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Most-read articles are from the articles published in 2023 during the last three month.

Reviews
Guideline/Fact Sheet
2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae Jin Kim, Hyun Min Kim, Jung Hae Ko, Nam Hoon Kim, Chong Hwa Kim, Jeeyun Ahn, Tae Jung Oh, Soo-Kyung Kim, Jaehyun Kim, Eugene Han, Sang-Man Jin, Won Suk Choi, Min Kyong Moon, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2023;47(5):575-594.   Published online September 26, 2023
DOI: https://doi.org/10.4093/dmj.2023.0282
  • 4,013 View
  • 543 Download
  • 2 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Citations

Citations to this article as recorded by  
  • 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
  • Letter by In-Kyung Jeong Regarding Article, Trends in Prevalence of Hypertriglyceridemia and Related Factors in Korean Adults: A Serial Cross-Sectional Study
    In-Kyung Jeong
    Journal of Lipid and Atherosclerosis.2024; 13(1): 80.     CrossRef
  • Association between cardiovascular disease risk and incident type 2 diabetes mellitus in individuals with prediabetes: A retrospective cohort study
    Myung Jin Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee
    Diabetes Research and Clinical Practice.2024; 208: 111125.     CrossRef
  • Korea Hypertension Fact Sheet 2023: analysis of nationwide population-based data with a particular focus on hypertension in special populations
    Hyeon Chang Kim, Hokyou Lee, Hyeok-Hee Lee, Dasom Son, Minsung Cho, Sojung Shin, Yeeun Seo, Eun-Jin kim, Song Vogue Ahn, Sun Ha Jee, Sungha Park, Hae-Young Lee, Min Ho Shin, Sang-Hyun Ihm, Seung Won Lee, Jong Ku Park, Il Suh, Tae-Yong Lee
    Clinical Hypertension.2024;[Epub]     CrossRef
  • Diabetes Duration, Cholesterol Levels, and Risk of Cardiovascular Diseases in Individuals With Type 2 Diabetes
    Mee Kyoung Kim, Kyu Na Lee, Kyungdo Han, Seung-Hwan Lee
    The Journal of Clinical Endocrinology & Metabolism.2024;[Epub]     CrossRef
  • Management of Dyslipidemia in Patients with Diabetes Mellitus
    Kyung Ae Lee
    The Journal of Korean Diabetes.2023; 24(3): 111.     CrossRef
  • 2023 Clinical Practice Guidelines for Diabetes: Recommendations for Pharmacological Treatment of Type 2 Diabetes
    Junghyun Noh
    The Journal of Korean Diabetes.2023; 24(3): 127.     CrossRef
  • 2023 Clinical Practice Guidelines for Diabetes
    Min Kyong Moon
    The Journal of Korean Diabetes.2023; 24(3): 120.     CrossRef
  • 2023 Clinical Practice Guidelines for Diabetes: Management of Cardiovascular Risk Factors
    Ye Seul Yang
    The Journal of Korean Diabetes.2023; 24(3): 135.     CrossRef
  • A 33-Year-Old Man Presented with Abdominal Pain and Vomiting Starting a Day Ago
    Jong Han Choi
    The Korean Journal of Medicine.2023; 98(6): 289.     CrossRef
  • Comorbidity Patterns and Management in Inpatients with Endocrine Diseases by Age Groups in South Korea: Nationwide Data
    Sung-Soo Kim, Hun-Sung Kim
    Journal of Personalized Medicine.2023; 14(1): 42.     CrossRef
Pathophysiology
Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance
Yajie Fan, Zhipeng Yan, Tingting Li, Aolin Li, Xinbiao Fan, Zhongwen Qi, Junping Zhang
Diabetes Metab J. 2024;48(1):19-36.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2023.0110
  • 1,603 View
  • 154 Download
AbstractAbstract PDFPubReader   ePub   
Insulin resistance has been regarded as a hallmark of diabetes heart disease (DHD). Numerous studies have shown that insulin resistance can affect blood circulation and myocardium, which indirectly cause cardiac hypertrophy and ventricular remodeling, participating in the pathogenesis of DHD. Meanwhile, hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with insulin resistance can directly impair the metabolism and function of the heart. Targeting insulin resistance is a potential therapeutic strategy for the prevention of DHD. Currently, the role of insulin resistance in the pathogenic development of DHD is still under active research, as the pathological roles involved are complex and not yet fully understood, and the related therapeutic approaches are not well developed. In this review, we describe insulin resistance and add recent advances in the major pathological and physiological changes and underlying mechanisms by which insulin resistance leads to myocardial remodeling and dysfunction in the diabetic heart, including exosomal dysfunction, ferroptosis, and epigenetic factors. In addition, we discuss potential therapeutic approaches to improve insulin resistance and accelerate the development of cardiovascular protection drugs.
Pathophysiology
Attention to Innate Circadian Rhythm and the Impact of Its Disruption on Diabetes
Da Young Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Nan Hee Kim
Diabetes Metab J. 2024;48(1):37-52.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2023.0193
  • 1,572 View
  • 189 Download
AbstractAbstract PDFPubReader   ePub   
Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian system may be a potential candidate for the prevention of diabetes. We reviewed evidence from animal, clinical, and epidemiological studies linking the circadian system to various aspects of the pathophysiology and clinical outcomes of diabetes. The circadian clock governs genetic, metabolic, hormonal, and behavioral signals in anticipation of cyclic 24-hour events through interactions between a “central clock” in the suprachiasmatic nucleus and “peripheral clocks” in the whole body. Currently, circadian rhythmicity in humans can be subjectively or objectively assessed by measuring melatonin and glucocorticoid levels, core body temperature, peripheral blood, oral mucosa, hair follicles, rest-activity cycles, sleep diaries, and circadian chronotypes. In this review, we summarized various circadian misalignments, such as altered light-dark, sleep-wake, rest-activity, fasting-feeding, shift work, evening chronotype, and social jetlag, as well as mutations in clock genes that could contribute to the development of diabetes and poor glycemic status in patients with diabetes. Targeting critical components of the circadian system could deliver potential candidates for the treatment and prevention of type 2 diabetes mellitus in the future.
Basic Research
Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases
Benyuan Zhang, Joon Young Chang, Min Hee Lee, Sang-Hyeon Ju, Hyon-Seung Yi, Minho Shong
Diabetes Metab J. 2024;48(1):1-18.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2023.0115
  • 1,538 View
  • 234 Download
AbstractAbstract PDFPubReader   ePub   
Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPRmt) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPRmt, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life.
Technology/Device
Advances in Continuous Glucose Monitoring and Integrated Devices for Management of Diabetes with Insulin-Based Therapy: Improvement in Glycemic Control
Jee Hee Yoo, Jae Hyeon Kim
Diabetes Metab J. 2023;47(1):27-41.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0271
  • 5,647 View
  • 369 Download
  • 8 Web of Science
  • 14 Crossref
AbstractAbstract PDFPubReader   ePub   
Continuous glucose monitoring (CGM) technology has evolved over the past decade with the integration of various devices including insulin pumps, connected insulin pens (CIPs), automated insulin delivery (AID) systems, and virtual platforms. CGM has shown consistent benefits in glycemic outcomes in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) treated with insulin. Moreover, the combined effect of CGM and education have been shown to improve glycemic outcomes more than CGM alone. Now a CIP is the expected future technology that does not need to be worn all day like insulin pumps and helps to calculate insulin doses with a built-in bolus calculator. Although only a few clinical trials have assessed the effectiveness of CIPs, they consistently show benefits in glycemic outcomes by reducing missed doses of insulin and improving problematic adherence. AID systems and virtual platforms made it possible to achieve target glycosylated hemoglobin in diabetes while minimizing hypoglycemia, which has always been challenging in T1DM. Now fully automatic AID systems and tools for diabetes decisions based on artificial intelligence are in development. These advances in technology could reduce the burden associated with insulin treatment for diabetes.

Citations

Citations to this article as recorded by  
  • Accuracy and Safety of the 15-Day CareSens Air Continuous Glucose Monitoring System
    Kyung-Soo Kim, Seung-Hwan Lee, Won Sang Yoo, Cheol-Young Park
    Diabetes Technology & Therapeutics.2024;[Epub]     CrossRef
  • 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 Andrade, Boyang Chen, Jae Hyeon Kim
    Diabetes Technology & Therapeutics.2024;[Epub]     CrossRef
  • Recent advances in the precision control strategy of artificial pancreas
    Wuyi Ming, Xudong Guo, Guojun Zhang, Yinxia Liu, Yongxin Wang, Hongmei Zhang, Haofang Liang, Yuan Yang
    Medical & Biological Engineering & Computing.2024;[Epub]     CrossRef
  • Glycemic Outcomes During Early Use of the MiniMed™ 780G Advanced Hybrid Closed-Loop System with Guardian™ 4 Sensor
    Toni L. Cordero, Zheng Dai, Arcelia Arrieta, Fang Niu, Melissa Vella, John Shin, Andrew S. Rhinehart, Jennifer McVean, Scott W. Lee, Robert H. Slover, Gregory P. Forlenza, Dorothy I. Shulman, Rodica Pop-Busui, James R. Thrasher, Mark S. Kipnes, Mark P. Ch
    Diabetes Technology & Therapeutics.2023; 25(9): 652.     CrossRef
  • Navigating the Seas of Glycemic Control: The Role of Continuous Glucose Monitoring in Type 1 Diabetes Mellitus
    Jun Sung Moon
    Diabetes & Metabolism Journal.2023; 47(3): 345.     CrossRef
  • APSec1.0: Innovative Security Protocol Design with Formal Security Analysis for the Artificial Pancreas System
    Jiyoon Kim, Jongmin Oh, Daehyeon Son, Hoseok Kwon, Philip Virgil Astillo, Ilsun You
    Sensors.2023; 23(12): 5501.     CrossRef
  • Advances and Development of Electronic Neural Interfaces
    Xue Jiaxiang, Liu Zhixin
    Journal of Computing and Natural Science.2023; : 147.     CrossRef
  • Continuous Glucose Monitoring (CGM) and Metabolic Control in a Cohort of Patients with Type 1 Diabetes and Coeliac Disease
    Flavia Amaro, Maria Alessandra Saltarelli, Marina Primavera, Marina Cerruto, Stefano Tumini
    Endocrines.2023; 4(3): 595.     CrossRef
  • Comparison of Glycemia Risk Index with Time in Range for Assessing Glycemic Quality
    Ji Yoon Kim, Jee Hee Yoo, Jae Hyeon Kim
    Diabetes Technology & Therapeutics.2023; 25(12): 883.     CrossRef
  • The Benefits Of Continuous Glucose Monitoring In Pregnancy
    Jee Hee Yoo, Jae Hyeon Kim
    Endocrinology and Metabolism.2023; 38(5): 472.     CrossRef
  • The Growing Challenge of Diabetes Management in an Aging Society
    Seung-Hwan Lee
    Diabetes & Metabolism Journal.2023; 47(5): 630.     CrossRef
  • Recent advances in artificial intelligence-assisted endocrinology and diabetes
    Ioannis T. Oikonomakos, Ranjit M. Anjana, Viswanathan Mohan, Charlotte Steenblock, Stefan R. Bornstein
    Exploration of Endocrine and Metabolic Disease.2023; 1(1): 16.     CrossRef
  • An Observational Pilot Study of a Tailored Environmental Monitoring and Alert System for Improved Management of Chronic Respiratory Diseases
    Mohammed Alotaibi, Fady Alnajjar, Badr A Alsayed, Tareq Alhmiedat, Ashraf M Marei, Anas Bushnag, Luqman Ali
    Journal of Multidisciplinary Healthcare.2023; Volume 16: 3799.     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
Complications
Pharmacological and Nonpharmacological Treatments for Painful Diabetic Peripheral Neuropathy
Han Na Jang, Tae Jung Oh
Diabetes Metab J. 2023;47(6):743-756.   Published online September 6, 2023
DOI: https://doi.org/10.4093/dmj.2023.0018
  • 3,211 View
  • 493 Download
  • 1 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%–25% of patients with diabetes experience neuropathic pain, referred to as “painful DPN.” Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.

Citations

Citations to this article as recorded by  
  • J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking mo
    A. Kuo, M. Z. Imam, R. Li, L. Lin, A. Raboczyj, A. E. Bohmer, J. R. Nicholson, L. Corradini, M. T. Smith
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • The Chronic Wound–Related Pain Model
    Kevin Woo
    Clinics in Geriatric Medicine.2024;[Epub]     CrossRef
Original Article
Drug/Regimen
Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus
Ji Hye Han, Kyong Hye Joung, Jun Choul Lee, Ok Soon Kim, Sorim Choung, Ji Min Kim, Yea Eun Kang, Hyon-Seung Yi, Ju Hee Lee, Bon Jeong Ku, Hyun Jin Kim
Diabetes Metab J. 2024;48(1):112-121.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2022.0402
  • 1,426 View
  • 186 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM.
Methods
A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment.
Results
The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups.
Conclusion
Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Citations

Citations to this article as recorded by  
  • Combining Ezetimibe and Rosuvastatin: Impacts on Insulin Sensitivity and Vascular Inflammation in Patients with Type 2 Diabetes Mellitus
    Eun Roh
    Diabetes & Metabolism Journal.2024; 48(1): 55.     CrossRef
Review
Lifestyle
Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies
Jakub Mesinovic, Jackson J. Fyfe, Jason Talevski, Michael J. Wheeler, Gloria K.W. Leung, Elena S. George, Melkamu T. Hunegnaw, Costas Glavas, Paul Jansons, Robin M. Daly, David Scott
Diabetes Metab J. 2023;47(6):719-742.   Published online September 14, 2023
DOI: https://doi.org/10.4093/dmj.2023.0112
  • 3,897 View
  • 419 Download
AbstractAbstract PDFPubReader   ePub   
Type 2 diabetes mellitus (T2DM) and sarcopenia (low skeletal muscle mass and function) share a bidirectional relationship. The prevalence of these diseases increases with age and they share common risk factors. Skeletal muscle fat infiltration, commonly referred to as myosteatosis, may be a major contributor to both T2DM and sarcopenia in older adults via independent effects on insulin resistance and muscle health. Many strategies to manage T2DM result in energy restriction and subsequent weight loss, and this can lead to significant declines in muscle mass in the absence of resistance exercise, which is also a first-line treatment for sarcopenia. In this review, we highlight recent evidence on established treatments and emerging therapies targeting weight loss and muscle mass and function improvements in older adults with, or at risk of, T2DM and/or sarcopenia. This includes dietary, physical activity and exercise interventions, new generation incretin-based agonists and myostatin-based antagonists, and endoscopic bariatric therapies. We also highlight how digital health technologies and health literacy interventions can increase uptake of, and adherence to, established and emerging treatments and therapies in older adults with T2DM and/or sarcopenia.
Original Articles
Basic Research
Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification
Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Diabetes Metab J. 2024;48(1):83-96.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2022.0363
  • 1,283 View
  • 152 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the cardiovascular system.
Methods
To examine the protective effects of GLP-1RAs on proliferation and migration of vascular smooth muscle cells (VSMCs), A-10 cells exposed to angiotensin II (Ang II) were treated with either exendin-4, liraglutide, or dulaglutide. To examine the effects of GLP-1RAs on vascular calcification, cells exposed to high concentration of inorganic phosphate (Pi) were treated with exendin-4, liraglutide, or dulaglutide.
Results
Ang II increased proliferation and migration of VSMCs, gene expression levels of Ang II receptors AT1 and AT2, proliferation marker of proliferation Ki-67 (Mki-67), proliferating cell nuclear antigen (Pcna), and cyclin D1 (Ccnd1), and the protein expression levels of phospho-extracellular signal-regulated kinase (p-Erk), phospho-c-JUN N-terminal kinase (p-JNK), and phospho-phosphatidylinositol 3-kinase (p-Pi3k). Exendin-4, liraglutide, and dulaglutide significantly decreased the proliferation and migration of VSMCs, the gene expression levels of Pcna, and the protein expression levels of p-Erk and p-JNK in the Ang II-treated VSMCs. Erk inhibitor PD98059 and JNK inhibitor SP600125 decreased the protein expression levels of Pcna and Ccnd1 and proliferation of VSMCs. Inhibition of GLP-1R by siRNA reversed the reduction of the protein expression levels of p-Erk and p-JNK by exendin-4, liraglutide, and dulaglutide in the Ang II-treated VSMCs. Moreover, GLP-1 (9-36) amide also decreased the proliferation and migration of the Ang II-treated VSMCs. In addition, these GLP-1RAs decreased calcium deposition by inhibiting activating transcription factor 4 (Atf4) in Pi-treated VSMCs.
Conclusion
These data show that GLP-1RAs ameliorate aberrant proliferation and migration in VSMCs through both GLP-1Rdependent and independent pathways and inhibit Pi-induced vascular calcification.
Basic Research
DWN12088, A Prolyl-tRNA Synthetase Inhibitor, Alleviates Hepatic Injury in Nonalcoholic Steatohepatitis
Dong-Keon Lee, Su Ho Jo, Eun Soo Lee, Kyung Bong Ha, Na Won Park, Deok-Hoon Kong, Sang-In Park, Joon Seok Park, Choon Hee Chung
Diabetes Metab J. 2024;48(1):97-111.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2022.0367
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Nonalcoholic steatohepatitis (NASH) is a liver disease caused by obesity that leads to hepatic lipoapoptosis, resulting in fibrosis and cirrhosis. However, the mechanism underlying NASH is largely unknown, and there is currently no effective therapeutic agent against it. DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the role of DWN12088 in NASH progression.
Methods
Mice were fed a chow diet or methionine-choline deficient (MCD)-diet, which was administered with DWN12088 or saline by oral gavage for 6 weeks. The effects of DWN12088 on NASH were evaluated by pathophysiological examinations, such as real-time quantitative reverse transcription polymerase chain reaction, immunoblotting, biochemical analysis, and immunohistochemistry. Molecular and cellular mechanisms of hepatic injury were assessed by in vitro cell culture.
Results
DWN12088 attenuated palmitic acid (PA)-induced lipid accumulation and lipoapoptosis by downregulating the Rho-kinase (ROCK)/AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and protein kinase R-like endoplasmic reticulum kinase (PERK)/α subunit of eukaryotic initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) signaling cascades. PA increased but DWN12088 inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 (Ser536, Ser276) and the expression of proinflammatory genes. Moreover, the DWN12088 inhibited transforming growth factor β (TGFβ)-induced pro-fibrotic gene expression by suppressing TGFβ receptor 1 (TGFβR1)/Smad2/3 and TGFβR1/glutamyl-prolyl-tRNA synthetase (EPRS)/signal transducer and activator of transcription 6 (STAT6) axis signaling. In the case of MCD-diet-induced NASH, DWN12088 reduced hepatic steatosis, inflammation, and lipoapoptosis and prevented the progression of fibrosis.
Conclusion
Our findings provide new insights about DWN12088, namely that it plays an important role in the overall improvement of NASH. Hence, DWN12088 shows great potential to be developed as a new integrated therapeutic agent for NASH.
Sulwon Lecture 2022
Others
Opening the Precision Diabetes Care through Digital Healthcare
Joonyub Lee, Jin Yu, Kun-Ho Yoon
Diabetes Metab J. 2023;47(3):307-314.   Published online March 29, 2023
DOI: https://doi.org/10.4093/dmj.2022.0386
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AbstractAbstract PDFPubReader   ePub   
The national healthcare systems of every country in the world cannot sustain the rise in healthcare expenditure caused by chronic diseases and their complications. To sustain the national healthcare system, a novel system should be developed to improve the quality of care and minimize healthcare costs. For 20 years, our team developed patient-communicating digital healthcare platforms and proved their efficacy. National scale randomized control trials are underway to systematically measure the efficacy and economic benefits of this digital health care system. Precision medicine aims to maximize effectiveness of disease management by considering individual variability. Digital health technologies enable precision medicine at a reasonable cost that was not available before. The government launched the “National Integrated Bio-big Data Project” which will collect diverse health data from the participants. Individuals will share their health information to physicians or researchers at their will by gateway named “My-Healthway.’ Taken together, now we stand in front of the evolution of medical care, so-called “Precision medicine.” led by various kinds of technologies and a huge amount of health information exchange. We should lead these new trends as pioneers, not as followers, to establish and implement the best care for our patients that can help them to withstand their devastating diseases.
Review
Basic Research
Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
Byung Soo Kong, Changhan Lee, Young Min Cho
Diabetes Metab J. 2023;47(3):315-324.   Published online February 24, 2023
DOI: https://doi.org/10.4093/dmj.2022.0333
  • 5,019 View
  • 262 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFPubReader   ePub   
Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.

Citations

Citations to this article as recorded by  
  • Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
    Satadeepa Kal, Sumana Mahata, Suborno Jati, Sushil K. Mahata
    Peptides.2024; 172: 171147.     CrossRef
  • Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases
    Benyuan Zhang, Joon Young Chang, Min Hee Lee, Sang-Hyeon Ju, Hyon-Seung Yi, Minho Shong
    Diabetes & Metabolism Journal.2024; 48(1): 1.     CrossRef
  • Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes
    Alejandra María Rivera Nieves, Brian Michael Wauford, Accalia Fu
    Frontiers in Molecular Biosciences.2024;[Epub]     CrossRef
Original Articles
Drug Regimen
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study
Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won
Diabetes Metab J. 2023;47(6):818-825.   Published online November 24, 2023
DOI: https://doi.org/10.4093/dmj.2023.0171
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Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.
Basic Research
A New Concept in Antidiabetic Therapeutics: A Concerted Removal of Labile Iron and Intracellular Deposition of Zinc
Vladimir Vinokur, Eduard Berenshtein, Mordechai Chevion, Dror Chevion
Diabetes Metab J. 2024;48(1):59-71.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2022.0292
Retraction in: https://doi.org/
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Drug Regimen
Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial
Kyung Ah Han, Yong Hyun Kim, Doo Man Kim, Byung Wan Lee, Suk Chon, Tae Seo Sohn, In Kyung Jeong, Eun-Gyoung Hong, Jang Won Son, Jae Jin Nah, Hwa Rang Song, Seong In Cho, Seung-Ah Cho, Kun Ho Yoon
Diabetes Metab J. 2023;47(6):796-807.   Published online February 9, 2023
DOI: https://doi.org/10.4093/dmj.2022.0315
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  • 2 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500).
Results
Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated.
Conclusion
Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials
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    Cardiovascular Diabetology.2024;[Epub]     CrossRef
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  • Navigating the Future of Diabetes Treatment with New Drugs: Focusing on the Possibilities and Prospects of Enavogliflozin
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