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Basic Research
Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis
Kyung Bong Ha, Eun Soo Lee, Na Won Park, Su Ho Jo, Soyeon Shim, Dae-Kee Kim, Chan Mug Ahn, Choon Hee Chung
Diabetes Metab J. 2023;47(4):500-513.   Published online April 25, 2023
DOI: https://doi.org/10.4093/dmj.2022.0110
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Background
Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial.
Methods
Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks.
Results
TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score.
Conclusion
Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.
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
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  • 6 Citations
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

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  • Reply to G. Wang et al
    Joo-Hyun Park, Jung Yong Hong, Kyungdo Han
    Journal of Clinical Oncology.2023; 41(32): 5070.     CrossRef
  • 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.2023;[Epub]     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
  • 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.2023;[Epub]     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
Metabolic Risk/Epidemiology
Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography
Hwi Seung Kim, Jiwoo Lee, Eun Hee Kim, Min Jung Lee, In Young Bae, Woo Je Lee, Joong-Yeol Park, Hong-Kyu Kim, Chang Hee Jung
Diabetes Metab J. 2023;47(1):104-117.   Published online January 26, 2023
DOI: https://doi.org/10.4093/dmj.2022.0081
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  • 6 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population.
Methods
Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores.
Results
According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all).
Conclusion
A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.

Citations

Citations to this article as recorded by  
  • Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography (Diabetes Metab J 2023;47:104-17)
    Hwi Seung Kim, Hong-Kyu Kim, Chang Hee Jung
    Diabetes & Metabolism Journal.2023; 47(2): 304.     CrossRef
  • Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography (Diabetes Metab J 2023;47:104-17)
    Eun Roh
    Diabetes & Metabolism Journal.2023; 47(2): 301.     CrossRef
  • Sarcopenia, a condition shared by various diseases: can we alleviate or delay the progression?
    Giovanni Tarantino, Gaia Sinatti, Vincenzo Citro, Silvano Santini, Clara Balsano
    Internal and Emergency Medicine.2023; 18(7): 1887.     CrossRef
  • Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity
    Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe
    Clinical and Molecular Hepatology.2023; 29(4): 987.     CrossRef
  • Current view of the surgical anatomy of the anterolateral abdominal wall muscles and their aponeuroses
    A.V. Pavlov, A.S. Baranova, A.V. Fedoseyev, A.I. Vvedensky, G.S. Lazutina, N.V. Ovchinnikova, I.V. Bakharev
    Operativnaya khirurgiya i klinicheskaya anatomiya (Pirogovskii nauchnyi zhurnal).2023; 7(3): 44.     CrossRef
  • Muscle Fat Content Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Chinese Adults
    W. Guo, X. Zhao, D. Cheng, X. Liang, M. Miao, X. Li, J. Lu, N. Xu, Shuang Hu, Qun Zhang
    The journal of nutrition, health & aging.2023; 27(11): 960.     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
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  • 1 Citations
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  
  • 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
Metabolic Risk/Epidemiology
Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
Diabetes Metab J. 2023;47(2):220-231.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2021.0327
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  • 5 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We investigated whether metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with an elevated risk of all-cause and cardiovascular mortality using a large-scale health examination cohort.
Methods
A total of 394,835 subjects in the Kangbuk Samsung Health Study cohort were enrolled from 2002 to 2012. Participants were categorized by the presence of nonalcoholic fatty liver disease (NAFLD) and MAFLD as follows: normal subjects; patients with both NAFLD and MAFLD; patients with NAFLD only; and patients with MAFLD only. Cox proportional hazards models were used to analyze the risk of mortality.
Results
During a median 5.7 years of follow-up, 20.69% was patients with both NAFLD and MAFLD, 1.51% was patients with NAFLD only, and 4.29% was patients with MAFLD only. All-cause and cardiovascular death was higher in patients with MAFLD than those without MAFLD (P<0.001, respectively). In patients with MAFLD only, the hazard ratio (HR) of all-cause and cardiovascular death was 1.35 (95% confidence interval [CI], 1.13 to 1.60) and 1.90 (95% CI, 1.26 to 2.88) after adjusting for age, which lost its statistical significance by multivariable adjustments. Compared to patients with less than two components of metabolic dysfunction, patients with more than two components of metabolic dysfunction were a higher risk of cardiovascular death (HR, 2.05; 95% CI, 1.25 to 3.38) and only women with more than two components of metabolic dysfunction were a higher risk of all-cause death (HR, 1.44; 95% CI, 1.02 to 2.03).
Conclusion
MAFLD criteria could identify a high-risk group for all-cause and cardiovascular death.

Citations

Citations to this article as recorded by  
  • Comparison of Outcomes Between Metabolic Dysfunction-Associated Fatty Liver Disease and Non-alcoholic Fatty Liver Disease: A Meta-Analysis
    Ghazala S Virk, Jaahnavi Vajje, Nausheen K Virk, Raam Mannam, Wajeeh Rehman, Naglaa G Ghobriel , Irfan-ud-din Mian, Muhammad Usama
    Cureus.2023;[Epub]     CrossRef
  • Trends in prevalence and all-cause mortality of metabolic dysfunction-associated fatty liver disease among adults in the past three decades: Results from the NHANES study
    Zhi-Qin Xie, Hong-Xia Li, Bing-Kun Wang, Zhao-Ming Yang, Zi-Yu Zhang, Wen-Liang Tan, Wen-Xin Li, Qing-Bin Wang, Lei Yang, Hong-Kai Zhuang, Chen-Wei Tang, Chang-Zhen Shang, Ya-Jin Chen
    European Journal of Internal Medicine.2023; 110: 62.     CrossRef
  • Comparing the Mortality Risk between Metabolic Dysfunction-Associated Fatty Liver Disease and Non-Alcoholic Fatty Liver Disease
    Han Na Jung, Chang Hee Jung
    Diabetes & Metabolism Journal.2023; 47(2): 198.     CrossRef
  • Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis
    Hye Jin Chun, Eun Ran Kim, Minyoung Lee, Da Hyun Choi, Soo Hyun Kim, Eugene Shin, Jin-Hong Kim, Jin Won Cho, Dai Hoon Han, Bong-Soo Cha, Yong-ho Lee
    Metabolism.2023; 145: 155612.     CrossRef
  • Current understanding and future perspectives on the impact of changing NAFLD to MAFLD on global epidemiology and clinical outcomes
    Karl Vaz, Daniel Clayton-Chubb, Ammar Majeed, John Lubel, David Simmons, William Kemp, Stuart K. Roberts
    Hepatology International.2023; 17(5): 1082.     CrossRef
Basic Research
Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice
Songling Jiang, Md Jamal Uddin, Xiaoying Yu, Lingjuan Piao, Debra Dorotea, Goo Taeg Oh, Hunjoo Ha
Diabetes Metab J. 2022;46(6):829-842.   Published online June 24, 2022
DOI: https://doi.org/10.4093/dmj.2021.0274
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  • 4 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes. Peroxisomes are single membrane-enclosed organelles that play a role in the metabolism of lipid and reactive oxygen species. The present study examined the role of peroxisomes in high-fat diet (HFD)-induced NAFLD using fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist.
Methods
Eight-week-old male C57BL/6J mice were fed either a normal diet or HFD for 12 weeks, and fenofibrate (50 mg/kg/day) was orally administered along with the initiation of HFD.
Results
HFD-induced liver injury as measured by increased alanine aminotransferase, inflammation, oxidative stress, and lipid accumulation was effectively prevented by fenofibrate. Fenofibrate significantly increased the expression of peroxisomal genes and proteins involved in peroxisomal biogenesis and function. HFD-induced attenuation of peroxisomal fatty acid oxidation was also significantly restored by fenofibrate, demonstrating the functional significance of peroxisomal fatty acid oxidation. In Ppara deficient mice, fenofibrate failed to maintain peroxisomal biogenesis and function in HFD-induced liver injury.
Conclusion
The present data highlight the importance of PPARα-mediated peroxisomal fitness in the protective effect of fenofibrate against NAFLD.

Citations

Citations to this article as recorded by  
  • Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD
    Manuela Vitulo, Elisa Gnodi, Giulia Rosini, Raffaella Meneveri, Roberto Giovannoni, Donatella Barisani
    International Journal of Molecular Sciences.2023; 24(16): 12748.     CrossRef
  • Pharmacological potential of ginseng and ginsenosides in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
    Young-Su Yi
    Journal of Ginseng Research.2023;[Epub]     CrossRef
  • PPARα agonist fenofibrate prevents postoperative cognitive dysfunction by enhancing fatty acid oxidation in mice
    Tiantian Liu, Xinlu Chen, Ziqi Wei, Xue Han, Yujia Liu, Zhengliang Ma, Tianjiao Xia, Xiaoping Gu
    Translational Neuroscience.2023;[Epub]     CrossRef
  • Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet
    Ying Zhang, Xiu-Bin Jia, Yun-Chao Liu, Wen-Qian Yu, Yan-Hong Si, Shou-Dong Guo
    Frontiers in Nutrition.2022;[Epub]     CrossRef
Review
Metabolic Risk/Epidemiology
Lifestyle Interventions for Non-Obese Patients Both with, and at Risk, of Non-Alcoholic Fatty Liver Disease
Xin-Lei Zhang, Ting-Yao Wang, Giovanni Targher, Christopher D. Byrne, Ming-Hua Zheng
Diabetes Metab J. 2022;46(3):391-401.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0048
  • 4,279 View
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  • 7 Citations
AbstractAbstract PDFPubReader   ePub   
Non-alcoholic fatty liver disease occurring in non-obese subjects (the so-called non-obese NAFLD) is a highly prevalent but neglected liver condition, which is closely associated with metabolic disorders and suboptimal lifestyles. Landmark studies have shown that lifestyle interventions are potentially beneficial in decreasing the risk of developing non-obese NAFLD and in ameliorating NAFLD in non-obese individuals with pre-existing NAFLD. Lifestyle interventions usually refer to changes in eating habits and physical activity, both of which have a powerful effect on non-obese NAFLD and on risk factors for non-obese NAFLD. However, to date, patients and health-care professionals have a poor awareness and understanding of non-obese NAFLD and the beneficial effects of lifestyle interventions in this patient population. The aim of this narrative review is to briefly discuss the evidence for the effects of lifestyle changes and what changes are needed amongst medical personnel and other stakeholders in order to raise awareness of non-obese NAFLD.

Citations

Citations to this article as recorded by  
  • Patients with NAFLD exhibit more advanced fibrosis in liver biopsy than patients with other chronic liver diseases
    Lydia Rohr, Peter Lemmer, Marie Henning, Andrea Tannapfel, Theodor Baars, Paul Manka, Ali Canbay, Jan-Peter Sowa
    Zeitschrift für Gastroenterologie.2023; 61(01): 29.     CrossRef
  • Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes
    Seung Min Chung, Min Kyu Kang, Jun Sung Moon, Jung Gil Park
    Endocrinology and Metabolism.2023; 38(2): 277.     CrossRef
  • An international multidisciplinary consensus statement on MAFLD and the risk of CVD
    Xiao-Dong Zhou, Giovanni Targher, Christopher D. Byrne, Virend Somers, Seung Up Kim, C. Anwar A. Chahal, Vincent Wai-Sun Wong, Jingjing Cai, Michael D. Shapiro, Mohammed Eslam, Philippe Gabriel Steg, Ki-Chul Sung, Anoop Misra, Jian-Jun Li, Carlos Brotons,
    Hepatology International.2023; 17(4): 773.     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
  • Sex-Based Differences and Risk Factors for Comorbid Nonalcoholic Fatty Liver Disease in Patients with Bipolar Disorder: A Cross-Sectional Retrospective Study
    Ying Wang, Yiyi Liu, Xun Zhang, Qing Wu
    Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 3533.     CrossRef
  • Benefits of Physical Exercise as Approach to Prevention and Reversion of Non-Alcoholic Fatty Liver Disease in Children and Adolescents with Obesity
    Valeria Calcaterra, Vittoria Carlotta Magenes, Matteo Vandoni, Clarissa Berardo, Luca Marin, Alice Bianchi, Erika Cordaro, Giustino Simone Silvestro, Dario Silvestri, Vittoria Carnevale Pellino, Cristina Cereda, Gianvincenzo Zuccotti
    Children.2022; 9(8): 1174.     CrossRef
  • The effects of supplementation of probiotics, prebiotics, or synbiotics on patients with non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials
    Wenmin Xing, Wenyan Gao, Xiaoling Lv, Zhenlei Zhao, Genxiang Mao, Xiaoyan Dong, Zuyong Zhang
    Frontiers in Nutrition.2022;[Epub]     CrossRef
Original Article
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
  • 4,560 View
  • 262 Download
  • 14 Citations
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

Citations to this article as recorded by  
  • Esteatosis hepática metabólica y nefropatía diabética: una llamada a la acción
    Salvador Benlloch, Francesc Moncho, Jose Luis Górriz
    Nefrología.2023;[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
  • 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.2023;[Epub]     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
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    Diabetes & Metabolism Journal.2022; 46(6): 956.     CrossRef
Sulwon Lecture 2020
Pathophysiology
Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
Inês Sousa-Lima, Hyun Jeong Kim, John Jones, Young-Bum Kim
Diabetes Metab J. 2021;45(5):655-674.   Published online September 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0197
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.

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  • Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice
    Xixi Lin, Like Wang, Xiaojie Lu, Yuanyuan Zhang, Rongying Zheng, Ruijie Chen, Weixi Zhang
    Respiratory Research.2023;[Epub]     CrossRef
  • Selectivity matters: selective ROCK2 inhibitor ameliorates established liver fibrosis via targeting inflammation, fibrosis, and metabolism
    Alexandra Zanin-Zhorov, Wei Chen, Julien Moretti, Melanie S. Nyuydzefe, Iris Zhorov, Rashmi Munshi, Malavika Ghosh, Cindy Serdjebi, Kelli MacDonald, Bruce R. Blazar, Melissa Palmer, Samuel D. Waksal
    Communications Biology.2023;[Epub]     CrossRef
  • Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis
    Lei Wei, Jianjian Shi
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Paeoniflorin alleviates liver injury in hypercholesterolemic rats through the ROCK/AMPK pathway
    Tong Liu, Ning Zhang, Lingya Kong, Sijie Chu, Ting Zhang, Guangdi Yan, Donglai Ma, Jun Dai, Zhihong Ma
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Fasudil Increased the Sensitivity to Gefitinib in NSCLC by Decreasing Intracellular Lipid Accumulation
    Tingting Liao, Jingjing Deng, Wenjuan Chen, Juanjuan Xu, Guanghai Yang, Mei Zhou, Zhilei Lv, Sufei Wang, Siwei Song, Xueyun Tan, Zhengrong Yin, Yumei Li, Yang Jin
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Original Articles
Metabolic Risk/Epidemiology
Serum Retinol-Binding Protein Levels Are Associated with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Real-World Study
Zhi-Hui Zhang, Jiang-Feng Ke, Jun-Xi Lu, Yun Liu, Ai-Ping Wang, Lian-Xi Li
Diabetes Metab J. 2022;46(1):129-139.   Published online August 10, 2021
DOI: https://doi.org/10.4093/dmj.2020.0222
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Background
The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM.
Methods
This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed.
Results
After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients.
Conclusion
Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.

Citations

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  • The relationship between NAFLD and retinol-binding protein 4 - an updated systematic review and meta-analysis
    Rui Hu, Xiaoyue Yang, Xiaoyu He, Guangyao Song
    Lipids in Health and Disease.2023;[Epub]     CrossRef
  • Blood lactate levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease in type 2 diabetes: a real-world study
    Yi-Lin Ma, Jiang-Feng Ke, Jun-Wei Wang, Yu-Jie Wang, Man-Rong Xu, Lian-Xi Li
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • High‐normal unconjugated bilirubin is associated with decreased risk of chronic kidney disease in type 2 diabetes: A real‐world study
    Man‐Rong Xu, Chun‐Hua Jin, Jun‐Xi Lu, Mei‐Fang Li, Lian‐Xi Li
    Diabetes/Metabolism Research and Reviews.2023;[Epub]     CrossRef
  • Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis
    Elina En Li Cho, Chong Zhe Ang, Jingxuan Quek, Clarissa Elysia Fu, Lincoln Kai En Lim, Zane En Qi Heng, Darren Jun Hao Tan, Wen Hui Lim, Jie Ning Yong, Rebecca Zeng, Douglas Chee, Benjamin Nah, Cosmas Rinaldi Adithya Lesmana, Aung Hlaing Bwa, Khin Maung W
    Gut.2023; 72(11): 2138.     CrossRef
  • Serum iron is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes: A real-world study
    Jun-Wei Wang, Chun-Hua Jin, Jiang-Feng Ke, Yi-Lin Ma, Yu-Jie Wang, Jun-Xi Lu, Mei-Fang Li, Lian-Xi Li
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Low-normal serum unconjugated bilirubin levels are associated with late but not early carotid atherosclerotic lesions in T2DM subjects
    Chun-Hua Jin, Jun-Wei Wang, Jiang-Feng Ke, Jing-Bo Li, Mei-Fang Li, Lian-Xi Li
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Waist-to-height ratio is a simple and practical alternative to waist circumference to diagnose metabolic syndrome in type 2 diabetes
    Yi-Lin Ma, Chun-Hua Jin, Cui-Chun Zhao, Jiang-Feng Ke, Jun-Wei Wang, Yu-Jie Wang, Jun-Xi Lu, Gao-Zhong Huang, Lian-Xi Li
    Frontiers in Nutrition.2022;[Epub]     CrossRef
  • GA/HbA1c ratio is a simple and practical indicator to evaluate the risk of metabolic dysfunction-associated fatty liver disease in type 2 diabetes: an observational study
    Jun-Wei Wang, Chun-Hua Jin, Jiang-Feng Ke, Yi-Lin Ma, Yu-Jie Wang, Jun-Xi Lu, Mei-Fang Li, Lian-Xi Li
    Diabetology & Metabolic Syndrome.2022;[Epub]     CrossRef
  • Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes
    Yu-Jie Wang, Chun-Hua Jin, Jiang-Feng Ke, Jun-Wei Wang, Yi-Lin Ma, Jun-Xi Lu, Mei-Fang Li, Lian-Xi Li
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 3717.     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
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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.

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    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
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    Jaehyun Bae, Byung-Wan Lee
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  • 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
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Pathophysiology
Distinct Dose-Dependent Association of Free Fatty Acids with Diabetes Development in Nonalcoholic Fatty Liver Disease Patients
Fuxi Li, Junzhao Ye, Yanhong Sun, Yansong Lin, Tingfeng Wu, Congxiang Shao, Qianqian Ma, Xianhua Liao, Shiting Feng, Bihui Zhong
Diabetes Metab J. 2021;45(3):417-429.   Published online March 15, 2021
DOI: https://doi.org/10.4093/dmj.2020.0039
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear.
Methods
Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.
Results
There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals.
Conclusion
A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.

Citations

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  • Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study
    Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
    Diabetes & Metabolism Journal.2023; 47(2): 220.     CrossRef
  • Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development
    Yujin Jin, Kyung-Sun Heo
    The Korean Journal of Physiology & Pharmacology.2023; 27(4): 299.     CrossRef
  • Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
    Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
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    Shuyin Bao, Xiuzhi Wang, Qianqian Ma, Chengxi Wei, Jixing Nan, Wuliji Ao
    Chinese Herbal Medicines.2022; 14(3): 367.     CrossRef
  • Triglyceride Glucose-Waist Circumference Is Superior to the Homeostasis Model Assessment of Insulin Resistance in Identifying Nonalcoholic Fatty Liver Disease in Healthy Subjects
    Hwi Seung Kim, Yun Kyung Cho, Eun Hee Kim, Min Jung Lee, Chang Hee Jung, Joong-Yeol Park, Hong-Kyu Kim, Woo Je Lee
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Complications
Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Eugene Han, Mi Kyung Kim, Byoung Kuk Jang, Hye Soon Kim
Diabetes Metab J. 2021;45(5):698-707.   Published online February 2, 2021
DOI: https://doi.org/10.4093/dmj.2020.0118
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AbstractAbstract PDFPubReader   ePub   
Background
This study aimed to investigate the association between hepatic steatosis burden and albuminuria in Korean patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).
Methods
We recruited 100 patients with both T2DM and NAFLD, but without chronic kidney disease. Albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Transient elastography was performed, and the steatosis burden was quantified by controlled attenuation parameter (CAP) with significant steatosis defined as CAP >302 dB/m.
Results
The prevalence of significant steatosis and albuminuria was 56.0% and 21.0%, respectively. Subjects with significant steatosis were significantly younger and had a significantly shorter duration of T2DM, greater waist circumference, and higher body mass index, total cholesterol, triglyceride, and low density lipoprotein cholesterol levels, than subjects without severe NAFLD (all P<0.05). Albuminuria was higher in patients with significant steatosis than in patients without significant steatosis (32.1% vs. 6.8%, P=0.002). Urinary ACR showed a correlation with CAP (r=0.331, P=0.001), and multiple linear regression analysis revealed a significant association between a high degree of albuminuria and high CAP value (r=0.321, P=0.001). Additionally, multivariate logistic regression analysis demonstrated the independent association between urinary ACR and significant steatosis after adjustment for confounding factors including age, body mass index, duration of T2DM, low density lipoprotein level, and renin-angiotensin system blocker use (odds ratio, 1.88; 95% confidence interval, 1.31 to 2.71; P=0.001).
Conclusion
T2DM patients with NAFLD had a higher prevalence of albuminuria, which correlated with their steatosis burden.

Citations

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  • A Novel Anthropometric Parameter, Weight-Adjusted Waist Index Represents Sarcopenic Obesity in Newly Diagnosed Type 2 Diabetes Mellitus
    Min Jeong Park, Soon Young Hwang, Nam Hoon Kim, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo
    Journal of Obesity & Metabolic Syndrome.2023; 32(2): 130.     CrossRef
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    Jaehyun Bae, Byung-Wan Lee
    Biomedicines.2023; 11(7): 1928.     CrossRef
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    Eugene Han, Mi Kyung Kim, Seung-Soon Im, Byoung Kuk Jang, Hye Soon Kim
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    San Wang, Jieun Han, Se Young Jung, Tae Jung Oh, Sen Yao, Sanghee Lim, Hee Hwang, Ho-Young Lee, Haeun Lee
    Scientific Reports.2022;[Epub]     CrossRef
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    Eugene Han
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  • Muscle fat contents rather than muscle mass determines nonalcoholic steatohepatitis and liver fibrosis in patients with severe obesity
    Eugene Han, Mi Kyung Kim, Hye Won Lee, Seungwan Ryu, Hye Soon Kim, Byoung Kuk Jang, Youngsung Suh
    Obesity.2022; 30(12): 2440.     CrossRef
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    Yu-Jie Wang, Chun-Hua Jin, Jiang-Feng Ke, Jun-Wei Wang, Yi-Lin Ma, Jun-Xi Lu, Mei-Fang Li, Lian-Xi Li
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 3717.     CrossRef
  • Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2021;45:698-707)
    Eugene Han, Hye Soon Kim
    Diabetes & Metabolism Journal.2021; 45(6): 972.     CrossRef
  • Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2021;45:698-707)
    Mi-kyung Kim
    Diabetes & Metabolism Journal.2021; 45(6): 968.     CrossRef
  • Liver fibrosis indices are related to diabetic peripheral neuropathy in individuals with type 2 diabetes
    Kyuho Kim, Tae Jung Oh, Hyen Chung Cho, Yun Kyung Lee, Chang Ho Ahn, Bo Kyung Koo, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang
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Metabolic Risk/Epidemiology
Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease
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
Diabetes Metab J. 2021;45(5):739-752.   Published online October 28, 2020
DOI: https://doi.org/10.4093/dmj.2020.0137
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Graphical AbstractGraphical Abstract AbstractAbstract 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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Review
Metabolic Risk/Epidemiology
Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming
Soung Won Jeong
Diabetes Metab J. 2020;44(5):640-657.   Published online October 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0115
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AbstractAbstract PDFPubReader   ePub   
The worldwide prevalence of non-alcoholic fatty liver disease is around 25%, and that of nonalcoholic steatohepatitis (NASH) ranges from 1.5% to 6.45%. Patients with NASH, especially those with fibrosis, are at higher risk for adverse outcomes such as cirrhosis and liver-related mortality. Although vitamin E, pioglitazone, and liraglutide improved liver histology in randomized trials, there are currently no Food and Drug Administration-approved drugs for NASH. Five pharmacologic agents—obeticholic acid, elafibranor, cenicriviroc, resmetirom, and aramchol—are being evaluated in large, histology-based phase 3 trials. Within 2 to 4 years, new and effective drugs for the treatment of NASH are expected. Additionally, many phase 2 trials are ongoing for various agents. Based on the results of phase 2 and 3 trials, combination treatments are also being investigated. Future treatment strategies will comprise drug combinations and precision medicine based on the different phenotypes of NASH and treatment response of the individual patient.

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