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Volume 47(2); March 2023
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Reviews
Basic Research
The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4
Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee
Diabetes Metab J. 2023;47(2):153-163.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0305
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  • 6 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.

Citations

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  • Synthesis, activatory effects, molecular docking and ADME studies as rabbit muscle pyruvate kinase activators of ureido phenyl substituted 1,4-dihydropyridine derivatives
    Mustafa Oğuzhan Kaya, Tuna Demirci, Ümit Çalışır, Oğuzhan Özdemir, Yeşim Kaya, Mustafa Arslan
    Research on Chemical Intermediates.2024; 50(1): 437.     CrossRef
  • Unraveling the causes of sarcopenia: Roles of neuromuscular junction impairment and mitochondrial dysfunction
    Yanmei Miao, Leiyu Xie, Jiamei Song, Xing Cai, Jinghe Yang, Xinglong Ma, Shaolin Chen, Peng Xie
    Physiological Reports.2024;[Epub]     CrossRef
  • Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases
    Zonghao Qian, Yuzhen Huang, Yucong Zhang, Ni Yang, Ziwei Fang, Cuntai Zhang, Le Zhang
    Frontiers in Genetics.2024;[Epub]     CrossRef
  • Inhibition of Pyruvate Dehydrogenase Kinase 4 Protects Cardiomyocytes from lipopolysaccharide-Induced Mitochondrial Damage by Reducing Lactate Accumulation
    Tangtian Chen, Qiumin Xie, Bin Tan, Qin Yi, Han Xiang, Rui Wang, Qin Zhou, Bolin He, Jie Tian, Jing Zhu, Hao Xu
    Inflammation.2024;[Epub]     CrossRef
  • Effect of resistance training plus enriched probiotic supplement on sestrin2, oxidative stress, and mitophagy markers in elderly male Wistar rats
    Majid Mohabbat, Hamid Arazi
    Scientific Reports.2024;[Epub]     CrossRef
  • Comparison between single-muscle evaluation and cross-sectional area muscle evaluation for predicting the prognosis in patients with oral squamous cell carcinoma: a retrospective cohort study
    Hirotaka Takayama, Takuya Yoshimura, Hajime Suzuki, Yuka Hirano, Masahiro Tezuka, Takayuki Ishida, Kiyohide Ishihata, Marie Amitani, Haruka Amitani, Yasunori Nakamura, Yasushi Imamura, Akio Inui, Norifumi Nakamura
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases
    Yue Zhang, Meiyan Sun, Hongxiang Zhao, Zhengyan Wang, Yanan Shi, Jianxin Dong, Kaifang Wang, Xi Wang, Xingyue Li, Haiyan Qi, Xiaoyong Zhao
    International Journal of Nanomedicine.2023; Volume 18: 7559.     CrossRef
Basic Research
Multiple Roles of Sirtuin 6 in Adipose Tissue Inflammation
Eun Ju Bae, Byung-Hyun Park
Diabetes Metab J. 2023;47(2):164-172.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0270
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  • 4 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Adipose tissue (AT) inflammation is strongly associated with obesity-induced insulin resistance. When subjected to metabolic stress, adipocytes become inflamed and secrete a plethora of cytokines and chemokines, which recruit circulating immune cells to AT. Although sirtuin 6 (Sirt6) is known to control genomic stabilization, aging, and cellular metabolism, it is now understood to also play a pivotal role in the regulation of AT inflammation. Sirt6 protein levels are reduced in the AT of obese humans and animals and increased by weight loss. In this review, we summarize the potential mechanism of AT inflammation caused by impaired action of Sirt6 from the immune cells’ point of view. We first describe the properties and functions of immune cells in obese AT, with an emphasis on discrete macrophage subpopulations which are central to AT inflammation. We then highlight data that links Sirt6 to functional phenotypes of AT inflammation. Importantly, we discuss in detail the effects of Sirt6 deficiency in adipocytes, macrophages, and eosinophils on insulin resistance or AT browning. In our closing perspectives, we discuss emerging issues in this field that require further investigation.

Citations

Citations to this article as recorded by  
  • The Role of Increased Expression of Sirtuin 6 in the Prevention of Premature Aging Pathomechanisms
    Adrianna Dzidek, Olga Czerwińska-Ledwig, Małgorzata Żychowska, Wanda Pilch, Anna Piotrowska
    International Journal of Molecular Sciences.2023; 24(11): 9655.     CrossRef
  • Exploring the Influence of Age, Gender and Body Mass Index on Colorectal Cancer Location
    Dorel Popovici, Cristian Stanisav, Sorin Saftescu, Serban Negru, Radu Dragomir, Daniel Ciurescu, Razvan Diaconescu
    Medicina.2023; 59(8): 1399.     CrossRef
Basic Research
Heterogeneity of Islet Cells during Embryogenesis and Differentiation
Shugo Sasaki, Takeshi Miyatsuka
Diabetes Metab J. 2023;47(2):173-184.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0324
  • 3,945 View
  • 250 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
Diabetes is caused by insufficient insulin secretion due to β-cell dysfunction and/or β-cell loss. Therefore, the restoration of functional β-cells by the induction of β-cell differentiation from embryonic stem (ES) and induced-pluripotent stem (iPS) cells, or from somatic non-β-cells, may be a promising curative therapy. To establish an efficient and feasible method for generating functional insulin-producing cells, comprehensive knowledge of pancreas development and β-cell differentiation, including the mechanisms driving cell fate decisions and endocrine cell maturation is crucial. Recent advances in single-cell RNA sequencing (scRNA-seq) technologies have opened a new era in pancreas development and diabetes research, leading to clarification of the detailed transcriptomes of individual insulin-producing cells. Such extensive high-resolution data enables the inference of developmental trajectories during cell transitions and gene regulatory networks. Additionally, advancements in stem cell research have not only enabled their immediate clinical application, but also has made it possible to observe the genetic dynamics of human cell development and maturation in a dish. In this review, we provide an overview of the heterogeneity of islet cells during embryogenesis and differentiation as demonstrated by scRNA-seq studies on the developing and adult pancreata, with implications for the future application of regenerative medicine for diabetes.

Citations

Citations to this article as recorded by  
  • Newly discovered knowledge pertaining to glucagon and its clinical applications
    Dan Kawamori, Shugo Sasaki
    Journal of Diabetes Investigation.2023; 14(7): 829.     CrossRef
Cardiovascular Risk/Epidemiology
Intensified Multifactorial Intervention in Patients with Type 2 Diabetes Mellitus
Takayoshi Sasako, Toshimasa Yamauchi, Kohjiro Ueki
Diabetes Metab J. 2023;47(2):185-197.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0325
  • 5,455 View
  • 366 Download
  • 9 Web of Science
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AbstractAbstract PDFPubReader   ePub   
In the management of diabetes mellitus, one of the most important goals is to prevent its micro- and macrovascular complications, and to that end, multifactorial intervention is widely recommended. Intensified multifactorial intervention with pharmacotherapy for associated risk factors, alongside lifestyle modification, was first shown to be efficacious in patients with microalbuminuria (Steno-2 study), then in those with less advanced microvascular complications (the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care [ADDITION]-Europe and the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases [J-DOIT3]), and in those with advanced microvascular complications (the Nephropathy In Diabetes-Type 2 [NID-2] study and Diabetic Nephropathy Remission and Regression Team Trial in Japan [DNETT-Japan]). Thus far, multifactorial intervention led to a reduction in cardiovascular and renal events, albeit not necessarily significant. It should be noted that not only baseline characteristics but also the control status of the risk factors and event rates during intervention among the patients widely varied from one trial to the next. Further evidence is needed for the efficacy of multifactorial intervention in a longer duration and in younger or elderly patients. Moreover, now that new classes of antidiabetic drugs are available, it should be addressed whether strict and safe glycemic control, alongside control of other risk factors, could lead to further risk reductions in micro- and macrovascular complications, thereby decreasing all-cause mortality in patients with type 2 diabetes mellitus.

Citations

Citations to this article as recorded by  
  • Exploring mechanisms underlying diabetes comorbidities and strategies to prevent vascular complications
    Takayoshi Sasako
    Diabetology International.2024; 15(1): 34.     CrossRef
  • Targeting ERS-mitophagy in hippocampal neurons to explore the improvement of memory by tea polyphenols in aged type 2 diabetic rats
    Wenjuan Feng, Chenhui Lv, Le Cheng, Xin Song, Xuemin Li, Haoran Xie, Shuangzhi Chen, Xi Wang, Lushan Xue, Cheng Zhang, Jie Kou, Lili Wang, Haifeng Zhao
    Free Radical Biology and Medicine.2024; 213: 293.     CrossRef
  • Risk of Dementia Among Patients With Diabetes in a Multidisciplinary, Primary Care Management Program
    Kailu Wang, Shi Zhao, Eric Kam-Pui Lee, Susan Zi-May Yau, Yushan Wu, Chi-Tim Hung, Eng-Kiong Yeoh
    JAMA Network Open.2024; 7(2): e2355733.     CrossRef
  • Causes of In-Hospital Death and Pharmaceutical Associations with Age of Death during a 10-Year Period (2011–2020) in Individuals with and without Diabetes at a Japanese Community General Hospital
    Minae Hosoki, Taiki Hori, Yousuke Kaneko, Kensuke Mori, Saya Yasui, Seijiro Tsuji, Hiroki Yamagami, Saki Kawata, Tomoyo Hara, Shiho Masuda, Yukari Mitsui, Kiyoe Kurahashi, Takeshi Harada, Shingen Nakamura, Toshiki Otoda, Tomoyuki Yuasa, Akio Kuroda, Itsur
    Journal of Clinical Medicine.2024; 13(5): 1283.     CrossRef
  • External validation of a minimal-resource model to predict reduced estimated glomerular filtration rate in people with type 2 diabetes without diagnosis of chronic kidney disease in Mexico: a comparison between country-level and regional performance
    Camilla Sammut-Powell, Rose Sisk, Ruben Silva-Tinoco, Gustavo de la Pena, Paloma Almeda-Valdes, Sonia Citlali Juarez Comboni, Susana Goncalves, Rory Cameron
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Gut Microbiota Targeted Approach by Natural Products in Diabetes Management: An Overview
    Priyanka Sati, Praveen Dhyani, Eshita Sharma, Dharam Chand Attri, Arvind Jantwal, Rajni Devi, Daniela Calina, Javad Sharifi-Rad
    Current Nutrition Reports.2024;[Epub]     CrossRef
  • Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort
    Song Lu, Qun Wang, Hengcheng Lu, Maobin Kuang, Min Zhang, Guotai Sheng, Yang Zou, Xiaoping Peng
    BMC Endocrine Disorders.2024;[Epub]     CrossRef
  • Potential of FGF21 in type 2 diabetes mellitus treatment based on untargeted metabolomics
    Shuai Li, Zilong Song, Chunxiang Fan, Weiwei Zhang, Tianyi Ma, Xu Li, Qi Zhang, Ming Zhao, Tianfei Yu, Shanshan Li
    Biochemical Pharmacology.2024; 225: 116306.     CrossRef
  • Cardiovascular Risk Reduction in Type 2 Diabetes: Further Insights into the Power of Weight Loss and Exercise
    Seung-Hwan Lee
    Endocrinology and Metabolism.2023; 38(3): 302.     CrossRef
  • Sarcopenia: Loss of mighty armor against frailty and aging
    Takayoshi Sasako, Kohjiro Ueki
    Journal of Diabetes Investigation.2023; 14(10): 1145.     CrossRef
Editorial
Comparing the Mortality Risk between Metabolic Dysfunction-Associated Fatty Liver Disease and Non-Alcoholic Fatty Liver Disease
Han Na Jung, Chang Hee Jung
Diabetes Metab J. 2023;47(2):198-200.   Published online March 15, 2023
DOI: https://doi.org/10.4093/dmj.2023.0038
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  • 145 Download
PDFPubReader   ePub   
Original Articles
Guideline/Fact Sheet
Comparison of Operational Definition of Type 2 Diabetes Mellitus Based on Data from Korean National Health Insurance Service and Korea National Health and Nutrition Examination Survey
Jong Ha Baek, Yong-Moon Park, Kyung Do Han, Min Kyong Moon, Jong Han Choi, Seung-Hyun Ko
Diabetes Metab J. 2023;47(2):201-210.   Published online February 8, 2023
DOI: https://doi.org/10.4093/dmj.2022.0375
  • 3,518 View
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We evaluated the validity and reliability of the operational definition of type 2 diabetes mellitus (T2DM) based on the Korean National Health Insurance Service (NHIS) database.
Methods
Adult subjects (≥40 years old) included in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2017 were merged with those from the NHIS health check-up database, producing a cross-sectional dataset. We evaluated the sensitivity, specificity, accuracy, and agreement of the NHIS criteria for defining T2DM by comparing them with the KNHANES criteria as a standard reference.
Results
In the study population (n=13,006), two algorithms were devised to determine from the NHIS dataset whether the diagnostic claim codes for T2DM were accompanied by prescription codes for anti-diabetic drugs (algorithm 1) or not (algorithm 2). Using these algorithms, the prevalence of T2DM was 14.9% (n=1,942; algorithm 1) and 20.8% (n=2,707; algorithm 2). Good reliability in defining T2DM was observed for both algorithms (Kappa index, 0.73 [algorithm 1], 0.63 [algorithm 2]). However, the accuracy (0.93 vs. 0.89) and specificity (0.96 vs. 0.90) tended to be higher for algorithm 1 than for algorithm 2. The validity (accuracy, ranging from 0.91 to 0.95) and reliability (Kappa index, ranging from 0.68 to 0.78) of defining T2DM by NHIS criteria were independent of age, sex, socioeconomic status, and accompanied hypertension or dyslipidemia.
Conclusion
The operational definition of T2DM based on population-based NHIS claims data, including diagnostic codes and prescription codes, could be a valid tool to identify individuals with T2DM in the Korean population.

Citations

Citations to this article as recorded by  
  • Metabolic dysfunction-associated fatty liver disease increases the risk of type 2 diabetes mellitus in young Korean adults
    Junchul Ha, Oak-Kee Hong, Kyungdo Han, Hyuk-Sang Kwon
    Diabetes Research and Clinical Practice.2024; 212: 111584.     CrossRef
  • Gamma‐glutamyl transferase and the risk of all‐cause and disease‐specific mortality in patients with diabetes: A nationwide cohort study
    Goh Eun Chung, Su‐Min Jeong, Su Jong Yu, Jeong‐Ju Yoo, Yuri Cho, Kyu‐na Lee, Dong Wook Shin, Yoon Jun Kim, Jung‐Hwan Yoon, Kyungdo Han, Eun Ju Cho
    Journal of Diabetes.2024;[Epub]     CrossRef
  • Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study
    Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee
    Endocrinology and Metabolism.2023; 38(5): 525.     CrossRef
Guideline/Fact Sheet
Insulin Fact Sheet in Type 1 and 2 Diabetes Mellitus and Trends of Antidiabetic Medication Use in Insulin Users with Type 2 Diabetes Mellitus: 2002 to 2019
Jiyun Park, Gyuri Kim, Bong-Sung Kim, Kyung-Do Han, So Yoon Kwon, So Hee Park, You-Bin Lee, Sang-Man Jin, Jae Hyeon Kim
Diabetes Metab J. 2023;47(2):211-219.   Published online February 7, 2023
DOI: https://doi.org/10.4093/dmj.2022.0346
  • 3,924 View
  • 271 Download
  • 3 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigated the trends of insulin use among Korean patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Changes in prescription of antidiabetic medications in T2DM patients taking insulin therapy were evaluated.
Methods
We analyzed data from the National Health Insurance Service database in Korea to evaluate the prevalence of insulin users and trends of insulin use in T1DM and T2DM patients from January 2002 to December 2019. We also investigated numbers and types of antidiabetic medications in insulin users with T2DM.
Results
The overall total number of insulin users increased from 2002 to 2019, reaching 348,254 for T2DM and 20,287 for T1DM in 2019 compared with 109,974 for T2DM and 34,972 for T1DM in 2002. The proportion of patients using basal analogs and short acting analogs have increased and those using human insulin, premixed insulin, or biphasic human insulin have decreased (rapid acting analogs: 71.85% and 24.12% in T1DM and T2DM, respectively, in 2019; basal analogs: 76.75% and 75.09% in T1DM and T2DM, respectively, in 2019). The use of other antidiabetic medication in addition to insulin increased for T2DM, especially in dual therapy, reaching up to 52.35% in 2019 compared with 16.72% in 2002.
Conclusion
The proportion of the patients using basal or rapid acting analogs increased among all insulin users in both T1DM and T2DM patients. Among patients with T2DM, the proportion of patients using antidiabetic medications in addition to insulin was significantly increased compared to those who used insulin alone.

Citations

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  • Real-World Continuous Glucose Monitoring Data from a Population with Type 1 Diabetes in South Korea: Nationwide Single-System Analysis
    Ji Yoon Kim, Sang-Man Jin, Sarah B. Andrade, Boyang Chen, Jae Hyeon Kim
    Diabetes Technology & Therapeutics.2024;[Epub]     CrossRef
  • Continuous glucose monitoring for glycaemic control and cardiovascular risk reduction in patients with type 2 diabetes not on insulin therapy: A clinical trial
    Joseph Reed, Tony Dong, Elke Eaton, Janice Friswold, Jodie Porges, Sadeer G. Al‐Kindi, Sanjay Rajagopalan, Ian J. Neeland
    Diabetes, Obesity and Metabolism.2024;[Epub]     CrossRef
  • Gastrointestinal safety evaluation of semaglutide for the treatment of type 2 diabetes mellitus: A meta-analysis
    Xiaoyan Huang, Miaohui Wu, Jiaojiao Lin, Lunpan Mou, Yaping Zhang, Jianjia Jiang
    Medicine.2024; 103(21): e38236.     CrossRef
  • Evaluation of pharmacokinetic interactions between lobeglitazone, empagliflozin, and metformin in healthy subjects
    Heeyoung Kim, Choon Ok Kim, Hyeonsoo Park, Min Soo Park, Dasohm Kim, Taegon Hong, Yesong Shin, Byung Hak Jin
    Translational and Clinical Pharmacology.2023; 31(1): 59.     CrossRef
  • Smart Insulin Pen: Managing Insulin Therapy for People with Diabetes in the Digital Era
    Jee Hee Yoo, Jae Hyeon Kim
    The Journal of Korean Diabetes.2023; 24(4): 190.     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
  • 65,535 View
  • 285 Download
  • 10 Web of Science
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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

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  • 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
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    Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
    BMJ.2024; : e076388.     CrossRef
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    Huimin Zhou, Haiyan Chen, Hanxiao Lu, Bo Wu, Shuo Zhang, Yuanlong Gu, Guangwen Zhou, Jie Xiang, Jun Yang
    Liver International.2024;[Epub]     CrossRef
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    Zhenmin Liu, Taiyong Fang
    Journal of Health, Population and Nutrition.2024;[Epub]     CrossRef
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    Ghazala S Virk, Jaahnavi Vajje, Nausheen K Virk, Raam Mannam, Wajeeh Rehman, Naglaa G Ghobriel , Irfan-ud-din Mian, Muhammad Usama
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    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
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    Karl Vaz, Daniel Clayton-Chubb, Ammar Majeed, John Lubel, David Simmons, William Kemp, Stuart K. Roberts
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  • Mitochondrial Quality Control: Its Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
    Soyeon Shin, Jaeyoung Kim, Ju Yeon Lee, Jun Kim, Chang-Myung Oh
    Journal of Obesity & Metabolic Syndrome.2023; 32(4): 289.     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
  • 3,862 View
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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
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    Chao Deng, Qifeng Ou, Xuee Ou, Ding Pan
    BMJ Open.2024; 14(5): e078933.     CrossRef
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    Manouchehr Khoshbaten, Sepideh H. Maleki, Sara Hadad, Amrit Baral, Ana V. Rocha, Laxmi Poudel, Alireza Abdshah
    Health Science Reports.2023;[Epub]     CrossRef
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    Yu. G. Samoilova, M. V. Matveeva, E. A. Khoroshunova, D. V. Podchinenova, L. L. Maksimova, G. G. Gorbach, A. B. Trivozhenko, V. A. Avkhimenko
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Complications
Association of Body Mass Index and Fracture Risk Varied by Affected Bones in Patients with Diabetes: A Nationwide Cohort Study
Se-Won Lee, Kyungdo Han, Hyuk-Sang Kwon
Diabetes Metab J. 2023;47(2):242-254.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2022.0001
  • 3,093 View
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  • 5 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Body mass index (BMI) is a risk factor for the type 2 diabetes (T2DM), and T2DM accompanies various complications, such as fractures. We investigated the effects of BMI and T2DM on fracture risk and analyzed whether the association varied with fracture locations.
Methods
This study is a nationwide population-based cohort study that included all people with T2DM (n=2,746,078) who received the National Screening Program during 2009–2012. According to the anatomical location of the fracture, the incidence rate and hazard ratio (HR) were analyzed by dividing it into four categories: vertebra, hip, limbs, and total fracture.
Results
The total fracture had higher HR in the underweight group (HR, 1.268; 95% CI, 1.228 to 1.309) and lower HR in the obese group (HR, 0.891; 95% CI, 0.882 to 0.901) and the morbidly obese group (HR, 0.873; 95% CI, 0.857 to 0.89), compared to reference (normal BMI group). Similar trends were observed for HR of vertebra fracture. The risk of hip fracture was most prominent, the risk of hip fracture increased in the underweight group (HR, 1.896; 95% CI, 1.178 to 2.021) and decreased in the obesity (HR, 0.643; 95% CI, 0.624 to 0.663) and morbidly obesity group (HR, 0.627; 95% CI, 0.591 to 0.665). Lastly, fracture risk was least affected by BMI for limbs.
Conclusion
In T2DM patients, underweight tends to increase fracture risk, and overweight tends to lower fracture risk, but association between BMI and fracture risk varied depending on the affected bone lesions.

Citations

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    Naoyuki Otani, Motoshi Ouchi, Einosuke Mizuta, Asuka Morita, Tomoe Fujita, Naohiko Anzai, Ichiro Hisatome
    Biomedicines.2023; 11(5): 1255.     CrossRef
  • Association of Body Mass Index and Fracture Risk Varied by Affected Bones in Patients with Diabetes: A Nationwide Cohort Study (Diabetes Metab J 2023;47:242-54)
    Se-Won Lee, Kyungdo Han, Hyuk-Sang Kwon
    Diabetes & Metabolism Journal.2023; 47(3): 439.     CrossRef
  • Association of Body Mass Index and Fracture Risk Varied by Affected Bones in Patients with Diabetes: A Nationwide Cohort Study (Diabetes Metab J 2023;47:242-54)
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    Diabetes & Metabolism Journal.2023; 47(3): 437.     CrossRef
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    Osteoporosis International.2023; 34(12): 2013.     CrossRef
Genetics
Genome-Wide Association Study on Longitudinal Change in Fasting Plasma Glucose in Korean Population
Heejin Jin, Soo Heon Kwak, Ji Won Yoon, Sanghun Lee, Kyong Soo Park, Sungho Won, Nam H. Cho
Diabetes Metab J. 2023;47(2):255-266.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0375
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Genome-wide association studies (GWAS) on type 2 diabetes mellitus (T2DM) have identified more than 400 distinct genetic loci associated with diabetes and nearly 120 loci for fasting plasma glucose (FPG) and fasting insulin level to date. However, genetic risk factors for the longitudinal deterioration of FPG have not been thoroughly evaluated. We aimed to identify genetic variants associated with longitudinal change of FPG over time.
Methods
We used two prospective cohorts in Korean population, which included a total of 10,528 individuals without T2DM. GWAS of repeated measure of FPG using linear mixed model was performed to investigate the interaction of genetic variants and time, and meta-analysis was conducted. Genome-wide complex trait analysis was used for heritability calculation. In addition, expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression project.
Results
A small portion (4%) of the genome-wide single nucleotide polymorphism (SNP) interaction with time explained the total phenotypic variance of longitudinal change in FPG. A total of four known genetic variants of FPG were associated with repeated measure of FPG levels. One SNP (rs11187850) showed a genome-wide significant association for genetic interaction with time. The variant is an eQTL for NOC3 like DNA replication regulator (NOC3L) gene in pancreas and adipose tissue. Furthermore, NOC3L is also differentially expressed in pancreatic β-cells between subjects with or without T2DM. However, this variant was not associated with increased risk of T2DM nor elevated FPG level.
Conclusion
We identified rs11187850, which is an eQTL of NOC3L, to be associated with longitudinal change of FPG in Korean population.
Basic Research
Long Non-Coding RNA TUG1 Attenuates Insulin Resistance in Mice with Gestational Diabetes Mellitus via Regulation of the MicroRNA-328-3p/SREBP-2/ERK Axis
Xuwen Tang, Qingxin Qin, Wenjing Xu, Xuezhen Zhang
Diabetes Metab J. 2023;47(2):267-286.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0216
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Long non-coding RNAs (lncRNAs) have been illustrated to contribute to the development of gestational diabetes mellitus (GDM). In the present study, we aimed to elucidate how lncRNA taurine upregulated gene 1 (TUG1) influences insulin resistance (IR) in a high-fat diet (HFD)-induced mouse model of GDM.
Methods
We initially developed a mouse model of HFD-induced GDM, from which islet tissues were collected for RNA and protein extraction. Interactions among lncRNA TUG1/microRNA (miR)-328-3p/sterol regulatory element binding protein 2 (SREBP-2) were assessed by dual-luciferase reporter assay. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA pancreatic β-cell function (HOMA-β), insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and insulinogenic index (IGI) levels in mouse serum were measured through conducting gain- and loss-of-function experiments.
Results
Abundant expression of miR-328 and deficient expression of lncRNA TUG1 and SREBP-2 were characterized in the islet tissues of mice with HFD-induced GDM. LncRNA TUG1 competitively bound to miR-328-3p, which specifically targeted SREBP-2. Either depletion of miR-328-3p or restoration of lncRNA TUG1 and SREBP-2 reduced the FBG, FINS, HOMA-β, and HOMA-IR levels while increasing ISOGTT and IGI levels, promoting the expression of the extracellular signal-regulated kinase (ERK) signaling pathway-related genes, and inhibiting apoptosis of islet cells in GDM mice. Upregulation miR-328-3p reversed the alleviative effects of SREBP-2 and lncRNA TUG1 on IR.
Conclusion
Our study provides evidence that the lncRNA TUG1 may prevent IR following GDM through competitively binding to miR-328-3p and promoting the SREBP-2-mediated ERK signaling pathway inactivation.

Citations

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  • Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1
    Mohammed Ageeli Hakami
    Saudi Journal of Biological Sciences.2024; 31(5): 103976.     CrossRef
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    Ritu Rani, Havagiray Chitme, Avinash Kumar Sharma
    Women & Health.2023; 63(5): 359.     CrossRef
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    Ritu Rani, Avinash Kumar Sharma, Havagiray R Chitme
    Clinical Medicine Insights: Endocrinology and Diabetes.2023;[Epub]     CrossRef
  • The role of ncRNA regulatory mechanisms in diseases—case on gestational diabetes
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    Briefings in Bioinformatics.2023;[Epub]     CrossRef
  • lncRNA TUG1 as Potential Novel Biomarker for Prognosis of Cardiovascular Diseases
    Habib Haybar, Narjes Sadat Sadati, Daryush Purrahman, Mohammad Reza Mahmoudian-Sani, Najmaldin Saki
    Epigenomics.2023; 15(23): 1273.     CrossRef
Basic Research
N6-Methyladenosine Methyltransferase METTL3 Alleviates Diabetes-Induced Testicular Damage through Modulating TUG1/Clusterin Axis
Yuan Tian, Yue-Hai Xiao, Chao Sun, Bei Liu, Fa Sun
Diabetes Metab J. 2023;47(2):287-300.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0306
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AbstractAbstract PDFPubReader   ePub   
Background
The present study investigated the regulatory effects of N6-methyladenosine (m6A) methyltransferase like-3 (METTL3) in diabetes-induced testicular damage.
Methods
In vivo diabetic mice and high glucose (HG) treated GC-1 spg cells were established. The mRNA and protein expressions were determined by real-time quantitative polymerase chain reaction, Western blot, immunofluorescence and immunohistochemistry staining. Levels of testosterone, blood glucose, cell viability, and apoptosis were detected by enzyme-linked immunosorbent assay, MTT, and flow cytometry, respectively. Molecular interactions were verified by RNA immunoprecipitation and RNA pull-down assay. Histopathological staining was performed to evaluate testicular injury.
Results
METTL3 and long non-coding RNA taurine up-regulated 1 (lncRNA TUG1) were downregulated in testicular tissues of diabetic mice and HG-treated GC-1 spg cells. METTL3 overexpression could reduce the blood glucose level, oxidative stress and testicular damage but enhance testosterone secretion in diabetic mouse model and HG-stimulated GC-1 spg cells. Mechanically, METTL3-mediated m6A methylation enhanced the stability of TUG1, then stabilizing the clusterin mRNA via recruiting serine and arginine rich splicing factor 1. Moreover, inhibition of TUG1/clusterin signaling markedly reversed the protective impacts of METTL3 overexpression on HG-stimulated GC-1 spg cells.
Conclusion
This study demonstrated that METTL3 ameliorated diabetes-induced testicular damage by upregulating the TUG1/clusterin signaling. These data further elucidate the potential regulatory mechanisms of m6A modification on diabetes-induced testicular injury.

Citations

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  • Negative Regulation of LINC01013 by METTL3 and YTHDF2 Enhances the Osteogenic Differentiation of Senescent Pre‐Osteoblast Cells Induced by Hydrogen Peroxide
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    Advanced Biology.2024;[Epub]     CrossRef
  • Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1
    Mohammed Ageeli Hakami
    Saudi Journal of Biological Sciences.2024; 31(5): 103976.     CrossRef
Letter
Response
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 Metab J. 2023;47(2):304-305.   Published online March 15, 2023
DOI: https://doi.org/10.4093/dmj.2023.0058
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