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Volume 46(3); May 2022
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Reviews
Guideline/Fact Sheet
Effect of Carbohydrate-Restricted Diets and Intermittent Fasting on Obesity, Type 2 Diabetes Mellitus, and Hypertension Management: Consensus Statement of the Korean Society for the Study of Obesity, Korean Diabetes Association, and Korean Society of Hypertension
Jong Han Choi, Yoon Jeong Cho, Hyun-Jin Kim, Seung-Hyun Ko, Suk Chon, Jee-Hyun Kang, Kyoung-Kon Kim, Eun Mi Kim, Hyun Jung Kim, Kee-Ho Song, Ga Eun Nam, Kwang Il Kim, Committee of Clinical Practice Guidelines, Korean Society for the Study of Obesity (KSSO), Committee of Clinical Practice Guidelines and Committee of Food and Nutrition, Korean Diabetes Association (KDA), Policy Committee of Korean Society of Hypertension (KSH), Policy Development Committee of National Academy of Medicine of Korea (NAMOK)
Diabetes Metab J. 2022;46(3):355-376.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0038
  • 11,006 View
  • 588 Download
  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

Citations

Citations to this article as recorded by  
  • Metabolic changes with intermittent fasting
    Maria G. Lange, Alice A. Coffey, Paul C. Coleman, Thomas M. Barber, Thijs Van Rens, Oyinlola Oyebode, Sally Abbott, Petra Hanson
    Journal of Human Nutrition and Dietetics.2024; 37(1): 256.     CrossRef
  • Papel do Jejum Intermitente e da Dieta Restrita em Carboidratos na Prevenção de Doenças Cardiovasculares em Pacientes Pré-Diabéticos
    Mohamed Khalfallah, Basma Elnagar, Shaimaa S. Soliman, Ahmad Eissa, Amany Allaithy
    Arquivos Brasileiros de Cardiologia.2023;[Epub]     CrossRef
  • Medical nutrition therapy for diabetes mellitus
    Suk Chon
    Journal of the Korean Medical Association.2023; 66(7): 421.     CrossRef
  • Euglycemic diabetic ketoacidosis development in a patient with type 2 diabetes receiving a sodium-glucose cotransporter-2 inhibitor and a carbohydrate-restricted diet
    Gwanpyo Koh, Jisun Bang, Soyeon Yoo, Sang Ah Lee
    Journal of Medicine and Life Science.2023; 20(3): 126.     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
  • The Related Metabolic Diseases and Treatments of Obesity
    Ming Yang, Shuai Liu, Chunye Zhang
    Healthcare.2022; 10(9): 1616.     CrossRef
  • Updated Meta-Analysis of Studies from 2011 to 2021 Comparing the Effectiveness of Intermittent Energy Restriction and Continuous Energy Restriction
    Kyoung-Kon Kim, Jee-Hyun Kang, Eun Mi Kim
    Journal of Obesity & Metabolic Syndrome.2022; 31(3): 230.     CrossRef
Guideline/Fact Sheet
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 Hypertension
Jong Han Choi, Jee-Hyun Kang, Suk Chon
Diabetes Metab J. 2022;46(3):377-390.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0051
  • 4,945 View
  • 249 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFPubReader   ePub   
The Joint Committee of the Korean Diabetes Association, the Korean Society for the Study of Obesity, and the Korean Society of Hypertension announced a consensus statement on carbohydrate-restricted diets and intermittent fasting, representing an emerging and popular dietary pattern. In this statement, we recommend moderately-low-carbohydrate or low-carbohydrate diets, not a very-low-carbohydrate diet, for patients with type 2 diabetes mellitus. These diets can be considered a dietary regimen to improve glycemic control and reduce body weight in adults with type 2 diabetes mellitus. This review provides the detailed results of a meta-analysis and systematic literature review on the potential harms and benefits of carbohydrate-restricted diets in patients with diabetes. We expect that this review will help experts and patients by fostering an in-depth understanding and appropriate application of carbohydrate-restricted diets in the comprehensive management of diabetes.

Citations

Citations to this article as recorded by  
  • Efficacy of convenience meal-type foods designed for diabetes in the management of metabolic syndrome based on a 3-week trial
    Do Gyeong Lee, In Gyeong Kang, Tae Seok Kim, Yun Ahn, Sang Yun Lee, Hye Jin Ahn, Yoo Kyoung Park
    Nutrition.2024; 118: 112287.     CrossRef
  • Long-Term Results of a Digital Diabetes Self-Management and Education Support Program Among Adults With Type 2 Diabetes: A Retrospective Cohort Study
    Ashley Berthoumieux, Sarah Linke, Melinda Merry, Alison Megliola, Jessie Juusola, Jenna Napoleone
    The Science of Diabetes Self-Management and Care.2024; 50(1): 19.     CrossRef
  • Medical nutrition therapy for diabetes mellitus
    Suk Chon
    Journal of the Korean Medical Association.2023; 66(7): 421.     CrossRef
Metabolic Risk/Epidemiology
Lifestyle Interventions for Non-Obese Patients Both with, and at Risk, of Non-Alcoholic Fatty Liver Disease
Xin-Lei Zhang, Ting-Yao Wang, Giovanni Targher, Christopher D. Byrne, Ming-Hua Zheng
Diabetes Metab J. 2022;46(3):391-401.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0048
  • 5,251 View
  • 274 Download
  • 9 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   ePub   
Non-alcoholic fatty liver disease occurring in non-obese subjects (the so-called non-obese NAFLD) is a highly prevalent but neglected liver condition, which is closely associated with metabolic disorders and suboptimal lifestyles. Landmark studies have shown that lifestyle interventions are potentially beneficial in decreasing the risk of developing non-obese NAFLD and in ameliorating NAFLD in non-obese individuals with pre-existing NAFLD. Lifestyle interventions usually refer to changes in eating habits and physical activity, both of which have a powerful effect on non-obese NAFLD and on risk factors for non-obese NAFLD. However, to date, patients and health-care professionals have a poor awareness and understanding of non-obese NAFLD and the beneficial effects of lifestyle interventions in this patient population. The aim of this narrative review is to briefly discuss the evidence for the effects of lifestyle changes and what changes are needed amongst medical personnel and other stakeholders in order to raise awareness of non-obese NAFLD.

Citations

Citations to this article as recorded by  
  • Triglycerides Mediate the Influence of Body Mass Index on Non-Alcoholic Fatty Liver Disease in a Non-Obese Chinese Population with Normal Low-Density Lipoprotein Cholesterol Levels
    Xixi Han, Jingwen Kong, Hemin Zhang, Yuan Zhao, Yafeng Zheng, Chao Wei
    Obesity Facts.2024; 17(2): 191.     CrossRef
  • Patients with NAFLD exhibit more advanced fibrosis in liver biopsy than patients with other chronic liver diseases
    Lydia Rohr, Peter Lemmer, Marie Henning, Andrea Tannapfel, Theodor Baars, Paul Manka, Ali Canbay, Jan-Peter Sowa
    Zeitschrift für Gastroenterologie.2023; 61(01): 29.     CrossRef
  • Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes
    Seung Min Chung, Min Kyu Kang, Jun Sung Moon, Jung Gil Park
    Endocrinology and Metabolism.2023; 38(2): 277.     CrossRef
  • An international multidisciplinary consensus statement on MAFLD and the risk of CVD
    Xiao-Dong Zhou, Giovanni Targher, Christopher D. Byrne, Virend Somers, Seung Up Kim, C. Anwar A. Chahal, Vincent Wai-Sun Wong, Jingjing Cai, Michael D. Shapiro, Mohammed Eslam, Philippe Gabriel Steg, Ki-Chul Sung, Anoop Misra, Jian-Jun Li, Carlos Brotons,
    Hepatology International.2023; 17(4): 773.     CrossRef
  • Lean or Non-obese Nonalcoholic Fatty Liver Disease Patients: Are They Really Lean?
    Eugene Han, Yong-ho Lee
    Clinical and Molecular Hepatology.2023; 29(4): 980.     CrossRef
  • Sex-Based Differences and Risk Factors for Comorbid Nonalcoholic Fatty Liver Disease in Patients with Bipolar Disorder: A Cross-Sectional Retrospective Study
    Ying Wang, Yiyi Liu, Xun Zhang, Qing Wu
    Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 3533.     CrossRef
  • Benefits of Physical Exercise as Approach to Prevention and Reversion of Non-Alcoholic Fatty Liver Disease in Children and Adolescents with Obesity
    Valeria Calcaterra, Vittoria Magenes, Matteo Vandoni, Clarissa Berardo, Luca Marin, Alice Bianchi, Erika Cordaro, Giustino Silvestro, Dario Silvestri, Vittoria Carnevale Pellino, Cristina Cereda, Gianvincenzo Zuccotti
    Children.2022; 9(8): 1174.     CrossRef
  • The effects of supplementation of probiotics, prebiotics, or synbiotics on patients with non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials
    Wenmin Xing, Wenyan Gao, Xiaoling Lv, Zhenlei Zhao, Genxiang Mao, Xiaoyan Dong, Zuyong Zhang
    Frontiers in Nutrition.2022;[Epub]     CrossRef
Sulwon Lecture 2021
Basic Research
Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c)
Tae Kwan Yoon, Chan Hee Lee, Obin Kwon, Min-Seon Kim
Diabetes Metab J. 2022;46(3):402-413.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0092
  • 5,350 View
  • 238 Download
  • 8 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
Low levels of mitochondrial stress are beneficial for organismal health and survival through a process known as mitohormesis. Mitohormetic responses occur during or after exercise and may mediate some salutary effects of exercise on metabolism. Exercise-related mitohormesis involves reactive oxygen species production, mitochondrial unfolded protein response (UPRmt), and release of mitochondria-derived peptides (MDPs). MDPs are a group of small peptides encoded by mitochondrial DNA with beneficial metabolic effects. Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise. MOTS-c expression levels increase in skeletal muscles, systemic circulation, and the hypothalamus upon exercise. Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses and by enhancing metabolic adaptation to exercise. Exogenous MOTS-c also stimulates thermogenesis in subcutaneous white adipose tissues, thereby enhancing energy expenditure and contributing to the anti-obesity effects of exercise training. This review briefly summarizes the mitohormetic mechanisms of exercise with an emphasis on MOTS-c.

Citations

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  • Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
    Satadeepa Kal, Sumana Mahata, Suborno Jati, Sushil K. Mahata
    Peptides.2024; 172: 171147.     CrossRef
  • Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging
    Se Hee Min, Gil Myoung Kang, Jae Woo Park, Min-Seon Kim
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    Jie Zhang, Yunfang Gao, Jiangwei Yan
    Metabolites.2024; 14(2): 88.     CrossRef
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    Fabiola Olivieri, Francesco Prattichizzo, Fabrizia Lattanzio, Anna Rita Bonfigli, Liana Spazzafumo
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    Yuejun Zheng, Zilin Wei, Tianhui Wang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
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    Zewei Zhang, Dongmei Chen, Kaili Du, Yaping Huang, Xingzhe Li, Quwen Li, Xiaoting Lv
    Mitochondrion.2023; 71: 76.     CrossRef
  • Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
    Byung Soo Kong, Changhan Lee, Young Min Cho
    Diabetes & Metabolism Journal.2023; 47(3): 315.     CrossRef
  • MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake—A Preliminary Study
    Remigiusz Domin, Michał Pytka, Mikołaj Żołyński, Jan Niziński, Marcin Rucinski, Przemysław Guzik, Jacek Zieliński, Marek Ruchała
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Editorial
Implication of Sex Differences in Visceral Fat for the Assessment of Incidence Risk of Type 2 Diabetes Mellitus
Sang Hyeon Ju, Hyon-Seung Yi
Diabetes Metab J. 2022;46(3):414-416.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0089
  • 2,737 View
  • 154 Download
  • 3 Web of Science
  • 3 Crossref
PDFPubReader   ePub   

Citations

Citations to this article as recorded by  
  • Prediction of high visceral adipose tissue for sex‐specific community residents in Taiwan
    Yu‐Hsuan Chang, Chin‐Sung Chang, Chieh‐Yu Liu, Yin‐Fan Chang, Shiow‐Ching Shun
    Nursing & Health Sciences.2024;[Epub]     CrossRef
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    Hiroshi Kataoka, Kosaku Nitta, Junichi Hoshino
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • The predictive significance of lipid accumulation products for future diabetes in a non-diabetic population from a gender perspective: an analysis using time-dependent receiver operating characteristics
    Jiajun Qiu, Maobin Kuang, Yang Zou, Ruijuan Yang, Qing Shangguan, Dingyang Liu, Guotai Sheng, Wei Wang
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Original Articles
Guideline/Fact Sheet
Diabetes Fact Sheet in Korea 2021
Jae Hyun Bae, Kyung-Do Han, Seung-Hyun Ko, Ye Seul Yang, Jong Han Choi, Kyung Mook Choi, Hyuk-Sang Kwon, Kyu Chang Won, on Behalf of the Committee of Media-Public Relation of the Korean Diabetes Association
Diabetes Metab J. 2022;46(3):417-426.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0106
  • 13,722 View
  • 1,655 Download
  • 76 Web of Science
  • 99 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to investigate the prevalence and management of diabetes mellitus, risk-factor control, and comorbidities among Korean adults.
Methods
We conducted a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey to assess the prevalence, treatment, risk factors, comorbidities, and self-management behaviors of diabetes mellitus from 2019 to 2020. We also analyzed data from the Korean National Health Insurance Service to evaluate the use of antidiabetic medications in people with diabetes mellitus from 2002 through 2018.
Results
Among Korean adults aged 30 years or older, the estimated prevalence of diabetes mellitus was 16.7% in 2020. From 2019 through 2020, 65.8% of adults with diabetes mellitus were aware of the disease and treated with antidiabetic medications. The percentage of adults with diabetes mellitus who achieved glycosylated hemoglobin (HbA1c) <6.5% was 24.5% despite the increased use of new antidiabetic medications. We found that adults with diabetes mellitus who achieved all three goals of HbA1c <6.5%, blood pressure (BP) <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL were 9.7%. The percentage of self-management behaviors was lower in men than women. Excess energy intake was observed in 16.7% of adults with diabetes mellitus.
Conclusion
The prevalence of diabetes mellitus among Korean adults remained high. Only 9.7% of adults with diabetes mellitus achieved all glycemic, BP, and lipid controls from 2019 to 2020. Continuous evaluation of national diabetes statistics and a national effort to increase awareness of diabetes mellitus and improve comprehensive diabetes care are needed.

Citations

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  • Weight change in patients with new‐onset type 2 diabetes mellitus and its association with remission: Comprehensive real‐world data
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    Hack-Lyoung Kim
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    Eun-Gyoung Hong, Kyung-Wan Min, Jung Soo Lim, Kyu-Jeung Ahn, Chul Woo Ahn, Jae-Myung Yu, Hye Soon Kim, Hyun Jin Kim, Won Kim, Dong Han Kim, Hak Chul Jang
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  • Analysis of dietary behavior and intake related to glycemic control in patients with type 2 diabetes aged 30 years or older in Korea: Utilizing the 8th Korea National Health and Nutrition Examination Survey (2019–2021)
    Jin-Ah Seok, Yeon-Kyung Lee
    Nutrition Research and Practice.2024; 18(2): 239.     CrossRef
  • Management of Early-Onset Type 2 Diabetes
    Jin Hwa Kim
    The Journal of Korean Diabetes.2024; 25(1): 4.     CrossRef
  • Baseline glycated albumin level and risk of type 2 diabetes mellitus in Healthy individuals: a retrospective longitudinal observation in Korea
    Kang-Su Shin, Min-Seung Park, Mi Yeon Lee, Eun Hye Cho, Hee-Yeon Woo, Hyosoon Park, Min-Jung Kwon
    Scandinavian Journal of Clinical and Laboratory Investigation.2024; : 1.     CrossRef
  • The Potential Role of Presepsin in Predicting Severe Infection in Patients with Diabetic Foot Ulcers
    Eun Yeong Ha, Il Rae Park, Seung Min Chung, Young Nam Roh, Chul Hyun Park, Tae-Gon Kim, Woong Kim, Jun Sung Moon
    Journal of Clinical Medicine.2024; 13(8): 2311.     CrossRef
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    Incheol Seo, Jin-Mo Park
    Neurological Sciences.2024;[Epub]     CrossRef
  • Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis
    Mee Kyoung Kim, Kyungdo Han, Hyuk-Sang Kwon, Soon Jib Yoo
    Endocrinology and Metabolism.2023; 38(4): 426.     CrossRef
  • Diabetes screening in South Korea: a new estimate of the number needed to screen to detect diabetes
    Kyoung Hwa Ha, Kyung Ae Lee, Kyung-Do Han, Min Kyong Moon, Dae Jung Kim
    The Korean Journal of Internal Medicine.2023; 38(1): 93.     CrossRef
  • Sex differences in the impact of diabetes mellitus on tuberculosis recurrence: a retrospective national cohort study
    Dararat Eksombatchai, Dawoon Jeong, Jeongha Mok, Doosoo Jeon, Hee-Yeon Kang, Hee Jin Kim, Hee-Sun Kim, Hongjo Choi, Young Ae Kang
    International Journal of Infectious Diseases.2023; 127: 1.     CrossRef
  • Response to Letter to the Editor From Han and Xu: “Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes”
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COVID-19
Association of Metabolic Syndrome with COVID-19 in the Republic of Korea
Woo-Hwi Jeon, Jeong-Yeon Seon, So-Youn Park, In-Hwan Oh
Diabetes Metab J. 2022;46(3):427-438.   Published online November 26, 2021
DOI: https://doi.org/10.4093/dmj.2021.0105
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AbstractAbstract PDFPubReader   ePub   
Background
Metabolic syndrome (MetS) is reportedly a crucial risk factor for coronavirus disease 2019 (COVID-19). Since the epidemiological studies that examine this association are few and include small samples, we investigated the relationship between MetS and COVID-19 severity and death using a larger sample in the Republic of Korea.
Methods
We analyzed 66,321 patients, 4,066 of whom had COVID-19. We used chi-square tests to examine patients’ characteristics. We performed logistic regression analysis to analyze differences in COVID-19 infection and clinical outcomes according to the presence of MetS.
Results
Although MetS was not significantly associated with COVID-19 risk, acquiring MetS was significantly associated with the risk of severe COVID-19 outcomes (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.34 to 2.91; P=0.001). The mortality risk was significantly higher in COVID-19 patients with MetS (OR, 1.74; 95% CI, 1.17 to 2.59; P=0.006). Patients with abnormal waist circumference were approximately 2.07 times more likely to develop severe COVID-19 (P<0.001), and high-density lipoprotein cholesterol (HDL-C) levels were significantly associated with COVID-19; the mortality risk due to COVID-19 was 1.74 times higher in men with an HDL-C level of <40 mg/dL and in women with an HDL-C level of <50 mg/dL (P=0.012).
Conclusion
COVID-19 is likely associated with severity and death in patients with MetS or in patients with MetS risk factors. Therefore, patients with MetS or those with abnormal waist circumference and HDL-C levels need to be treated with caution.

Citations

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  • Heterogeneity in familial clustering of metabolic syndrome components in the multiethnic GENNID study
    Jia Y. Wan, Deborah Goodman, Sukh Makhnoon, Trina M. Norden‐Krichmar, Baolin Wu, Karen L. Edwards
    Obesity.2024; 32(1): 176.     CrossRef
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Drug/Regimen
Comparison of Prevailing Insulin Regimens at Different Time Periods in Hospitalized Patients: A Real-World Experience from a Tertiary Hospital
Sun Joon Moon, Hun Jee Choe, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho
Diabetes Metab J. 2022;46(3):439-450.   Published online October 20, 2021
DOI: https://doi.org/10.4093/dmj.2021.0065
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Prevailing insulin regimens for glycemic control in hospitalized patients have changed over time. We aimed to determine whether the current basal-bolus insulin (BBI) regimen is superior to the previous insulin regimen, mainly comprising split-mixed insulin therapy.
Methods
This was a single tertiary center, retrospective observational study that included non-critically ill patients with type 2 diabetes mellitus who were treated with split-mixed insulin regimens from 2004 to 2007 (period 1) and with BBI from 2008 to 2018 (period 2). Patients from each period were analyzed after propensity score matching. The mean difference in glucose levels and the achievement of fasting and preprandial glycemic targets by day 6 of admission were assessed. The total daily insulin dose, incidence of hypoglycemia, and length of hospital stay were also evaluated.
Results
Among 244 patients from each period, both fasting glucose (estimated mean±standard error, 147.4±3.1 mg/dL vs. 129.4±3.2 mg/dL, P<0.001, day 6) and preprandial glucose (177.7±2.8 mg/dL vs. 152.8±2.8 mg/dL, P<0.001, day 6) were lower in period 2 than in period 1. By day 6 of hospital admission, 42.6% and 67.2% of patients achieved a preprandial glycemic target of <140 mg/dL in periods 1 and 2, respectively (relative risk, 2.00; 95% confidence interval, 1.54 to 2.59), without an increased incidence of hypoglycemia. Length of stay was shorter in period 2 (10.23±0.26 days vs. 8.70±0.26 days, P<0.001).
Conclusion
BBI improved glycemic control in a more efficacious manner than a split-mixed insulin regimen without increasing the risk of hypoglycemia in a hospital setting.
Type 1 Diabetes
Identification of Key Genes and Pathways in Peripheral Blood Mononuclear Cells of Type 1 Diabetes Mellitus by Integrated Bioinformatics Analysis
Xing Li, Mingyu Liao, Jiangheng Guan, Ling Zhou, Rufei Shen, Min Long, Jiaqing Shao
Diabetes Metab J. 2022;46(3):451-463.   Published online April 1, 2022
DOI: https://doi.org/10.4093/dmj.2021.0018
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM.
Methods
Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb).
Results
We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM.
Conclusion
These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

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  • Single-cell and transcriptomic analyses reveal the influence of diabetes on ovarian cancer
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  • Probing biological network in concurrent carcinomas and Type-2 diabetes for potential biomarker screening: An advanced computational paradigm
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Metabolic Risk/Epidemiology
Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin Yun, In-Kyung Jeong, Jin-Hye Cha, Juneyoung Lee, Ho Chan Cho, Sung Hee Choi, SungWan Chun, Hyun Jeong Jeon, Ho-Cheol Kang, Sang Soo Kim, Seung-Hyun Ko, Gwanpyo Koh, Su Kyoung Kwon, Jae Hyuk Lee, Min Kyong Moon, Junghyun Noh, Cheol-Young Park, Sungrae Kim
Diabetes Metab J. 2022;46(3):464-475.   Published online March 3, 2022
DOI: https://doi.org/10.4093/dmj.2021.0088
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines.
Methods
This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe.
Results
Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy.
Conclusion
According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.

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    Do Kyeong Song, Young Sun Hong, Yeon-Ah Sung, Hyejin Lee, Hidetaka Hamasaki
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Metabolic Risk/Epidemiology
Normalized Creatinine-to-Cystatin C Ratio and Risk of Diabetes in Middle-Aged and Older Adults: The China Health and Retirement Longitudinal Study
Shanhu Qiu, Xue Cai, Bo Xie, Yang Yuan, Zilin Sun, Tongzhi Wu
Diabetes Metab J. 2022;46(3):476-485.   Published online March 7, 2022
DOI: https://doi.org/10.4093/dmj.2021.0074
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Background
Creatinine-to-cystatin C ratio is recently suggested to be a surrogate marker for sarcopenia. However, little is known about its association with diabetes. This study aimed to fill in this gap based on a large-scale prospective cohort.
Methods
A population-based representative sample of 5,055 participants aged ≥45 years from the China Health and Retirement Longitudinal Study was enrolled between 2011 and 2012 and followed at least once during the subsequent surveys at 2013, 2015, or 2018. Creatinine-to-cystatin C ratio was calculated and normalized by body weight. Incident diabetes was ascertained by plasma glucose, glycosylated hemoglobin, self-reported history, or use of anti-diabetic drugs. Logistic regression analysis and mediation analysis were employed.
Results
During follow-up, 634 participants developed diabetes. The risk of diabetes was gradually and significantly decreased with increased normalized creatinine–cystatin C ratio. The multivariable-adjusted odds ratio for diabetes was 0.91 (95% confidence interval, 0.83 to 0.99) per 1 standard deviation higher of normalized creatinine-to-cystatin C ratio, and this relationship remained significant after controlling for muscle strength. The risk reduction in diabetes was significantly larger in participants with normal-weight and high normalized creatinine-to-cystatin C ratio compared with those with overweight/obesity and high normalized creatinine-to-cystatin C ratio (Pinteraction=0.01). Insulin resistance and inflammation appeared to be key mediators accounting for the observed relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes, with their mediating effect being 93.1% and 22.0%, respectively.
Conclusion
High normalized creatinine-to-cystatin C ratio is associated with reduced risk of diabetes in middle-aged and older adults.

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    Shanhu Qiu, Xue Cai, Xiaoying Zhou, Jinshui Xu, Zilin Sun, Haijian Guo, Tongzhi Wu
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    Yun-Yun He, Mei-Ling Jin, Jing Chang, Xiao-Juan Wang
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    Eyun Song, Soon Young Hwang, Min Jeong Park, Ahreum Jang, Kyeong Jin Kim, Ji Hee Yu, Nam Hoon Kim, Hye Jin Yoo, Ji A. Seo, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Kyung Mook Choi
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Metabolic Risk/Epidemiology
Sex Differences of Visceral Fat Area and Visceral-to-Subcutaneous Fat Ratio for the Risk of Incident Type 2 Diabetes Mellitus
Eun Hee Kim, Hong-Kyu Kim, Min Jung Lee, Sung-Jin Bae, Jaewon Choe, Chang Hee Jung, Chul-Hee Kim, Joong-Yeol Park, Woo Je Lee
Diabetes Metab J. 2022;46(3):486-498.   Published online November 18, 2021
DOI: https://doi.org/10.4093/dmj.2021.0095
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to determine the optimal cut-off values of visceral fat area (VFA) and visceral-to-subcutaneous fat ratio (VSR) for predicting incident type 2 diabetes mellitus (T2DM).
Methods
A total of 10,882 individuals (6,835 men; 4,047 women) free of T2DM at baseline aged between 30 and 79 years who underwent abdominal computed tomography scan between 2012 and 2013 as a part of routine health check-ups were included and followed. VFA, subcutaneous fat area, and VSR on L3 vertebral level were measured at baseline.
Results
During a median follow-up of 4.8 years, 730 (8.1% for men; 4.3% for women) incident cases of T2DM were identified. Receiver operating characteristic curve analysis showed that the optimal cut-off values of VFA and VSR for predicting incident T2DM were 130.03 cm2 and 1.08 in men, respectively, and 85.7 cm2 and 0.48 in women, respectively. Regardless of sex, higher VFA and VSR were significantly associated with a higher risk of incident T2DM. Compared with the lowest quartiles of VFA and VSR, the highest quartiles had adjusted odds ratios of 2.62 (95% confidence interval [CI], 1.73 to 3.97) and 1.55 (95% CI, 1.14 to 2.11) in men, respectively, and 32.49 (95% CI, 7.42 to 142.02) and 11.07 (95% CI, 3.89 to 31.50) in women, respectively.
Conclusion
Higher VFA and VSR at baseline were independent risk factors for the development of T2DM. Sex-specific reference values for visceral fat obesity (VFA ≥130 cm2 or VSR ≥1.0 in men; VFA ≥85 cm2 or VSR ≥0.5 in women) are proposed for the prediction of incident T2DM.

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Short Communications
Metabolic Risk/Epidemiology
Influence of Pre-Pregnancy Underweight Body Mass Index on Fetal Abdominal Circumference, Estimated Weight, and Pregnancy Outcomes in Gestational Diabetes Mellitus
Minji Kim, Kyu-Yeon Hur, Suk-Joo Choi, Soo-Young Oh, Cheong-Rae Roh
Diabetes Metab J. 2022;46(3):499-505.   Published online January 24, 2022
DOI: https://doi.org/10.4093/dmj.2021.0059
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
This study aimed to determine the influence of pre-pregnancy body mass index on pregnancy outcomes in gestational diabetes mellitus (GDM), comparing underweight patients with GDM with normal weight patients with GDM. Maternal baseline characteristics, ultrasonographic results, and pregnancy and neonatal outcomes were reviewed in 946 women with GDM with singleton pregnancies. Underweight patients with GDM showed a benign course in most aspects during pregnancy, except for developing a higher risk of giving birth to small for gestational age neonates. Underweight women with GDM required less insulin treatment, had a higher rate of vaginal delivery, and had a lower rate of cesarean delivery. In addition, their neonates were more likely to have fetal abdominal circumference and estimated fetal weight below the 10th percentile both at the time of GDM diagnosis and before delivery. Notably, their risk for preeclampsia and macrosomia were lower. Collectively, our data suggest that underweight women with GDM may require a different approach in terms of diagnosis and management throughout their pregnancy.

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Basic Research
GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells
Joo Won Kim, Eun Roh, Kyung Mook Choi, Hye Jin Yoo, Hwan-Jin Hwang, Sei Hyun Baik
Diabetes Metab J. 2022;46(3):506-511.   Published online January 24, 2022
DOI: https://doi.org/10.4093/dmj.2021.0092
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AbstractAbstract PDFPubReader   ePub   
Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB activation. LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium.

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Letter
Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus (Diabetes Metab J 2022;46:93-103)
Gyuri Kim
Diabetes Metab J. 2022;46(3):512-514.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0134
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