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Brief Reports
Type 1 Diabetes
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In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors
Seung-Ah Lee, Subin Kim, Seog-Young Kim, Jong Yoen Park, Hye Seung Jung, Sung Soo Chung, Kyong Soo Park
Received April 2, 2024  Accepted June 17, 2024  Published online October 24, 2024  
DOI: https://doi.org/10.4093/dmj.2024.0174    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Four soluble factors—putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102—were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45–55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.
Genetics
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Clinical Characteristics of Diabetes in People with Mitochondrial DNA 3243A>G Mutation in Korea
Eun Hoo Rho, Sang Ik Baek, Heerah Lee, Moon-Woo Seong, Jong-Hee Chae, Kyong Soo Park, Soo Heon Kwak
Diabetes Metab J. 2024;48(3):482-486.   Published online February 1, 2024
DOI: https://doi.org/10.4093/dmj.2023.0078
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  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Maternally inherited diabetes and deafness (MIDD) is a rare mitochondrial disorder primarily resulting from m.3243A>G mutation. The clinical characteristics of MIDD exhibit significant heterogeneity. Our study aims to delineate these characteristics and determine the potential correlation with m.3243A>G heteroplasmy levels. This retrospective, descriptive study encompassed patients with confirmed m.3243A>G mutation and diabetes mellitus at Seoul National University Hospital. Our cohort comprises 40 patients with MIDD, with a mean age at study enrollment of 33.3±12.9 years and an average % of heteroplasmy of 30.0%± 14.6% in the peripheral blood. The most prevalent comorbidity was hearing loss (90%), followed by albuminuria (61%), seizure (38%), and stroke (33%). We observed a significant negative correlation between % of heteroplasmy and age at diabetes diagnosis. These clinical features can aid in the suspicion of MIDD and further consideration of genetic testing for m.3243A>G mutation.

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  • Clinical Characteristics of Diabetes in People with Mitochondrial DNA 3243A>G Mutation in Korea (Diabetes Metab J 2024;48:482-6)
    Eun Hoo Rho, Soo Heon Kwak
    Diabetes & Metabolism Journal.2024; 48(4): 818.     CrossRef
  • MIDD Patients Should Not Be Confused with MELAS Patients, Even Though Both Carry the m.3243A>G Variant
    Josef Finsterer, Sounira Mehri
    Diabetes & Metabolism Journal.2024; 48(4): 816.     CrossRef
Original Articles
Basic Research
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Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner
Seoil Moon, Ji Yoon Lim, Mirang Lee, Youngmin Han, Hongbeom Kim, Wooil Kwon, Jin-Young Jang, Mi Na Kim, Kyong Soo Park, Hye Seung Jung
Diabetes Metab J. 2024;48(2):231-241.   Published online September 6, 2023
DOI: https://doi.org/10.4093/dmj.2022.0366
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it.
Methods
Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy.
Results
PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion.
Conclusion
This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.

Citations

Citations to this article as recorded by  
  • Genetic knock-in of EIF2AK3 variants reveals differences in PERK activity in mouse liver and pancreas under endoplasmic reticulum stress
    Shivesh Ghura, Noah R. Beratan, Xinglong Shi, Elena Alvarez-Periel, Sarah E. Bond Newton, Cagla Akay-Espinoza, Kelly L. Jordan-Sciutto
    Scientific Reports.2024;[Epub]     CrossRef
  • Pancreatic β-Cells, Diabetes and Autophagy
    Yang Ou, Yan-Li Zhao, Heng Su
    Endocrine Research.2024; : 1.     CrossRef
Basic Research
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Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes
Praise Chanmee Kim, Ji Seon Lee, Sung Soo Chung, Kyong Soo Park
Diabetes Metab J. 2023;47(3):382-393.   Published online March 6, 2023
DOI: https://doi.org/10.4093/dmj.2022.0156
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  • 1 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Leptin is a 16-kDa fat-derived hormone with a primary role in controlling adipose tissue levels. Leptin increases fatty acid oxidation (FAO) acutely through adenosine monophosphate-activated protein kinase (AMPK) and on delay through the SUMO-specific protease 2 (SENP2)–peroxisome proliferator-activated receptor δ/γ (PPARδ/γ) pathway in skeletal muscle. Leptin also directly increases FAO and decreases lipogenesis in adipocytes; however, the mechanism behind these effects remains unknown. Here, we investigated the role of SENP2 in the regulation of fatty acid metabolism by leptin in adipocytes and white adipose tissues.
Methods
The effects of leptin mediated by SENP2 on fatty acid metabolism were tested by siRNA-mediated knockdown in 3T3-L1 adipocytes. The role of SENP2 was confirmed in vivo using adipocyte-specific Senp2 knockout (Senp2-aKO) mice. We revealed the molecular mechanism involved in the leptin-induced transcriptional regulation of carnitine palmitoyl transferase 1b (Cpt1b) and long-chain acyl-coenzyme A synthetase 1 (Acsl1) using transfection/reporter assays and chromatin immunoprecipitation.
Results
SENP2 mediated the increased expression of FAO-associated enzymes, CPT1b and ACSL1, which peaked 24 hours after leptin treatment in adipocytes. In contrast, leptin stimulated FAO through AMPK during the initial several hours after treatment. In white adipose tissues, FAO and mRNA levels of Cpt1b and Acsl1 were increased by 2-fold 24 hours after leptin injection in control mice but not in Senp2-aKO mice. Leptin increased PPARα binding to the Cpt1b and Acsl1 promoters in adipocytes through SENP2.
Conclusion
These results suggest that the SENP2-PPARα pathway plays an important role in leptin-induced FAO in white adipocytes.

Citations

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  • Intermittent cold stimulation affects energy metabolism and improves stress resistance in broiler heart
    Tingting Li, Haidong Wei, Shijie Zhang, Xiaotao Liu, Lu Xing, Yuanyuan Liu, Rixin Gong, Jianhong Li
    Poultry Science.2024; 103(1): 103190.     CrossRef
Genetics
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Genome-Wide Association Study on Longitudinal Change in Fasting Plasma Glucose in Korean Population
Heejin Jin, Soo Heon Kwak, Ji Won Yoon, Sanghun Lee, Kyong Soo Park, Sungho Won, Nam H. Cho
Diabetes Metab J. 2023;47(2):255-266.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0375
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Genome-wide association studies (GWAS) on type 2 diabetes mellitus (T2DM) have identified more than 400 distinct genetic loci associated with diabetes and nearly 120 loci for fasting plasma glucose (FPG) and fasting insulin level to date. However, genetic risk factors for the longitudinal deterioration of FPG have not been thoroughly evaluated. We aimed to identify genetic variants associated with longitudinal change of FPG over time.
Methods
We used two prospective cohorts in Korean population, which included a total of 10,528 individuals without T2DM. GWAS of repeated measure of FPG using linear mixed model was performed to investigate the interaction of genetic variants and time, and meta-analysis was conducted. Genome-wide complex trait analysis was used for heritability calculation. In addition, expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression project.
Results
A small portion (4%) of the genome-wide single nucleotide polymorphism (SNP) interaction with time explained the total phenotypic variance of longitudinal change in FPG. A total of four known genetic variants of FPG were associated with repeated measure of FPG levels. One SNP (rs11187850) showed a genome-wide significant association for genetic interaction with time. The variant is an eQTL for NOC3 like DNA replication regulator (NOC3L) gene in pancreas and adipose tissue. Furthermore, NOC3L is also differentially expressed in pancreatic β-cells between subjects with or without T2DM. However, this variant was not associated with increased risk of T2DM nor elevated FPG level.
Conclusion
We identified rs11187850, which is an eQTL of NOC3L, to be associated with longitudinal change of FPG in Korean population.

Citations

Citations to this article as recorded by  
  • Unraveling the understudied influence of a lead variant in the 9p21 locus on the atherogenic index among type 2 diabetes patients with coronary artery disease
    Mahsa Naserian, Ahad Alizadeh, Mani Nosrati, Abdolkarim Mahrooz
    Journal of Diabetes & Metabolic Disorders.2024;[Epub]     CrossRef
  • Abdominal aortic aneurysm and cardiometabolic traits share strong genetic susceptibility to lipid metabolism and inflammation
    Shufen Zheng, Philip S. Tsao, Cuiping Pan
    Nature Communications.2024;[Epub]     CrossRef
Drug/Regimen
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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.
Drug/Regimen
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Efficacy and Safety of Self-Titration Algorithms of Insulin Glargine 300 units/mL in Individuals with Uncontrolled Type 2 Diabetes Mellitus (The Korean TITRATION Study): A Randomized Controlled Trial
Jae Hyun Bae, Chang Ho Ahn, Ye Seul Yang, Sun Joon Moon, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho
Diabetes Metab J. 2022;46(1):71-80.   Published online June 16, 2021
DOI: https://doi.org/10.4093/dmj.2020.0274
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  • 4 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM).
Methods
In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without noct urnal hypoglycemia at week 12.
Results
Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014).
Conclusion
The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).

Citations

Citations to this article as recorded by  
  • Time for Using Machine Learning for Dose Guidance in Titration of People With Type 2 Diabetes? A Systematic Review of Basal Insulin Dose Guidance
    Camilla Heisel Nyholm Thomsen, Stine Hangaard, Thomas Kronborg, Peter Vestergaard, Ole Hejlesen, Morten Hasselstrøm Jensen
    Journal of Diabetes Science and Technology.2024; 18(5): 1185.     CrossRef
  • Comparative efficacy and safety of weekly tirzepatide versus weekly insulin in type 2 diabetes: A network meta‐analysis of randomized clinical trials
    Hazem Ayesh, Sajida Suhail, Suhail Ayesh, Kevin Niswender
    Diabetes, Obesity and Metabolism.2024; 26(9): 3801.     CrossRef
  • Basal insulin titration algorithms in patients with type 2 diabetes: the simplest is the best (?)
    V.I. Katerenchuk
    INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2023; 19(1): 72.     CrossRef
  • Issues of insulin therapy for type 2 diabetes and ways to solve them
    V.I. Katerenchuk, A.V. Katerenchuk
    INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2023; 19(3): 240.     CrossRef
Reviews
Genetics
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Update on Monogenic Diabetes in Korea
Ye Seul Yang, Soo Heon Kwak, Kyong Soo Park
Diabetes Metab J. 2020;44(5):627-639.   Published online October 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0214
  • 7,545 View
  • 263 Download
  • 11 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   ePub   
Monogenic diabetes, including maturity-onset diabetes of the young, neonatal diabetes, and other rare forms of diabetes, results from a single gene mutation. It has been estimated to represent around 1% to 6% of all diabetes. With the advances in genome sequencing technology, it is possible to diagnose more monogenic diabetes cases than ever before. In Korea, 11 studies have identified several monogenic diabetes cases, using Sanger sequencing and whole exome sequencing since 2001. The recent largest study, using targeted exome panel sequencing, found a molecular diagnosis rate of 21.1% for monogenic diabetes in clinically suspected patients. Mutations in glucokinase (GCK), hepatocyte nuclear factor 1α (HNF1A), and HNF4A were most commonly found. Genetic diagnosis of monogenic diabetes is important as it determines the therapeutic approach required for patients and helps to identify affected family members. However, there are still many challenges, which include a lack of simple clinical criterion for selecting patients for genetic testing, difficulties in interpreting the genetic test results, and high costs for genetic testing. In this review, we will discuss the latest updates on monogenic diabetes in Korea, and suggest an algorithm to screen patients for genetic testing. The genetic tests and non-genetic markers for accurate diagnosis of monogenic diabetes will be also reviewed.

Citations

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  • Targeted gene panel analysis of Japanese patients with maturity‐onset diabetes of the young‐like diabetes mellitus: Roles of inactivating variants in the ABCC8 and insulin resistance genes
    Tohru Yorifuji, Yoh Watanabe, Kana Kitayama, Yuki Yamada, Shinji Higuchi, Jun Mori, Masaru Kato, Toru Takahashi, Tokuko Okuda, Takane Aoyama
    Journal of Diabetes Investigation.2023; 14(3): 387.     CrossRef
  • Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort
    Hyejin Jung, Tiana Won, Ga-Yeon Kim, Jowon Jang, Sujung Yeo, Sabina Lim
    Journal of Integrative Medicine.2023; 21(2): 176.     CrossRef
  • Identification of rare variants in candidate genes associated with monogenic diabetes in polish mody-x patients
    Paulina Jakiel, K. Gadzalska, E. Juścińska, M. Gorządek, T. Płoszaj, S. Skoczylas, M. Borowiec, A. Zmysłowska
    Journal of Diabetes & Metabolic Disorders.2023; 23(1): 545.     CrossRef
  • Genetic perspectives on childhood monogenic diabetes: Diagnosis, management, and future directions
    Hong-Yan Sun, Xiao-Yan Lin
    World Journal of Diabetes.2023; 14(12): 1738.     CrossRef
  • Maturity-Onset Diabetes of the Young (MODY)
    Seung Shin Park, Soo Heon Kwak
    The Journal of Korean Diabetes.2022; 23(3): 157.     CrossRef
  • The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
    Asma A. Elashi, Salman M. Toor, Ilhame Diboun, Yasser Al-Sarraj, Shahrad Taheri, Karsten Suhre, Abdul Badi Abou-Samra, Omar M. E. Albagha
    International Journal of Molecular Sciences.2022; 24(1): 130.     CrossRef
  • Age at Diagnosis and the Risk of Diabetic Nephropathy in Young Patients with Type 1 Diabetes Mellitus (Diabetes Metab J 2021;45:46-54)
    Ye Seul Yang, Tae Seo Sohn
    Diabetes & Metabolism Journal.2021; 45(2): 277.     CrossRef
  • Sequencing Cell-free Fetal DNA in Pregnant Women With GCK-MODY
    Soo Heon Kwak, Camille E Powe, Se Song Jang, Michael J Callahan, Sarah N Bernstein, Seung Mi Lee, Sunyoung Kang, Kyong Soo Park, Hak C Jang, Jose C Florez, Jong-Il Kim, Jong Hee Chae
    The Journal of Clinical Endocrinology & Metabolism.2021; 106(9): 2678.     CrossRef
  • Muscle strength, an independent determinant of glycemic control in older adults with long-standing type 2 diabetes: a prospective cohort study
    Bo Kyung Koo, Seoil Moon, Min Kyong Moon
    BMC Geriatrics.2021;[Epub]     CrossRef
  • A rare, likely pathogenic GCK variant related to maturity-onset diabetes of the young type 2: A case report
    Min-Kyung So, Jungwon Huh, Hae Soon Kim
    Journal of Genetic Medicine.2021; 18(2): 132.     CrossRef
Clinical Care/Education
Article image
2019 Clinical Practice Guidelines for Type 2 Diabetes Mellitus in Korea
Mee Kyoung Kim, Seung-Hyun Ko, Bo-Yeon Kim, Eun Seok Kang, Junghyun Noh, Soo-Kyung Kim, Seok-O Park, Kyu Yeon Hur, Suk Chon, Min Kyong Moon, Nan-Hee Kim, Sang Yong Kim, Sang Youl Rhee, Kang-Woo Lee, Jae Hyeon Kim, Eun-Jung Rhee, SungWan Chun, Sung Hoon Yu, Dae Jung Kim, Hyuk-Sang Kwon, Kyong Soo Park
Diabetes Metab J. 2019;43(4):398-406.   Published online August 20, 2019
DOI: https://doi.org/10.4093/dmj.2019.0137
  • 18,594 View
  • 504 Download
  • 166 Web of Science
  • 173 Crossref
AbstractAbstract PDFPubReader   

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.

Citations

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  • Serum-based ATR-FTIR spectroscopy combined with multivariate analysis for the diagnosis of pre-diabetes and diabetes
    Weiyi Pang, Yu Xing, Camilo L. M. Morais, Qiufeng Lao, Shengle Li, Zipeng Qiao, You Li, Maneesh N. Singh, Valério G. Barauna, Francis L. Martin, Zhiyong Zhang
    The Analyst.2024; 149(2): 497.     CrossRef
  • Fruits and the Risk of Type 2 Diabetes: The Korean Genome and Epidemiology Study Cohort
    Hojun Yu, Cheol Min Lee, Seung-Won Oh
    Korean Journal of Family Medicine.2024; 45(1): 44.     CrossRef
  • Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Added to Dual or Triple Treatment in Patients with Type 2 Diabetes Mellitus
    Yesol Hong, Yoomin Jeon, Yoona Choi, Tae Kyu Chung, Howard Lee
    Diabetes Therapy.2024; 15(2): 487.     CrossRef
  • Risk factors for carotid plaque formation in type 2 diabetes mellitus
    Jin Chen, Wenwen Li, Jingzhu Cao, Yuhan Lu, Chaoqun Wang, Jin Lu
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study
    Byeong Yun Ahn, Bokyung Kim, Sanghyun Park, Sang Gyun Kim, Kyungdo Han, Soo‐Jeong Cho
    Cancer.2024; 130(10): 1807.     CrossRef
  • Effects of a Health Partnership Program Using Mobile Health Application for Male Workers with Cardiovascular Risk Factors in Small and Medium Enterprises: A Randomized Controlled Trial
    Eun Jin Kim, Seon Young Hwang
    Journal of Korean Academy of Nursing.2024; 54(1): 44.     CrossRef
  • The clinical relevance of a polygenic risk score for type 2 diabetes mellitus in the Korean population
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    Scientific Reports.2024;[Epub]     CrossRef
  • Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300 Units/mL in Insulin-Naïve Korean People with Type 2 Diabetes: TOBE Study
    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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  • 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
  • Health and Productivity Benefits with Early Intensified Treatment in Patients with Type 2 Diabetes: Results from Korea
    Foteini Tsotra, Ankur Malhotra, Platon Peristeris, Ioannis Athanasiou, Malina Müller, Giovanni Bader
    INQUIRY: The Journal of Health Care Organization, Provision, and Financing.2024;[Epub]     CrossRef
  • Bile acids, fibroblast growth factor-19, and glucagon-like peptide-1 levels in the long term after bariatric surgery
    Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Hyun Baek, Ki-Ho Song
    Asian Journal of Surgery.2024;[Epub]     CrossRef
  • Safety of sodium–glucose cotransporter 2 inhibitors in Asian type 2 diabetes populations
    Jaime A Davidson, Norlela Sukor, Fen‐Lee Hew, Mafauzy Mohamed, Zanariah Hussein
    Journal of Diabetes Investigation.2023; 14(2): 167.     CrossRef
  • β-hydroxybutyrate as a biomarker of β-cell function in new-onset type 2 diabetes and its association with treatment response at 6 months
    Minyoung Lee, Yongin Cho, Yong-ho Lee, Eun Seok Kang, Bong-soo Cha, Byung-Wan Lee
    Diabetes & Metabolism.2023; 49(4): 101427.     CrossRef
  • Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
    Journal of Lipid and Atherosclerosis.2023; 12(1): 12.     CrossRef
  • Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
    Diabetes & Metabolism Journal.2023; 47(1): 1.     CrossRef
  • Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus
    Min Kyong Moon, Junghyun Noh, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong
    Diabetes & Metabolism Journal.2023; 47(1): 45.     CrossRef
  • Impaired ketogenesis is associated with metabolic-associated fatty liver disease in subjects with type 2 diabetes
    Sejeong Lee, Jaehyun Bae, Doo Ri Jo, Minyoung Lee, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Identifying the Associations of Nightly Fasting Duration and Meal Timing with Type 2 Diabetes Mellitus Using Data from the 2016–2020 Korea National Health and Nutrition Survey
    Junkyung Kwak, Kyeong-A Jang, Haeng-Ran Kim, Min-Sook Kang, Kyung Won Lee, Dayeon Shin
    Nutrients.2023; 15(6): 1385.     CrossRef
  • Development and Adaptability of Smartphone-based Dietary Coaching Program for Patients Undergoing Diabetes and Prediabetes with Continuous Glucose Monitoring Device
    Myoung Soo Kim, Jung Mi Ryu, Minkyeong Kang, Jiwon Park, Yeh Chan Ahn, Yang Seok Kim
    Journal of Health Informatics and Statistics.2023; 48(1): 36.     CrossRef
  • Glucose Control in Korean Patients with Type 2 Diabetes Mellitus according to Body Mass Index
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    Journal of Obesity & Metabolic Syndrome.2023; 32(1): 55.     CrossRef
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Original Articles
Epidemiology
Article image
Diabetes Fact Sheets in Korea, 2018: An Appraisal of Current Status
Bo-Yeon Kim, Jong Chul Won, Jae Hyuk Lee, Hun-Sung Kim, Jung Hwan Park, Kyoung Hwa Ha, Kyu Chang Won, Dae Jung Kim, Kyong Soo Park
Diabetes Metab J. 2019;43(4):487-494.   Published online July 17, 2019
DOI: https://doi.org/10.4093/dmj.2019.0067
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AbstractAbstract PDFPubReader   
Background

The objective of this study was to investigate the prevalence, management, and comorbidities of diabetes among Korean adults aged 30 years and older.

Methods

This study used 2013 to 2016 data from the Korea National Health and Nutrition Examination Survey, a nationally-representative survey of the Korean population. Diabetes was defined as fasting glucose ≥126 mg/dL, current use of antidiabetic medication, a previous history of diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%.

Results

In 2016, 14.4% (approximately 5.02 million) of Korean adults had diabetes. The prevalence of impaired fasting glucose was 25.3% (8.71 million). From 2013 to 2016, the awareness, control, and treatment rates for diabetes were 62.6%, 56.7%, and 25.1%, respectively. People with diabetes had the following comorbidities: obesity (50.4%), abdominal obesity (47.8%), hypertension (55.3%), and hypercholesterolemia (34.9%). The 25.1%, 68.4%, and 44.2% of people with diabetes achieved HbA1c <6.5%, blood pressure <140/85 mm Hg, and low density lipoprotein cholesterol <100 mg/dL. Only 8.4% of people with diabetes had good control of all three targets.

Conclusion

This study confirms that diabetes is as an important public health problem. Efforts should be made to increase awareness, detection, and comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

Citations

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Pathophysiology
Metformin Ameliorates Lipotoxic β-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action
Hong Il Kim, Ji Seon Lee, Byung Kook Kwak, Won Min Hwang, Min Joo Kim, Young-Bum Kim, Sung Soo Chung, Kyong Soo Park
Diabetes Metab J. 2019;43(6):854-866.   Published online June 27, 2019
DOI: https://doi.org/10.4093/dmj.2018.0179
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AbstractAbstract PDFPubReader   
Background

Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.

Methods

NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.

Results

We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.

Conclusion

This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.

Citations

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Clinical Diabetes & Therapeutics
Progression to Gestational Diabetes Mellitus in Pregnant Women with One Abnormal Value in Repeated Oral Glucose Tolerance Tests
Sunyoung Kang, Min Hyoung Kim, Moon Young Kim, Joon-Seok Hong, Soo Heon Kwak, Sung Hee Choi, Soo Lim, Kyong Soo Park, Hak C. Jang
Diabetes Metab J. 2019;43(5):607-614.   Published online February 28, 2019
DOI: https://doi.org/10.4093/dmj.2018.0159
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AbstractAbstract PDFPubReader   
Background

Women with one abnormal value (OAV) in a 100 g oral glucose tolerance test (OGTT) during pregnancy are reported to have an increased risk of adverse pregnancy outcomes. However, there is limited data about whether women with OAV will progress to gestational diabetes mellitus (GDM) when the OGTT is repeated.

Methods

To identify clinical and metabolic predictors for GDM in women with OAV, we conducted a retrospective study and identified women with OAV in the OGTT done at 24 to 30 weeks gestational age (GA) and repeated the second OGTT between 32 and 34 weeks of GA.

Results

Among 137 women with OAV in the initial OGTT, 58 (42.3%) had normal, 40 (29.2%) had OAV and 39 (28.5%) had GDM in the second OGTT. Maternal age, prepregnancy body mass index, weight gain from prepregnancy to the second OGTT, GA at the time of the OGTT, and parity were similar among normal, OAV, and GDM groups. Plasma glucose levels in screening tests were different (151.8±15.7, 155.8±14.6, 162.5±20.3 mg/dL, P<0.05), but fasting, 1-, 2-, and 3-hour glucose levels in the initial OGTT were not. Compared to women with screen negative, women with untreated OAV had a higher frequency of macrosomia.

Conclusion

We demonstrated that women with OAV in the initial OGTT significantly progressed to GDM in the second OGTT. Clinical parameters predicting progression to GDM were not found. Repeating the OGTT in women with OAV in the initial test may be helpful to detect GDM progression.

Citations

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    Humberto Navarro-Martinez, Juana-Antonia Flores-Le Roux, Gemma Llauradó, Lucia Gortazar, Antonio Payà, Laura Mañé, Juan Pedro-Botet, David Benaiges
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Epidemiology
Oral Glucose Tolerance Testing Allows Better Prediction of Diabetes in Women with a History of Gestational Diabetes Mellitus
Tae Jung Oh, Yeong Gi Kim, Sunyoung Kang, Joon Ho Moon, Soo Heon Kwak, Sung Hee Choi, Soo Lim, Kyong Soo Park, Hak C. Jang, Joon-Seok Hong, Nam H. Cho
Diabetes Metab J. 2019;43(3):342-349.   Published online December 7, 2018
DOI: https://doi.org/10.4093/dmj.2018.0086
  • 5,596 View
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AbstractAbstract PDFPubReader   
Background

We aimed to identify the postpartum metabolic factors that were associated with the development of diabetes in women with a history of gestational diabetes mellitus (GDM). In addition, we examined the role of the oral glucose tolerance test (OGTT) in the prediction of future diabetes.

Methods

We conducted a prospective study of 179 subjects who previously had GDM but did not have diabetes at 2 months postpartum. The initial postpartum examination including a 75-g OGTT and the frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed 12 months after delivery, and annual follow-up visits were made thereafter.

Results

The insulinogenic index (IGI30) obtained from the OGTT was significantly correlated with the acute insulin response to glucose (AIRg) obtained from the FSIVGTT. The disposition indices obtained from the OGTT and FSIVGTT were also significantly correlated. Women who progressed to diabetes had a lower insulin secretory capacity including IGI30, AIRg, and disposition indices obtained from the FSIVGTT and OGTT compared with those who did not. However, the insulin sensitivity indices obtained from the OGTT and FSIVGTT did not differ between the two groups. Multivariate logistic regression analysis showed that the 2-hour glucose and disposition index obtained from the FSIVGTT were significant postpartum metabolic risk factors for the development of diabetes.

Conclusion

We identified a crucial role of β-cell dysfunction in the development of diabetes in Korean women with previous GDM. The 2-hour glucose result from the OGTT is an independent predictor of future diabetes. Therefore, the OGTT is crucial for better prediction of future diabetes in Korean women with previous GDM.

Citations

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Epidemiology
Application of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline to the Korean National Health and Nutrition Examination Surveys from 1998 to 2012
Young Shin Song, Tae Jung Oh, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang, Kyong Soo Park, Soo Lim
Diabetes Metab J. 2017;41(1):38-50.   Published online December 16, 2016
DOI: https://doi.org/10.4093/dmj.2017.41.1.38
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline for the treatment of blood cholesterol recommends statin therapy for individuals at high risk of atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate serial trends in the percentages of Korean adults considered eligible for statin therapy according to the new ACC/AHA cholesterol guideline.

Methods

Data from the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998, n=7,698), II (2001, n=5,654), III (2005, n=5,269), IV (2007 to 2009, n=15,727), and V (2010 to 2012, n=16,304), which used a stratified, multistage, probability sampling design, were used as representative of the entire Korean population.

Results

The percentage of adults eligible for statin therapy according to the ACC/AHA cholesterol guideline increased with time: 17.0%, 19.0%, 20.8%, 20.2%, and 22.0% in KNHANES I, II, III, IV, and V, respectively (P=0.022). The prevalence of ASCVD was 1.4% in KNHANES I and increased to 3.3% in KNHANES V. The percentage of diabetic patients aged 40 to 75 years with a low density lipoprotein cholesterol levels of 70 to 189 mg/dL increased from 4.8% in KNHANES I to 6.1% in KNHANES V. People with an estimated 10-year ASCVD risk ≥7.5% and aged 40 to 75 years accounted for the largest percentage among the four statin benefit groups: 9.1% in KNHANES I and 11.0% in KNHANES V.

Conclusion

Application of the 2013 ACC/AHA guideline has found that the percentage of Korean adults in the statin benefit groups has increased over the past 15 years.

Citations

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  • Sex differences in risk factors for subclinical hypothyroidism
    Jeonghoon Ha, Jeongmin Lee, Kwanhoon Jo, Dong-Jun Lim, Moo Il Kang, Bong Yun Cha, Min-Hee Kim
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Others
Rg3 Improves Mitochondrial Function and the Expression of Key Genes Involved in Mitochondrial Biogenesis in C2C12 Myotubes
Min Joo Kim, Young Do Koo, Min Kim, Soo Lim, Young Joo Park, Sung Soo Chung, Hak C. Jang, Kyong Soo Park
Diabetes Metab J. 2016;40(5):406-413.   Published online August 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.406
  • 5,703 View
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  • 22 Web of Science
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AbstractAbstract PDFPubReader   
Background

Panax ginseng has glucose-lowering effects, some of which are associated with the improvement in insulin resistance in skeletal muscle. Because mitochondria play a pivotal role in the insulin resistance of skeletal muscle, we investigated the effects of the ginsenoside Rg3, one of the active components of P. ginseng, on mitochondrial function and biogenesis in C2C12 myotubes.

Methods

C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot. Cellular adenosine triphosphate (ATP) levels and the oxygen consumption rate were measured. The protein or mRNA levels of mitochondrial complexes were evaluated by Western blot and quantitative reverse transcription polymerase chain reaction analysis.

Results

Rg3 treatment to C2C12 cells activated the insulin signaling pathway proteins, insulin receptor substrate-1 and Akt. Rg3 increased ATP production and the oxygen consumption rate, suggesting improved mitochondrial function. Rg3 increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor, which are transcription factors related to mitochondrial biogenesis. Subsequent increased expression of mitochondrial complex IV and V was also observed.

Conclusion

Our results suggest that Rg3 improves mitochondrial function and the expression of key genes involved in mitochondrial biogenesis, leading to an improvement in insulin resistance in skeletal muscle. Rg3 may have the potential to be developed as an anti-hyperglycemic agent.

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