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      Effectiveness of the ALT/AST ratio for predicting insulin resistance in a Korean population: A large-scale, cross-sectional cohort study

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          Abstract

          Insulin resistance is a common pathophysiology in patients with type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Thus, screening for the risk of insulin resistance is important to prevent disease progression. We evaluated the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio to predict insulin resistance in the general population, regardless of comorbidities. Datasets from the 2015, 2019, and 2020 Korea National Health and Nutrition Examination Surveys were used, and the following four indices were implemented to indicate insulin resistance: fasting serum glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and β-cell function. We analyzed the degree of association between the liver enzyme profile and insulin resistance indices using Pearson’s correlation coefficient and determined the associations using linear or logistic regression analysis. Accordingly, ALT levels in both sexes were positively and consistently correlated with the four aforementioned insulin resistance indices in stratification analyses based on diabetes, dyslipidemia, alcohol consumption, and obesity status. In multivariate linear regression, when comparing with ALT levels, the ALT/AST ratio exhibited superior predictive performance for fasting serum glucose and HOMA-β in Korean men and improved outcomes for all insulin resistance indices in Korean women. In this analysis that included a large community-based population, the ALT/AST ratio was a more useful predictive marker than the HOMA-IR. Regarding the predicted presence or absence of insulin resistance, the ALT/AST ratio could better predict HOMA-IR than the ALT level alone in Koreans. A simple, precise marker that represents the ALT/AST ratio could be a practical method to screen for insulin resistance in the general population, regardless of diabetes mellitus, alcohol intake, and sex.

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          Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.

          The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
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            Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

            The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.
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              Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4.

              Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation, and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in non-bone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draft
                Role: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                17 May 2024
                2024
                : 19
                : 5
                : e0303333
                Affiliations
                [1 ] Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
                [2 ] Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
                [3 ] Department of Family Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
                [4 ] Division of Data Mining and Computational Biology, Institute of Global Health Care and Development, Wonju, Korea
                Universita degli Studi della Campania Luigi Vanvitelli Scuola di Medicina e Chirurgia, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-5852-4323
                https://orcid.org/0000-0002-2501-2206
                Article
                PONE-D-23-35138
                10.1371/journal.pone.0303333
                11101110
                38758828
                b80d8614-6b73-4927-a353-2478d6f07897
                © 2024 Han et al

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

                History
                : 17 November 2023
                : 23 April 2024
                Page count
                Figures: 4, Tables: 1, Pages: 13
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Nutrition
                Diet
                Alcohol Consumption
                Medicine and Health Sciences
                Nutrition
                Diet
                Alcohol Consumption
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Insulin Resistance
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Insulin Resistance
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Fatty Liver
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzymes
                Transferases
                Aminotransferases
                Biology and Life Sciences
                Biochemistry
                Proteins
                Enzymes
                Transferases
                Aminotransferases
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Dyslipidemia
                Medicine and Health Sciences
                Endocrinology
                Diabetic Endocrinology
                Insulin
                Biology and Life Sciences
                Biochemistry
                Hormones
                Insulin
                Custom metadata
                The KNHANES is publicly available at https://knhanes.kdca.go.kr/-knhanes/eng/index.do.

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