- Metabolic Risk/Epidemiology
- A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease
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Seung Joon Choi, Sungjin Yoon, Kyoung-Kon Kim, Doojin Kim, Hye Eun Lee, Kwang Gi Kim, Seung Kak Shin, Ie Byung Park, Seong Min Kim, Dae Ho Lee
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Diabetes Metab J. 2024;48(4):740-751. Published online February 1, 2024
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DOI: https://doi.org/10.4093/dmj.2023.0189
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Abstract
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- Background
We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis).
Methods A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination.
Results A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.934 (95% confidence interval [CI], 0.888 to 0.981), 0.902 (95% CI, 0.832 to 0.971), and 0.918 (95% CI, 0.862 to 0.974), respectively. However, the performance of this blood composite biomarker was inferior to that various magnetic resonance (MR)-based composite biomarkers, such as proton density fat fraction/MR elastography- liver stiffness measurement (MRE-LSM)/ALT/AST for NASH, MRE-LSM+fibrosis-4 index for advanced fibrosis, and the known MR imaging-AST (MAST) score for high-risk NASH.
Conclusion Our blood composite biomarker can be useful to distinguish progressive forms of NAFLD as an initial noninvasive test when MR-based tools are not available.
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- Aldo-keto reductase (AKR) superfamily website and database: An update
Andrea Andress Huacachino, Jaehyun Joo, Nisha Narayanan, Anisha Tehim, Blanca E. Himes, Trevor M. Penning Chemico-Biological Interactions.2024; 398: 111111. CrossRef
- Metabolic Risk/Epidemiology
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- Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease
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Seung Joon Choi, Seong Min Kim, Yun Soo Kim, Oh Sang Kwon, Seung Kak Shin, Kyoung Kon Kim, Kiyoung Lee, Ie Byung Park, Cheol Soo Choi, Dong Hae Chung, Jaehun Jung, MunYoung Paek, Dae Ho Lee
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Diabetes Metab J. 2021;45(5):739-752. Published online October 28, 2020
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DOI: https://doi.org/10.4093/dmj.2020.0137
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Graphical Abstract
Abstract
PDFSupplementary MaterialPubReader ePub
- Background
Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods.
Methods A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54).
Results MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa).
Conclusion Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.
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- A Novel Score Based on Controlled Attenuation Parameter Accurately Predicts Hepatic Steatosis in Individuals With Metabolic Dysfunction Associated Steatotic Liver Disease: A Derivation and Independent Validation Study
Zi-Ming An, Qiao-Hong Liu, Xin-Jian Ye, Qian Zhang, Hua-Fu Pei, Xin Xin, Jie Yuan, Qian Huang, Kun Liu, Fang Lu, Zhi-Han Yan, Yu Zhao, Yi-Yang Hu, Ming-Hua Zheng, Qin Feng Clinical and Translational Gastroenterology.2024; 15(3): e00680. CrossRef - Diagnostic performance of non-invasive tests in patients with MetALD in a health check-up cohort
Joo Hyun Oh, Sang Bong Ahn, Seon Cho, Eun-Hee Nah, Eileen L. Yoon, Dae Won Jun Journal of Hepatology.2024;[Epub] CrossRef - A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease
Seung Joon Choi, Sungjin Yoon, Kyoung-Kon Kim, Doojin Kim, Hye Eun Lee, Kwang Gi Kim, Seung Kak Shin, Ie Byung Park, Seong Min Kim, Dae Ho Lee Diabetes & Metabolism Journal.2024; 48(4): 740. CrossRef - Imaging Methods Applicable in the Diagnostics of Alzheimer’s Disease, Considering the Involvement of Insulin Resistance
Petra Hnilicova, Ema Kantorova, Stanislav Sutovsky, Milan Grofik, Kamil Zelenak, Egon Kurca, Norbert Zilka, Petra Parvanovova, Martin Kolisek International Journal of Molecular Sciences.2023; 24(4): 3325. CrossRef - Polyunsaturated and Saturated Oxylipin Plasma Levels Allow Monitoring the Non-Alcoholic Fatty Liver Disease Progression to Severe Stages
Miguel D. Ferrer, Clara Reynés, Margalida Monserrat-Mesquida, Magdalena Quetglas-Llabrés, Cristina Bouzas, Silvia García, David Mateos, Miguel Casares, Cristina Gómez, Lucía Ugarriza, Josep A. Tur, Antoni Sureda, Antoni Pons Antioxidants.2023; 12(3): 711. CrossRef - An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography
Jia-xu Liang, Javier Ampuero, Hao Niu, Kento Imajo, Mazen Noureddin, Jaideep Behari, Dae Ho Lee, Richard L. Ehman, Fredrik Rorsman, Johan Vessby, Juan R. Lacalle, Ferenc E. Mózes, Michael Pavlides, Quentin M. Anstee, Stephen A. Harrison, Javier Castell, R Journal of Hepatology.2023; 79(3): 592. CrossRef - Relationship between controlled attenuated parameter and magnetic resonance imaging–proton density fat fraction for evaluating hepatic steatosis in patients with NAFLD
Ziming An, Qiaohong Liu, Wenli Zeng, Yan Wang, Qian Zhang, Huafu Pei, Xin Xin, Shuohui Yang, Fang Lu, Yu Zhao, Yiyang Hu, Qin Feng Hepatology Communications.2022; 6(8): 1975. CrossRef - Noninvasive imaging of hepatic dysfunction: A state-of-the-art review
Ting Duan, Han-Yu Jiang, Wen-Wu Ling, Bin Song World Journal of Gastroenterology.2022; 28(16): 1625. CrossRef - Diagnosis and Pathogenesis of Sarcopenia in Chronic Liver Disease Using Liver Magnetic Resonance Imaging
Atsushi Nakamura, Tsubasa Yoshimura, Tomomi Sato, Takeshi Ichikawa Cureus.2022;[Epub] CrossRef - Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis
Aron Park, Seung Joon Choi, Sungjin Park, Seong Min Kim, Hye Eun Lee, Minjae Joo, Kyoung Kon Kim, Doojin Kim, Dong Hae Chung, Jae Been Im, Jaehun Jung, Seung Kak Shin, Byung-Chul Oh, Cheolsoo Choi, Seungyoon Nam, Dae Ho Lee International Journal of Molecular Sciences.2022; 23(9): 5035. CrossRef - Contribution of a genetic risk score to ethnic differences in fatty liver disease
Maddie J. Kubiliun, Jonathan C. Cohen, Helen H. Hobbs, Julia Kozlitina Liver International.2022; 42(10): 2227. CrossRef - Plasma Metabolomics and Machine Learning-Driven Novel Diagnostic Signature for Non-Alcoholic Steatohepatitis
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E. Roeb, A. Canbay, H. Bantel, J. Bojunga, J. de Laffolie, M. Demir, U. W. Denzer, A. Geier, W. P. Hofmann, C. Hudert, T. Karlas, M. Krawczyk, T. Longerich, T. Luedde, M. Roden, J. Schattenberg, M. Sterneck, A. Tannapfel, P. Lorenz, F. Tacke Zeitschrift für Gastroenterologie.2022; 60(09): 1346. CrossRef - Ultrasound Methods for the Assessment of Liver Steatosis: A Critical Appraisal
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- Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association
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Byung-Wan Lee, Yong-ho Lee, Cheol-Young Park, Eun-Jung Rhee, Won-Young Lee, Nan-Hee Kim, Kyung Mook Choi, Keun-Gyu Park, Yeon-Kyung Choi, Bong-Soo Cha, Dae Ho Lee, Korean Diabetes Association (KDA) Fatty Liver Research Group
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Diabetes Metab J. 2020;44(3):382-401. Published online May 11, 2020
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DOI: https://doi.org/10.4093/dmj.2020.0010
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This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.
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- Corrigenda: Table Correction. Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
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Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
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Diabetes Metab J. 2019;43(5):731-731. Published online October 24, 2019
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DOI: https://doi.org/10.4093/dmj.2019.0188
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Corrects: Diabetes Metab J 2019;43(1):31
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Kyung-Soo Kim, Byung-Wan Lee, Yong Jin Kim, Dae Ho Lee, Bong-Soo Cha, Cheol-Young Park
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Diabetes Metab J. 2019;43(2):127-143. Published online April 15, 2019
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DOI: https://doi.org/10.4093/dmj.2019.0034
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Abstract
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Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders that are often comorbid conditions. Among many proposed treatments, weight reduction is the only approved option for NAFLD to date. However, it is not easy to maintain weight loss by lifestyle modification alone; pharmacological treatments are helpful in this regard. Although many drugs have been investigated, pioglitazone could be a first-line therapy in patients with NAFLD and diabetes. Many more drugs are currently being developed and investigated, and it is likely that combination strategies will be used for future treatment of NAFLD and diabetes. Attention should be paid to the management of NAFLD and diabetes and efforts should be made to intervene early and individualize treatment of NAFLD in patients with diabetes.
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- Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
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Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
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Diabetes Metab J. 2019;43(1):31-45. Published online December 17, 2018
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DOI: https://doi.org/10.4093/dmj.2019.0011
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Correction in: Diabetes Metab J 2019;43(5):731
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Abstract
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Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders whose prevalence rates are expected to rise worldwide, corresponding to aging and increasingly obese populations. Compared to the general population (around 25%), 50% to 70% of people with diabetes have NAFLD, and NAFLD severity (including fibrosis) tends to be worsened by the presence of diabetes. NAFLD is considered an emerging risk factor for type 2 diabetes mellitus and a contributor to the development of chronic diabetes-related complications. This reciprocal relationship demonstrates the importance of confirming suspected NAFLD in patients with diabetes. Due to the invasive nature of liver biopsy to assess NAFLD status, various alternative non-invasive modalities have been developed and validated. Here, we summarized the epidemiology of NAFLD in patients with diabetes and reviewed currently available imaging modalities and biomarker-based prediction models for their ability to detect liver steatosis and/or fibrosis.
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Dae Ho Lee
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Diabetes Metab J. 2015;39(4):348-349. Published online August 17, 2015
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DOI: https://doi.org/10.4093/dmj.2015.39.4.348
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Dae Ho Lee
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Diabetes Metab J. 2014;38(4):274-277. Published online August 20, 2014
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DOI: https://doi.org/10.4093/dmj.2014.38.4.274
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- Clinical Characteristics of Type 2 Diabetes Patients according to Family History of Diabetes
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Seung Uk Jeong, Dong Gu Kang, Dae Ho Lee, Kang Woo Lee, Dong-Mee Lim, Byung Joon Kim, Keun-Yong Park, Hyoun-Jung Chin, Gwanpyo Koh
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Korean Diabetes J. 2010;34(4):222-228. Published online August 31, 2010
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DOI: https://doi.org/10.4093/kdj.2010.34.4.222
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Abstract
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- Background
Type 2 diabetes mellitus (T2DM) has a strong genetic component, and its prevalence is notably increased in the family members of T2DM patients. However, there are few studies about the family history of T2DM. We carried out this study to assess the influences of family history on clinical characteristics in T2DM patients. MethodsThis is a cross-sectional study involving 651 T2DM patients. Patient history and physical examination were performed and fasting blood was taken. If any first degree relative was diabetic, a family history of diabetes was considered to exist. ResultsAmong the total 621 patients, 38.4% had a family history of diabetes. Patients with a family history had a younger age, higher weight, younger age at diagnosis and higher triglyceride level than did those without a family history. Dyslipidemia medication and metabolic syndrome were more prevalent in familial diabetes. Sex, blood pressure, previous treatment for diabetes, HbA1c, C-peptide, total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were not different between familial and non-familial diabetes. Upon multiple linear regression analysis, the family history of diabetes remained significantly associated with serum triglyceride level. ConclusionIn T2DM patients with a family history of diabetes, the disease tended to develop earlier. Metabolic syndrome and cardiovascular risk factors are more prevalent in familial T2DM than they were in non-familial T2DM. These results support the necessity of earlier screening for diabetes in family members of T2DM patients and more active prevention against cardiovascular disease in T2DM patients with a family history.
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- Complications
- Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus
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Inha Jung, Seungyoon Nam, Da Young Lee, So Young Park, Ji Hee Yu, Ji A Seo, Dae Ho Lee, Nan Hee Kim
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Received October 23, 2023 Accepted May 6, 2024 Published online July 1, 2024
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DOI: https://doi.org/10.4093/dmj.2023.0377
[Epub ahead of print]
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Abstract
PDFSupplementary MaterialPubReader ePub
- Background
Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.
Methods We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573).
Results Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria.
Conclusion Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.
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