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      The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD)

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          Abstract

          Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) remain as one of the most global problematic metabolic diseases with rapidly increasing prevalence and incidence. Epidemiological studies noted that T2DM patients have by two-fold increase to develop NAFLD, and vice versa. This complex and intricate association is supported and mediated by insulin resistance (IR). In this review, we discuss the NAFLD immunopathogenesis, connection with IR and T2DM, the role of screening and noninvasive tools, and mostly the impact of the current antidiabetic drugs on steatosis liver and new potential therapeutic targets.

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          Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999–2019: a systematic review and meta-analysis

          Jie Li, Biyao Zou, Yee Yeo … (2019)
          Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Asia is a large, heterogeneous area with substantial variation in socioeconomic status and prevalence of obesity. We estimated the prevalence, incidence, and outcomes of NAFLD in the Asian population to assist stakeholders in understanding NAFLD disease burden.
          Article 0 comments Cited 376 times – based on 0 reviews     Review now
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            Lipotoxicity and the gut-liver axis in NASH pathogenesis.

            Gianluca Svegliati-Baroni, Fabio Marra (2018)
            The pathogenesis of non-alcoholic fatty liver disease, particularly the mechanisms whereby a minority of patients develop a more severe phenotype characterised by hepatocellular damage, inflammation, and fibrosis is still incompletely understood. Herein, we discuss two pivotal aspects of the pathogenesis of NASH. We first analyse the initial mechanisms responsible for hepatocellular damage and inflammation, which derive from the toxic effects of excess lipids. Accumulating data indicate that the total amount of triglycerides stored in hepatocytes is not the major determinant of lipotoxicity, and that specific lipid classes act as damaging agents on liver cells. In particular, the role of free fatty acids such as palmitic acid, cholesterol, lysophosphatidylcholine and ceramides has recently emerged. These lipotoxic agents affect the cell behaviour via multiple mechanisms, including activation of signalling cascades and death receptors, endoplasmic reticulum stress, modification of mitochondrial function, and oxidative stress. In the second part of this review, the cellular and molecular players involved in the cross-talk between the gut and the liver are considered. These include modifications to the microbiota, which provide signals through the intestine and bacterial products, as well as hormones produced in the bowel that affect metabolism at different levels including the liver. Finally, the activation of nuclear receptors by bile acids is analysed.
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              Risk of Hepatocellular Cancer in Patients with Non-alcoholic Fatty Liver Disease

              Fasiha Kanwal, Peter Richardson, Liang Li … (2018)
              Background There are limited data on the risk of hepatocellular cancer (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to estimate the risk of incident HCC among patients with NAFLD. Methods We conducted a retrospective cohort study from a total of 130 facilities in the Veterans Health Administration. Patients with NAFLD diagnosed between 1/1/2004 and 12/31/2008 were included and followed until HCC diagnosis, death or 12/31/2015. We also identified a gender and age-matched control cohort without NAFLD. We ascertained all new HCC cases from the Central Cancer Registry and manual chart reviews. We calculated incidence rates for HCC by NAFLD status as well as in subgroups of NAFLD patients. We used competing risk models to compare the risk of HCC in patients with vs . those without NAFLD. We reviewed electronic medical records of all HCC cases that developed in NAFLD patients without cirrhosis. Results We compared 296,707 NAFLD patients with 296,707 matched controls. During 2,382,289 person-years [PY] of follow-up, 490 NAFLD patients developed HCC (0.21/1000 PY). HCC incidence was significantly higher among NAFLD patients vs. controls (0.02/1000 PY; hazard ratio, 7.62, 95% confidence interval=5.76–10.09). Among patients with NAFLD, those with cirrhosis had the highest annual incidence of HCC (10.6 /1000 PY). Among patients with NAFLD cirrhosis, HCC risk ranged from 1.6 to 23.7 per 1000 PY based on other demographic characteristics; the risk of HCC was the highest in older Hispanics with cirrhosis. In medical record reviews, 20% of NAFLD patients with HCC had no evidence of cirrhosis. Conclusions Risk of HCC was higher in NAFLD patients than that observed in general clinical population. Most HCC cases in NAFLD developed in patients with cirrhosis. The absolute risk of HCC was higher than the accepted thresholds for HCC surveillance for most patients with NAFLD cirrhosis.
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                Author and article information

                Contributors
                Evelina Maria Gosav:
                ORCID: https://orcid.org/0000-0003-1730-9306
                Journal
                Journal ID (nlm-ta): J Diabetes Res
                Journal ID (iso-abbrev): J Diabetes Res
                Journal ID (publisher-id): JDR
                Title: Journal of Diabetes Research
                Publisher: Hindawi
                ISSN (Print): 2314-6745
                ISSN (Electronic): 2314-6753
                Publication date Collection: 2020
                Publication date (Electronic): 31 July 2020
                Volume: 2020
                Electronic Location Identifier: 3920196
                Affiliations
                1Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
                2Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
                3Department of Ophthalmology, “Grigore T. Popa” University of Medicine and Pharmacy, Romania
                42nd Ophthalmology Clinic, “Prof. Dr. Nicolae Oblu” Emergency Clinical Hospital, Iasi, Romania
                5Department of Pathophysiology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
                6Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
                7Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
                8Department of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
                9Internal Medicine Clinic, Emergency Military Clinical Hospital, Iasi, Romania
                Author notes

                Academic Editor: Guanghong Jia

                Author information
                https://orcid.org/0000-0002-7144-2506
                https://orcid.org/0000-0003-1730-9306
                https://orcid.org/0000-0002-9240-2175
                https://orcid.org/0000-0001-8923-8194
                https://orcid.org/0000-0002-9465-1503
                Article
                DOI: 10.1155/2020/3920196
                PMC ID: 7424491
                SO-VID: 54af5011-383a-46f9-80f6-51f328347c64
                Copyright © Copyright © 2020 Daniela Maria Tanase et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 10 May 2020
                Date accepted : 17 July 2020
                Categories
                Subject: Review Article

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