Diabetes & Metabolism Journal

Volume 45(6); November 2021

Reviews

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

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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.

Citations

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Hormonal Gut–Brain Signaling for the Treatment of Obesity
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Relationship Between Physical Exercise and Cognitive Impairment Among Older Adults with Type 2 Diabetes: Chain Mediating Roles of Sleep Quality and Depression
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The Function of MondoA and ChREBP Nutrient—Sensing Factors in Metabolic Disease
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Mechanism of Cephalophyllum cephalus Intervention in Diabetes Based on Network Pharmacology and Molecular Docking Technology
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Development and validation of a prognostic model based on metabolic risk score to predict overall survival of endometrial cancer in Chinese patients
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Obesity, diabetes, and cancer: epidemiology, pathophysiology, and potential interventions
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Global, Regional, and National Epidemiology of Diabetes in Children From 1990 to 2019
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The effects of physical exercise therapy on weight control: its regulation of adipocyte physiology and metabolic capacity
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The Ephrin tyrosine kinase a3 (EphA3) is a novel mediator of RAGE-prompted motility of breast cancer cells
Marianna Talia, Francesca Cirillo, Asia Spinelli, Azzurra Zicarelli, Domenica Scordamaglia, Lucia Muglia, Salvatore De Rosis, Damiano Cosimo Rigiracciolo, Gianfranco Filippelli, Ida Daniela Perrotta, Mariano Davoli, Rosanna De Rosa, Rachele Macirella, Elv
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Signal detection in real‐world data and confirmation in clinical trials: Diabetes as a case study for a conversation worth having
Elad Sharon, Megan Othus, Zoe Eloise Quandt
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Ultra-Processed Food Consumption and Obesity in Korean Adults
Jee-Seon Shim, Kyoung Hwa Ha, Dae Jung Kim, Hyeon Chang Kim
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Decoding the role of leptin and adiponectin in obesity-related gastrointestinal cancer
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Additive impact of diabetes and sarcopenia on all-cause and cardiovascular mortality: A longitudinal nationwide population-based study
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Obesity and Colorectal Cancer
Jundeok Lee, Su Young Kim
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Post-treatment serum triglyceride: An effective biomarker for body fat mass and overall survival in esophageal squamous cell cancer patients treated with chemoradiotherapy
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Research Progress of MicroRNA-122 in Obesity and Type 2 Diabetes
路路潘
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Cancer and Obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022
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Obesity Fact Sheet in Korea, 2021: Trends in Obesity Prevalence and Obesity-Related Comorbidity Incidence Stratified by Age from 2009 to 2019
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Intermittent Fasting Is Associated With a Decreased Risk of Age-Related Macular Degeneration
Eun Young Choi, Min Kim, Christopher Seungkyu Lee, Suk Ho Byeon, Sung Soo Kim, Minyoung Lee
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Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice
Chun-Jung Chen, Chih-Cheng Wu, Cheng-Yi Chang, Jian-Ri Li, Yen-Chuan Ou, Wen-Ying Chen, Su-Lan Liao, Jiaan-Der Wang
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Visceral fat area and body fat percentage measured by bioelectrical impedance analysis correlate with glycometabolism
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BMC Endocrine Disorders.2022;[Epub] CrossRef
Insight on the Role of Leptin: A Bridge from Obesity to Breast Cancer
Roberto Buonaiuto, Fabiana Napolitano, Sara Parola, Pietro De Placido, Valeria Forestieri, Giovanna Pecoraro, Alberto Servetto, Luigi Formisano, Pietro Formisano, Mario Giuliano, Grazia Arpino, Sabino De Placido, Carmine De Angelis
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Adipokines as Regulators of Autophagy in Obesity-Linked Cancer
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Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet
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Targeting Adiponectin in Breast Cancer
Rawan Nehme, Mona Diab-Assaf, Caroline Decombat, Laetitia Delort, Florence Caldefie-Chezet
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Multidisciplinary Progress in Obesity Research
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The association between serum copper and obesity and all-cause mortality: the NHANES 2011–2016
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Environmental Science and Pollution Research.2022; 30(11): 31395. CrossRef
The crosstalk within the breast tumor microenvironment in type II diabetes: Implications for cancer disparities
Christina S. Ennis, Pablo Llevenes, Yuhan Qiu, Ruben Dries, Gerald V. Denis
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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

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16 Citations

Graphical Abstract Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

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.

Citations

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100 Years of insulin: A chemical engineering perspective
B. Wayne Bequette
Korean Journal of Chemical Engineering.2023; 40(1): 1. CrossRef
Efficacy of intermittent short‐term use of a real‐time continuous glucose monitoring system in non‐insulin–treated patients with type 2 diabetes: A randomized controlled trial
Sun Joon Moon, Kyung‐Soo Kim, Woo Je Lee, Mi Yeon Lee, Robert Vigersky, Cheol‐Young Park
Diabetes, Obesity and Metabolism.2023; 25(1): 110. CrossRef
Identifiable prediction animal model for the bi-hormonal intraperitoneal artificial pancreas
Karim Davari Benam, Hasti Khoshamadi, Marte Kierulf Åm, Øyvind Stavdahl, Sebastien Gros, Anders Lyngvi Fougner
Journal of Process Control.2023; 121: 13. CrossRef
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 & Metabolism Journal.2023; 47(1): 27. CrossRef
CGM accuracy: Contrasting CE marking with the governmental controls of the USA (FDA) and Australia (TGA): A narrative review
John S Pemberton, Emma G Wilmot, Katharine Barnard‐Kelly, Lalantha Leelarathna, Nick Oliver, Tabitha Randell, Craig E Taplin, Pratik Choudhary, Peter Adolfsson
Diabetes, Obesity and Metabolism.2023; 25(4): 916. CrossRef
Evaluation of awareness and attitude of paediatric nursing students, nurses, and adolescents regarding type one diabetes advanced devices and virtual nursing
Howaida Moawad Ahmed Ali
Kontakt.2023; 25(2): 100. CrossRef
Predicting the output error of the suboptimal state estimator to improve the performance of the MPC-based artificial pancreas
Martin Dodek, Eva Miklovičová
Control Theory and Technology.2023;[Epub] CrossRef
A Markov Model of Gap Occurrence in Continuous Glucose Monitoring Data for Realistic in Silico Clinical Trials
Martina Vettoretti, Martina Drecogna, Simone Del Favero, Andrea Facchinetti, Giovanni Sparacino
Computer Methods and Programs in Biomedicine.2023; 240: 107700. CrossRef
Drug delivery breakthrough technologies – A perspective on clinical and societal impact
Beate Bittner, Manuel Sánchez-Félix, Dennis Lee, Athanas Koynov, Joshua Horvath, Felix Schumacher, Simon Matoori
Journal of Controlled Release.2023; 360: 335. CrossRef
Importance of continuous glucose monitoring in the treatment of diabetes mellitus
Sun Joon Moon, Won-Young Lee
Journal of the Korean Medical Association.2023; 66(7): 432. CrossRef
Constrained Versus Unconstrained Model Predictive Control for Artificial Pancreas
Chiara Toffanin, Lalo Magni
IEEE Transactions on Control Systems Technology.2023; 31(5): 2288. CrossRef
Intelligent Insulin vs. Artificial Intelligence for Type 1 Diabetes: Will the Real Winner Please Stand Up?
Valentina Maria Cambuli, Marco Giorgio Baroni
International Journal of Molecular Sciences.2023; 24(17): 13139. CrossRef
Novel Glycemic Index Based on Continuous Glucose Monitoring to Predict Poor Clinical Outcomes in Critically Ill Patients: A Pilot Study
Eun Yeong Ha, Seung Min Chung, Il Rae Park, Yin Young Lee, Eun Young Choi, Jun Sung Moon
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Baoqi Zeng, Hao Jia, Le Gao, Qingqing Yang, Kai Yu, Feng Sun
Diabetes, Obesity and Metabolism.2022; 24(10): 1967. CrossRef
Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Systematic Review
Alezandra Torres-Castaño, Amado Rivero-Santana, Lilisbeth Perestelo-Pérez, Andrea Duarte-Díaz, Analia Abt-Sacks, Vanesa Ramos-García, Yolanda Álvarez-Pérez, Ana M. Wäagner, Mercedes Rigla, Pedro Serrano-Aguilar
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History of insulin treatment of pediatric patients with diabetes in Korea
Jae Hyun Kim, Choong Ho Shin, Sei Won Yang
Annals of Pediatric Endocrinology & Metabolism.2021; 26(4): 237. CrossRef

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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11 Citations

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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.

Citations

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Thermogenic Brown Fat in Humans: Implications in Energy Homeostasis, Obesity and Metabolic Disorders
Masayuki Saito, Yuko Okamatsu-Ogura
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Interplay of skeletal muscle and adipose tissue: sarcopenic obesity
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White adipose tissue undergoes browning during preweaning period in association with microbiota formation in mice
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Age-Related Expression Dynamics of Uncoupling Protein 1 in Adipose Tissues of ICR Outbred Mice during Postnatal Ontogenesis
A. V. Yakunenkov, E. I. Elsukova, I. O. Natochy
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Possible roles of exercise and apelin against pregnancy complications
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Relationships between the expression of adipose genes and profiles of hospitalized dogs
Yukina Sugiyama, Fumie Shimokawa, Kazutoshi Sugiyama, Takashi Kobayashi, Yusuke Yamashita, Kei Kazama, Ken Onda, Masayuki Funaba, Masaru Murakami
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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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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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gp130 Activates Mitochondrial Dynamics for Hepatocyte Survival in a Model of Steatohepatitis
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Editorial

The Role of Carnitine Orotate Complex in Fatty Liver: Hyon-Seung Yi; Diabetes Metab J. 2021;45(6):866-867. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0272

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Original Articles

Complications
Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: Hua-Xing Huang, Liang-Lan Shen, Hai-Yan Huang, Li-Hua Zhao, Feng Xu, Dong-Mei Zhang, Xiu-Lin Zhang, Tong Chen, Xue-Qin Wang, Yan Xie, Jian-Bin Su; Diabetes Metab J. 2021;45(6):868-879. Published online March 23, 2021; DOI: https://doi.org/10.4093/dmj.2020.0149

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients.
Methods
Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUC_gla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m² and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD.
Results
Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUC_gla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUC_gla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUC_gla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUC_gla were still independently associated with DKD.
Conclusion
Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

Citations

Citations to this article as recorded by

Glucagon in type 2 diabetes: Friend or foe?
Irene Caruso, Nicola Marrano, Giuseppina Biondi, Valentina Annamaria Genchi, Rossella D'Oria, Gian Pio Sorice, Sebastio Perrini, Angelo Cignarelli, Annalisa Natalicchio, Luigi Laviola, Francesco Giorgino
Diabetes/Metabolism Research and Reviews.2023;[Epub] CrossRef

Metabolic Risk/Epidemiology
Trends and Risk Factors of Metabolic Syndrome among Korean Adolescents, 2007 to 2018: Jiun Chae, Moon Young Seo, Shin-Hye Kim, Mi Jung Park; Diabetes Metab J. 2021;45(6):880-889. Published online July 6, 2021; DOI: https://doi.org/10.4093/dmj.2020.0185

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Background
There is a lack of recent research on the changes in risk factors for metabolic syndrome (MetS) in the Asian pediatric population. We aimed to determine the 12-year trends in the prevalence of MetS and relevant lifestyle factors such as smoking, exercise, and calorie intake among Korean adolescents.
Methods
We investigated trends in MetS and lifestyle factors among 6,308 adolescents aged 12 to 18 years from the Korea National Health and Nutrition Examination Survey, 2007 to 2018.
Results
The prevalence of MetS was stable from 2007 to 2018 (1.7% to 2.2%). There were significant increases in the prevalence of central obesity (from 8.1% to 11.2%, P=0.012) and hyperglycemia (from 5.3% to 10.4%, P<0.001) and decreases in hypo-high-density lipoprotein (HDL)-cholesterolemia (from 22.4% to 14.8%, P<0.001). Total calorie intake and calorie intake from fat significantly increased (P<0.001), whereas calorie intake from carbohydrates significantly decreased (P<0.001) during the study period. The proportions of tobacco smokers and regular walkers significantly decreased from 2007 to 2018. After controlling for all covariates, total calorie intake was positively correlated with waist circumference (P<0.05). HDL-cholesterol was negatively associated with carbohydrate consumption (P<0.01) and positively associated with fat consumption (P<0.001). Regular walking and regular strength training were associated with lower waist circumference (P<0.05). Smoking was associated with lower fasting glucose levels (P<0.01).
Conclusion
Although the prevalence rate of MetS is stable among Korean adolescents, the prevalence of central obesity and hyperglycemia has increased greatly in the recent decade. Public education on proper dietary intake and lifestyle modification is required.

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Ongoing increasing trends in central precocious puberty incidence among Korean boys and girls from 2008 to 2020
Sinyoung Kang, Mi Jung Park, Jung Min Kim, Jin-Sung Yuk, Shin-Hye Kim, Jun Mori
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The association between urinary cotinine level and metabolic syndrome profiles among adolescents: findings from the Ewha Birth and growth study
Hyunjin Park, Ui-Jeong Kim, Eun Jeong Choi, Seunghee Jun, Bomi Park, Hye Ah Lee, Hae Soon Kim, Hyesook Park
BMC Public Health.2023;[Epub] CrossRef
Artificial Intelligence-Based Speech Analysis System for Medical Support
Eui-Sun Kim, Dong Jin Shin, Sung Tae Cho, Kyung Jin Chung
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The effect of hypothalamic involvement and growth hormone treatment on cardiovascular risk factors during the transition period in patients with childhood-onset craniopharyngioma
Sang Hee Park, Yun Jeong Lee, Jung-Eun Cheon, Choong Ho Shin, Hae Woon Jung, Young Ah Lee
Annals of Pediatric Endocrinology & Metabolism.2023; 28(2): 107. CrossRef
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Jung Eun Choi, Hye Ah Lee, Sung Won Park, Jung Won Lee, Ji Hyen Lee, Hyesook Park, Hae Soon Kim
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The Prevalence of Abdominal Obesity and Metabolic Syndrome in Korean Children and Adolescents
Ja Hyang Cho
Journal of Obesity & Metabolic Syndrome.2023; 32(2): 103. CrossRef
Temporal Trends of the Prevalence of Abdominal Obesity and Metabolic Syndrome in Korean Children and Adolescents between 2007 and 2020
Jieun Lee, Sung-Chan Kang, Obin Kwon, Seung-sik Hwang, Jin Soo Moon, Hyun Wook Chae, Jaehyun Kim
Journal of Obesity & Metabolic Syndrome.2023; 32(2): 170. CrossRef
Trends and Risk Factors of Metabolic Syndrome among Korean Adolescents, 2007 to 2018 (Diabetes Metab J 2021;45:880-9)
Dae Jung Kim
Diabetes & Metabolism Journal.2022; 46(2): 349. CrossRef
Trends and Risk Factors of Metabolic Syndrome among Korean Adolescents, 2007 to 2018 (Diabetes Metab J 2021;45:880-9)
Jiun Chae, Moon Young Seo, Shin-Hye Kim, Mi Jung Park
Diabetes & Metabolism Journal.2022; 46(2): 351. CrossRef
Comprehensive Understanding for Application in Korean Patients with Type 2 Diabetes Mellitus of the Consensus Statement on Carbohydrate-Restricted Diets by Korean Diabetes Association, Korean Society for the Study of Obesity, and Korean Society of Hyperte
Jong Han Choi, Jee-Hyun Kang, Suk Chon
Diabetes & Metabolism Journal.2022; 46(3): 377. CrossRef
Environmental polycyclic aromatic hydrocarbon exposure in relation to metabolic syndrome in US adults
Xue Yang, Qingping Xue, Ying Wen, Yichao Huang, Yi Wang, Gaga Mahai, Tong Yan, Yanjun Liu, Tao Rong, Yixin Wang, Da Chen, Shuqin Zeng, Chun-Xia Yang, Xiong-Fei Pan
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Commentary on "Single point insulin sensitivity estimator for predicting type 2 diabetes mellitus in obese adolescents"
Shin-Hye Kim
Annals of Pediatric Endocrinology & Metabolism.2022; 27(3): 155. CrossRef

Metabolic Risk/Epidemiology
Increased Visit-to-Visit Liver Enzyme Variability Is Associated with Incident Diabetes: A Community-Based 12-Year Prospective Cohort Study: Kyuhoon Bang, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung, You-Cheol Hwang; Diabetes Metab J. 2021;45(6):890-898. Published online March 17, 2021; DOI: https://doi.org/10.4093/dmj.2020.0208

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub Crossref - TDM: Background
Fatty liver and/or increased liver enzyme values have been reported to be associated with incident diabetes. We sought to determine whether increased visit-to-visit liver enzyme variability is associated with incident diabetes.
Methods
Study participants were recruited from the Korean Genome and Epidemiologic Study (KoGES). A total of 4,151 people aged 40 to 69 years was recruited and tested every 2 years for up to 12 years. Visit-to-visit aspartate aminotransferase (AST) and alanine aminotransferase (ALT) variability was evaluated in first the 6-year period through the use of various variability measurements: standard deviation (SD), average successive variability, coefficient of variation (CV), and variation independent of mean (VIM). Oral glucose tolerance test was performed at every visit.
Results
During the 6-year follow‐up appointments, 13.0% (538/4,151) of people developed incident diabetes. Visit-to-visit AST variability was associated with an increased risk of diabetes independent of conventional risk factors for diabetes (hazard ratio per 1-SD increment [95% confidence interval]: 1.06 [1.00 to 1.11], 1.12 [1.04 to 1.21], and 1.13 [1.04 to 1.22] for SD, CV, and VIM, respectively; all P<0.05); however, no such associations were observed in the visit-to-visit ALT variability. According to alcohol consumption status, both AST and ALT variability were independent predictors for incident diabetes in subjects with heavy alcohol consumption; however, neither AST nor ALT variability was associated with diabetes risk in subjects who did not drink alcohol heavily.
Conclusion
Visit-to-visit liver enzyme variability is an independent predictor of incident diabetes. Such association was more evident in those who consumed significant amounts of alcohol.

Genetics
The rs2304256 Polymorphism in TYK2 Gene Is Associated with Protection for Type 1 Diabetes Mellitus: Felipe Mateus Pellenz, Cristine Dieter, Guilherme Coutinho Kullmann Duarte, Luís Henrique Canani, Bianca Marmontel de Souza, Daisy Crispim; Diabetes Metab J. 2021;45(6):899-908. Published online May 24, 2021; DOI: https://doi.org/10.4093/dmj.2020.0194

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Graphical Abstract Abstract PDF PubReader ePub Crossref - TDM: Background
Tyrosine kinase 2 (TYK2) is a candidate gene for type 1 diabetes mellitus (T1DM) since it plays an important role in regulating apoptotic and pro-inflammatory pathways in pancreatic β-cells through modulation of the type I interferon signaling pathway. The rs2304256 single nucleotide polymorphism (SNP) in TYK2 gene has been associated with protection for different autoimmune diseases. However, to date, only two studies have evaluated the association between this SNP and T1DM, with discordant results. This study thus aimed to investigate the association between the TYK2 rs2304256 SNP and T1DM in a Southern Brazilian population.
Methods
This case-control study comprised 478 patients with T1DM and 518 non-diabetic subjects. The rs2304256 (C/A) SNP was genotyped by real-time polymerase chain reaction technique using TaqMan minor groove binder (MGB) probes.
Results
Genotype and allele frequencies of the rs2304256 SNP differed between T1DM patients and non-diabetic subjects (P<0.0001 and P=0.001, respectively). Furthermore, the A allele was associated with protection against T1DM under recessive (odds ratio [OR], 0.482; 95% confidence interval [CI], 0.288 to 0.806) and additive (OR, 0.470; 95% CI, 0.278 to 0.794) inheritance models, adjusting for human leukocyte antigen (HLA) DR/DQ genotypes, gender, and ethnicity.
Conclusion
The A/A genotype of TYK2 rs2304256 SNP is associated with protection against T1DM in a Southern Brazilian population.

Basic Research
Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7: Lili Kong, Hongyue Wang, Chenhao Li, Huiyan Cheng, Yan Cui, Li Liu, Ying Zhao; Diabetes Metab J. 2021;45(6):909-920. Published online June 4, 2021; DOI: https://doi.org/10.4093/dmj.2020.0168

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Background
The dietary agent sulforaphane (SFN) has been reported to reduce diabetes-induced renal fibrosis, as well as inhibit histone deacetylase (HDAC) activity. Bone morphologic protein 7 (BMP-7) has been shown to reduce renal fibrosis induced by transforming growth factor-beta1. The aim of this study was to investigate the epigenetic effect of SFN on BMP-7 expression in diabetes-induced renal fibrosis.
Methods
Streptozotocin (STZ)-induced diabetic mice and age-matched controls were subcutaneously injected with SFN or vehicle for 4 months to measure the in vivo effects of SFN on the kidneys. The human renal proximal tubular (HK11) cell line was used to mimic diabetic conditions in vitro. HK11 cells were transfected to over-express HDAC2 and treated with high glucose/palmitate (HG/Pal) to explore the epigenetic modulation of BMP-7 in SFN-mediated protection against HG/Pal-induced renal fibrosis.
Results
SFN significantly attenuated diabetes-induced renal fibrosis in vivo. Among all of the HDACs we detected, HDAC2 activity was markedly elevated in the STZ-induced diabetic kidneys and HG/Pal-treated HK11 cells. SFN inhibited the diabetes-induced increase in HDAC2 activity which was associated with histone acetylation and transcriptional activation of the BMP-7 promoter. HDAC2 over-expression reduced BMP-7 expression and abolished the SFN-mediated protection against HG/Pal-induced fibrosis in vitro.
Conclusion
Our study demonstrates that the HDAC inhibitor SFN protects against diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7.

Citations

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Critical Reviews in Food Science and Nutrition.2023; : 1. CrossRef
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Chun Ouyang, Lei Huang, Xiaoqiang Ye, Mingming Ren, Zhen Han
Experimental and Clinical Endocrinology & Diabetes.2022; 130(10): 660. CrossRef
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Jiayu Wang, Jiaxing Li, Xin Zhang, Min Zhang, Xiaopeng Hu, Hang Yin
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Mengjiao Wang, Min Chen, Rui Guo, Yangyang Ding, Haihui Zhang, Yuanqing He
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Basic Research
Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway: Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha; Diabetes Metab J. 2021;45(6):921-932. Published online February 22, 2021; DOI: https://doi.org/10.4093/dmj.2020.0187

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

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Journal of Cardiovascular Pharmacology.2023; 81(1): 4. CrossRef
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Mazen Noureddin, Manal F. Abdelmalek
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Ema Schönberger, Vjera Mihaljević, Kristina Steiner, Sandra Šarić, Tomislav Kurevija, Ljiljana Trtica Majnarić, Ines Bilić Ćurčić, Silvija Canecki-Varžić
International Journal of Environmental Research and Public Health.2023; 20(17): 6671. CrossRef
Direct cardio-protection of Dapagliflozin against obesity-related cardiomyopathy via NHE1/MAPK signaling
Ke Lin, Na Yang, Wu Luo, Jin-fu Qian, Wei-wei Zhu, Shi-ju Ye, Chen-xin Yuan, Di-yun Xu, Guang Liang, Wei-jian Huang, Pei-ren Shan
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Pleiotropic effects of SGLT2 inhibitors and heart failure outcomes
Panagiotis Theofilis, Marios Sagris, Evangelos Oikonomou, Alexios S. Antonopoulos, Gerasimos Siasos, Kostas Tsioufis, Dimitris Tousoulis
Diabetes Research and Clinical Practice.2022; 188: 109927. CrossRef
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Basic Research
Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway: Jung-Hee Hong, Moon-Kyu Lee; Diabetes Metab J. 2021;45(6):933-947. Published online August 19, 2021; DOI: https://doi.org/10.4093/dmj.2020.0223

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Graphical Abstract Abstract PDF PubReader ePub Crossref - TDM

Background
Carnitine orotate complex (Godex) has been shown to decrease glycated hemoglobin levels and improve steatosis in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. However, the mechanisms of Godex in glucose metabolism remain unclear.
Methods
Male C57BL/6J mice were divided into four groups: normal-fat diet, high-fat diet, a high-fat diet supplemented with intraperitoneal injection of (500 mg or 2,000 mg/kg/day) Godex for 8 weeks. Computed tomography, indirect calorimetry, and histological analyses including electron microscopy of the liver were performed, and biochemical profiles and oral glucose tolerance test and insulin tolerance test were undertaken. Expressions of genes in the lipid and glucose metabolism, activities of oxidative phosphorylation enzymes, carnitine acetyltransferase, pyruvate dehydrogenase, and acetyl-coenzyme A (CoA)/CoA ratio were evaluated.
Results
Godex improved insulin sensitivity and significantly decreased fasting plasma glucose, homeostatic model assessment for insulin resistance, steatosis, and gluconeogenesis, with a marked increase in fatty acid oxidation as well as better use of glucose in high-fat diet-fed mice. It preserved mitochondrial function and ultrastructure, restored oxidative phosphorylation enzyme activities, decreased acetyl-CoA/CoA ratio, and increased carnitine acetyltransferase content and pyruvate dehydrogenase activity. Carnitine acetyltransferase knockdown partially reversed the effects of Godex in liver and in vitro.
Conclusion
Godex improved insulin resistance and steatosis by regulating carnitine acetyltransferase in liver in high-fat diet-fed mice.

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Short Communication

Drug/Regimen
Dulaglutide as an Effective Replacement for Prandial Insulin in Kidney Transplant Recipients with Type 2 Diabetes Mellitus: A Retrospective Review: Hwi Seung Kim, Jiwoo Lee, Chang Hee Jung, Joong-Yeol Park, Woo Je Lee; Diabetes Metab J. 2021;45(6):948-953. Published online February 5, 2021; DOI: https://doi.org/10.4093/dmj.2020.0180

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Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], –0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P<0.001), and in basal insulin dose by 9.52 IU (95% CI, 5.80 to 3.23; P<0.001). Once-weekly dulaglutide may be an effective alternative for thrice-daily prandial insulin in KT recipients with T2DM currently receiving MDI therapy.

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Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post‐transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation
S. Elise Lawrence, Mary Moss Chandran, Jeong M. Park, Helen Sweiss, Thomas Jensen, Palak Choksi, Barrett Crowther
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Novel Drugs for the Management of Diabetes Kidney Transplant Patients: A Literature Review
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Life.2023; 13(6): 1265. CrossRef
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Luis Alberto Vigara, Florentino Villanego, Cristhian Orellana, Myriam Eady, María Gabriela Sánchez, Marta Alonso, María Belén García, José Manuel Amaro, Teresa García, Auxiliadora Mazuecos
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Brief Reports

Drug/Regimen
Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Soon-Jib Yoo, Sang-Ah Chang, Tae Seo Sohn, Hyuk-Sang Kwon, Jong Min Lee, Sungdae Moon, Pieter Proot, Päivi M Paldánius, Kun Ho Yoon; Diabetes Metab J. 2021;45(6):954-959. Published online November 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0173

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c] ≥7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.

Citations

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2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
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,
Diabetes & Metabolism Journal.2021; 45(4): 461. CrossRef

Metabolic Risk/Epidemiology
Short-Term Effects of the Internet-Based Korea Diabetes Prevention Study: 6-Month Results of a Community-Based Randomized Controlled Trial: Jin-Hee Lee, Sun-Young Lim, Seon-Ah Cha, Chan-Jung Han, Ah Reum Jung, Kook-Rye Kim, Kun-Ho Yoon, Seung-Hyun Ko; Diabetes Metab J. 2021;45(6):960-965. Published online March 17, 2021; DOI: https://doi.org/10.4093/dmj.2020.0225

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134 Download
5 Citations

Graphical Abstract Abstract PDF PubReader ePub Crossref - TDM

The aims of this study were to determine the short-term effectiveness of an internet-based lifestyle modification (LSM) program in preventing the onset of type 2 diabetes mellitus (T2DM) in prediabetes patients in community settings. A total of 415 subjects who were diagnosed with prediabetes were randomly assigned to the LSM and standard management (SM) groups. After the 6-month intervention, the LSM group had a statistically significant reduction in body weight, body mass index compared to the SM group participants. In the LSM group, blood glucose levels were significantly decreased after intervention and the clinical improvement effect was evident in the group that achieved the target weight loss of 5% or more of the initial weight for 6 months. Internet-based 6-month-intensive LSM programs conducted by public health center personnel are an effective way to provide lifestyle intervention programs and encourage maintenance of healthy behaviors in subjects with a high risk of T2DM in community settings.

Citations

Citations to this article as recorded by

U-shaped association between online information exchange and app usage frequency: a large-scale survey of China ‘s online young and middle-aged people with pre diabetes and diabetes
Hanbin Guo, Yibiao Xiao, Canlin Liao, Jiating Sun, Yanchun Xie, Yitong Zheng, Guanhua Fan
Frontiers in Endocrinology.2023;[Epub] CrossRef
Efficacy of Personalized Diabetes Self-care Using an Electronic Medical Record–Integrated Mobile App in Patients With Type 2 Diabetes: 6-Month Randomized Controlled Trial
Eun Young Lee, Seon-Ah Cha, Jae-Seung Yun, Sun-Young Lim, Jin-Hee Lee, Yu-Bae Ahn, Kun-Ho Yoon, Min Kyung Hyun, Seung-Hyun Ko
Journal of Medical Internet Research.2022; 24(7): e37430. CrossRef
Prevention of type 2 diabetes through remotely administered lifestyle programs: A systematic review
Valaree Villegas, Alisha Shah, JoAnn E. Manson, Deirdre K. Tobias
Contemporary Clinical Trials.2022; 119: 106817. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
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,
Diabetes & Metabolism Journal.2021; 45(4): 461. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Seung-Hyun Ko
The Journal of Korean Diabetes.2021; 22(4): 244. CrossRef

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