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Guideline/Fact Sheet
Fatty Liver & Diabetes Statistics in Korea: Nationwide Data 2009 to 2017
Eugene Han, Kyung-Do Han, Yong-ho Lee, Kyung-Soo Kim, Sangmo Hong, Jung Hwan Park, Cheol-Young Park, on Behalf of Fatty Liver Research Group of the Korean Diabetes Association
Diabetes Metab J. 2023;47(3):347-355.   Published online March 29, 2023
DOI: https://doi.org/10.4093/dmj.2022.0444
  • 3,537 View
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  • 5 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigated the changes of fatty liver disease prevalence in general Korean population.
Methods
This study analyzed data from the Korean National Health Insurance Service from 2009 to 2017 that included individuals aged 20 years or older who had undergone a medical health examination. Fatty liver disease was assessed using the fatty liver index (FLI). The disease severity was defined by FLI cutoff, ≥30 as moderate, and ≥60 as severe fatty liver disease.
Results
The prevalence of Korean adults aged 20 years or over with fatty liver disease (FLI ≥60) increased from 13.3% in 2009 to 15.5% in 2017 (P for trend <0.001). The increase in fatty liver disease prevalence was prominent in men (from 20.5% to 24.2%) and the young age (20 to 39 years) group (from 12.8% to 16.4%) (P for interaction <0.001). The prevalence of fatty liver disease was the highest in type 2 diabetes mellitus (T2DM, 29.6%) population compared to that of prediabetes or normoglycemia (10.0% and 21.8%) in 2017. The prevalence of fatty liver disease had statistically increased in individuals with T2DM and prediabetes (P for trend <0.001). Its prevalence increased more steeply in the young-aged population with T2DM, from 42.2% in 2009 to 60.1% in 2017. When applying a lower FLI cutoff (≥30) similar results were observed.
Conclusion
The prevalence of fatty liver disease in the Korean population has increased. Individuals who are young, male, and have T2DM are vulnerable to fatty liver disease.

Citations

Citations to this article as recorded by  
  • Longitudinal changes in fatty liver index are associated with risk of hepatocellular carcinoma: A nationwide cohort study in Korea
    Min Gu Kang, Chang Hun Lee, Chen Shen, Jong Seung Kim, Ji Hyun Park
    Journal of Hepatology.2024; 80(5): e216.     CrossRef
  • Repeated detection of non‐alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults
    Jin Hwa Kim, Young Sang Lyu, Mee Kyoung Kim, Sang Yong Kim, Ki‐Hyun Baek, Ki‐Ho Song, Kyungdo Han, Hyuk‐Sang Kwon
    Diabetes, Obesity and Metabolism.2024; 26(1): 180.     CrossRef
  • Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study
    Eugene Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Sang Hoon Ahn, Yong-ho Lee, Seung Up Kim
    Metabolism.2024; 152: 155789.     CrossRef
  • Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study
    Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
    BMJ.2024; : e076388.     CrossRef
  • Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome
    Scott L. Friedman
    Diabetes & Metabolism Journal.2024; 48(2): 161.     CrossRef
  • Reply to G. Wang et al
    Joo-Hyun Park, Jung Yong Hong, Kyungdo Han
    Journal of Clinical Oncology.2023; 41(32): 5070.     CrossRef
  • The Role of the Fatty Liver Index (FLI) in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review
    Teodora Biciusca, Sorina Ionelia Stan, Mara Amalia Balteanu, Ramona Cioboata, Alice Elena Ghenea, Suzana Danoiu, Ana-Maria Bumbea, Viorel Biciusca
    Diagnostics.2023; 13(21): 3316.     CrossRef
  • Lean or Non-obese Nonalcoholic Fatty Liver Disease Patients: Are They Really Lean?
    Eugene Han, Yong-ho Lee
    Clinical and Molecular Hepatology.2023; 29(4): 980.     CrossRef
  • Approach to Fatty Liver Disease in Patients with Type 2 Diabetes
    Ji Cheol Bae
    The Journal of Korean Diabetes.2023; 24(3): 107.     CrossRef
Complications
Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus
Yongin Cho, Hye-Sun Park, Byung Wook Huh, Yong-ho Lee, Seong Ha Seo, Da Hea Seo, Seong Hee Ahn, Seongbin Hong, So Hun Kim
Diabetes Metab J. 2023;47(2):232-241.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0355
  • 3,598 View
  • 222 Download
  • 1 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM).
Methods
We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis.
Results
Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients.
Conclusion
NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.

Citations

Citations to this article as recorded by  
  • Metabolic-associated fatty liver disease and sarcopenia: A double whammy
    Aditya Viswanath, Sherouk Fouda, Cornelius James Fernandez, Joseph M Pappachan
    World Journal of Hepatology.2024; 16(2): 152.     CrossRef
  • Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease
    Suprabhat Giri, Prajna Anirvan, Sumaswi Angadi, Ankita Singh, Anurag Lavekar
    World Journal of Gastrointestinal Pathophysiology.2024;[Epub]     CrossRef
  • Association of nonalcoholic fatty liver disease and carotid media‐intima thickness: A systematic review and a meta‐analysis
    Manouchehr Khoshbaten, Sepideh H. Maleki, Sara Hadad, Amrit Baral, Ana V. Rocha, Laxmi Poudel, Alireza Abdshah
    Health Science Reports.2023;[Epub]     CrossRef
  • Cardiometabolic risk factors in patients with type 2 diabetes and sarcopenia
    Yu. G. Samoilova, M. V. Matveeva, E. A. Khoroshunova, D. V. Podchinenova, L. L. Maksimova, G. G. Gorbach, A. B. Trivozhenko, V. A. Avkhimenko
    Cardiovascular Therapy and Prevention.2023; 23(1): 3655.     CrossRef
Complications
Advanced Liver Fibrosis Is Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Da Hea Seo, Young Ju Suh, Yongin Cho, Seong Hee Ahn, Seongha Seo, Seongbin Hong, Yong-ho Lee, Young Ju Choi, Eunjig Lee, So Hun Kim
Diabetes Metab J. 2022;46(4):630-639.   Published online January 26, 2022
DOI: https://doi.org/10.4093/dmj.2021.0130
  • 5,520 View
  • 273 Download
  • 14 Web of Science
  • 16 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Nonalcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). However, the causal relationship between NAFLD and CKD is uncertain, particularly in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between the presence and severity of NAFLD and incident CKD in patients with T2DM.
Methods
In this longitudinal cohort study of patients with T2DM, 3,188 patients with preserved renal function were followed up for the occurrence of incident CKD. NAFLD was defined as the presence of hepatic steatosis on ultrasonography, without any other causes of chronic liver disease. Advanced liver fibrosis of NAFLD was defined as a fibrosis-4 index ≥2.67. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2.
Results
At baseline, 1,729 (54.2%) patients had NAFLD, of whom 94 (5.4%) had advanced liver fibrosis. During the follow-up of 8.3±3.6 years, 472 (14.8%) patients developed incident CKD: 220 (15.1%) in the non-NAFLD group, 231 (14.1%) in the NAFLD without advanced fibrosis group and 28 (31.1%) in the NAFLD with advanced fibrosis group. There was no increased risk of incident CKD in the NAFLD group compared to the non-NAFLD group (P=0.435). However, among patients with NAFLD, advanced liver fibrosis was associated with an increased risk of CKD (adjusted hazard ratio, 1.75; 95% confidence interval, 1.15 to 2.66; P=0.009).
Conclusion
Advanced liver fibrosis in patients with NAFLD is independently associated with an increased risk of incident CKD in patients with T2DM.

Citations

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  • Esteatosis hepática metabólica y nefropatía diabética: una llamada a la acción
    Salvador Benlloch, Francesc Moncho, Jose Luis Górriz
    Nefrología.2024; 44(2): 129.     CrossRef
  • Longitudinal Outcomes Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-analysis of 129 Studies
    Kai En Chan, Elden Yen Hng Ong, Charlotte Hui Chung, Christen En Ya Ong, Benjamin Koh, Darren Jun Hao Tan, Wen Hui Lim, Jie Ning Yong, Jieling Xiao, Zhen Yu Wong, Nicholas Syn, Apichat Kaewdech, Margaret Teng, Jiong-Wei Wang, Nicholas Chew, Dan Yock Young
    Clinical Gastroenterology and Hepatology.2024; 22(3): 488.     CrossRef
  • Association of NAFLD/NASH, and MAFLD/MASLD with chronic kidney disease: an updated narrative review
    Amedeo Lonardo
    Metabolism and Target Organ Damage.2024;[Epub]     CrossRef
  • Targeting metabolic-associated fatty liver disease in diabetic kidney disease: A call to action
    Salvador Benlloch, Francesc Moncho, Jose Luis Górriz
    Nefrología (English Edition).2024;[Epub]     CrossRef
  • MAFLD and NAFLD in the prediction of incident chronic kidney disease
    So Yoon Kwon, Jiyun Park, So Hee Park, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Janghyun Koh, Jae Hwan Jee, Jae Hyeon Kim, Mira Kang, Sang-Man Jin
    Scientific Reports.2023;[Epub]     CrossRef
  • Associations of non-invasive indices of liver steatosis and fibrosis with progressive kidney impairment in adults with type 2 diabetes
    Mei Chung Moh, Sharon Li Ting Pek, Kenny Ching Pan Sze, Serena Low, Tavintharan Subramaniam, Keven Ang, Wern Ee Tang, Simon Biing Ming Lee, Chee Fang Sum, Su Chi Lim
    Acta Diabetologica.2023; 60(6): 827.     CrossRef
  • Pancreatic beta-cell specific BAG3 knockout results in chronic hyperinsulinemia inducing insulin resistance
    Verena Damiani, Alessia Lamolinara, Ilaria Cicalini, Maria Concetta Cufaro, Francesco Del Pizzo, Federica Di Marco, Piero Del Boccio, Beatrice Dufrusine, Michael Hahne, Rossano Lattanzio, Damiana Pieragostino, Manuela Iezzi, Massimo Federici, Maria Cateri
    Molecular Metabolism.2023; 74: 101752.     CrossRef
  • Utility of non-invasive liver fibrosis markers to predict the incidence of chronic kidney disease (CKD): A systematic review, meta-analysis, and meta-regression
    Rudi Supriyadi, Theo Audi Yanto, Timotius Ivan Hariyanto, Ketut Suastika
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(8): 102814.     CrossRef
  • Significance of Diabetic Kidney Disease Biomarkers in Predicting Metabolic-Associated Fatty Liver Disease
    Jaehyun Bae, Byung-Wan Lee
    Biomedicines.2023; 11(7): 1928.     CrossRef
  • Hepatic Fibrosis Evaluated in Patients with Type 2 Diabetes with and without Chronic Kidney Disease
    Therese Adrian, Mads Hornum, Filip Krag Knop, Karl Bang Christensen, Thomas Almdal, Peter Rossing, Lisa Í Lídaa, Niels Søndergaard Heinrich, Vincent Oltman Boer, Anouk Marsman, Esben Thade Petersen, Hartwig Roman Siebner, Bo Feldt-Rasmussen
    Nephron.2023; 147(11): 673.     CrossRef
  • Clinical Interest of Serum Alpha-2 Macroglobulin, Apolipoprotein A1, and Haptoglobin in Patients with Non-Alcoholic Fatty Liver Disease, with and without Type 2 Diabetes, before or during COVID-19
    Olivier Deckmyn, Thierry Poynard, Pierre Bedossa, Valérie Paradis, Valentina Peta, Raluca Pais, Vlad Ratziu, Dominique Thabut, Angelique Brzustowski, Jean-François Gautier, Patrice Cacoub, Dominique Valla
    Biomedicines.2022; 10(3): 699.     CrossRef
  • Fibrosis Risk in Nonalcoholic Fatty Liver Disease Is Related to Chronic Kidney Disease in Older Type 2 Diabetes Patients
    Yifan Sun, Liang Hong, Zhe Huang, Lihong Wang, Yanqin Xiong, Shuhang Zong, Rui Zhang, Jun Liu, Shufei Zang
    The Journal of Clinical Endocrinology & Metabolism.2022; 107(9): e3661.     CrossRef
  • Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease
    Eugene Han
    Diabetes & Metabolism Journal.2022; 46(4): 564.     CrossRef
  • A higher FIB‐4 index is associated with an increased incidence of renal failure in the general population
    Eva Maria Schleicher, Simon Johannes Gairing, Peter Robert Galle, Julia Weinmann‐Menke, Jörn M. Schattenberg, Karel Kostev, Christian Labenz
    Hepatology Communications.2022; 6(12): 3505.     CrossRef
  • Advanced Liver Fibrosis Is Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2022;46:630-9)
    Ji Hye Huh
    Diabetes & Metabolism Journal.2022; 46(6): 953.     CrossRef
  • Advanced Liver Fibrosis Is Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2022;46:630-9)
    Da Hea Seo, So Hun Kim
    Diabetes & Metabolism Journal.2022; 46(6): 956.     CrossRef
Cardiovascular Risk/Epidemiology
Performance of Diabetes and Kidney Disease Screening Scores in Contemporary United States and Korean Populations
Liela Meng, Keun-Sang Kwon, Dae Jung Kim, Yong-ho Lee, Jeehyoung Kim, Abhijit V. Kshirsagar, Heejung Bang
Diabetes Metab J. 2022;46(2):273-285.   Published online September 9, 2021
DOI: https://doi.org/10.4093/dmj.2021.0054
  • 65,535 View
  • 238 Download
  • 3 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Risk assessment tools have been actively studied, and they summarize key predictors with relative weights/importance for a disease. Currently, standardized screening scores for type 2 diabetes mellitus (DM) and chronic kidney disease (CKD)—two key global health problems—are available in United States and Korea. We aimed to compare and evaluate screening scores for DM (or combined with prediabetes) and CKD, and assess the risk in contemporary United States and Korean populations.
Methods
Four (2×2) models were evaluated in the United States-National Health and Nutrition Examination Survey (NHANES 2015–2018) and Korea-NHANES (2016–2018)—8,928 and 16,209 adults. Weighted statistics were used to describe population characteristics. We used logistic regression for predictors in the models to assess associations with study outcomes (undiagnosed DM and CKD) and diagnostic measures for temporal and cross-validation.
Results
Korean adult population (mean age 47.5 years) appeared to be healthier than United States counterpart, in terms of DM and CKD risks and associated factors, with exceptions of undiagnosed DM, prediabetes and prehypertension. Models performed well in own country and external populations regarding predictor-outcome association and discrimination. Risk tests (high vs. low) showed area under the curve >0.75, sensitivity >84%, specificity >45%, positive predictive value >8%, and negative predictive value >99%. Discrimination was better for DM, compared to the combined outcome of DM and prediabetes, and excellent for CKD due to age.
Conclusion
Four easy-to-use screening scores for DM and CKD are well-validated in contemporary United States and Korean populations. Prevention of DM and CKD may serve as first-step in public health, with these self-assessment tools as basic tools to help health education and disparity.

Citations

Citations to this article as recorded by  
  • A meta‐analysis of diabetes risk prediction models applied to prediabetes screening
    Yujin Liu, Sunrui Yu, Wenming Feng, Hangfeng Mo, Yuting Hua, Mei Zhang, Zhichao Zhu, Xiaoping Zhang, Zhen Wu, Lanzhen Zheng, Xiaoqiu Wu, Jiantong Shen, Wei Qiu, Jianlin Lou
    Diabetes, Obesity and Metabolism.2024; 26(5): 1593.     CrossRef
  • Performance Analysis and Assessment of Type 2 Diabetes Screening Scores in Patients with Non-Alcoholic Fatty Liver Disease
    Norma Latif Fitriyani, Muhammad Syafrudin, Siti Maghfirotul Ulyah, Ganjar Alfian, Syifa Latif Qolbiyani, Chuan-Kai Yang, Jongtae Rhee, Muhammad Anshari
    Mathematics.2023; 11(10): 2266.     CrossRef
  • A Comprehensive Analysis of Chinese, Japanese, Korean, US-PIMA Indian, and Trinidadian Screening Scores for Diabetes Risk Assessment and Prediction
    Norma Latif Fitriyani, Muhammad Syafrudin, Siti Maghfirotul Ulyah, Ganjar Alfian, Syifa Latif Qolbiyani, Muhammad Anshari
    Mathematics.2022; 10(21): 4027.     CrossRef
Complications
Renal Tubular Damage Marker, Urinary N-acetyl-β-D-Glucosaminidase, as a Predictive Marker of Hepatic Fibrosis in Type 2 Diabetes Mellitus
Hae Kyung Kim, Minyoung Lee, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
Diabetes Metab J. 2022;46(1):104-116.   Published online July 13, 2021
DOI: https://doi.org/10.4093/dmj.2020.0273
  • 5,671 View
  • 191 Download
  • 4 Web of Science
  • 5 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM.
Methods
A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured.
Results
Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P<0.01).
Conclusion
The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.

Citations

Citations to this article as recorded by  
  • Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial
    Xiao Tong Teong, Kai Liu, Andrew D. Vincent, Julien Bensalem, Bo Liu, Kathryn J. Hattersley, Lijun Zhao, Christine Feinle-Bisset, Timothy J. Sargeant, Gary A. Wittert, Amy T. Hutchison, Leonie K. Heilbronn
    Nature Medicine.2023; 29(4): 963.     CrossRef
  • Significance of Diabetic Kidney Disease Biomarkers in Predicting Metabolic-Associated Fatty Liver Disease
    Jaehyun Bae, Byung-Wan Lee
    Biomedicines.2023; 11(7): 1928.     CrossRef
  • Abdominal adipose tissue and type 2 diabetic kidney disease: adipose radiology assessment, impact, and mechanisms
    Fei Lu, Jinlei Fan, Fangxuan Li, Lijing Liu, Zhiyu Chen, Ziyu Tian, Liping Zuo, Dexin Yu
    Abdominal Radiology.2023; 49(2): 560.     CrossRef
  • β‐Amyrin ameliorates diabetic nephropathy in mice and regulates the miR‐181b‐5p/HMGB2 axis in high glucose‐stimulated HK‐2 cells
    Wenhua Xu, Hongwu Zhang, Qinfeng Zhang, Jialan Xu
    Environmental Toxicology.2022; 37(3): 637.     CrossRef
  • High Glycated Hemoglobin Instead of High Body Mass Index Might Increase the Urine N-Acetyl-β-D-glucosaminidase Con-Centration in Children and Adolescents with Diabetes Mellitus
    Jin-Soon Suh, Kyoung Soon Cho, Seul Ki Kim, Shin-Hee Kim, Won Kyoung Cho, Min Ho Jung, Moon Bae Ahn
    Life.2022; 12(6): 879.     CrossRef
Basic Research
Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway
Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
Diabetes Metab J. 2021;45(6):921-932.   Published online February 22, 2021
DOI: https://doi.org/10.4093/dmj.2020.0187
  • 8,463 View
  • 410 Download
  • 20 Web of Science
  • 21 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

Citations

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    Xiang Xiao, Shuming Ji, Junlin Zhang, Deying Kang, Fang Liu
    Renal Failure.2023;[Epub]     CrossRef
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    Zhicheng Gao, Jiaqi Bao, Yilan Hu, Junjie Tu, Lifang Ye, Lihong Wang
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  • SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1
    Weijie Wang, Yilan Li, Yanxiu Zhang, Tao Ye, Kui Wang, Shuijie Li, Yao Zhang
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
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    Ke Lin, Na Yang, Wu Luo, Jin-fu Qian, Wei-wei Zhu, Shi-ju Ye, Chen-xin Yuan, Di-yun Xu, Guang Liang, Wei-jian Huang, Pei-ren Shan
    Acta Pharmacologica Sinica.2022; 43(10): 2624.     CrossRef
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    Panagiotis Theofilis, Marios Sagris, Evangelos Oikonomou, Alexios S. Antonopoulos, Gerasimos Siasos, Kostas Tsioufis, Dimitris Tousoulis
    Diabetes Research and Clinical Practice.2022; 188: 109927.     CrossRef
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    Sandra Feijóo-Bandín, Alana Aragón-Herrera, Manuel Otero-Santiago, Laura Anido-Varela, Sandra Moraña-Fernández, Estefanía Tarazón, Esther Roselló-Lletí, Manuel Portolés, Oreste Gualillo, José Ramón González-Juanatey, Francisca Lago
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Response
Response: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J 2020;44:267–76)
Hokyou Lee, Gyuri Kim, Yong-ho Lee
Diabetes Metab J. 2020;44(3):486-487.   Published online June 29, 2020
DOI: https://doi.org/10.4093/dmj.2020.0127
[Original]
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  • Association of Metabolic Dysfunction-Associated Fatty Liver Disease With Left Ventricular Diastolic Function and Cardiac Morphology
    Dandan Peng, Zhenqiu Yu, Mingwei Wang, Junping Shi, Lei Sun, Yuanyuan Zhang, Wenbin Zhao, Chen Chen, Jiake Tang, Chunyi Wang, Jie Ni, Wen Wen, Jingjie Jiang
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
Review
Guideline/Fact Sheet
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
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
Diabetes Metab J. 2020;44(3):382-401.   Published online May 11, 2020
DOI: https://doi.org/10.4093/dmj.2020.0010
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AbstractAbstract PDFPubReader   

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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Corrigendum
Corrigenda: Table Correction. Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
Diabetes Metab J. 2019;43(5):731-731.   Published online October 24, 2019
DOI: https://doi.org/10.4093/dmj.2019.0188
Corrects: Diabetes Metab J 2019;43(1):31
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Original Articles
Drug/Regimen
Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Ji Eun Jun, In-Kyung Jeong, Jae Myung Yu, Sung Rae Kim, In Kye Lee, Kyung-Ah Han, Sung Hee Choi, Soo-Kyung Kim, Hyeong Kyu Park, Ji-Oh Mok, Yong-ho Lee, Hyuk-Sang Kwon, So Hun Kim, Ho-Cheol Kang, Sang Ah Lee, Chang Beom Lee, Kyung Mook Choi, Sung-Ho Her, Won Yong Shin, Mi-Seung Shin, Hyo-Suk Ahn, Seung Ho Kang, Jin-Man Cho, Sang-Ho Jo, Tae-Joon Cha, Seok Yeon Kim, Kyung Heon Won, Dong-Bin Kim, Jae Hyuk Lee, Moon-Kyu Lee
Diabetes Metab J. 2020;44(1):78-90.   Published online June 20, 2019
DOI: https://doi.org/10.4093/dmj.2018.0265
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.

Methods

This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.

Results

After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.

Conclusion

The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Citations

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Metabolic Risk/Epidemiology
Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus
Hokyou Lee, Gyuri Kim, Young Ju Choi, Byung Wook Huh, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Eun Jig Lee, Yong-ho Lee, Kap Bum Huh
Diabetes Metab J. 2020;44(2):267-276.   Published online February 28, 2019
DOI: https://doi.org/10.4093/dmj.2019.0001
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AbstractAbstract PDFPubReader   
Background

Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.

Methods

We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.

Results

LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002).

Conclusions

Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

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Clinical Diabetes & Therapeutics
Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors
Ji-Yeon Lee, Yongin Cho, Minyoung Lee, You Jin Kim, Yong-ho Lee, Byung-Wan Lee, Bong-Soo Cha, Eun Seok Kang
Diabetes Metab J. 2019;43(2):158-173.   Published online January 25, 2019
DOI: https://doi.org/10.4093/dmj.2018.0057
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We investigated the predictive markers for the therapeutic efficacy and the best combination of sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and ipragliflozin) therapy in patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 804 patients with T2DM who had taken SGLT2 inhibitor as monotherapy or an add-on therapy were analyzed. Multivariate regression analyses were performed to identify the predictors of SGLT2 inhibitor response including the classes of baseline anti-diabetic medications.

Results

After adjusting for age, sex, baseline body mass index (BMI), diabetes duration, duration of SGLT2 inhibitor use, initial glycosylated hemoglobin (HbA1c) level, estimated glomerular filtration rate (eGFR), and other anti-diabetic agent usage, multivariate analysis revealed that shorter diabetes duration, higher initial HbA1c and eGFR were associated with better glycemic response. However, baseline BMI was inversely correlated with glycemic status; lean subjects with well-controlled diabetes and obese subjects with inadequately controlled diabetes received more benefit from SGLT2 inhibitor treatment. In addition, dipeptidyl peptidase 4 (DPP4) inhibitor use was related to a greater reduction in HbA1c in patients with higher baseline HbA1c ≥7%. Sulfonylurea users experienced a larger change from baseline HbA1c but the significance was lost after adjustment for covariates and metformin and thiazolidinedione use did not affect the glycemic outcome.

Conclusion

A better response to SGLT2 inhibitors is expected in Korean T2DM patients who have higher baseline HbA1c and eGFR with a shorter diabetes duration. Moreover, the add-on of an SGLT2 inhibitor to a DPP4 inhibitor is likely to show the greatest glycemic response.

Citations

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    Kyung-Soo Kim
    Diabetes & Metabolism Journal.2019; 43(3): 377.     CrossRef
  • Response: Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors (Diabetes Metab J 2019;43:158–73)
    Ji-Yeon Lee, Eun Seok Kang
    Diabetes & Metabolism Journal.2019; 43(3): 379.     CrossRef
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Review
Complications
Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
Diabetes Metab J. 2019;43(1):31-45.   Published online December 17, 2018
DOI: https://doi.org/10.4093/dmj.2019.0011
Correction in: Diabetes Metab J 2019;43(5):731
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AbstractAbstract PDFPubReader   

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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Original Article
Epidemiology
Development and Validation of the Korean Diabetes Risk Score: A 10-Year National Cohort Study
Kyoung Hwa Ha, Yong-ho Lee, Sun Ok Song, Jae-woo Lee, Dong Wook Kim, Kyung-hee Cho, Dae Jung Kim
Diabetes Metab J. 2018;42(5):402-414.   Published online July 6, 2018
DOI: https://doi.org/10.4093/dmj.2018.0014
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

A diabetes risk score in Korean adults was developed and validated.

Methods

This study used the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) of 359,349 people without diabetes at baseline to derive an equation for predicting the risk of developing diabetes, using Cox proportional hazards regression models. External validation was conducted using data from the Korean Genome and Epidemiology Study. Calibration and discrimination analyses were performed separately for men and women in the development and validation datasets.

Results

During a median follow-up of 10.8 years, 37,678 cases (event rate=10.4 per 1,000 person-years) of diabetes were identified in the development cohort. The risk score included age, family history of diabetes, alcohol intake (only in men), smoking status, physical activity, use of antihypertensive therapy, use of statin therapy, body mass index, systolic blood pressure, total cholesterol, fasting glucose, and γ glutamyl transferase (only in women). The C-statistics for the models for risk at 10 years were 0.71 (95% confidence interval [CI], 0.70 to 0.73) for the men and 0.76 (95% CI, 0.75 to 0.78) for the women in the development dataset. In the validation dataset, the C-statistics were 0.63 (95% CI, 0.53 to 0.73) for men and 0.66 (95% CI, 0.55 to 0.76) for women.

Conclusion

The Korean Diabetes Risk Score may identify people at high risk of developing diabetes and may be an effective tool for delaying or preventing the onset of condition as risk management strategies involving modifiable risk factors can be recommended to those identified as at high risk.

Citations

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Review
Clinical Diabetes & Therapeutics
Past and Current Status of Adult Type 2 Diabetes Mellitus Management in Korea: A National Health Insurance Service Database Analysis
Seung-Hyun Ko, Kyungdo Han, Yong-ho Lee, Junghyun Noh, Cheol-Young Park, Dae-Jung Kim, Chang Hee Jung, Ki-Up Lee, Kyung-Soo Ko
Diabetes Metab J. 2018;42(2):93-100.   Published online April 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.42.2.93
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AbstractAbstract PDFPubReader   

Korea's National Healthcare Program, the National Health Insurance Service (NHIS), a government-affiliated agency under the Korean Ministry of Health and Welfare, covers the entire Korean population. The NHIS supervises all medical services in Korea and establishes a systematic National Health Information database (DB). A health information DB system including all of the claims, medications, death information, and health check-ups, both in the general population and in patients with various diseases, is not common worldwide. On June 9, 2014, the NHIS signed a memorandum of understanding with the Korean Diabetes Association (KDA) to provide limited open access to its DB. By October 31, 2017, seven papers had been published through this collaborative research project. These studies were conducted to investigate the past and current status of type 2 diabetes mellitus and its complications and management in Korea. This review is a brief summary of the collaborative projects between the KDA and the NHIS over the last 3 years. According to the analysis, the national health check-up DB or claim DB were used, and the age category or study period were differentially applied.

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