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      Adipocytokines as Predictors of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Development in Type 2 Diabetes Mellitus Patients

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          Abstract

          Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver condition. Due to pathophysiological processes, MASLD's relation to type 2 diabetes mellitus (T2DM) is still unclear, especially when the role of adipocytokines is taken into consideration.

          Objective: This study aims to examine the potential predictive value of adiponectin and resistin for MASLD in T2DM.

          Patients and methods: In a two-year study, 71 T2DM patients were categorized into MASLD-T2DM and non-MASLD-T2DM groups according to MASLD development. Serum samples were tested for resistin, adiponectin, high-density lipoprotein cholesterol, fasting glucose, and triglycerides. An appropriate equation is used to calculate the adiponectin/resistin (A/R) index. The optimal cut-off values for differentiating MASLD patients from non-MASLD patients were determined using receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUC). To predict the onset of MASLD in patients with T2DM, a logistic regression analysis was performed.

          Results: There were significant differences in adiponectin (p<0.001), resistin (p<0.001), and A/R index (p<0.001) between T2DM individuals with and without MASLD. The ROC curve for resistin produced an AUC of 0.997 (p<0.001) with a sensitivity of 96.1% and a specificity of 100% for the cut-off point of 253.15. Adiponectin (OR, 0.054; 95% CI, 0.011-0.268; p<0.001) and resistin (OR, 1.745; 95% CI, 1.195-2,548; p=0.004) were found to be independent predictors for MASLD by logistic regression analysis.

          Conclusion: This study confirms the potential of adiponectin and resistin as predictors of MASLD development in T2DM.

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          Most cited references30

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          Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease

          Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the United States, where they are a growing cause of cirrhosis and hepatocellular carcinoma (HCC) and increasingly an indicator for liver transplantation. A Markov model was used to forecast NAFLD disease progression. Incidence of NAFLD was based on historical and projected changes in adult prevalence of obesity and type 2 diabetes mellitus (DM). Assumptions were derived from published literature where available and validated using national surveillance data for incidence of NAFLD‐related HCC. Projected changes in NAFLD‐related cirrhosis, advanced liver disease, and liver‐related mortality were quantified through 2030. Prevalent NAFLD cases are forecasted to increase 21%, from 83.1 million (2015) to 100.9 million (2030), while prevalent NASH cases will increase 63% from 16.52 million to 27.00 million cases. Overall NAFLD prevalence among the adult population (aged ≥15 years) is projected at 33.5% in 2030, and the median age of the NAFLD population will increase from 50 to 55 years during 2015‐2030. In 2015, approximately 20% of NAFLD cases were classified as NASH, increasing to 27% by 2030, a reflection of both disease progression and an aging population. Incidence of decompensated cirrhosis will increase 168% to 105,430 cases by 2030, while incidence of HCC will increase by 137% to 12,240 cases. Liver deaths will increase 178% to an estimated 78,300 deaths in 2030. During 2015‐2030, there are projected to be nearly 800,000 excess liver deaths. Conclusion: With continued high rates of adult obesity and DM along with an aging population, NAFLD‐related liver disease and mortality will increase in the United States. Strategies to slow the growth of NAFLD cases and therapeutic options are necessary to mitigate disease burden. (Hepatology 2018;67:123‐133).
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            PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD

            Obesity is a worldwide epidemic that predisposes individuals to cardiometabolic complications, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), which are all related to inappropriate ectopic lipid deposition. Identification of the pathogenic molecular mechanisms and effective therapeutic approaches are highly needed. The peroxisome proliferator-activated receptors (PPARs) modulate several biological processes that are perturbed in obesity, including inflammation, lipid and glucose metabolism and overall energy homeostasis. Here, we review how PPARs regulate the functions of adipose tissues, such as adipogenesis, lipid storage and adaptive thermogenesis, under healthy and pathological conditions. We also discuss the clinical use and mechanism of PPAR agonists in the treatment of obesity comorbidities such as dyslipidaemia, T2DM and NAFLD. First generation PPAR agonists, primarily those acting on PPARγ, are associated with adverse effects that outweigh their clinical benefits, which led to the discontinuation of their development. An improved understanding of the physiological roles of PPARs might, therefore, enable the development of safe, new PPAR agonists with improved therapeutic potential.
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              A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease

              Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of diseases, including simple steatosis, nonalcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma. Lipotoxicity, insulin resistance (IR) and inflammation are involved in the disease process. Lipotoxicity promotes inflammation and IR, which in turn, increase adipocyte lipolysis and exacerbates lipotoxicity. Furthermore, IR and inflammation form a vicious circle, with each condition promoting the other and accelerating the development of NAFLD in the presence of lipotoxicity. As an integrator of inflammatory pathway networks, nuclear factor-kappa B (NF-κB) regulates expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and anti-inflammatory cytokines, such as adiponectin in NAFLD. In this review, the relationships between lipotoxicity, IR and inflammation in NAFLD are discussed, with particular emphasis on the inflammatory pathways.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                6 March 2024
                March 2024
                : 16
                : 3
                : e55673
                Affiliations
                [1 ] Department of Pathophysiology, University of Sarajevo Faculty of Medicine, Sarajevo, BIH
                [2 ] Department of Internal Medicine, General Hospital “Prim. Dr. Abdulah Nakas”, Sarajevo, BIH
                [3 ] Department of Human Physiology, University of Sarajevo Faculty of Medicine, Sarajevo, BIH
                Author notes
                Article
                10.7759/cureus.55673
                10917643
                38455340
                5bb082f4-7d41-4d4c-a753-35b818b49ca6
                Copyright © 2024, Fajkić et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 March 2024
                Categories
                Endocrinology/Diabetes/Metabolism
                Internal Medicine

                metabolic dysfunction-associated steatotic liver disease (masld),type 2 diabetes mellitus (t2dm),liver steatosis,resistin,adiponectin

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