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Cardiovascular Risk/Epidemiology
Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes
Min Jeong Park, Kyung Mook Choi
Diabetes Metab J. 2022;46(1):49-62.   Published online January 27, 2022
DOI: https://doi.org/10.4093/dmj.2021.0316
  • 5,675 View
  • 221 Download
  • 5 Web of Science
  • 7 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Despite strenuous efforts to reduce cardiovascular disease (CVD) risk by improving cardiometabolic risk factors, such as glucose and cholesterol levels, and blood pressure, there is still residual risk even in patients reaching treatment targets. Recently, researchers have begun to focus on the variability of metabolic variables to remove residual risks. Several clinical trials and cohort studies have reported a relationship between the variability of metabolic parameters and CVDs. Herein, we review the literature regarding the effect of metabolic factor variability and CVD risk, and describe possible mechanisms and potential treatment perspectives for reducing cardiometabolic risk factor variability.

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  • Long-term variability in physiological measures in relation to mortality and epigenetic aging: prospective studies in the USA and China
    Hui Chen, Tianjing Zhou, Shaowei Wu, Yaying Cao, Geng Zong, Changzheng Yuan
    BMC Medicine.2023;[Epub]     CrossRef
  • Dose–response relationship between physical activity and cardiometabolic risk in obese children and adolescents: A pre-post quasi-experimental study
    Zekai Chen, Lin Zhu
    Frontiers in Physiology.2023;[Epub]     CrossRef
  • Association of body weight change with all-cause and cause-specific mortality: A nationwide population-based study
    So Yoon Kwon, Gyuri Kim, Jungkuk Lee, Jiyun Park, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
    Diabetes Research and Clinical Practice.2023; 199: 110666.     CrossRef
  • Association between lipid variability and the risk of mortality in cancer patients not receiving lipid-lowering agents
    Seohyun Kim, Gyuri Kim, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Association between visit-to-visit lipid variability and risk of ischemic heart disease: a cohort study in China
    Yonghao Wu, Peng Shen, Lisha Xu, Zongming Yang, Yexiang Sun, Luhua Yu, Zhanghang Zhu, Tiezheng Li, Dan Luo, Hongbo Lin, Liming Shui, Mengling Tang, Mingjuan Jin, Kun Chen, Jianbing Wang
    Endocrine.2023;[Epub]     CrossRef
  • Variability of Metabolic Risk Factors: Causative Factor or Epiphenomenon?
    Hye Jin Yoo
    Diabetes & Metabolism Journal.2022; 46(2): 257.     CrossRef
  • Long-Term Variability in Physiological Measures in Relation to Mortality and Epigenetic Aging: Prospective Studies in the US and China
    Hui Chen, Tianjing Zhou, Shaowei Wu, Yaying Cao, Geng Zong, Changzheng Yuan
    SSRN Electronic Journal .2022;[Epub]     CrossRef
Islet Studies and Transplantation
Regulation of Pancreatic β-Cell Mass by Gene-Environment Interaction
Shun-ichiro Asahara, Hiroyuki Inoue, Yoshiaki Kido
Diabetes Metab J. 2022;46(1):38-48.   Published online January 27, 2022
DOI: https://doi.org/10.4093/dmj.2021.0045
  • 4,513 View
  • 197 Download
  • 5 Web of Science
  • 5 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The main pathogenic mechanism of diabetes consists of an increase in insulin resistance and a decrease in insulin secretion from pancreatic β-cells. The number of diabetic patients has been increasing dramatically worldwide, especially in Asian people whose capacity for insulin secretion is inherently lower than that of other ethnic populations. Causally, changes of environmental factors in addition to intrinsic genetic factors have been considered to have an influence on the increased prevalence of diabetes. Particular focus has been placed on “gene-environment interactions” in the development of a reduced pancreatic β-cell mass, as well as type 1 and type 2 diabetes mellitus. Changes in the intrauterine environment, such as intrauterine growth restriction, contribute to alterations of gene expression in pancreatic β-cells, ultimately resulting in the development of pancreatic β-cell failure and diabetes. As a molecular mechanism underlying the effect of the intrauterine environment, epigenetic modifications have been widely investigated. The association of diabetes susceptibility genes or dietary habits with gene-environment interactions has been reported. In this review, we provide an overview of the role of gene-environment interactions in pancreatic β-cell failure as revealed by previous reports and data from experiments.

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  • Increased risk of incident diabetes after therapy with immune checkpoint inhibitor compared with conventional chemotherapy: A longitudinal trajectory analysis using a tertiary care hospital database
    Minyoung Lee, Kyeongseob Jeong, Yu Rang Park, Yumie Rhee
    Metabolism.2023; 138: 155311.     CrossRef
  • The ameliorating effects of mesenchymal stem cells compared to α‐tocopherol on apoptosis and autophagy in streptozotocin‐induced diabetic rats: Implication of PI3K/Akt signaling pathway and entero‐insular axis
    Heba A. Mubarak, Manal M. Kamal, Yossra Mahmoud, Fatma S. Abd‐Elsamea, Eman Abdelbary, Marwa G. Gamea, Reham I. El‐Mahdy
    Journal of Cellular Biochemistry.2023; 124(11): 1705.     CrossRef
  • Leptin Rs7799039 polymorphism is associated with type 2 diabetes mellitus Egyptian patients
    Amal Ahmed Mohamed, Dina M. Abo-Elmatty, Alaa S. Wahba, Omnia Ezzat Esmail, Hadeer Saied Mahmoud Salim, Wafaa Salah Mohammed Hegab, Mona Mostafa Farid Ghanem, Nadia Youssef Riad, Doaa Ghaith, Lamiaa I Daker, Shorouk Issa, Noha Hassan Radwan, Eman Sultan,
    Archives of Physiology and Biochemistry.2023; : 1.     CrossRef
  • Association of Polygenic Variants with Type 2 Diabetes Risk and Their Interaction with Lifestyles in Asians
    Haeng Jeon Hur, Hye Jeong Yang, Min Jung Kim, Kyun-Hee Lee, Myung-Sunny Kim, Sunmin Park
    Nutrients.2022; 14(15): 3222.     CrossRef
  • Chemical Compounds and Ambient Factors Affecting Pancreatic Alpha-Cells Mass and Function: What Evidence?
    Gaia Chiara Mannino, Elettra Mancuso, Stefano Sbrignadello, Micaela Morettini, Francesco Andreozzi, Andrea Tura
    International Journal of Environmental Research and Public Health.2022; 19(24): 16489.     CrossRef
Pathophysiology
Insulin Resistance: From Mechanisms to Therapeutic Strategies
Shin-Hae Lee, Shi-Young Park, Cheol Soo Choi
Diabetes Metab J. 2022;46(1):15-37.   Published online December 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0280
  • 30,208 View
  • 2,646 Download
  • 158 Web of Science
  • 187 Crossref
AbstractAbstract PDFPubReader   ePub   
Insulin resistance is the pivotal pathogenic component of many metabolic diseases, including type 2 diabetes mellitus, and is defined as a state of reduced responsiveness of insulin-targeting tissues to physiological levels of insulin. Although the underlying mechanism of insulin resistance is not fully understood, several credible theories have been proposed. In this review, we summarize the functions of insulin in glucose metabolism in typical metabolic tissues and describe the mechanisms proposed to underlie insulin resistance, that is, ectopic lipid accumulation in liver and skeletal muscle, endoplasmic reticulum stress, and inflammation. In addition, we suggest potential therapeutic strategies for addressing insulin resistance.

Citations

Citations to this article as recorded by  
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    Indian Journal of Clinical Biochemistry.2024; 39(1): 3.     CrossRef
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  • β-Thalassemia and Diabetes Mellitus: Current State and Future Directions
    Jalal Taneera, Eglal Mahgoub, Reem Qannita, Ayah Alalami, Ola Al Shehadat, Mona Youssef, Ayah Dib, Alaa Al Hajji, Amani Al Hajji, Fatheya Al-Khaja, Hany Dewedar, Mawieh Hamad
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    Yue Zhang, Liang Li, Tao Chai, Han Xu, Hong-yan Du, Yan Jiang
    Journal of Ethnopharmacology.2024; 319: 117307.     CrossRef
  • Thyroid cancer and insulin resistance
    Gabriela Brenta, Fernando Di Fermo
    Reviews in Endocrine and Metabolic Disorders.2024; 25(1): 19.     CrossRef
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    Hobby Aggarwal, Jyoti Gautam, Deepika Kumari, Sonu Kumar Gupta, Sneh Bajpai, Kartikey Chaturvedi, Yashwant Kumar, Madhu Dikshit
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    Patricia O. Benedet, Nooshin S. Safikhan, Maria J. Pereira, Bryan M. Lum, José Diego Botezelli, Cheng-Hsiang Kuo, Hua-Lin Wu, Barbara P. Craddock, W. Todd Miller, Jan W. Eriksson, Jessica T.Y. Yue, Edward M. Conway
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    Yi Fang, Jun Wang, Yu Cao, Wenrui Liu, Lianxiang Duan, Jing Hu, Jinghua Peng
    Journal of Medicinal Food.2024; 27(1): 1.     CrossRef
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    Ying Wei, Jiaxin Sun, Liya Su, Tunhai Xu
    Pharmacognosy Magazine.2024; 20(2): 646.     CrossRef
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    Ruidan Wang, Zhaohui Jin, Qiaoxia Zhen, Lin Qi, Cui Liu, Ping Wang, Yonghong Liu, Jinping Fang, Yanjun Liu, Yuan Su, Yixuan Wang, Detao Meng, Hongjiao Yan, Yi Zhen, Zhenzhen Li, Boyan Fang
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    Biocybernetics and Biomedical Engineering.2024; 44(1): 55.     CrossRef
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    Ewa Szczepanska-Sadowska
    International Journal of Molecular Sciences.2024; 25(2): 1310.     CrossRef
  • High-Density Lipoprotein Is Located Alongside Insulin in the Islets of Langerhans of Normal and Rodent Models of Diabetes
    Sahar Mohsin, Haba Elabadlah, Mariam K. Alotaiba, Suhail AlAmry, Shamma J. Almehairbi, Maha M. K. Harara, Aisha M. H. Almuhsin, Saeed Tariq, Frank Christopher Howarth, Ernest A. Adeghate
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    Foods.2024; 13(3): 444.     CrossRef
  • Atractylodes macrocephala Koidz. and Cuscuta chinensis Lam. extract relieves insulin resistance via PI3K/Akt signalling in diabetic Drosophila
    Yinghong Li, Ye Xu, Biwei Zhang, Zhigang Wang, Leilei Ma, Longyu Sun, Xiuping Wang, Yimin Lin, Ji-an Li, Chenxi Wu
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  • Brain insulin resistance and Alzheimer’s disease: a systematic review
    Luis Jesuino de Oliveira Andrade, Luís Matos de Oliveira, Alcina Maria Vinhaes Bittencourt, Letícia Góes de Carvalho Lourenço, Gabriela Correia Matos de Oliveira
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    Sundus Ali Dawood, Hayder Ali Lafta Mossa, Mufeeda Ali Jwad
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    Molecular and Cellular Endocrinology.2024; 586: 112195.     CrossRef
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    Diabetes, Obesity and Metabolism.2024;[Epub]     CrossRef
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    International Journal of Biological Macromolecules.2024; 265: 130961.     CrossRef
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    Frontiers in Endocrinology.2024;[Epub]     CrossRef
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    World Journal of Diabetes.2024; 15(3): 568.     CrossRef
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    European Journal of Pharmacology.2024; 971: 176529.     CrossRef
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    Xian Yang, Xudong Li, Manjiang Hu, Jie Huang, Siyan Yu, Huanting Zeng, Limei Mao
    The Journal of Nutritional Biochemistry.2024; : 109648.     CrossRef
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    Olivia Kelly, Jillian Sullivan, Natalie Carris, Samantha Geci, Athena Martinez, Varvara Liashenko, James Colvin, Emily Misko, Gary Vanderlaan, He Liu, Prasad S. Dalvi
    Brain Disorders.2024; : 100135.     CrossRef
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    Sixu Li, Feng Xiong, Songbo Zhang, Jinghua Liu, Guangping Gao, Jun Xie, Yi Wang
    Molecular Therapy - Nucleic Acids.2024; 35(2): 102184.     CrossRef
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    Samo Ribarič
    International Journal of Molecular Sciences.2024; 25(8): 4358.     CrossRef
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    Wenkai Zhang, Weifeng Huo, Huifang Hu, Tianze Li, Lijun Yuan, Jinli Zhang, Yifei Feng, Yuying Wu, Xueru Fu, Yamin Ke, Mengmeng Wang, Longkang Wang, Yaobing Chen, Yajuan Gao, Xi Li, Liang Sun, Jinyuan Pang, Zeqiang Zheng, Fulan Hu, Ming Zhang, Yu Liu, Dong
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    Open Health.2024;[Epub]     CrossRef
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    Metabolic Syndrome and Related Disorders.2023; 21(2): 109.     CrossRef
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    Najeebul Tarfeen, Khair Ul Nisa, Mir Bilal Ahmad, Ajaz Ahmad Waza, Bashir Ahmad Ganai
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Technology/Device
Current Advances of Artificial Pancreas Systems: A Comprehensive Review of the Clinical Evidence
Sun Joon Moon, Inha Jung, Cheol-Young Park
Diabetes Metab J. 2021;45(6):813-839.   Published online November 22, 2021
DOI: https://doi.org/10.4093/dmj.2021.0177
  • 14,413 View
  • 796 Download
  • 28 Web of Science
  • 28 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Since Banting and Best isolated insulin in the 1920s, dramatic progress has been made in the treatment of type 1 diabetes mellitus (T1DM). However, dose titration and timely injection to maintain optimal glycemic control are often challenging for T1DM patients and their families because they require frequent blood glucose checks. In recent years, technological advances in insulin pumps and continuous glucose monitoring systems have created paradigm shifts in T1DM care that are being extended to develop artificial pancreas systems (APSs). Numerous studies that demonstrate the superiority of glycemic control offered by APSs over those offered by conventional treatment are still being published, and rapid commercialization and use in actual practice have already begun. Given this rapid development, keeping up with the latest knowledge in an organized way is confusing for both patients and medical staff. Herein, we explore the history, clinical evidence, and current state of APSs, focusing on various development groups and the commercialization status. We also discuss APS development in groups outside the usual T1DM patients and the administration of adjunct agents, such as amylin analogues, in APSs.

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Basic Research
Mitochondrial TFAM as a Signaling Regulator between Cellular Organelles: A Perspective on Metabolic Diseases
Jin-Ho Koh, Yong-Woon Kim, Dae-Yun Seo, Tae-Seo Sohn
Diabetes Metab J. 2021;45(6):853-865.   Published online November 22, 2021
DOI: https://doi.org/10.4093/dmj.2021.0138
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  • 275 Download
  • 12 Web of Science
  • 15 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Tissues actively involved in energy metabolism are more likely to face metabolic challenges from bioenergetic substrates and are susceptible to mitochondrial dysfunction, leading to metabolic diseases. The mitochondria receive signals regarding the metabolic states in cells and transmit them to the nucleus or endoplasmic reticulum (ER) using calcium (Ca2+) for appropriate responses. Overflux of Ca2+ in the mitochondria or dysregulation of the signaling to the nucleus and ER could increase the incidence of metabolic diseases including insulin resistance and type 2 diabetes mellitus. Mitochondrial transcription factor A (Tfam) may regulate Ca2+ flux via changing the mitochondrial membrane potential and signals to other organelles such as the nucleus and ER. Since Tfam is involved in metabolic function in the mitochondria, here, we discuss the contribution of Tfam in coordinating mitochondria-ER activities for Ca2+ flux and describe the mechanisms by which Tfam affects mitochondrial Ca2+ flux in response to metabolic challenges.

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Metabolic risk/Epidemiology
Obesity, Diabetes, and Increased Cancer Progression
Dae-Seok Kim, Philipp E. Scherer
Diabetes Metab J. 2021;45(6):799-812.   Published online November 22, 2021
DOI: https://doi.org/10.4093/dmj.2021.0077
  • 14,129 View
  • 666 Download
  • 70 Web of Science
  • 76 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

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Technology/Device
Assessment of Insulin Secretion and Insulin Resistance in Human
So Young Park, Jean-François Gautier, Suk Chon
Diabetes Metab J. 2021;45(5):641-654.   Published online September 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0220
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/ sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.

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  • 15 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The year 2021 marks the 100th anniversary of the discovery of insulin, which has greatly changed the lives of people with diabetes and become a cornerstone of advances in medical science. A rapid bench-to-bedside application of the lifesaving pancreatic extract and its immediate commercialization was the result of a promising idea, positive drive, perseverance, and collaboration of Banting and colleagues. As one of the very few proteins isolated in a pure form at that time, insulin also played a key role in the development of important methodologies and in the beginning of various fields of modern science. Since its discovery, insulin has evolved continuously to optimize the care of people with diabetes. Since the 1980s, recombinant DNA technology has been employed to engineer insulin analogs by modifying their amino acid sequence, which has resulted in the production of insulins with various profiles that are currently used. However, unmet needs in insulin treatment still exist, and several forms of future insulins are under development. In this review, we discuss the past, present, and future of insulin, including a history of ceaseless innovations and collective intelligence. We believe that this story will be a solid foundation and an unerring guide for the future.

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Guideline/Fact Sheet
2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim, Sang Youl Rhee, You-Bin Lee, Sang-Man Jin, Jae Hyeon Kim, Chong Hwa Kim, Dae Jung Kim, SungWan Chun, Eun-Jung Rhee, Hyun Min Kim, Hyun Jung Kim, Donghyun Jee, Jae Hyun Kim, Won Seok Choi, Eun-Young Lee, Kun-Ho Yoon, Seung-Hyun Ko, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2021;45(4):461-481.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0156
  • 23,945 View
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

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Metabolic Risk/Epidemiology
Computed Tomography-Derived Myosteatosis and Metabolic Disorders
Iva Miljkovic, Chantal A. Vella, Matthew Allison
Diabetes Metab J. 2021;45(4):482-491.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2020.0277
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The role of ectopic adipose tissue infiltration into skeletal muscle (i.e., myosteatosis) for metabolic disorders has received considerable and increasing attention in the last 10 years. The purpose of this review was to evaluate and summarize existing studies focusing on computed tomography (CT)-derived measures of myosteatosis and metabolic disorders. There is consistent evidence that CT-derived myosteatosis contributes to dysglycemia, insulin resistance, type 2 diabetes mellitus, and inflammation, and, to some extent, dyslipidemia, independent of general obesity, visceral fat, and other relevant risk factors, suggesting that it may serve as a tool for metabolic risk prediction. Identification of which muscles should be examined, and the standardized CT protocols to be employed, are necessary to enhance the applicability of findings from epidemiologic studies of myosteatosis. Additional and longer longitudinal studies are necessary to confirm a role of myosteatosis in the development of type 2 diabetes mellitus, and examine these associations in a variety of muscles across multiple race/ethnic populations. Given the emerging role of myosteatosis in metabolic health, well-designed intervention studies are needed to investigate relevant lifestyle and pharmaceutical approaches.

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Cardiovascular Risk/Epidemiology
Management of Cardiovascular Risk in Perimenopausal Women with Diabetes
Catherine Kim
Diabetes Metab J. 2021;45(4):492-501.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2020.0262
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Cardiovascular disease is the primary cause of mortality in women and men with diabetes. Due to age and worsening of risk factors over the menopausal transition, risk of coronary heart disease events increases in postmenopausal women with diabetes. Randomized studies have conflicted regarding the beneficial impact of estrogen therapy upon intermediate cardiovascular disease markers and events. Therefore, estrogen therapy is not currently recommended for indications other than symptom management. However, for women at low risk of adverse events, estrogen therapy can be used to minimize menopausal symptoms. The risk of adverse events can be estimated using risk engines for the calculation of cardiovascular risk and breast cancer risk in conjunction with screening tools such as mammography. Use of estrogen therapy, statins, and anti-platelet agents can be guided by such calculators particularly for younger women with diabetes. Risk management remains focused upon lifestyle behaviors and achieving optimal levels of cardiovascular risk factors, including lipids, glucose, and blood pressure. Use of pharmacologic therapies to address these risk factors, particularly specific hypoglycemic agents, may provide some additional benefit for risk prevention. The minimal benefit for women with limited life expectancy and risk of complications with intensive therapy should also be considered.

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Basic Research
Brown Fat as a Regulator of Systemic Metabolism beyond Thermogenesis
Okamatsu-Ogura Yuko, Masayuki Saito
Diabetes Metab J. 2021;45(6):840-852.   Published online June 25, 2021
DOI: https://doi.org/10.4093/dmj.2020.0291
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Brown adipose tissue (BAT) is a specialized tissue for nonshivering thermogenesis to dissipate energy as heat. Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT in adult humans has dramatically promoted the translational studies on BAT in health and diseases. Moreover, several remarkable advancements have been made in brown fat biology over the past decade: The molecular and functional analyses of inducible thermogenic adipocytes (socalled beige adipocytes) arising from a developmentally different lineage from classical brown adipocytes have been accelerated. In addition to a well-established thermogenic activity of uncoupling protein 1 (UCP1), several alternative thermogenic mechanisms have been discovered, particularly in beige adipocytes. It has become clear that BAT influences other peripheral tissues and controls their functions and systemic homeostasis of energy and metabolic substrates, suggesting BAT as a metabolic regulator, other than for thermogenesis. This notion is supported by discovering that various paracrine and endocrine factors are secreted from BAT. We review the current understanding of BAT pathophysiology, particularly focusing on its role as a metabolic regulator in small rodents and also in humans.

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Drug/Regimen
Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
Diabetes Metab J. 2021;45(3):326-336.   Published online April 19, 2021
DOI: https://doi.org/10.4093/dmj.2020.0272
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Among available oral antidiabetic agents, only the thiazolidinediones (TZDs) primarily target insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ. Rosiglitazone and pioglitazone have been used widely for T2DM treatment due to their potent glycemic efficacy and low risk of hypoglycemia. However, their use has decreased because of side effects and safety issues, such as cardiovascular concerns and bladder cancer. Lobeglitazone (Chong Kun Dang Pharmaceutical Corporation), a novel TZD, was developed to meet the demands for an effective and safe TZD. Lobeglitazone shows similar glycemic efficacy to pioglitazone, with a lower effective dose, and favorable safety results. It also showed pleiotropic effects in preclinical and clinical studies. In this article, we summarize the pharmacologic, pharmacokinetic, and clinical characteristics of lobeglitazone.

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Pathophysiology
Hyperinsulinemia in Obesity, Inflammation, and Cancer
Anni M.Y. Zhang, Elizabeth A. Wellberg, Janel L. Kopp, James D. Johnson
Diabetes Metab J. 2021;45(3):285-311.   Published online March 29, 2021
DOI: https://doi.org/10.4093/dmj.2020.0250
Correction in: Diabetes Metab J 2021;45(4):622
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The relative insufficiency of insulin secretion and/or insulin action causes diabetes. However, obesity and type 2 diabetes mellitus can be associated with an absolute increase in circulating insulin, a state known as hyperinsulinemia. Studies are beginning to elucidate the cause-effect relationships between hyperinsulinemia and numerous consequences of metabolic dysfunctions. Here, we review recent evidence demonstrating that hyperinsulinemia may play a role in inflammation, aging and development of cancers. In this review, we will focus on the consequences and mechanisms of excess insulin production and action, placing recent findings that have challenged dogma in the context of the existing body of literature. Where relevant, we elaborate on the role of specific signal transduction components in the actions of insulin and consequences of chronic hyperinsulinemia. By discussing the involvement of hyperinsulinemia in various metabolic and other chronic diseases, we may identify more effective therapeutics or lifestyle interventions for preventing or treating obesity, diabetes and cancer. We also seek to identify pertinent questions that are ripe for future investigation.

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Cardiovascular Risk/Epidemiology
Diabetes Management in Patients with Heart Failure
Jia Shen, Barry H. Greenberg
Diabetes Metab J. 2021;45(2):158-172.   Published online March 25, 2021
DOI: https://doi.org/10.4093/dmj.2020.0296
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Diabetes and heart failure (HF) are common diseases, each affecting large segments of the world population. Moreover, prevalence rates for both are expected to rise dramatically over coming decades. The high prevalence rates of both diseases and wellrecognized association of diabetes as a risk factor for HF make it inevitable that both diseases co-exist in a large number of patients, complicating their management and increasing the risk of a poor outcome. Management of diabetes has been shown to impact clinical events in patients with HF and there is emerging evidence that agents used to treat diabetes can reduce HF events, even in non-diabetic patients. In this review we summarize the clinical course and treatment of patients with type 2 diabetes mellitus (T2DM) and HF and review the efficacy and safety of pharmacological agents in patients with T2DM at risk for HF and those with established disease.

Citations

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