsche L, Perakakis N, Heni M, Nawroth PP, Kopf S, Pfeiffer AFH, Kabisch S, Stumvoll M, Schwarz PEH, Hauner H, Lechner A, Seissler J, Yurchenko I, Icks A, Solimena M, Häring HU, Szendroedi J, Schürmann A, de Angelis MH, Blüher M, Roden M, Bornstein SR, Stefan N, Fritsche A, Birkenfeld AL. Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS). Lancet Diabetes Endocrinol 2023; 11:798-810. [PMID: 37769677 DOI: 10.1016/s2213-8587(23)00235-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 08/02/2023] [Accepted: 08/04/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Remission of type 2 diabetes can occur as a result of weight loss and is characterised by liver fat and pancreas fat reduction and recovered insulin secretion. In this analysis, we aimed to investigate the mechanisms of weight loss- induced remission in people with prediabetes. METHODS In this prespecified post-hoc analysis, weight loss-induced resolution of prediabetes in the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS) was assessed, and the results were validated against participants from the Diabetes Prevention Program (DPP) study. For PLIS, between March 1, 2012, and Aug 31, 2016, participants were recruited from eight clinical study centres (including seven university hospitals) in Germany and randomly assigned to receive either a control intervention, a standard lifestyle intervention (ie, DPP-based intervention), or an intensified lifestyle intervention for 12 months. For DPP, participants were recruited from 23 clinical study centres in the USA between July 31, 1996, and May 18, 1999, and randomly assigned to receive either a standard lifestyle intervention, metformin, or placebo. In both PLIS and DPP, only participants who were randomly assigned to receive lifestyle intervention or placebo and who lost at least 5% of their bodyweight were included in this analysis. Responders were defined as people who returned to normal fasting plasma glucose (FPG; <5·6 mmol/L), normal glucose tolerance (<7·8 mmol/L), and HbA1c less than 39 mmol/mol after 12 months of lifestyle intervention or placebo or control intervention. Non-responders were defined as people who had FPG, 2 h glucose, or HbA1c more than these thresholds. The main outcomes for this analysis were insulin sensitivity, insulin secretion, visceral adipose tissue (VAT), and intrahepatic lipid content (IHL) and were evaluated via linear mixed models. FINDINGS Of 1160 participants recruited to PLIS, 298 (25·7%) had weight loss of 5% or more of their bodyweight at baseline. 128 (43%) of 298 participants were responders and 170 (57%) were non-responders. Responders were younger than non-responders (mean age 55·6 years [SD 9·9] vs 60·4 years [8·6]; p<0·0001). The DPP validation cohort included 683 participants who lost at least 5% of their bodyweight at baseline. Of these, 132 (19%) were responders and 551 (81%) were non-responders. In PLIS, BMI reduction was similar between responders and non-responders (responders mean at baseline 32·4 kg/m2 [SD 5·6] to mean at 12 months 29·0 kg/m2 [4·9] vs non-responders 32·1 kg/m2 [5·9] to 29·2 kg/m2 [5·4]; p=0·86). However, whole-body insulin sensitivity increased more in responders than in non-responders (mean at baseline 291 mL/[min × m2], SD 60 to mean at 12 months 378 mL/[min × m2], 56 vs 278 mL/[min × m2], 62, to 323 mL/[min × m2], 66; p<0·0001), whereas insulin secretion did not differ within groups over time or between groups (responders mean at baseline 175 pmol/mmol [SD 64] to mean at 12 months 163·7 pmol/mmol [60·6] vs non-responders 158·0 pmol/mmol [55·6] to 154·1 pmol/mmol [56·2]; p=0·46). IHL decreased in both groups, without a difference between groups (responders mean at baseline 10·1% [SD 8·7] to mean at 12 months 3·5% [3·9] vs non-responders 10·3% [8·1] to 4·2% [4·2]; p=0·34); however, VAT decreased more in responders than in non-responders (mean at baseline 6·2 L [SD 2·9] to mean at 12 months 4·1 L [2·3] vs 5·7 L [2·3] to 4·5 L [2·2]; p=0·0003). Responders had a 73% lower risk of developing type 2 diabetes than non-responders in the 2 years after the intervention ended. INTERPRETATION By contrast to remission of type 2 diabetes, resolution of prediabetes was characterised by an improvement in insulin sensitivity and reduced VAT. Because return to normal glucose regulation (NGR) prevents development of type 2 diabetes, we propose the concept of remission of prediabetes in analogy to type 2 diabetes. We suggest that remission of prediabetes should be the primary therapeutic aim in individuals with prediabetes. FUNDING German Federal Ministry for Education and Research via the German Center for Diabetes Research; the Ministry of Science, Research and the Arts Baden-Württemberg; the Helmholtz Association and Helmholtz Munich; the Cluster of Excellence Controlling Microbes to Fight Infections; and the German Research Foundation.
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Affiliation(s)
- Arvid Sandforth
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Reiner Jumpertz von Schwartzenberg
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Cluster of Excellence Controlling Microbes to Fight Infections, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Elsa Vazquez Arreola
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Robert L Hanson
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Gencer Sancar
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Sarah Katzenstein
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Karl Lange
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Hubert Preißl
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Simon I Dreher
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Cora Weigert
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Robert Wagner
- German Center for Diabetes Research, Neuherberg, Germany; Department of Endocrinology and Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Medical Faculty and University Hospital, Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Kostantinos Kantartzis
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Jürgen Machann
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Department of Radiology, Section on Experimental Radiology, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Fritz Schick
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Department of Radiology, Section on Experimental Radiology, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Rainer Lehmann
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Andreas Peter
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Nikoletta Katsouli
- Central Institute for Translational Cancer Research, Technical University of Munich, Munich, Germany; Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Munich, Germany
| | - Vasilis Ntziachristos
- Central Institute for Translational Cancer Research, Technical University of Munich, Munich, Germany; Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Munich, Germany
| | - Corinna Dannecker
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Louise Fritsche
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Nikolaos Perakakis
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine III, Technical University Dresden, Dresden, Germany
| | - Martin Heni
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Peter Paul Nawroth
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Stefan Kopf
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Andreas F H Pfeiffer
- German Center for Diabetes Research, Neuherberg, Germany; Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Stefan Kabisch
- German Center for Diabetes Research, Neuherberg, Germany; German Institute of Human Nutrition Potsdam-Rehbrücke, Brandenburg, Germany
| | - Michael Stumvoll
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Leipzig, Germany
| | - Peter E H Schwarz
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine III, Technical University Dresden, Dresden, Germany
| | - Hans Hauner
- German Center for Diabetes Research, Neuherberg, Germany; Institute of Nutritional Medicine, Technical University of Munich, Munich, Germany
| | - Andreas Lechner
- German Center for Diabetes Research, Neuherberg, Germany; Diabetes Research Group, Medical Department, Ludwig-Maximilians University Munich, Munich, Germany
| | - Jochen Seissler
- German Center for Diabetes Research, Neuherberg, Germany; Diabetes Research Group, Medical Department, Ludwig-Maximilians University Munich, Munich, Germany
| | - Iryna Yurchenko
- German Center for Diabetes Research, Neuherberg, Germany; Medical Faculty and University Hospital, Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Andrea Icks
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Health Services Research and Health Economics, Centre for Health and Society, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Institute for Health Services Research and Health Economics, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michele Solimena
- German Center for Diabetes Research, Neuherberg, Germany; Paul-Langerhans-Institut Dresden, Helmholtz Center Munich, University Clinic Carl Gustav Carus, Dresden, Germany
| | - Hans-Ulrich Häring
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Julia Szendroedi
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Annette Schürmann
- German Center for Diabetes Research, Neuherberg, Germany; German Institute of Human Nutrition Potsdam-Rehbrücke, Brandenburg, Germany
| | - Martin Hrabé de Angelis
- German Center for Diabetes Research, Neuherberg, Germany; School of Medicine and School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany; Institute of Experimental Genetics, Helmholtz Center Munich, Munich, Germany
| | - Matthias Blüher
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Leipzig, Germany
| | - Michael Roden
- German Center for Diabetes Research, Neuherberg, Germany; Department of Endocrinology and Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Medical Faculty and University Hospital, Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Stefan R Bornstein
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine III, Technical University Dresden, Dresden, Germany; Department of Diabetes, Life Sciences and Medicine, Cardiovascular Medicine and Sciences, Kings College London, London, UK
| | - Norbert Stefan
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Andreas Fritsche
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Andreas L Birkenfeld
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Department of Diabetes, Life Sciences and Medicine, Cardiovascular Medicine and Sciences, Kings College London, London, UK.
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6
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Cui B, Duan J, Zhu L, Wang G, Sun X, Su Z, Liao Y, Yi B, Li P, Li W, Song Z, Li Z, Tang H, Rong P, Zhu S. Effect of laparoscopic sleeve gastrectomy on mobilization of site-specific body adipose depots: a prospective cohort study. Int J Surg 2023; 109:3013-3020. [PMID: 37352520 PMCID: PMC10583911 DOI: 10.1097/js9.0000000000000573] [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: 04/03/2023] [Accepted: 06/11/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND Effect of bariatric surgery on mobilization of site-specific body adipose depots is not well investigated. Herein, the authors conducted a prospective cohort study to assess whether bariatric surgery can differentially affect specific fat storage pools and to further investigate correlations between site-specific fat mobilization and clinical outcomes. MATERIALS AND METHODS In this single-centre prospective cohort study, 49 participants underwent laparoscopic sleeve gastrectomy (LSG) from 24 May 2022 to 20 October 2022 and underwent MRI to estimate subcutaneous fat area, visceral fat area (VFA), hepatic and pancreatic proton density fat fraction (PDFF) at baseline and 3 months after surgery. The protocol for this study was registered on clinicaltrials.gov. RESULTS Among 49 patients who met all inclusion criteria, the median [interquartile range (IQR)] age was 31.0 (23.0-37.0) years, the median (IQR) BMI was 38.1 (33.7-42.2) kg/m 2 and 36.7% were male. Median (IQR) percentage hepatic PDFF loss was the greatest after bariatric surgery at 68.8% (47.3-79.7%), followed by percentage pancreatic PDFF loss at 51.2% (37.0-62.1%), percentage VFA loss at 36.0% (30.0-42.4%), and percentage subcutaneous fat area loss at 22.7% (17.2-32.4%) ( P <0.001). By calculating Pearson correlation coefficient and partial correlation coefficient, the positive correlations were confirmed between change in VFA and change in glycated haemoglobin ( r =0.394, P =0.028; partial r =0.428, P =0.042) and between change in hepatic PDFF and change in homoeostatic model assessment of insulin resistance ( r =0.385, P =0.025; partial r =0.403, P =0.046). CONCLUSIONS LSG preferentially mobilized hepatic fat, followed by pancreatic fat and visceral adipose tissue, while subcutaneous adipose tissue was mobilized to the least extent. Reduction in visceral adipose tissue and hepatic fat is independently associated with the improvement of glucose metabolism after LSG.
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Affiliation(s)
| | - Junhong Duan
- Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | | | | | | | | | - Yunjie Liao
- Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Bo Yi
- Departments of General Surgery
| | | | | | | | | | | | - Pengfei Rong
- Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
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7
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Yang M, Chen J, Yue J, He S, Fu J, Qi Y, Liu W, Xu H, Li S, Lu Q, Ma J. Liver fat is superior to visceral and pancreatic fat as a risk biomarker of impaired glucose regulation in overweight/obese subjects. Diabetes Obes Metab 2023; 25:716-725. [PMID: 36346108 DOI: 10.1111/dom.14918] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/24/2022] [Accepted: 11/05/2022] [Indexed: 11/10/2022]
Abstract
AIM To investigate the distribution of abdominal fat, particularly ectopic fat accumulation, in relation to glucose metabolism in overweight/obese patients. MATERIALS AND METHODS This study included 257 overweight/obese subjects with body mass index ≥23 kg/m2 . All the subjects underwent an oral glucose tolerance test. Magnetic resonance imaging-proton density fat fraction was used to measure fat accumulation in the liver, pancreas and abdomen. Impaired glucose regulation (IGR) was defined as the presence of prediabetes or diabetes. RESULTS Liver fat content (LFC) and visceral adipose tissue (VAT) were higher in overweight/obese subjects with diabetes than in those with normal glucose tolerance (NGT). No significant differences were observed in the pancreas fat content and subcutaneous fat area between subjects with NGT and IGR. LFC was an independent risk factor of IGR (odds ratio = 1.824 per standard deviation unit, 95% CI 1.242-2.679, p = .002). Compared with the lowest tertile of LFC, the multivariate-adjusted odds ratio for the prevalence of IGR in the highest tertile was 2.842 (95% CI 1.205-6.704). However, no association was observed between the VAT per standard deviation increment and tertiles after adjusting for multiple factors. For discordant visceral and liver fat phenotypes, the high LFC-low VAT and high LFC-high VAT groups had a higher prevalence of IGR than the low LFC-low VAT group. However, there was no difference in the prevalence of IGR between the low LFC-low VAT and low LFC-high VAT groups. CONCLUSION Compared with visceral and pancreatic fat content, LFC is a superior risk biomarker for IGR in overweight/obese subjects.
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Affiliation(s)
- Minglan Yang
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Chen
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiang Yue
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shenyun He
- Department of Radiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingjing Fu
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yicheng Qi
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen Liu
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hua Xu
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shengxian Li
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Lu
- Department of Radiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Ma
- Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Predicting Factors for Metabolic Non-Response to a Complex Lifestyle Intervention-A Replication Analysis to a Randomized-Controlled Trial. Nutrients 2022; 14:nu14224721. [PMID: 36432409 PMCID: PMC9699496 DOI: 10.3390/nu14224721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/17/2022] [Accepted: 11/07/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND T2DM heterogeneity affects responsiveness to lifestyle treatment. Beta-cell failure and nonalcoholic fatty liver disease (NAFLD) independently predict T2DM, but NAFLD inconsistently predicts metabolic response to lifestyle intervention. AIM We attempt to replicate a prediction model deducted from the Tübinger Lifestyle Intervention Program by assessing similar metabolic factors to predict conversion to normal glucose regulation (NGR) in a comparable lifestyle intervention trial. METHODS In the Optimal Fiber Trial (OptiFiT), 131 Caucasian participants with prediabetes completed a one-year lifestyle intervention program and received a fiber or placebo supplement. We compared baseline parameters for responders and non-responders, assessed correlations of major metabolic changes and conducted a logistic regression analysis for predictors of remission to NGR. RESULTS NGR was achieved by 33 participants, respectively. At baseline, for the placebo group only, 1 h and 2 h glucose levels, glucose AUC and Cederholm index predicted conversion to NGR. HOMA-beta, HOMA-IR or liver fat indices did not differ between responders and non-responders of the placebo or the fiber group. Changes in waist circumference or fatty liver index correlated with changes in glycemia and insulin resistance, but not with changes in insulin secretion. Insulin-resistant NAFLD did not predict non-response. Differences in compliance did not explain the results. CONCLUSIONS Higher post-challenge glucose levels strongly predicted the metabolic non-response to complex lifestyle intervention in our cohort. Depending on the specific intervention and the investigated cohort, fasting glucose levels and insulin sensitivity might contribute to the risk pattern. Beta-cell function did not improve in accordance with other metabolic improvements, qualifying as a potential risk factor for non-response. We could not replicate previous data suggesting that an insulin-resistant fatty liver is a specific risk factor for treatment failure. Replication studies are required.
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9
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Ha NB, Cho S, Mohamad Y, Kent D, Jun G, Wong R, Swarnakar V, Lin S, Maher JJ, Lai JC. Visceral Adipose Tissue Inflammation and Radiographic Visceral-to-Subcutaneous Adipose Tissue Ratio in Patients with Cirrhosis. Dig Dis Sci 2022; 67:3436-3444. [PMID: 34136974 PMCID: PMC8815298 DOI: 10.1007/s10620-021-07099-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 06/07/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Accumulation of visceral adipose tissue is associated with hepatic inflammation and fibrosis, suggestive of its metabolic and inflammatory properties. We aimed to examine the histologic findings of visceral and subcutaneous adipose tissue and to associate these findings with clinical and radiologic characteristics in patients with cirrhosis. METHODS Included were 55 adults with cirrhosis who underwent liver transplantation from 3/2017-12/2018 and had an abdominal computed tomography (CT) scan within 6 months prior to transplant. Visceral-to-subcutaneous adipose tissue ratio (VSR) was calculated using visceral (VATI) and subcutaneous adipose tissue index (SATI) quantified by CT at the L3-vertebral level and normalized for height (cm2/m2). VAT (greater omentum), SAT (abdominal wall), and skeletal muscle (rectus abdominis) biopsies were collected at transplant. RESULTS Majority of patients had VAT inflammation (71%); only one patient (2%) had SAT inflammation. Patients with VAT inflammation had similar median VATI (42 vs 41 cm2/m2), lower median SATI (64 vs 97 cm2/m2), and higher median VSR (0.63 vs 0.37, p = 0.002) than patients without inflammation. In univariable logistic regression, VSR was associated with VAT inflammation (OR 1.47, 95%CI 1.11-1.96); this association remained significant even after adjusting for age, sex, BMI, HCC, or MELD-Na on bivariable analyses. CONCLUSION In patients with cirrhosis undergoing liver transplantation, histologic VAT inflammation was common, but SAT inflammation was not. Increased VSR was independently associated with VAT inflammation. Given the emerging data demonstrating the prognostic value of VSR, our findings support the value of CT-quantified VSR as a prognostic marker for adverse outcomes in the liver transplant setting.
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Affiliation(s)
- Nghiem B. Ha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Soo‑Jin Cho
- Department of Pathology, University of California, San Francisco, CA, USA
| | - Yara Mohamad
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Dorothea Kent
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Grace Jun
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Randi Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Vivek Swarnakar
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Shezhang Lin
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Jacquelyn J. Maher
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA,Liver Center, University of California, San Francisco, CA, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA,Liver Center, University of California, San Francisco, CA, USA
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10
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Márkus B, Temesszentandrási G, Vörös K, Jakab L, Fekete B, Farkas H, Prohászka Z, Masszi T, Kalabay L. Serum fetuin-A level is independent of Helicobacter pylori postinfection status in systemic lupus erythematosus. Acta Microbiol Immunol Hung 2022. [PMID: 35446783 DOI: 10.1556/030.2022.01744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/11/2022] [Indexed: 11/19/2022]
Abstract
Helicobacter pylori is a common pathogen causing gastric inflammation and malignancy. Fetuin-A is a multifunctional protein that is involved in the regulation of calcification, insulin resistance and inflammation. Reports on serum levels of fetuin-A in acute H. pylori infection are contradictory. We intended to see whether H. pylori post-infection status has a long-term effect on serum fetuin-A levels in a well-characterized series of systemic lupus erythematosus cases. In this cross-sectional study 117 patients with systemic lupus erythematosus were enrolled. Helicobacter infection status and serum fetuin-A concentration were determined by ELISA and radial immunodiffusion, respectively. H. pylori positive patients had higher serum fetuin-A concentration than negative ones: 517 (456-603) vs. 476 (408-544) mg L-1, median (25-75% percentiles), P = 0.020. No other parameters differed between these groups. During univariate regression analysis fetuin-A levels were associated with Erythrocyte sedimentation rate (ESR), White blood cell count (WBC), C-reactive protein (CRP), serum total protein, albumin, and the SLEDAI index at the time of diagnosis but only serum albumin remained a significant determinant in multivariate regression study.
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Affiliation(s)
- Bernadett Márkus
- 1 Department of Family Medicine, Semmelweis University, Budapest, Hungary
| | | | - Krisztián Vörös
- 1 Department of Family Medicine, Semmelweis University, Budapest, Hungary
| | - László Jakab
- 2 Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
| | - Béla Fekete
- 2 Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
| | - Henriette Farkas
- 2 Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
- 3 National Angioedema Center, Semmelweis University, Budapest, Hungary
| | - Zoltán Prohászka
- 2 Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
- 3 National Angioedema Center, Semmelweis University, Budapest, Hungary
| | - Tamás Masszi
- 2 Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
| | - László Kalabay
- 1 Department of Family Medicine, Semmelweis University, Budapest, Hungary
- 2 Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
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11
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Dobbie LJ, Kassab M, Davison AS, Grace P, Cuthbertson DJ, Hydes TJ. Low Screening Rates Despite a High Prevalence of Significant Liver Fibrosis in People with Diabetes from Primary and Secondary Care. J Clin Med 2021; 10:jcm10245755. [PMID: 34945051 PMCID: PMC8706667 DOI: 10.3390/jcm10245755] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/06/2021] [Accepted: 12/07/2021] [Indexed: 12/14/2022] Open
Abstract
Diabetes is a driver of non-alcoholic fatty liver disease (NAFLD) and fibrosis. We determine current practices in examining liver fibrosis in people with diabetes and record prevalence levels in primary and secondary care. We extracted HbA1c results ≥48 mmol/mol to identify people with diabetes, then examined the proportion who had AST, ALT, and platelets results, facilitating calculation of non-invasive fibrosis tests (NIT), or an enhanced liver fibrosis score. Fibrosis markers were requested in only 1.49% (390/26,090), of which 29.7% (n = 106) had evidence of significant fibrosis via NIT. All patients at risk of fibrosis had undergone transient elastography (TE), biopsy or imaging. TE and biopsy data showed that 80.6% of people with raised fibrosis markers had confirmed significant fibrosis. We also show that fibrosis levels as detected by NIT are marginally lower in patients treated with newer glucose lowering agents (sodium-glucose transporter protein 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists). In conclusion by utilising a large consecutively recruited dataset we demonstrate that liver fibrosis is infrequently screened for in patients with diabetes despite high prevalence rates of advanced fibrosis. This highlights the need for cost-effectiveness analyses to support the incorporation of widespread screening into national guidelines and the requirement for healthcare practitioners to incorporate NAFLD screening into routine diabetes care.
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Affiliation(s)
- Laurence J. Dobbie
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L9 7AL, UK; (L.J.D.); (D.J.C.)
| | - Mohamed Kassab
- Department of Gastroenterology and Hepatology, Liverpool University Hospitals Foundation Trust, Liverpool L7 8XP, UK;
| | - Andrew S. Davison
- Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Liverpool University Hospitals Foundation Trust, Liverpool L7 8XP, UK;
- Liverpool Clinical Laboratories, Liverpool University Hospitals Foundation Trust, Liverpool L7 8XP, UK;
| | - Pete Grace
- Liverpool Clinical Laboratories, Liverpool University Hospitals Foundation Trust, Liverpool L7 8XP, UK;
| | - Daniel J. Cuthbertson
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L9 7AL, UK; (L.J.D.); (D.J.C.)
| | - Theresa J. Hydes
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L9 7AL, UK; (L.J.D.); (D.J.C.)
- Department of Gastroenterology and Hepatology, Liverpool University Hospitals Foundation Trust, Liverpool L7 8XP, UK;
- Correspondence:
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12
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Rodriguez LA, Kanaya AM, Shiboski SC, Fernandez A, Herrington D, Ding J, Bradshaw PT. Does NAFLD mediate the relationship between obesity and type 2 diabetes risk? evidence from the multi-ethnic study of atherosclerosis (MESA). Ann Epidemiol 2021; 63:15-21. [PMID: 34293421 PMCID: PMC8500945 DOI: 10.1016/j.annepidem.2021.07.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE To estimate the effect of obesity on type 2 diabetes (T2DM) risk and evaluate to what extent non-alcoholic fatty liver disease (NAFLD) mediates this association. METHODS Data came from 4,522 adults ages 45-84 participating in the Multi-Ethnic Study of Atherosclerosis cohort. Baseline obesity was defined using established BMI categories. NAFLD was measured by CT scans at baseline and incident T2DM defined as fasting glucose ≥126 mg/dL or use of diabetes medications. RESULTS Over a median 9.1 years of follow-up between 2000 and 2012, 557 new cases of T2DM occurred. After adjusting for age, sex, race/ethnicity, education, diet and exercise, those with obesity had 4.5 times the risk of T2DM compared to normal weight (hazard ratio [HR] = 4.5, 95% confidence interval [CI]: 3.0, 5.9). The mediation analysis suggested that NAFLD accounted for ~36% (95% CI: 27, 44) of the effect (direct effect HR = 3.2, 95% CI: 2.3, 4.6; indirect effect through NAFLD, HR = 1.4, 95% CI: 1.3, 1.5). CONCLUSIONS These data suggest that the association between obesity and T2DM risk is partially explained by the presence of NAFLD. Future studies should evaluate if NAFLD could be an effective target to reduce the effect of obesity on T2DM.
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Affiliation(s)
- Luis A Rodriguez
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA; Kaiser Permanente Northern California, Division of Research, Oakland, CA.
| | - Alka M Kanaya
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA; University of California, San Francisco, Division of General Internal Medicine, San Francisco, CA
| | - Stephen C Shiboski
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA
| | - Alicia Fernandez
- University of California, San Francisco, Department of Medicine, San Francisco, CA
| | - David Herrington
- Wake Forest School of Medicine, Department of Internal Medicine, Winston-Salem, NC
| | - Jingzhong Ding
- Wake Forest School of Medicine, Sticht Center on Aging, Winston-Salem, NC
| | - Patrick T Bradshaw
- University of California, Berkeley, School of Public Health, Division of Epidemiology & Biostatistics, Berkeley, CA
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13
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Wu MJ, Fang QL, Zou SY, Zhu Y, Lu W, Du X, Shi BM. Influencing factors for hepatic fat accumulation in patients with type 2 diabetes mellitus. World J Clin Cases 2021; 9:7717-7728. [PMID: 34621822 PMCID: PMC8462247 DOI: 10.12998/wjcc.v9.i26.7717] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/23/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide, which originates from the accumulation of triglyceride (TG) in the liver. Patients with type 2 diabetes mellitus (T2DM) are considered to have a predisposition to hepatic steatosis. However, the influencing factors for hepatic fat accumulation in T2DM patients remain unclear.
AIM To investigate the influencing factors for hepatic fat accumulation in T2DM patients.
METHODS We enrolled 329 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Soochow University, who underwent MR mDIXON-Quant examination to quantify the hepatic fat fraction (HFF). According to body mass index (BMI), the patients were divided into normal weight, overweight, and obese groups. The differences in general statistics, biochemical parameters, islet function, and HFF were compared among the three groups. The associations between HFF and other parameters and the influences of various parameters on the severity of hepatic fat accumulation were analyzed.
RESULTS The HFF of T2DM patients gradually increased in the normal weight, overweight, and obese groups (P < 0.05). Spearman correlation analysis showed that in T2DM patients, HFF was negatively correlated with age and high-density lipoprotein cholesterol (P < 0.05), whereas it was positively correlated with BMI, waist-hip ratio, fasting plasma glucose, alanine aminotransferase (ALT), aspartate aminotransferase, bilirubin, glutamyl transpeptidase, lactate dehydrogenase, albumin (ALB), uric acid (UA), total cholesterol, TG, low-density lipoprotein cholesterol (LDL-C), C-reactive protein, free triiodothyronine, fasting insulin, fasting C-peptide, and homeostasis model assessment of insulin resistance (P < 0.05). Multiple linear regression analysis showed significant positive influences of BMI, ALT, LDL-C, UA, and ALB on HFF in T2DM patients (P < 0.05). Binary logistic regression analysis showed that BMI, ALT, ALB, and LDL-C were independent risk factors for moderate to severe fatty liver in T2DM patients, and obesity increased the risk of being complicated with moderate to severe fatty liver by 4.03 times (P < 0.05).
CONCLUSION The HFF of T2DM patients increases with BMI. Higher BMI, ALT, ALB, and LDL-C are independent risk factors for moderate to severe fatty liver in T2DM patients.
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Affiliation(s)
- Meng-Jiao Wu
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Qiong-Lei Fang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Sheng-Yi Zou
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Yan Zhu
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Wen Lu
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Xuan Du
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Bi-Min Shi
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
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14
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Detection and Characterization of Phosphorylation, Glycosylation, and Fatty Acid Bound to Fetuin A in Human Blood. J Clin Med 2021; 10:jcm10030411. [PMID: 33499061 PMCID: PMC7865524 DOI: 10.3390/jcm10030411] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/12/2021] [Accepted: 01/18/2021] [Indexed: 01/12/2023] Open
Abstract
The hepatokine fetuin A (Fet A) has been associated with diverse pathological states such as insulin resistance, type 2 diabetes, macrovascular disease, and systemic ectopic and vascular calcification. Fet A may also play a role in tumor growth and metastasis. The biological activity of Fet A may be affected by various modifications, including phosphorylation, O- and N-glycosylation and fatty acid binding. We developed an antibody-based assay for the detection of Fet A phosphorylated at serine 312. Fatty acid pattern was determined by gas chromatography. Using the antibody, we found that the phosphorylation was stable in human plasma or serum at room temperature for 8 h. We observed that Fet A is present in several glycosylation forms in human plasma, but the extent of Ser312 phosphorylation was not associated with glycosylation. The phosphorylation pattern did not change during an oral glucose tolerance test (0–120 min). We further found that human Fet A binds preferentially saturated fatty acids (>90%) at the expense of mono- and poly-unsaturated fatty acids. Our results indicate that different molecular species of Fet A are present in human plasma and that these different modifications may determine the different biological effects of Fet A.
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15
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Bardugo A, Bendor CD, Zucker I, Lutski M, Cukierman-Yaffe T, Derazne E, Mosenzon O, Tzur D, Beer Z, Pinhas-Hamiel O, Ben-Ami M, Fishman B, Ben-Ami Shor D, Raz I, Afek A, Gerstein HC, Häring HU, Tirosh A, Levi Z, Twig G. Adolescent Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Young Adulthood. J Clin Endocrinol Metab 2021; 106:e34-e44. [PMID: 33075820 DOI: 10.1210/clinem/dgaa753] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Indexed: 02/08/2023]
Abstract
CONTEXT The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. OBJECTIVE To assess type 2 diabetes risk among adolescents with NAFLD. DESIGN AND SETTING A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997-2011 and were followed until December 31, 2016. PARTICIPANTS A total of 1 025 796 normoglycemic adolescents were included. INTERVENTIONS Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. MAIN OUTCOME MEASURES Type 2 diabetes incidence. RESULTS During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47-4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). CONCLUSIONS Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.
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Affiliation(s)
- Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Cole D Bendor
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Miri Lutski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Zivan Beer
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Michal Ben-Ami
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Boris Fishman
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Internal Medicine D and Hypertension Unit, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Dana Ben-Ami Shor
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology, Tel-Aviv Medical Center, Tel Aviv, Israel
| | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | | | - Hans-Ulrich Häring
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research, Tübingen, Germany
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Zohar Levi
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Gastroenterology Department, Rabin Medical Center, Petach Tikva, Israel
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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16
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Fiorentino TV, Succurro E, Sciacqua A, Andreozzi F, Perticone F, Sesti G. Non-alcoholic fatty liver disease is associated with cardiovascular disease in subjects with different glucose tolerance. Diabetes Metab Res Rev 2020; 36:e3333. [PMID: 32356922 DOI: 10.1002/dmrr.3333] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/23/2020] [Accepted: 04/24/2020] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) in patients with type 2 diabetes; nonetheless, it is unknown whether the relationship between NAFLD and CVD occurs also in subjects with prediabetes. Herein, we evaluated whether NAFLD is associated with prevalent CVD in subjects with different glucose tolerance states independently of cardiovascular risk factors. MATERIALS AND METHODS Presence of NALFD, defined by liver ultrasound, and its association with prevalent composite and individual CVD, including coronary artery disease (CAD) and cerebrovascular disease, was assessed in a cohort of 1254 Caucasian subjects classified as having normal glucose tolerance (NGT, n = 517), prediabetes (n = 397) or type 2 diabetes (n = 340). RESULTS Prevalence of NAFLD in the study population was 47.9%. Presence of NAFLD was linked to an augmented prevalence of composite CVD and individual CAD in all the three glucose tolerance groups. In a logistic regression model adjusted for several cardio-metabolic risk factors, subjects with NGT and NAFLD exhibited a 3.2- and 3.4-fold increased risk of having CVD or CAD, respectively, as compared with those without NAFLD. Similarly, subjects with prediabetes and NAFLD showed an increased risk of having CVD or CAD by 2.3- and 2.0-fold, respectively, in comparison to their counterpart without NAFLD. Within the group with type 2 diabetes, subjects having NAFLD displayed a 2.3- and 2.0-fold higher risk of having CVD or CAD, respectively, in comparison to those without NAFLD. CONCLUSION Ultrasonography-defined NAFLD is independently associated with an increased risk of having CVD in individuals with different glucose tolerance.
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Affiliation(s)
- Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesco Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
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17
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Robison LS, Gannon OJ, Thomas MA, Salinero AE, Abi-Ghanem C, Poitelon Y, Belin S, Zuloaga KL. Role of sex and high-fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer's disease. J Neuroinflammation 2020; 17:285. [PMID: 32993686 PMCID: PMC7526387 DOI: 10.1186/s12974-020-01956-5] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 09/18/2020] [Indexed: 12/14/2022] Open
Abstract
Background Hypothalamic dysfunction occurs early in the clinical course of Alzheimer’s disease (AD), likely contributing to disturbances in feeding behavior and metabolic function that are often observed years prior to the onset of cognitive symptoms. Late-life weight loss and low BMI are associated with increased risk of dementia and faster progression of disease. However, high-fat diet and metabolic disease (e.g., obesity, type 2 diabetes), particularly in mid-life, are associated with increased risk of AD, as well as exacerbated AD pathology and behavioral deficits in animal models. In the current study, we explored possible relationships between hypothalamic function, diet/metabolic status, and AD. Considering the sex bias in AD, with women representing two-thirds of AD patients, we sought to determine whether these relationships vary by sex. Methods WT and 3xTg-AD male and female mice were fed a control (10% fat) or high-fat (HF 60% fat) diet from ~ 3–7 months of age, then tested for metabolic and hypothalamic disturbances. Results On control diet, male 3xTg-AD mice displayed decreased body weight, reduced fat mass, hypoleptinemia, and mild systemic inflammation, as well as increased expression of gliosis- and inflammation-related genes in the hypothalamus (Iba1, GFAP, TNF-α, IL-1β). In contrast, female 3xTg-AD mice on control diet displayed metabolic disturbances opposite that of 3xTg-AD males (increased body and fat mass, impaired glucose tolerance). HF diet resulted in expected metabolic alterations across groups (increased body and fat mass; glucose intolerance; increased plasma insulin and leptin, decreased ghrelin; nonalcoholic fatty liver disease-related pathology). HF diet resulted in the greatest weight gain, adiposity, and glucose intolerance in 3xTg-AD females, which were associated with markedly increased hypothalamic expression of GFAP and IL-1β, as well as GFAP labeling in several hypothalamic nuclei that regulate energy balance. In contrast, HF diet increased diabetes markers and systemic inflammation preferentially in AD males but did not exacerbate hypothalamic inflammation in this group. Conclusions These findings provide further evidence for the roles of hypothalamic and metabolic dysfunction in AD, which in the 3xTg-AD mouse model appears to be dependent on both sex and diet.
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Affiliation(s)
- Lisa S Robison
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Olivia J Gannon
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Melissa A Thomas
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Abigail E Salinero
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Charly Abi-Ghanem
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Yannick Poitelon
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Sophie Belin
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Kristen L Zuloaga
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA.
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18
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Khalangot M, Krasnienkov D, Vaiserman A. Telomere length in different metabolic categories: Clinical associations and modification potential. Exp Biol Med (Maywood) 2020; 245:1115-1121. [PMID: 32515222 PMCID: PMC7400729 DOI: 10.1177/1535370220931509] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Metabolic disorders are known to be associated with accelerated telomere attrition. Their pathophysiological heterogeneity suggests the importance of multiple tests in examining these associations. However, oral glucose tolerance test (OGTT) has rarely been performed in such studies to date. There are few studies aimed at determining leukocyte telomere length (LTL) in different categories of impaired glucose tolerance (IGT), and those that do exist do not take into account the impaired fasting glucose (IFG)/IGT categorization. Therefore, we believe our study, when the OGTT was used, is important to the field. This testing made it possible to determine whether LTLs are associated with glucose levels in different hyperglycemic categories. Our data indicate that relationships between LTLs and IFG/IGT levels are not the same. This distinction can potentially be used in categorization of metabolic disorders and in determining the effectiveness of interventions aimed at treating diabetes and other metabolic abnormalities.
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Affiliation(s)
- Mykola Khalangot
- Epidemiology Department, Komisarenko Institute of Endocrinology and Metabolism, Kyiv 04114, Ukraine
- Endocrinology Department, Shupyk National Medical Academy of Postgraduate Education, Kyiv 04112, Ukraine
| | - Dmytro Krasnienkov
- Laboratory of Epigenetics, Chebotariov Institute of Gerontology, Kyiv 04114, Ukraine
| | - Alexander Vaiserman
- Laboratory of Epigenetics, Chebotariov Institute of Gerontology, Kyiv 04114, Ukraine
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19
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Campbell MD, Sathish T, Zimmet PZ, Thankappan KR, Oldenburg B, Owens DR, Shaw JE, Tapp RJ. Benefit of lifestyle-based T2DM prevention is influenced by prediabetes phenotype. Nat Rev Endocrinol 2020; 16:395-400. [PMID: 32060416 DOI: 10.1038/s41574-019-0316-1] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/23/2019] [Indexed: 01/11/2023]
Abstract
The prevention of type 2 diabetes mellitus (T2DM) is a target priority for the WHO and the United Nations and is a key priority in the 2018 Berlin Declaration, which is a global call for early actions related to T2DM. Health-care policies advocate that individuals at high risk of developing T2DM undertake lifestyle modification, irrespective of whether the prediabetes phenotype is defined by hyperglycaemia in the postprandial state (impaired glucose tolerance) and/or fasting state (impaired fasting glucose) or by intermediate HbA1c levels. However, current evidence indicates that diabetes prevention programmes based on lifestyle change have not been successful in preventing T2DM in individuals with isolated impaired fasting glucose. We propose that further research is needed to identify effective lifestyle interventions for individuals with isolated impaired fasting glucose. Furthermore, we call for the identification of innovative approaches that better identify people with impaired glucose tolerance, who benefit from the currently available lifestyle-based diabetes prevention programmes.
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Affiliation(s)
- Matthew D Campbell
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
- School of Food Science and Bioengineering, Zhejiang Gongshang University, Hangzhou, China
| | - Thirunavukkarasu Sathish
- Population Health Research Institute, McMaster University, Hamilton, ON, Canada
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
- Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Paul Z Zimmet
- Department of Diabetes, Central Clinical School, Monash University, Clayton, VIC, Australia
| | | | - Brian Oldenburg
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
- WHO Collaborating Centre on Implementation Research for Prevention and Control of Noncommunicable Diseases, University of Melbourne, Melbourne, VIC, Australia
| | - David R Owens
- Diabetes Research Unit Cymru, Swansea University, Swansea, UK
| | - Jonathan E Shaw
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Robyn J Tapp
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
- Population Health Research Institute, St George's, University of London, London, UK.
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20
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Miljkovic I, Kuipers AL, Cvejkus RK, Carr JJ, Terry JG, Thyagarajan B, Wheeler VW, Nair S, Zmuda JM. Hepatic and Skeletal Muscle Adiposity Are Associated with Diabetes Independent of Visceral Adiposity in Nonobese African-Caribbean Men. Metab Syndr Relat Disord 2020; 18:275-283. [PMID: 32392448 DOI: 10.1089/met.2019.0097] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background: Adipose tissue (AT) around and within non-AT organs (i.e., ectopic adiposity) is emerging as a strong risk factor for type 2 diabetes (T2D). Not known is whether major ectopic adiposity depots, such as hepatic, skeletal muscle, and pericardial adiposity (PAT), are associated with T2D independent of visceral adiposity (VAT). More data are particularly needed among high-risk nonobese minority populations, as the race/ethnic gap in T2D risk is greatest among nonobese. Methods: Thus, we measured several ectopic adiposity depots by computed tomography in 718 (mean age = 64 years) African-Caribbean men on the Island of Tobago overall, and stratified by obesity (obese N = 187 and nonobese N = 532). Results: In age, lifestyle risk factors, health status, lipid-lowering medication intake, body mass index and all other adiposity-adjusted regression analyses, and hepatic and skeletal muscle adiposity were associated with T2D among nonobese men only (all P < 0.05), despite no association between VAT and PAT and T2D. Conclusions: Our results support the "ectopic fat syndrome" theory in the pathogenesis of T2D among nonobese African-Caribbean men. Longitudinal studies are needed to clarify the independent role of ectopic adiposity in T2D, and to identify possible biological mechanisms underlying this relationship, particularly in high-risk African ancestry and other nonwhite populations.
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Affiliation(s)
- Iva Miljkovic
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Allison L Kuipers
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ryan K Cvejkus
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - J Jeffrey Carr
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - James G Terry
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Bharat Thyagarajan
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Victor W Wheeler
- Tobago Health Studies Office, Scarborough, Tobago, Trinidad & Tobago, West Indies
| | - Sangeeta Nair
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Joseph M Zmuda
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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21
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Gehrke N, Schattenberg JM. Metabolic Inflammation-A Role for Hepatic Inflammatory Pathways as Drivers of Comorbidities in Nonalcoholic Fatty Liver Disease? Gastroenterology 2020; 158:1929-1947.e6. [PMID: 32068022 DOI: 10.1053/j.gastro.2020.02.020] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 02/05/2020] [Accepted: 02/11/2020] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a global and growing health concern. Emerging evidence points toward metabolic inflammation as a key process in the fatty liver that contributes to multiorgan morbidity. Key extrahepatic comorbidities that are influenced by NAFLD are type 2 diabetes, cardiovascular disease, and impaired neurocognitive function. Importantly, the presence of nonalcoholic steatohepatitis and advanced hepatic fibrosis increase the risk for systemic comorbidity in NAFLD. Although the precise nature of the crosstalk between the liver and other organs has not yet been fully elucidated, there is emerging evidence that metabolic inflammation-in part, emanating from the fatty liver-is the engine that drives cellular dysfunction, cell death, and deleterious remodeling within various body tissues. This review describes several inflammatory pathways and mediators that have been implicated as links between NAFLD and type 2 diabetes, cardiovascular disease, and neurocognitive decline.
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Affiliation(s)
- Nadine Gehrke
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Center, Mainz, Germany.
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Center, Mainz, Germany
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22
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Dieny FF, Tsani AFA, Setyaningsih RF, Fitranti DY, Jauharany FF, Putra YD. Abdominal Diameter Profiles have Relationship with Insulin Resistance in Obese Female Adolescents. ELECTRONIC JOURNAL OF GENERAL MEDICINE 2020. [DOI: 10.29333/ejgm/7882] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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23
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Effects of Periodic Fasting on Fatty Liver Index-A Prospective Observational Study. Nutrients 2019; 11:nu11112601. [PMID: 31671589 PMCID: PMC6893587 DOI: 10.3390/nu11112601] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 02/07/2023] Open
Abstract
This prospective observational trial investigated effects and safety of periodic fasting in subjects with and without type 2 diabetes mellitus (T2DM). The primary end point was set as the change of fatty liver index (FLI) as a surrogate parameter of non-alcoholic fatty liver disease (NAFLD). Six-hundred and ninety-seven subjects (38 with T2DM) were enrolled. A baseline FLI ≥ 60 (the threshold for fatty liver) was found in 264 subjects (37.9%). The mean duration of fasting was 8.5 ± 4.0 days (range 6–38). FLI decreased significantly (−14.02 ± 11.67; p < 0.0001), with a larger effect in individuals with T2DM (−19.15 ± 11.0; p < 0.0001; p = 0.002 compared to non-diabetic subjects). Body mass index (BMI) decreased by −1.51 ± 0.82 kg/m2, and 49.9% of the subjects lost ≥5% body weight. After fasting, nearly half of the 264 subjects with FLI ≥ 60 (highest risk category) shifted to a lower category. The improvement of FLI correlated with the number of fasting days (r = −0.20, p < 0.0001) and with the magnitude of BMI reduction (r = 0.14, p = 0.0001). Periodic fasting with concomitant weight reduction leads to significant rapid improvement of FLI in subjects with and without T2DM.
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24
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Abstract
Studies have linked obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD) and dementia. Their relationship to the incidence and progression of these disease states suggests an interconnected pathogenesis involving chronic low-grade inflammation and oxidative stress. Metabolic syndrome represents comorbidities of central obesity, insulin resistance, dyslipidemia, hypertension and hyperglycemia associated with increased risk of type 2 diabetes, NAFLD, atherosclerotic CVD and neurodegenerative disease. As the socioeconomic burden for these diseases has grown signficantly with an increasing elderly population, new and alternative pharmacologic solutions for these cardiometabolic diseases are required. Adipose tissue, skeletal muscle and liver are central endocrine organs that regulate inflammation, energy and metabolic homeostasis, and the neuroendocrine axis through synthesis and secretion of adipokines, myokines, and hepatokines, respectively. These organokines affect each other and communicate through various endocrine, paracrine and autocrine pathways. The ultimate goal of this review is to provide a comprehensive understanding of organ crosstalk. This will include the roles of novel organokines in normal physiologic regulation and their pathophysiological effect in obesity, metabolic syndrome, type 2 diabetes, CVD, NAFLD and neurodegenerative disorders.
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Affiliation(s)
- Hye Soo Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Seoul, South Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, South Korea.
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25
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Gepner Y, Shelef I, Komy O, Cohen N, Schwarzfuchs D, Bril N, Rein M, Serfaty D, Kenigsbuch S, Zelicha H, Yaskolka Meir A, Tene L, Bilitzky A, Tsaban G, Chassidim Y, Sarusy B, Ceglarek U, Thiery J, Stumvoll M, Blüher M, Stampfer MJ, Rudich A, Shai I. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol 2019; 71:379-388. [PMID: 31075323 DOI: 10.1016/j.jhep.2019.04.013] [Citation(s) in RCA: 158] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 03/26/2019] [Accepted: 04/17/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIM It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. METHODS In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. RESULTS Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. CONCLUSIONS %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. LAY SUMMARY High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.
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Affiliation(s)
- Yftach Gepner
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine and Sylvan Adams Sports Institute, Tel Aviv University, Israel
| | - Ilan Shelef
- Soroka University Medical Center, Beer-Sheva, Israel
| | - Oded Komy
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Noa Cohen
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Dan Schwarzfuchs
- Soroka University Medical Center, Beer-Sheva, Israel; Nuclear Research Center-Negev, Dimona, Israel
| | - Nitzan Bril
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Michal Rein
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Dana Serfaty
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Shira Kenigsbuch
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Hila Zelicha
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Anat Yaskolka Meir
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Lilac Tene
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Avital Bilitzky
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Gal Tsaban
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | | | | | - Uta Ceglarek
- Department of Medicine, University of Leipzig, Germany
| | | | | | | | - Meir J Stampfer
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard School of Public Health, Boston, MA, USA
| | - Assaf Rudich
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Iris Shai
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
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Pratte KA, Johnson A, Beals J, Bullock A, Manson SM, Jiang L. Regression to Normal Glucose Regulation in American Indians and Alaska Natives of a Diabetes Prevention Program. Diabetes Care 2019; 42:1209-1216. [PMID: 31177184 PMCID: PMC6609959 DOI: 10.2337/dc18-1964] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Accepted: 01/13/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE This study evaluated whether regression from impaired glucose regulation (IGR) to normal glucose regulation (NGR) after 1 year of a lifestyle intervention reduces diabetes risk in American Indians and Alaska Natives (AI/ANs). In addition, we sought to identify predictors for regression to NGR and understand possible mechanisms for the association between NGR and future diabetes risk. RESEARCH DESIGN AND METHODS Data from participants enrolled from 2006 to 2009 in the Special Diabetes Program for Indians Diabetes Prevention Program with IGR at baseline and an oral glucose tolerance test at year 1 were analyzed (N = 1,443). Cox regression models were used to estimate the subsequent diabetes risk (year 1 to year 3) by year 1 glucose status. Mediation analysis was used to estimate the proportions of the association between year 1 glycemic status and diabetes risk explained by specific factors. RESULTS Those who reverted to NGR at year 1 (38%) had lower diabetes risk than those with sustained IGR (adjusted hazard ratio 0.28, 95% CI 0.12-0.67). The lower risk associated with regression to NGR was explained by both baseline risk factors and differences in weight loss. Metformin use, weight loss, and an increase in exercise were modifiable risk factors associated with higher odds of regression to NGR. CONCLUSIONS Patients with prediabetes who reverted to NGR had a reduced risk of developing type 2 diabetes over the next 2 years. Both baseline and modifiable risk factors explained the risk reduction associated with NGR.
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Affiliation(s)
- Katherine A Pratte
- Department of Epidemiology, School of Medicine, University of California, Irvine, Irvine, CA
| | - Ann Johnson
- Centers for American Indian and Alaska Native Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Janette Beals
- Centers for American Indian and Alaska Native Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Ann Bullock
- Division of Diabetes Treatment and Prevention, Indian Health Service, Rockville, MD
| | - Spero M Manson
- Centers for American Indian and Alaska Native Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Luohua Jiang
- Department of Epidemiology, School of Medicine, University of California, Irvine, Irvine, CA
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Abstract
The health-promoting effects of physical activity to prevent and treat metabolic disorders are numerous. However, the underlying molecular mechanisms are not yet completely deciphered. In recent years, studies have referred to the liver as an endocrine organ, since it releases specific proteins called hepatokines. Some of these hepatokines are involved in whole body metabolic homeostasis and are theorized to participate in the development of metabolic disease. In this regard, the present review describes the role of Fibroblast Growth Factor 21, Fetuin-A, Angiopoietin-like protein 4, and Follistatin in metabolic disease and their production in response to acute exercise. Also, we discuss the potential role of hepatokines in mediating the beneficial effects of regular exercise and the future challenges to the discovery of new exercise-induced hepatokines.
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Affiliation(s)
- Gaël Ennequin
- PEPITE EA4267, EPSI, Université de Bourgogne Franche-Comté , Besançon , France
| | - Pascal Sirvent
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques (AME2P), CRNH Auvergne, Clermont-Ferrand , France
| | - Martin Whitham
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham , Birmingham , United Kingdom
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Sánchez-Crisóstomo I, Fernández-Martínez E, Cariño-Cortés R, Betanzos-Cabrera G, Bobadilla-Lugo RA. Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma. Curr Pharm Biotechnol 2019; 20:197-214. [DOI: 10.2174/1389201020666190219122357] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/10/2018] [Accepted: 02/09/2019] [Indexed: 12/17/2022]
Abstract
Background:
Liver ailments are among the leading causes of death; they originate from viral
infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of
cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic
Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is
the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological
treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective.
The use of medicinal herbs and functional foods is growing around the world as natural resources
of bioactive compounds that would set the basis for the development of new drugs.
Review and Conclusion:
Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant,
metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized
as anticancer agents, suggesting their application strongly as an alternative therapy in some
chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents,
but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids
due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating
nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the
prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.
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Affiliation(s)
- Isabel Sánchez-Crisóstomo
- Center for Research on Reproductive Biology, School of Health Sciences, Autonomous University of Hidalgo's State, Pachuca, Mexico
| | - Eduardo Fernández-Martínez
- Laboratory of Medicinal Chemistry and Pharmacology, Department of Medicine, School of Health Sciences, Autonomous University of Hidalgo's State, Pachuca, Mexico
| | - Raquel Cariño-Cortés
- Center for Research on Reproductive Biology, School of Health Sciences, Autonomous University of Hidalgo's State, Pachuca, Mexico
| | - Gabriel Betanzos-Cabrera
- Laboratory of Medicinal Chemistry and Pharmacology, Department of Medicine, School of Health Sciences, Autonomous University of Hidalgo's State, Pachuca, Mexico
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Shen B, Zhao C, Wang Y, Peng Y, Cheng J, Li Z, Wu L, Jin M, Feng H. Aucubin inhibited lipid accumulation and oxidative stress via Nrf2/HO-1 and AMPK signalling pathways. J Cell Mol Med 2019; 23:4063-4075. [PMID: 30950217 PMCID: PMC6533504 DOI: 10.1111/jcmm.14293] [Citation(s) in RCA: 119] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 03/04/2019] [Accepted: 03/07/2019] [Indexed: 02/06/2023] Open
Abstract
Aucubin (AU) is the main active ingredient of Aucuba japonica which has showed many positive effects such as anti‐inflammation and liver protection. Non‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. In this research, we explored the effects of AU on the tyloxapol‐induced NAFLD in mice and apolipoprotein C‐III (apoC‐III) induced‐3T3L1 cells. Tyloxapol (300 mg/kg) was injected to C57BL/6 mice with aucubin. The differentiated 3T3‐L1 cells were treated with or without aucubin after stimulation of apoC‐III (100 μg/mL). In results, aucubin inhibited hyperlipidaemia, oxidative stress and inflammation by influencing the content of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), myeloperoxidase (MPO), superoxide dismutase (SOD), tumour necrosis factor receptor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 in blood. AU activated NF‐E2‐related factor 2 (Nrf2), peroxisome proliferator‐activated receptor α (PPARα), PPARγ and hemeoxygenase‐1 (HO‐1) and promoted the phosphorylation of adenosine 5′‐monophosphate‐activated protein kinase (AMPKα), AMPKβ, acetyl‐CoA carboxylase (ACC) and protein kinase B (AKT). In conclusion, AU performed the function of hypolipidaemic by its obvious anti‐inflammation and antioxidant activity, which may become a kind of new drug targeting at NAFLD.
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Affiliation(s)
- Bingyu Shen
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, PR China
| | - Chenxu Zhao
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, PR China
| | - Yue Wang
- Department of Pediatric Hematology, The First Hospital of Jilin University, Changchun, Jilin, PR China
| | - Yi Peng
- Department of Hematology, The First Hospital of Jilin University, Changchun, Jilin, PR China
| | - Jiaqi Cheng
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, PR China
| | - Zheng Li
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, PR China
| | - Lin Wu
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, PR China
| | - Meiyu Jin
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, PR China
| | - Haihua Feng
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, PR China
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Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol 2019; 7:313-324. [PMID: 30174213 DOI: 10.1016/s2213-8587(18)30154-2] [Citation(s) in RCA: 576] [Impact Index Per Article: 96.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 05/02/2018] [Accepted: 05/04/2018] [Indexed: 02/06/2023]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. In some patients with NAFLD, isolated steatosis can progress to advanced stages with non-alcoholic steatohepatitis (NASH) and fibrosis, increasing the risk of cirrhosis and hepatocellular carcinoma. Furthermore, NAFLD is believed to be involved in the pathogenesis of common disorders such as type 2 diabetes and cardiovascular disease. In this Review, we highlight novel concepts related to diagnosis, risk prediction, and treatment of NAFLD. First, because NAFLD is a heterogeneous disease, the advanced stages of which seem to be strongly affected by comorbidities such as insulin resistance and type 2 diabetes, early use of reliable, non-invasive diagnostic tools is needed, particularly in patients with insulin resistance or diabetes, to allow the identification of patients at different disease stages. Second, although the strongest genetic risk alleles for NAFLD (ie, the 148Met allele in PNPLA3 and the 167Lys allele in TM6SF2) are associated with increased liver fat content and progression to NASH and cirrhosis, these alleles are also unexpectedly associated with an apparent protection from cardiovascular disease. If consistent across diverse populations, this discordance in NAFLD-related risk prediction between hepatic and extrahepatic disease might need to be accounted for in the management of NAFLD. Third, drug treatments assessed in NAFLD seem to differ with respect to cardiometabolic and antifibrotic efficacy, suggesting the need to better identify and tailor the most appropriate treatment approach, or to use a combination of approaches. These emerging concepts could contribute to the development of a multidisciplinary approach for endocrinologists and hepatologists working together in the management of NAFLD.
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Affiliation(s)
- Norbert Stefan
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases, Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research, Tübingen, Germany.
| | - Hans-Ulrich Häring
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases, Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research, Tübingen, Germany
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA; Division of Endocrinology, Malcom Randall Veterans Administration, Medical Center, Gainesville, FL, USA
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Park JH, Kim HJ, Han A, Kang DM, Park S. Effects of aerobic exercise training on the risk factors for liver diseases in elderly women with obesity and impaired fasting glucose: A pilot study. J Exerc Nutrition Biochem 2019; 23:21-27. [PMID: 31010271 PMCID: PMC6477817 DOI: 10.20463/jenb.2019.0004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 03/19/2019] [Indexed: 02/06/2023] Open
Abstract
[Purpose] In the present pilot study, we aimed to investigate the effects of the Silverrobics exercise program, which is similar to aerobic dance, on the factors related to glucose metabolism and liver enzymes. [Methods] Eight elderly women with obesity and impaired fasting glucose participated in the Silverrobics exercise program (60 minutes per session for five times a week for 8 weeks). The program was conducted at 50–60% of the heart rate reserve at 1 to 2 weeks and at 60–80% of the heart rate reserve at 3 to 8 weeks. To verify the effect of this 8-week exercise program on glucose metabolism and liver enzymes, blood analysis at pre- and post-training was performed. [Results] After the Silverrobics exercise program, there were significant decreases in the glucose (p<0.05), glycated hemoglobin A1c (p<0.05), 1,5-anhydroglucitol (p<0.05), and insulin levels (p<0.01) and homeostatic model assessment of insulin resistance score (p<0.05). However, there were no significant effects on the liver enzymes, except for alkaline phosphatase. The alkaline phosphatase level increased after the Silverrobics exercise program (p<0.05). [Conclusion] Although the Silverrobics exercise program had no beneficial effects on the liver enzymes, it may play an important role in preventing liver diseases considering the effects on glucose metabolism.
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Schübel R, Nonnenmacher T, Sookthai D, Gonzalez Maldonado S, Sowah SA, von Stackelberg O, Schlett CL, Grafetstätter M, Nabers D, Johnson T, Kirsten R, Ulrich CM, Kaaks R, Kauczor HU, Kühn T, Nattenmüller J. Similar Weight Loss Induces Greater Improvements in Insulin Sensitivity and Liver Function among Individuals with NAFLD Compared to Individuals without NAFLD. Nutrients 2019; 11:nu11030544. [PMID: 30836637 PMCID: PMC6471668 DOI: 10.3390/nu11030544] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 02/19/2019] [Accepted: 02/25/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Preliminary evidence suggests that weight loss among obese has differential metabolic effects depending on the presence of non-alcoholic fatty liver disease (NAFLD). We assessed whether NAFLD predisposes to differential changes in liver fat content, liver function, and metabolic parameters upon diet-induced weight loss in a 50-week intervention trial. METHODS 143 overweight and obese non-smokers underwent a 12-week dietary intervention and a 38-week follow-up. Diet-induced changes in anthropometric measures, circulating biomarkers, and magnetic resonance (MR)-derived liver fat content and adipose tissue volumes were evaluated by mixed linear models stratifying by NAFLD at baseline. RESULTS The prevalence of NAFLD at baseline was 52%. Diet-induced weight loss after 12 (NAFLD: 4.8 ± 0.5%, No NAFLD: 5.1 ± 0.5%) and 50 weeks (NAFLD: 3.5 ± 0.7%, No NAFLD: 3.5 ± 0.9%) was similar in both groups, while the decrease in liver fat was significantly greater in the NAFLD group (week 12: 32.9 ± 9.5% vs. 6.3 ± 4.0%; week 50: 23.3 ± 4.4% vs. 5.0 ± 4.2%). Decreases in biomarkers of liver dysfunction (GGT, ALT, AST) and HOMA IR were also significantly greater in the NAFLD group. Other metabolic parameters showed no significant differences. CONCLUSION Our data suggest that individuals with NAFLD show greater improvements of liver function and insulin sensitivity after moderate diet-induced weight loss than individuals without NAFLD.
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Affiliation(s)
- Ruth Schübel
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
- Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
| | - Tobias Nonnenmacher
- Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
| | - Disorn Sookthai
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
| | - Sandra Gonzalez Maldonado
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
| | - Solomon A Sowah
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
| | - Oyunbileg von Stackelberg
- Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
| | - Christopher L Schlett
- Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
| | - Mirja Grafetstätter
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
| | - Diana Nabers
- German Cancer Research Center (DKFZ), Division of Medical and Biological Informatics, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
| | - Theron Johnson
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
| | - Romy Kirsten
- National Center for Tumor Diseases (NCT), Liquid Biobank, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
| | - Cornelia M Ulrich
- Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112-5550, USA.
| | - Rudolf Kaaks
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
| | - Hans-Ulrich Kauczor
- Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
| | - Tilman Kühn
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
| | - Johanna Nattenmüller
- Heidelberg University Hospital, Diagnostic and Interventional Radiology, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
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Khalangot MD, Krasnienkov DS, Chizhova VP, Korkushko OV, Shatilo VB, Kukharsky VM, Kravchenko VI, Kovtun VA, Guryanov VG, Vaiserman AM. Additional Impact of Glucose Tolerance on Telomere Length in Persons With and Without Metabolic Syndrome in the Elderly Ukraine Population. Front Endocrinol (Lausanne) 2019; 10:128. [PMID: 30873125 PMCID: PMC6404635 DOI: 10.3389/fendo.2019.00128] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 02/11/2019] [Indexed: 12/30/2022] Open
Abstract
Rationale: Association between different components of metabolic syndrome and the rate of age-related telomere shortening was reported repeatedly, although some findings are inconsistent across studies, suggesting the need for further research on the topic. In the present study, we examined relationships between different components of metabolic syndrome (MetS); glucose tolerance reflected in 2-h post-load plasma glucose (2hPG) levels and age on the leukocyte telomere length (LTL) in Ukraine population. Methods: The study was conducted on the 115 adult individuals residing in the Kyiv region (Ukraine). Among them, 79 were diagnosed with MetS according to the International Diabetes Federation definition. LTL were determined by a qPCR-based method. Multivariate logistic regression (MLR) and artificial neural networks (ANN) modeling were used for the analysis of the results. ROC-analysis was also performed to compare the predictively values of this models. Results: MetS was associated with a high (OR = 3.0 CI 1.3-6.7; p = 0.01) risk of having shorter telomeres that remained significant after adjusting for age, gender and 2hPG levels. Fasting plasma glucose (FPG) levels and other MetS components did not affect the magnitude of the relationship and did not reveal the independent influence of these factors. The level of 2hPG in turn, demonstrated a significant relationship (OR = 1.3 CI 1.0-1.6 per 1 mmol/l; p = 0.04) with LTL regardless of the presence of MetS. The non-linearity of the interactions between age, gender and 2hPG level was revealed by neural network modeling (AUC = 0.76 CI 0.68-0.84). Conclusion: Our study found that impaired glucose tolerance, but not FPG levels, affected the association between LTL and MetS, which may be also indicative for pathophysiological differences in these hyperglycemia categories. 2hPG levels can provide an opportunity for a more accurate diagnostics of MetS and for evaluating the rate of aging in patients with MetS. Further research, however, is needed to verify this assumption.
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Affiliation(s)
- Mykola D. Khalangot
- Epidemiology Department, Komisarenko Institute of Endocrinology and Metabolism, Kyiv, Ukraine
- Endocrinology Department, Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine
| | | | | | - Oleg V. Korkushko
- Laboratory of Epigenetics, Chebotariov Institute of Gerontology, Kyiv, Ukraine
| | - Valery B. Shatilo
- Laboratory of Epigenetics, Chebotariov Institute of Gerontology, Kyiv, Ukraine
| | - Vitaly M. Kukharsky
- Laboratory of Epigenetics, Chebotariov Institute of Gerontology, Kyiv, Ukraine
| | - Victor I. Kravchenko
- Epidemiology Department, Komisarenko Institute of Endocrinology and Metabolism, Kyiv, Ukraine
| | - Volodymyr A. Kovtun
- Epidemiology Department, Komisarenko Institute of Endocrinology and Metabolism, Kyiv, Ukraine
| | - Vitaly G. Guryanov
- Public Health Management Department, Bogomolets National Medical University, Kyiv, Ukraine
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Okushin K, Tsutsumi T, Ikeuchi K, Kado A, Enooku K, Fujinaga H, Moriya K, Yotsuyanagi H, Koike K. Helicobacter pylori infection and liver diseases: Epidemiology and insights into pathogenesis. World J Gastroenterol 2018; 24:3617-3625. [PMID: 30166857 PMCID: PMC6113725 DOI: 10.3748/wjg.v24.i32.3617] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 05/30/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Both Helicobacter pylori (H. pylori) infection and liver diseases, including nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and hepatocellular carcinoma (HCC), have high prevalences worldwide, and the relationship between H. pylori infection and liver disease has been discussed for many years. Although positive correlations between H. pylori and NAFLD have been identified in some clinical and experimental studies, negative correlations have also been obtained in high-quality clinical studies. Associations between H. pylori and the pathogenesis of chronic viral hepatitis, mainly disease progression with fibrosis, have also been suggested in some clinical studies. Concerning HCC, a possible role for H. pylori in hepatocarcinogenesis has been identified since H. pylori genes have frequently been detected in resected HCC specimens. However, no study has revealed the direct involvement of H. pylori in promoting the development of HCC. Although findings regarding the correlations between H. pylori and liver disease pathogenesis have been accumulating, the existing data do not completely lead to an unequivocal conclusion. Further high-quality clinical and experimental analyses are necessary to evaluate the efficacy of H. pylori eradication in ameliorating the histopathological changes observed in each liver disease.
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Affiliation(s)
- Kazuya Okushin
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Kazuhiko Ikeuchi
- Department of Infectious Diseases, The University of Tokyo, Tokyo 113-8655, Japan
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Akira Kado
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Hidetaka Fujinaga
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kyoji Moriya
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Infectious Diseases, The University of Tokyo, Tokyo 113-8655, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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Phenotypic Multiorgan Involvement of Subclinical Disease as Quantified by Magnetic Resonance Imaging in Subjects With Prediabetes, Diabetes, and Normal Glucose Tolerance. Invest Radiol 2018; 53:357-364. [DOI: 10.1097/rli.0000000000000451] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Jiang B, Gu T, Zhou K, Zheng Y, Guo Y, Lu Y. Fatty Liver as a Potential Surrogate for Waist Circumference in the Diagnosis of Metabolic Syndrome: A Population-Based Study among Chinese Adults. Int J Endocrinol 2018; 2018:7903982. [PMID: 29849623 PMCID: PMC5914088 DOI: 10.1155/2018/7903982] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 12/18/2017] [Accepted: 01/21/2018] [Indexed: 01/11/2023] Open
Abstract
Increased waist circumference (WC) is an essential component of metabolic syndrome (MetS). Asians have been found to have more intra-abdominal adipose tissue than Caucasians, in spite of having smaller WC. The purpose of this study was to explore whether NAFLD could be used as a surrogate for MetS diagnosis in the normal WC population. A total of 9694 Chinese residents were selected from SPECT-China, a population-based survey of Chinese adults aged ≥ 18 years in East China. Insulin resistance was calculated by the homeostatic model assessment for insulin resistance (HOMA-IR). MetS z-score was used to evaluate the degree of total metabolic disorder. Logistic regression models were used to obtain the associations between different categories and metabolic syndrome (MetS) components. The prevalence of NAFLD was 27.6%, in which 35.2% were without abnormal WC. Subjects with only NAFLD had similarly severe insulin resistance and OR for clustering of MetS components compared with those with only abnormal WC. A considerable number of NAFLD cases, although had severe metabolic disorder, would not be detected by the current MetS definition. NAFLD could be used as a potential surrogate marker for the diagnosis of MetS in normal WC population.
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Affiliation(s)
- Boren Jiang
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting Gu
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kun Zhou
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanjun Zheng
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuyu Guo
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yingli Lu
- Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Lee S, Norheim F, Gulseth HL, Langleite TM, Kolnes KJ, Tangen DS, Stadheim HK, Gilfillan GD, Holen T, Birkeland KI, Jensen J, Drevon CA. Interaction between plasma fetuin-A and free fatty acids predicts changes in insulin sensitivity in response to long-term exercise. Physiol Rep 2017; 5:5/5/e13183. [PMID: 28270597 PMCID: PMC5350184 DOI: 10.14814/phy2.13183] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 01/30/2017] [Accepted: 02/05/2017] [Indexed: 12/12/2022] Open
Abstract
The hepatokine fetuin‐A can together with free fatty acids (FFAs) enhance adipose tissue (AT) inflammation and insulin resistance via toll‐like receptor 4 (TLR4). Although some of the health benefits of exercise can be explained by altered release of myokines from the skeletal muscle, it is not well documented if some of the beneficial effects of exercise can be explained by altered secretion of hepatokines. The aim of this study was to examine the effect of interaction between fetuin‐A and FFAs on insulin sensitivity after physical exercise. In this study, 26 sedentary men who underwent 12 weeks of combined endurance and strength exercise were included. Insulin sensitivity was measured using euglycemic‐hyperinsulinemic clamp, and AT insulin resistance was indicated by the product of fasting plasma concentration of FFAs and insulin. Blood samples and biopsies from skeletal muscle and subcutaneous AT were collected. Several phenotypic markers were measured, and mRNA sequencing was performed on the biopsies. AT macrophages were analyzed based on mRNA markers. The intervention improved hepatic parameters, reduced plasma fetuin‐A concentration (~11%, P < 0.01), slightly changed FFAs concentration, and improved glucose infusion rate (GIR) (~33%, P < 0.01) across all participants. The change in circulating fetuin‐A and FFAs interacted to predict some of the change in GIR (β = −42.16, P = 0.030), AT insulin resistance (β = 0.579, P = 0.003), gene expression related to TLR‐signaling in AT and AT macrophage mRNA (β = 94.10, P = 0.034) after exercise. We observed no interaction effects between FFAs concentrations and leptin and adiponectin on insulin sensitivity, or any interaction effects between Fetuin‐A and FFAs concentrations on skeletal muscle TLR‐signaling. The relationship between FFAs levels and insulin sensitivity seemed to be specific for fetuin‐A and the AT. Some of the beneficial effects of exercise on insulin sensitivity may be explained by changes in circulating fetuin‐A and FFAs, promoting less TLR4 signaling in AT perhaps by modulating AT macrophages.
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Affiliation(s)
- Sindre Lee
- Department of Nutrition, Institute of Basic Medical Sciences Faculty of Medicine University of Oslo, Oslo, Norway
| | - Frode Norheim
- Department of Nutrition, Institute of Basic Medical Sciences Faculty of Medicine University of Oslo, Oslo, Norway.,Division of Cardiology, Department of Medicine University of California at Los Angeles, Los Angeles, California
| | - Hanne L Gulseth
- Institute of Clinical Medicine, Faculty of Medicine University of Oslo, Oslo, Norway
| | - Torgrim M Langleite
- Department of Nutrition, Institute of Basic Medical Sciences Faculty of Medicine University of Oslo, Oslo, Norway
| | - Kristoffer J Kolnes
- Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway
| | - Daniel S Tangen
- Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway
| | - Hans K Stadheim
- Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway
| | - Gregor D Gilfillan
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Torgeir Holen
- Department of Nutrition, Institute of Basic Medical Sciences Faculty of Medicine University of Oslo, Oslo, Norway
| | - Kåre I Birkeland
- Institute of Clinical Medicine, Faculty of Medicine University of Oslo, Oslo, Norway.,Department of Endocrinology, Morbid Obesity and Preventive Medicine Oslo University Hospital, Oslo, Norway
| | - Jørgen Jensen
- Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway
| | - Christian A Drevon
- Department of Nutrition, Institute of Basic Medical Sciences Faculty of Medicine University of Oslo, Oslo, Norway
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38
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Fiorentino TV, Marini MA, Succurro E, Andreozzi F, Sciacqua A, Hribal ML, Perticone F, Sesti G. Association between hemoglobin glycation index and hepatic steatosis in non-diabetic individuals. Diabetes Res Clin Pract 2017; 134:53-61. [PMID: 28993156 DOI: 10.1016/j.diabres.2017.09.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Revised: 08/26/2017] [Accepted: 09/19/2017] [Indexed: 01/10/2023]
Abstract
AIMS Hemoglobin glycation index (HGI), which is the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose levels, represents a measure of the degree of non-enzymatic glycation of hemoglobin and it has been found to be positively associated with diabetic complications. Herein we investigated whether HGI is associated with hepatic steatosis and related biomarkers in subjects without diabetes. METHODS 1120 White individuals without diabetes were stratified in quartiles according to HGI levels. Hepatic steatosis was diagnosed by ultrasonography. RESULTS As compared with subjects in the lowest quartile of HGI those in the intermediate and high HGI groups displayed an unfavorable cardio-metabolic risk profile having significantly higher values of body mass index (BMI), waist circumference, % fat mass, total cholesterol, triglycerides, inflammatory markers such as high sensitivity C reactive protein, erythrocytes sedimentation rate, complement C3, platelets and white blood cell count, hepatic insulin resistance assessed by the liver IR index and lower concentrations of high-density lipoprotein. HGI was positively associated with the biomarker of liver damage alanine aminotransferase, and fatty liver index, an indicator of hepatic steatosis. In a logistic regression analysis adjusted for age, gender and BMI individuals in the highest quartile of HGI exhibited a 1.6-fold increased odd of having hepatic steatosis (95% CI: 1.03-2.41; p=0.03) as compared with subjects in the lowest quartile of HGI. CONCLUSIONS Higher levels of HGI may identify subjects without diabetes at increased risk of having hepatic steatosis.
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Affiliation(s)
- Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, Viale Europa, University Magna-Græcia of Catanzaro, 88100 Catanzaro, Italy
| | | | - Elena Succurro
- Department of Medical and Surgical Sciences, Viale Europa, University Magna-Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, Viale Europa, University Magna-Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, Viale Europa, University Magna-Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Marta Letizia Hribal
- Department of Medical and Surgical Sciences, Viale Europa, University Magna-Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Francesco Perticone
- Department of Medical and Surgical Sciences, Viale Europa, University Magna-Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Giorgio Sesti
- Department of Medical and Surgical Sciences, Viale Europa, University Magna-Græcia of Catanzaro, 88100 Catanzaro, Italy.
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赖 水, 洪 真, 陈 红, 林 锦, 邝 建, 李 延. [Correlation between ectopic fat accumulation and insulin sensitivity in obese individuals with different glucose tolerance levels]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2017; 37:1461-1466. [PMID: 29180325 PMCID: PMC6779651 DOI: 10.3969/j.issn.1673-4254.2017.11.06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVE To investigate the correlation between liver and skeletal muscle fat contents and insulin resistance in obese individuals with different levels of glucose tolerance. METHODS RESULTS: Ten non-obese individuals with normal glucose tolerance (NGT), 9 obese individuals with NGT, and 7 obese individuals with impaired glucose tolerance (IGT) were enrolled in this study. All the participants were examined for insulin sensitivity by hyperinsulinemic-euglycemic clamp and for liver and skeletal muscle fat accumulation quantified by proton magnetic resonance spectroscopy (1H MRS). The data were collected from the subjects including somatometric measurements, fasting plasma glucose, 2-h plasma glucose (2hPG), fasting insulin, and blood biochemistry. Linear correlation analysis and multiple linear stepwise regression analysis were used to analyze the relationship between ectopic fat accumulation and insulin resistance. RESULTS The glucose infusion rates (GIR, presented as the M value) differed significantly among IGT-obese (3.95∓1.66 mg·kg-1·min-1), NGT-obese (6.14∓1.90 mg·kg-1·min-1) and NGT-non-obese (8.78∓2.46 mg·kg-1·min-1) groups (P<0.05). The 3 groups also showed significant differences in liver fat contents [(15.23∓3.09)%, (6.25∓0.38)%, and (1.89∓0.90)%, respectively, P<0.05] and intramyocellular lipids in the tibialis anterior (2.69∓0.95, 2.61∓1.45, and 1.54∓0.66 mmol/kg, respectively, P<0.05). Linear analysis revealed that liver fat content, but not skeletal muscle fat content, was significantly correlated with the M value. Multiple linear stepwise regression analysis using M value as the dependent variable (Y) revealed that liver fat content (X) was an independent factor inversely correlated with the M value (regression equation: Y=-30.562X+9.007, R2=0.717, P<0.01). CONCLUSIONS Liver fat accumulation, but not skeletal muscle fat accumulation, is correlated with insulin resistance and impaired glucose metabolism.
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Affiliation(s)
- 水青 赖
- 广东省人民医院//广东省医学科学院内分泌科，广东 广州 510080Department of Endocrinology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - 真真 洪
- 广东省人民医院 中山大学附属第一医院内分泌科，广东 广州 510080Department of Endocrinology, First Affiliated Hospital of Sun Yat-set University, Guangzhou 510080, China
| | - 红梅 陈
- 广东省人民医院//广东省医学科学院内分泌科，广东 广州 510080Department of Endocrinology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - 锦信 林
- 广东省人民医院//广东省医学科学院内分泌科，广东 广州 510080Department of Endocrinology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - 建 邝
- 广东省人民医院//广东省医学科学院内分泌科，广东 广州 510080Department of Endocrinology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - 延兵 李
- 广东省人民医院 中山大学附属第一医院内分泌科，广东 广州 510080Department of Endocrinology, First Affiliated Hospital of Sun Yat-set University, Guangzhou 510080, China
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40
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Gepner Y, Shelef I, Schwarzfuchs D, Zelicha H, Tene L, Yaskolka Meir A, Tsaban G, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Komy O, Wolak A, Chassidim Y, Golan R, Avni-Hassid H, Bilitzky A, Sarusi B, Goshen E, Shemesh E, Henkin Y, Stumvoll M, Blüher M, Thiery J, Ceglarek U, Rudich A, Stampfer MJ, Shai I. Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial. Circulation 2017; 137:1143-1157. [PMID: 29142011 DOI: 10.1161/circulationaha.117.030501] [Citation(s) in RCA: 185] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 10/26/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. METHODS We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging. RESULTS Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m2), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (-21.0% versus -11.5% for the MED/LC; P<0.001), and the MED/LC group decreased reported carbohydrates intake (-39.5% versus -21.3% for the low-fat group; P<0.001). The PA+ groups significantly increased the metabolic equivalents per week versus the PA- groups (19.0 versus 2.1; P=0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LCPA+ group (P<0.05). VAT (-22%), intrahepatic (-29%), and intrapericardial (-11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA+ with either diet had a significantly greater effect on decreasing VAT (mean of difference, -6.67cm2; 95% confidence interval, -14.8 to -0.45) compared with PA-. The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats (P<0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin. CONCLUSIONS Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01530724.
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Affiliation(s)
- Yftach Gepner
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | | | - Dan Schwarzfuchs
- Soroka University Medical Center, Beer-Sheva, Israel (I.S., D.S., G.T., Y.C., Y.H.)
| | - Hila Zelicha
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Lilac Tene
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Anat Yaskolka Meir
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Gal Tsaban
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.).,Soroka University Medical Center, Beer-Sheva, Israel (I.S., D.S., G.T., Y.C., Y.H.)
| | - Noa Cohen
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Nitzan Bril
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Michal Rein
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Dana Serfaty
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Shira Kenigsbuch
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Oded Komy
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Arik Wolak
- Department of Cardiology, Cardiac Imaging Unit, Shaare Zedek Medical Center, Jerusalem, Israel (A.W.)
| | - Yoash Chassidim
- Soroka University Medical Center, Beer-Sheva, Israel (I.S., D.S., G.T., Y.C., Y.H.)
| | - Rachel Golan
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Hila Avni-Hassid
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Avital Bilitzky
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | | | - Eyal Goshen
- Nuclear Research Center-Negev, Dimona, Israel (B.S., E.G.)
| | - Elad Shemesh
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Yaakov Henkin
- Soroka University Medical Center, Beer-Sheva, Israel (I.S., D.S., G.T., Y.C., Y.H.)
| | - Michael Stumvoll
- Department of Medicine, University of Leipzig, Germany (M.S., M.B., J.T., U.C.)
| | - Matthias Blüher
- Department of Medicine, University of Leipzig, Germany (M.S., M.B., J.T., U.C.)
| | - Joachim Thiery
- Department of Medicine, University of Leipzig, Germany (M.S., M.B., J.T., U.C.)
| | - Uta Ceglarek
- Department of Medicine, University of Leipzig, Germany (M.S., M.B., J.T., U.C.)
| | - Assaf Rudich
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.)
| | - Meir J Stampfer
- Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health, Boston, MA (M.J.S.).
| | - Iris Shai
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.). .,Soroka University Medical Center, Beer-Sheva, Israel (I.S., D.S., G.T., Y.C., Y.H.)
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Abstract
Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ∼70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle. Hepatokines are proteins that are secreted by hepatocytes, and many hepatokines have been linked to the induction of metabolic dysfunction, including fetuin A, fetuin B, retinol-binding protein 4 (RBP4) and selenoprotein P. In this Review, we describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication.
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Affiliation(s)
- Ruth C R Meex
- Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program and the Department of Physiology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
- Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
| | - Matthew J Watt
- Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program and the Department of Physiology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
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Rachakonda V, Wills R, DeLany JP, Kershaw EE, Behari J. Differential Impact of Weight Loss on Nonalcoholic Fatty Liver Resolution in a North American Cohort with Obesity. Obesity (Silver Spring) 2017; 25:1360-1368. [PMID: 28605159 DOI: 10.1002/oby.21890] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Revised: 03/18/2017] [Accepted: 04/19/2017] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. In this study, a North American cohort with obesity enrolled in a lifestyle modification program was examined to determine the impact of weight loss on NAFLD resolution and sarcopenia. METHODS Nondiabetic individuals with World Health Organization Class II/III obesity enrolled in a 6-month weight loss intervention were included. Steatosis was measured using computed tomography (CT)-derived liver:spleen attenuation ratio. Body composition was assessed using dual X-ray absorptiometry, air-displacement plethysmography, and CT anthropometry. RESULTS At baseline, participants with NAFLD had greater visceral adipose tissue (VAT) but similar skeletal muscle area compared to those without NAFLD. After intervention, weight loss was similar in the two groups, but participants with NAFLD lost more VAT than those without NAFLD (-38.81 [-55.98 to -21.63] cm2 vs. -13.82 [-29.65 to -2.02] cm2 ; P = 0.017). In the subset with NAFLD at baseline, participants with NAFLD resolution after intervention lost more VAT than those with persistent NAFLD (-57.23 [-88.63 to -25.84) cm2 vs. -26.92 [-52.14 to -26.92] cm2 , P = 0.039). CONCLUSIONS In a Western cohort with obesity, NAFLD was not associated with sarcopenia. After lifestyle modification, there was a differential impact on NAFLD resolution, with twofold greater VAT loss in participants who resolved NAFLD compared with those with persistent NAFLD despite similar weight loss.
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Affiliation(s)
- Vikrant Rachakonda
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Rachel Wills
- Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - James P DeLany
- Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Erin E Kershaw
- Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Jaideep Behari
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Doulberis M, Kotronis G, Gialamprinou D, Kountouras J, Katsinelos P. Non-alcoholic fatty liver disease: An update with special focus on the role of gut microbiota. Metabolism 2017; 71:182-197. [PMID: 28521872 DOI: 10.1016/j.metabol.2017.03.013] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 03/19/2017] [Accepted: 03/27/2017] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a significant global health burden in children, adolescents and adults with substantial rise in prevalence over the last decades. Accumulating data from manifold studies support the idea of NAFLD as a hepatic manifestation of metabolic syndrome, being rather a systemic metabolic disease than a liver confined pathology. Emerging data support that the gut microbiome represents a significant environmental factor contributing to NAFLD development and progression. Apart from other regimens, probiotics may have a positive role in the management of NAFLD through a plethora of possible mechanisms. The current review focuses on the NAFLD multifactorial pathogenesis, including mainly the role of intestinal microbiome and all relevant issues are raised. Furthermore, the clinical manifestations and appropriate diagnostic approach of the disease are discussed, with all possible therapeutic measures that can be taken, also including the potential beneficial effect of probiotics.
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Affiliation(s)
- Michael Doulberis
- Bürgerspital Hospital, Department of Internal Medicine, Solothurn 4500, Switzerland.
| | - Georgios Kotronis
- Agios Pavlos Hospital, Department of Internal Medicine, Thessaloniki, Macedonia, 55134, Greece
| | - Dimitra Gialamprinou
- Papageorgiou General Hospital, Department of Pediatrics, Aristotle University of Thessaloniki, Macedonia, 56403, Greece
| | - Jannis Kountouras
- Ippokration Hospital, Department of Internal Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, 54642, Greece
| | - Panagiotis Katsinelos
- Ippokration Hospital, Department of Internal Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, 54642, Greece
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Jorge-Galarza E, Medina-Urrutia A, Posadas-Sánchez R, Posadas-Romero C, Cardoso-Saldaña G, Vargas-Alarcón G, Caracas-Portilla N, González-Salazar C, Torres-Tamayo M, Juárez-Rojas JG. Adipose tissue dysfunction increases fatty liver association with pre diabetes and newly diagnosed type 2 diabetes mellitus. Diabetol Metab Syndr 2016; 8:73. [PMID: 27843495 PMCID: PMC5105292 DOI: 10.1186/s13098-016-0189-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 11/05/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To evaluate the role of adipose tissue function on the association of fatty liver (FL) with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes mellitus (nT2D). METHODS In 1264 subjects, computed tomography was used to evaluate FL and elevated visceral adipose tissue (VAT). Fasting plasma glucose, <5.6, 5.6-6.9 and ≥7 mmol/l, were used to defined normoglycemic (NG), IFG or nT2D, respectively. Elevated free fatty acids, low serum adiponectin levels and adipose tissue insulin resistance (Adipo-IR), were used as markers of adipose tissue dysfunction. RESULTS Compared to NG subjects, those with IFG or nT2D had higher prevalence of FL and elevated VAT. FL was found to be independently associated with IFG and nT2D. Adipo-IR increased the association between FL and IFG [OR: 2.46 (95% I.C.: 1.73-3.49) to 5.42 (3.11-9.41)], whereas low adiponectin levels had a higher effect on the FL and nT2D association [OR: 4.26 (2.18-8.34) to 8.53 (2.96-24.55)]. CONCLUSION Fatty liver was independently associated with IFG and nT2D. Our results indicate for the first time, that adipose tissue dysfunction increases these associations.
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Affiliation(s)
- Esteban Jorge-Galarza
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Aida Medina-Urrutia
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Rosalinda Posadas-Sánchez
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Carlos Posadas-Romero
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Guillermo Cardoso-Saldaña
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Gilberto Vargas-Alarcón
- Molecular Biology Department, National Institute of Cardiology “Ignacio Chávez”, Mexico, Mexico
| | - Nacú Caracas-Portilla
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Carmen González-Salazar
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Margarita Torres-Tamayo
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Juan Gabriel Juárez-Rojas
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
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Impact of weight loss-associated changes in detailed body composition as assessed by whole-body MRI on plasma insulin levels and homeostatis model assessment index. Eur J Clin Nutr 2016; 71:212-218. [PMID: 27759067 DOI: 10.1038/ejcn.2016.189] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 08/11/2016] [Accepted: 08/18/2016] [Indexed: 01/03/2023]
Abstract
BACKGROUND/OBJECTIVES We assessed the effect of weight loss-associated changes in detailed body composition on plasma insulin levels and homeostatic model assessment (HOMA) index to calculate the magnitude of reduction in different adipose tissue depots required to improve insulin sensitivity. SUBJECTS/METHODS A total of 50 subjects aged 20-69 years were studied. The participants were compiled from low-calorie diet interventions and bariatric surgery and differed in their baseline body mass index (BMI; range 21.6-54.4 kg/m2) and degree of weight losses (range -3.3 to -56.9 kg). Detailed body composition and liver fat were measured using whole-body magnetic resonance imaging (MRI). Insulin resistance was assessed by HOMA. RESULTS Mean body weight decreased by -16.0±13.6 kg. Significant changes were observed in total adipose tissue (TATMRI, range -0.5 to -36.0 kg), total subcutaneous adipose tissue (SATMRI), visceral adipose tissue (VATMRI), skeletal muscle, liver fat, plasma insulin levels and HOMA. Decreases in insulin and HOMA were correlated with reductions in TATMRI, SATMRI, VATMRI (just with HOMA) and liver fat. Losses of 2.9 and 6.5 kg body weight, 2.0 and 5.0 kg TATMRI as well as 1.6 and 6% liver fat were required to decrease plasma insulin levels by 1 μU/ml and HOMAadjusted for baseline HOMA by 1 point. Multiple regression analysis showed that baseline liver fat and changes in liver fat explained 49.7% and 55.1% of the variance in weight loss-associated changes in plasma insulin and HOMA, respectively. CONCLUSIONS Decreases of adipose tissues and liver fat are the major determinants of reduction in plasma insulin levels and improvement in HOMA index.
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Identifying metabolic syndrome in a clinical cohort: Implications for prevention of chronic disease. Prev Med Rep 2016; 4:502-506. [PMID: 27699144 PMCID: PMC5045945 DOI: 10.1016/j.pmedr.2016.09.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 09/09/2016] [Accepted: 09/19/2016] [Indexed: 01/31/2023] Open
Abstract
In the clinical setting, calculating cardiovascular disease (CVD) risk is commonplace but the utility of the harmonised equation for metabolic syndrome (MetS) (Alberti et al., 2009) is less well established. The aims of this study were to apply this equation to an overweight clinical cohort to identify risk factors for being metabolically unhealthy and explore associations with chronic disease. Baseline data were analysed from a lifestyle intervention trial of Illawarra residents recruited in 2014/2015. Participants were aged 25–54 years with a BMI 25–40 kg/m2. Data included MetS, CVD risk, insulin sensitivity, weight, body fat, diet, peripheral artery disease (PAD), physical activity, socio-economic position and psychological profile. Backward stepwise regression tested the association of covariates with MetS status and linear or logistic regression tested associations between MetS and risk of CVD, coronary heart disease, PAD and insulin resistance. 374 participants were included in the analysis with 127 (34.0%) categorised with MetS. Covariates significantly and positively associated with MetS were higher BMI (odds 1.26, p < 0.01) and older age (odds 1.08, p < 0.01). MetS participants (n = 351) had a 4.50% increase in CVD risk and were 8.1 and 12.7 times (respectively) more likely to be at risk of CHD and insulin resistance, compared to participants without MetS. The utility of the harmonised equation in the clinical setting was confirmed in this overweight clinical cohort. Those classified as having MetS were more likely to be older, overweight/obese individuals and they had a substantially higher risk of developing CVD and insulin resistance than those without MetS.
Older, obese individuals at greatest risk of having Metabolic Syndrome (MetS) Stress, socioeconomic, fitness and diet factors were not associated with MetS. MetS individuals had increased cardiovascular risk of 4.50%. MetS were 12.7 times more likely to be insulin resistant. Study identifies those at risk in order to implement early lifestyle changes.
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von Loeffelholz C, Horn P, Birkenfeld AL, Claus RA, Metzing BU, Döcke S, Jahreis G, Heller R, Hoppe S, Stockmann M, Lock JF, Rieger A, Weickert MO, Settmacher U, Rauchfuß F, Pfeiffer AFH, Bauer M, Sponholz C. Fetuin A is a Predictor of Liver Fat in Preoperative Patients with Nonalcoholic Fatty Liver Disease. J INVEST SURG 2016; 29:266-274. [PMID: 26980291 DOI: 10.3109/08941939.2016.1149640] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are frequent comorbidities in perioperative patients. However, the predictive role of the hepatokine fetuin A was not evaluated in this collective. OBJECTIVE To study fetuin A as predictor of NAFLD/NASH in preoperative patients. METHODS 58 subjects were included. Fetuin A was studied in patients undergoing open abdominal surgery and in a subset with acute liver failure. Blood and liver specimens were sampled. NAFLD was histologically evaluated. Liver fat was additionally analyzed by an enzymatic approach, circulating fetuin A by enzyme linked-immunosorbent assay, fetuin A mRNA by reverse-transcription PCR. RESULTS Univariate correlation studies linked fetuin A to liver steatosis (r = 0.40, p = .029) and hepatocellular ballooning degeneration (r = 0.34, p = .026). Compared to non-NAFLD subjects fetuin A was increased in NAFLD (p = .009) and in NASH (p = .029). However, when corrected for main confounders by linear modeling, fetuin A remained related to hepatic steatosis, but not to ballooning degeneration or other NAFLD features. In support of this, biochemically analyzed liver lipids correlated with fetuin A in plasma (r = 0.34, p = .033) and with hepatic fetuin A mRNA (r = 0.54, p < .001). In addition, plasma fetuin A was related to hepatic mRNA (r = 0.32, p = .036), while circulating levels were reduced by 64% with acute liver failure (p < .001), confirming the liver as main fetuin A source. CONCLUSION Fetuin A is suggested as noninvasive biomarker of hepatic steatosis in preoperative settings.
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Affiliation(s)
- C von Loeffelholz
- a Department of Clinical Nutrition , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany
- b Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC) , Friedrich Schiller University , Jena , Germany
- c Department of Anaesthesiology and Intensive Care , Jena University Hospital , Jena , Germany
| | - P Horn
- b Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC) , Friedrich Schiller University , Jena , Germany
- c Department of Anaesthesiology and Intensive Care , Jena University Hospital , Jena , Germany
| | - A L Birkenfeld
- d Section of Metabolic and Vascular Medicine, Medical Clinic III , University Hospital Carl Gustav Carus , Dresden , Germany
| | - R A Claus
- b Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC) , Friedrich Schiller University , Jena , Germany
- c Department of Anaesthesiology and Intensive Care , Jena University Hospital , Jena , Germany
| | - B U Metzing
- b Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC) , Friedrich Schiller University , Jena , Germany
- c Department of Anaesthesiology and Intensive Care , Jena University Hospital , Jena , Germany
| | - S Döcke
- a Department of Clinical Nutrition , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany
| | - G Jahreis
- e Institute of Nutrition , Friedrich Schiller University , Jena , Germany
| | - R Heller
- b Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC) , Friedrich Schiller University , Jena , Germany
- f Institute for Molecular Cell Biology , Germany Center for Molecular Biomedicine, Jena University Hospital , Jena , Germany
| | - S Hoppe
- g Department of General, Visceral and Transplantation Surgery , Charité-Universitätsmedizin , Berlin , Germany
| | - M Stockmann
- g Department of General, Visceral and Transplantation Surgery , Charité-Universitätsmedizin , Berlin , Germany
| | - J F Lock
- h Department of General-, Visceral-, Vascular- and Paediatric Surgery , University Hospital of Wuerzburg , Wuerzburg , Germany
| | - A Rieger
- i Institute of Pathology , Charité-Universitätsmedizin , Berlin , Germany
| | - M O Weickert
- j Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism , University Hospitals Coventry and Warwickshire , CV2 2DX , Coventry , UK , Division of Metabolic & Vascular Health , University of Warwick , CV4 7AL , Coventry , UK
| | - U Settmacher
- k Department of General, Visceral and Transplantation Surgery , Friedrich Schiller University of Jena , Jena , Germany
| | - F Rauchfuß
- k Department of General, Visceral and Transplantation Surgery , Friedrich Schiller University of Jena , Jena , Germany
| | - A F H Pfeiffer
- a Department of Clinical Nutrition , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany
- l Department of Endocrinology, Diabetes, and Nutrition , Charité-Universitätsmedizin , Berlin , Germany
| | - M Bauer
- b Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC) , Friedrich Schiller University , Jena , Germany
- c Department of Anaesthesiology and Intensive Care , Jena University Hospital , Jena , Germany
| | - C Sponholz
- c Department of Anaesthesiology and Intensive Care , Jena University Hospital , Jena , Germany
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De Souza LR, Berger H, Retnakaran R, Vlachou PA, Maguire JL, Nathens AB, Connelly PW, Ray JG. Hepatic fat and abdominal adiposity in early pregnancy together predict impaired glucose homeostasis in mid-pregnancy. Nutr Diabetes 2016; 6:e229. [PMID: 27643724 PMCID: PMC5048015 DOI: 10.1038/nutd.2016.39] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 06/06/2016] [Accepted: 07/04/2016] [Indexed: 12/20/2022] Open
Abstract
Hepatic fat and abdominal adiposity individually reflect insulin resistance, but their combined effect on glucose homeostasis in mid-pregnancy is unknown. A cohort of 476 pregnant women prospectively underwent sonographic assessment of hepatic fat and visceral (VAT) and total (TAT) adipose tissue at 11–14 weeks' gestation. Logistic regression was used to assess the relation between the presence of maternal hepatic fat and/or the upper quartile (Q) of either VAT or TAT and the odds of developing the composite outcome of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or gestational diabetes mellitus at 24–28 weeks' gestation, based on a 75 g OGTT. Upon adjusting for maternal age, ethnicity, family history of DM and body mass index (BMI), the co-presence of hepatic fat and quartile 4 (Q4) of VAT (adjusted odds ratio (aOR) 6.5, 95% CI: 2.3–18.5) or hepatic fat and Q4 of TAT (aOR 7.8 95% CI 2.8–21.7) were each associated with the composite outcome, relative to women with neither sonographic feature. First-trimester sonographic evidence of maternal hepatic fat and abdominal adiposity may independently predict the development of impaired glucose homeostasis and GDM in mid-pregnancy.
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Affiliation(s)
- L R De Souza
- Department of Obstetrics and Gynecology, St Michael's Hospital, Toronto, ON, Canada.,Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - H Berger
- Department of Obstetrics and Gynecology, St Michael's Hospital, Toronto, ON, Canada.,Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, Canada
| | - R Retnakaran
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
| | - P A Vlachou
- Department of Medical Imaging, St Michael's Hospital, Toronto, ON, Canada
| | - J L Maguire
- Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, Canada
| | - A B Nathens
- Department of Surgery, Sunnybrook Health Sciences Center, Toronto, ON, Canada
| | - P W Connelly
- Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, Canada
| | - J G Ray
- Department of Obstetrics and Gynecology, St Michael's Hospital, Toronto, ON, Canada.,Institute of Medical Science, University of Toronto, Toronto, ON, Canada.,Keenan Research Centre for Biomedical Science of St Michael's Hospital, Toronto, Canada.,Department of Health Policy Management Evaluation, University of Toronto, Toronto, ON, Canada.,Department of Medicine, St Michael's Hospital, Toronto, ON, Canada
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Targher G, Marchesini G, Byrne CD. Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon? DIABETES & METABOLISM 2016; 42:142-56. [PMID: 27142870 DOI: 10.1016/j.diabet.2016.04.002] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 04/11/2016] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liver-related mortality and morbidity. Over the last 10years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes.
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Affiliation(s)
- G Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani, 1, 37126 Verona, Italy.
| | - G Marchesini
- Unit of Metabolic Diseases and Clinical Dietetics, "Alma Mater Studiorum" University, Bologna, Italy
| | - C D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton, UK
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Fujibayashi K, Gunji T, Yokokawa H, Naito T, Sasabe N, Okumura M, Iijima K, Shibuya K, Hisaoka T, Fukuda H. The Relationships between Metabolic Disorders (Hypertension, Dyslipidemia, and Impaired Glucose Tolerance) and Computed Tomography-Based Indices of Hepatic Steatosis or Visceral Fat Accumulation in Middle-Aged Japanese Men. PLoS One 2016; 11:e0149689. [PMID: 26938785 PMCID: PMC4777390 DOI: 10.1371/journal.pone.0149689] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 02/02/2016] [Indexed: 12/14/2022] Open
Abstract
Background Most studies on the relationships between metabolic disorders (hypertension, dyslipidemia, and impaired glucose tolerance) and hepatic steatosis (HS) or visceral fat accumulation (VFA) have been cross-sectional, and thus, these relationships remain unclear. We conducted a retrospective cohort study to clarify the relationships between components of metabolic disorders and HS/VFA. Methods The participants were 615 middle-aged men who were free from serious liver disorders, diabetes, and HS/VFA and underwent multiple general health check-ups at our institution between 2009 and 2013. The data from the initial and final check-ups were used. HS and VFA were assessed by computed tomography. HS was defined as a liver to spleen attenuation ratio of ≤1.0. VFA was defined as a visceral fat cross-sectional area of ≥100 cm2 at the level of the navel. Metabolic disorders were defined using Japan’s metabolic syndrome diagnostic criteria. The participants were divided into four groups based on the presence (+) or absence (-) of HS/VFA. The onset rates of each metabolic disorder were compared among the four groups. Results Among the participants, 521, 55, 24, and 15 were classified as HS(-)/VFA(-), HS(-)/VFA(+), HS(+)/VFA(-), and HS(+)/VFA(+), respectively, at the end of the study. Impaired glucose tolerance was more common among the participants that exhibited HS or VFA (p = 0.05). On the other hand, dyslipidemia was more common among the participants that displayed VFA (p = 0.01). Conclusions It is likely that VFA is associated with impaired glucose tolerance and dyslipidemia, while HS might be associated with impaired glucose tolerance. Unfortunately, our study failed to detect associations between HS/VFA and metabolic disorders due to the low number of subjects that exhibited fat accumulation. Although our observational study had major limitations, we consider that it obtained some interesting results. HS and VFA might affect different metabolic disorders. Further large-scale longitudinal studies are needed to reveal the relationships between the components of metabolic disorders and HS/VFA.
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Affiliation(s)
- Kazutoshi Fujibayashi
- Department of General Medicine, School of Medicine, Juntendo University, Tokyo, Japan
- * E-mail:
| | - Toshiaki Gunji
- Center for Preventive Medicine, NTT Medical Center Tokyo, Tokyo, Japan
| | - Hirohide Yokokawa
- Department of General Medicine, School of Medicine, Juntendo University, Tokyo, Japan
| | - Toshio Naito
- Department of General Medicine, School of Medicine, Juntendo University, Tokyo, Japan
| | - Noriko Sasabe
- Center for Preventive Medicine, NTT Medical Center Tokyo, Tokyo, Japan
| | - Mitsue Okumura
- Center for Preventive Medicine, NTT Medical Center Tokyo, Tokyo, Japan
| | - Kimiko Iijima
- Center for Preventive Medicine, NTT Medical Center Tokyo, Tokyo, Japan
| | - Katsuhiko Shibuya
- Department of General Medicine, School of Medicine, Juntendo University, Tokyo, Japan
| | - Teruhiko Hisaoka
- Department of General Medicine, School of Medicine, Juntendo University, Tokyo, Japan
| | - Hiroshi Fukuda
- Department of General Medicine, School of Medicine, Juntendo University, Tokyo, Japan
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