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Kyong Soo Park  (Park KS) 30 Articles
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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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.

Citations

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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
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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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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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
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
  • 7,555 View
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  • 11 Web of Science
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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
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    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
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    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
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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  • 15 Web of Science
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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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  • Metformin enhances METTL14-Mediated m6A methylation to alleviate NIT-1 cells apoptosis induced by hydrogen peroxide
    Si-min Zhou, Xin-ming Yao, Yi Cheng, Yu-jie Xing, Yue Sun, Qiang Hua, Shu-jun Wan, Xiang-jian Meng
    Heliyon.2024; 10(2): e24432.     CrossRef
  • Roles of m6A modification in regulating PPER pathway in cadmium-induced pancreatic β cell death
    Yifei Sun, Rongxian Li, Wenhong Li, Nan Zhang, Guofen Liu, Bo Zhao, Zongqin Mei, Shiyan Gu, Zuoshun He
    Ecotoxicology and Environmental Safety.2024; 282: 116672.     CrossRef
  • Reduced Expression Level of Protein PhosphatasePPM1EServes to Maintain Insulin Secretion in Type 2 Diabetes
    Sevda Gheibi, Luis Rodrigo Cataldo, Alexander Hamilton, Mi Huang, Sebastian Kalamajski, Malin Fex, Hindrik Mulder
    Diabetes.2023; 72(4): 455.     CrossRef
  • Metformin restores prohormone processing enzymes and normalizes aberrations in secretion of proinsulin and insulin in palmitate‐exposed human islets
    Quan Wen, Azazul Islam Chowdhury, Banu Aydin, Mudhir Shekha, Rasmus Stenlid, Anders Forslund, Peter Bergsten
    Diabetes, Obesity and Metabolism.2023; 25(12): 3757.     CrossRef
  • Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach
    Priyamvada Amol Arte, Kanchanlata Tungare, Mustansir Bhori, Renitta Jobby, Jyotirmoi Aich
    Human Cell.2023; 37(1): 54.     CrossRef
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    Maíra M.R. Valle, Eloisa Aparecida Vilas‐Boas, Camila F. Lucena, Simone A. Teixeira, Marcelo N. Muscara, Angelo R. Carpinelli
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    Nicolas Wiernsperger, Abdallah Al-Salameh, Bertrand Cariou, Jean-Daniel Lalau
    Diabetes & Metabolism.2022; 48(4): 101359.     CrossRef
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    Lei Wei, Jianjian Shi
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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    Qingrui Zhao, Shenghan Su, Yuqing Lin, Xuebei Li, Lingfeng Dan, Yunjin Zhang, Chunxiao Yang, Xiaohan Li, Yimeng Dong, Chenchen Geng, Changhao Sun, Xia Chu, Huimin Lu
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  • Metformin Dysregulates the Unfolded Protein Response and the WNT/β-Catenin Pathway in Endometrial Cancer Cells through an AMPK-Independent Mechanism
    Domenico Conza, Paola Mirra, Gaetano Calì, Luigi Insabato, Francesca Fiory, Francesco Beguinot, Luca Ulianich
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  • NADPH Oxidase (NOX) Targeting in Diabetes: A Special Emphasis on Pancreatic β-Cell Dysfunction
    Suma Elumalai, Udayakumar Karunakaran, Jun-Sung Moon, Kyu-Chang Won
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    Min Ho Kim, Hyung Jung Oh, Soon Hyo Kwon, Jin Seok Jeon, Hyunjin Noh, Dong Cheol Han, Hyoungnae Kim, Dong-Ryeol Ryu
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    Chi-Ming Chan, Ponarulselvam Sekar, Duen-Yi Huang, Shu-Hao Hsu, Wan-Wan Lin
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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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  • Analysis of the gut microflora in women with gestational diabetes mellitus
    Xuping Wang, Bingfeng Bian, Fuman Du, Chaofeng Xiang, Yu Liu, Na Li, Binhong Duan
    International Journal of Diabetes in Developing Countries.2024; 44(S1): 38.     CrossRef
  • Fetal abdominal obesity in women with one value abnormality on diagnostic test for gestational diabetes mellitus
    Wonjin Kim, Soo Kyung Park, Yoo Lee Kim, Clive J. Petry
    PLOS ONE.2024; 19(6): e0304875.     CrossRef
  • Maternal and fetal outcomes of pregnancies associated with single versus double abnormal values in 100 gr glucose tolerance test
    Mohammadali Shahriari, Ali Shahriari, Maryam Khooshideh, Anahita Dehghaninezhad, Arezoo Maleki-Hajiagha, Rana Karimi
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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
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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.

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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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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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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
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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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  • The problem of diabetes mellitus in obstetrics
    E.V. Popova-Petrosyan, A.A. Dovgan’, E.R. Kulieva
    Russian Bulletin of Obstetrician-Gynecologist.2024; 24(3): 25.     CrossRef
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    Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang
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    Tae Jung Oh
    Journal of the Korean Medical Association.2023; 66(7): 414.     CrossRef
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    Yi‐Ling Chiou, Chich‐Hsiu Hung, Ching‐Yun Yu, Te‐Fu Chan, Ming‐Gwo Liu
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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
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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.

Citations

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Clinical Care/Education
Feasibility of a Patient-Centered, Smartphone-Based, Diabetes Care System: A Pilot Study
Eun Ky Kim, Soo Heon Kwak, Seungsu Baek, Seung Lyeol Lee, Hak Chul Jang, Kyong Soo Park, Young Min Cho
Diabetes Metab J. 2016;40(3):192-201.   Published online April 8, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.3.192
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  • 23 Web of Science
  • 29 Crossref
AbstractAbstract PDFPubReader   
Background

We developed a patient-centered, smartphone-based, diabetes care system (PSDCS). This study aims to test the feasibility of glycosylated hemoglobin (HbA1c) reduction with the PSDCS.

Methods

This study was a single-arm pilot study. The participants with type 2 diabetes mellitus were instructed to use the PSDCS, which integrates a Bluetooth-connected glucometer, digital food diary, and wearable physical activity monitoring device. The primary end point was the change in HbA1c from baseline after a 12-week intervention.

Results

Twenty-nine patients aged 53.9±9.1 years completed the study. HbA1c and fasting plasma glucose levels decreased significantly from baseline (7.7%±0.7% to 7.1%±0.6%, P<0.0001; 140.9±39.1 to 120.1±31.0 mg/dL, P=0.0088, respectively). The frequency of glucose monitoring correlated with the magnitude of HbA1c reduction (r=–0.57, P=0.0013). The components of the diabetes self-care activities, including diet, exercise, and glucose monitoring, were significantly improved, particularly in the upper tertile of HbA1c reduction. There were no severe adverse events during the intervention.

Conclusion

A 12-week application of the PSDCS to patients with inadequately controlled type 2 diabetes resulted in a significant HbA1c reduction with tolerable safety profiles; these findings require confirmation in a future randomized controlled trial.

Citations

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Clinical Care/Education
Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging
Ji Won Yoon, Yong-Chan Ha, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Soo Lim, Young Joo Park, Jae Young Lim, Ki Woong Kim, Kyong Soo Park, Hak Chul Jang
Diabetes Metab J. 2016;40(2):140-146.   Published online March 31, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.2.140
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AbstractAbstract PDFPubReader   
Background

The study aimed to investigate the influence of hyperglycemia on muscle quality in older men with type 2 diabetes.

Methods

This was a subsidiary study of the Korean Longitudinal Study of Health and Aging. Among 326 older men consenting to tests of body composition and muscle strength, 269 men were ultimately analyzed after the exclusion because of stroke (n=30) and uncertainty about the diagnosis of diabetes (n=27). Body composition was measured using dual-energy X-ray absorptiometry and computed tomography. Muscle strength for knee extension was measured using an isokinetic dynamometer. Muscle quality was assessed from the ratio of leg strength to the entire corresponding leg muscle mass.

Results

The muscle mass, strength, and quality in patients with type 2 diabetes did not differ significantly from controls. However, when patients with diabetes were subdivided according to their glycemic control status, patients with a glycosylated hemoglobin (HbA1c) level of ≥8.5% showed significantly decreased leg muscle quality by multivariate analysis (odds ratio, 4.510; P=0.045) after adjustment for age, body mass index, smoking amount, alcohol consumption, physical activity, and duration of diabetes. Physical performance status was also impaired in subjects with an HbA1c of ≥8.5%.

Conclusion

Poor glycemic control in these older patients with diabetes was associated with significant risk of decreased muscle quality and performance status. Glycemic control with an HbA1c of <8.5% might be needed to reduce the risk of adverse skeletal and functional outcomes in this population.

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The Level of Autoantibodies Targeting Eukaryote Translation Elongation Factor 1 α1 and Ubiquitin-Conjugating Enzyme 2L3 in Nondiabetic Young Adults
Eunhee G. Kim, Soo Heon Kwak, Daehee Hwang, Eugene C. Yi, Kyong Soo Park, Bo Kyung Koo, Kristine M. Kim
Diabetes Metab J. 2016;40(2):154-160.   Published online November 13, 2015
DOI: https://doi.org/10.4093/dmj.2016.40.2.154
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AbstractAbstract PDFPubReader   
Background

The prevalence of novel type 1 diabetes mellitus (T1DM) antibodies targeting eukaryote translation elongation factor 1 alpha 1 autoantibody (EEF1A1-AAb) and ubiquitin-conjugating enzyme 2L3 autoantibody (UBE2L3-AAb) has been shown to be negatively correlated with age in T1DM subjects. Therefore, we aimed to investigate whether age affects the levels of these two antibodies in nondiabetic subjects.

Methods

EEF1A1-AAb and UBE2L3-AAb levels in nondiabetic control subjects (n=150) and T1DM subjects (n=101) in various ranges of age (18 to 69 years) were measured using an enzyme-linked immunosorbent assay. The cutoff point for the presence of each autoantibody was determined based on control subjects using the formula: [mean absorbance+3×standard deviation].

Results

In nondiabetic subjects, there were no significant correlations between age and EEF1A1-AAb and UBE2L3-AAb levels. However, there was wide variation in EEF1A1-AAb and UBE2L3-AAb levels among control subjects <40 years old; the prevalence of both EEF1A1-AAb and UBE2L3-AAb in these subjects was 4.4%. When using cutoff points determined from the control subjects <40 years old, the prevalence of both autoantibodies in T1DM subjects was decreased (EEFA1-AAb, 15.8% to 8.9%; UBE2L3-AAb, 10.9% to 7.9%) when compared to the prevalence using the cutoff derived from the totals for control subjects.

Conclusion

There was no association between age and EEF1A1-AAb or UBE2L3-AAb levels in nondiabetic subjects. However, the wide variation in EEF1A1-AAb and UBE2L3-AAb levels apparent among the control subjects <40 years old should be taken into consideration when determining the cutoff reference range for the diagnosis of T1DM.

Citations

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  • An autoantigen-ome from HS-Sultan B-Lymphoblasts offers a molecular map for investigating autoimmune sequelae of COVID-19
    Julia Y. Wang, Wei Zhang, Victor B. Roehrl, Michael W. Roehrl, Michael H. Roehrl, Mibel Aguilar
    Australian Journal of Chemistry.2023; 76(8): 525.     CrossRef
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    Julia Y. Wang, Wei Zhang, Victor B. Roehrl, Michael W. Roehrl, Michael H. Roehrl
    Frontiers in Immunology.2022;[Epub]     CrossRef
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    Li Qian, Yuxiao Zhu, Yan Luo, Mu Zhang, Liping Yu, Yu Liu, Tao Yang
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    Julia Y. Wang, Wei Zhang, Michael W. Roehrl, Victor B. Roehrl, Michael H. Roehrl
    Journal of Autoimmunity.2021; 120: 102644.     CrossRef
Clinical Care/Education
Clinical Characteristics and Metabolic Predictors of Rapid Responders to Dipeptidyl Peptidase-4 Inhibitor as an Add-on Therapy to Sulfonylurea and Metformin
Ye An Kim, Won Sang Yoo, Eun Shil Hong, Eu Jeong Ku, Kyeong Seon Park, Soo Lim, Young Min Cho, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi
Diabetes Metab J. 2015;39(6):489-497.   Published online November 27, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.489
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AbstractAbstract PDFPubReader   
Background

Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU). We evaluated the efficacy and safety of this triple therapy and the characteristics of rapid responders and hypoglycemia-prone patients.

Methods

We included 807 patients with type 2 diabetes who were prescribed a newly added DPP-4 inhibitor to ongoing metformin and SU in 2009 to 2011. Glycemia and other metabolic parameters at baseline, 12, 24, and 52 weeks, as well as episodes of hypoglycemia were analyzed. Rapid responders were defined as patients with ≥25% reduction in glycosylated hemoglobin (HbA1c) within 12 weeks.

Results

At baseline, while on the submaximal metformin and SU combination, the mean HbA1c level was 8.4%. Twelve weeks after initiation of DPP-4 inhibitor add-on, 269 patients (34.4%) achieved an HbA1c level ≤7%. Sixty-six patients (8.2%, 47 men) were rapid responders. The duration of diabetes was shorter in rapid responders, and their baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and homeostasis model assessment of insulin resistance were significantly higher. Patients who experienced hypoglycemia after taking DPP-4 inhibitor add-on were more likely to be female, to have a lower body weight and lower triglyceride and FPG levels, and to have higher homeostasis model assessment of β-cells.

Conclusion

An oral hypoglycemic triple agent combination including a DPP-4 inhibitor was effective in patients with uncontrolled diabetes. Proactive dose reduction of SU should be considered when a DPP-4 inhibitor is added for rapid responders and hypoglycemia-prone patients.

Citations

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  • A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes
    Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
    Medicine.2016; 95(44): e5155.     CrossRef
Genetics
Identification of Two Cases of Ciliopathy-Associated Diabetes and Their Mutation Analysis Using Whole Exome Sequencing
Min Kyeong Kim, Soo Heon Kwak, Shinae Kang, Hye Seung Jung, Young Min Cho, Seong Yeon Kim, Kyong Soo Park
Diabetes Metab J. 2015;39(5):439-443.   Published online October 22, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.5.439
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AbstractAbstract PDFPubReader   
Background

Alström syndrome and Bardet-Biedl syndrome are autosomal recessively inherited ciliopathies with common characteristics of obesity, diabetes, and blindness. Alström syndrome is caused by a mutation in the ALMS1 gene, and Bardet-Biedl syndrome is caused by mutations in BBS1-16 genes. Herein we report genetically confirmed cases of Alström syndrome and Bardet-Biedl syndrome in Korea using whole exome sequencing.

Methods

Exome capture was done using SureSelect Human All Exon Kit V4+UTRs (Agilent Technologies). HiSeq2000 system (Illumina) was used for massive parallel sequencing. Sanger sequencing was used for genotype confirmation and familial cosegregation analysis.

Results

A 21-year old Korean woman was clinically diagnosed with Alström syndrome. She had diabetes, blindness, obesity, severe insulin resistance, and hearing loss. Whole exome sequencing revealed a nonsense mutation in exon 10 of ALMS1 (c.8776C>T, p.R2926X) and a seven base-pair deletion resulting in frameshift mutation in exon 8 (c.6410_6416del, p.2137_2139del). A 24-year-old Korean man had Bardet-Biedl syndrome with diabetes, blindness, obesity, and a history of polydactyly. Whole exome sequencing revealed a nonsynonymous mutation in exon 11 of the BBS1 gene (c.1061A>G, p.E354G) and mutation at the normal splicing recognition site of exon 7 of the BBS1 gene (c.519-1G>T).

Conclusion

We found novel compound heterozygous mutations of Alström syndrome and Bardet-Biedl syndrome using whole exome sequencing. The whole exome sequencing successfully identified novel genetic variants of ciliopathy-associated diabetes.

Citations

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    Brais Bea-Mascato, Diana Valverde
    Journal of Medical Genetics.2024; 61(1): 18.     CrossRef
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    V. Tam, M. Turcotte, D. Meyre
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Response: Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance (Diabetes Metab J 2015;39:147-53)
Tae Jung Oh, Se Hee Min, Chang Ho Ahn, Eun Ky Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho
Diabetes Metab J. 2015;39(3):270-271.   Published online June 15, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.3.270
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PDFPubReader   

Citations

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  • Prevalence of Impaired Glucose Tolerance/Prediabetes in Local Adult Obese Population Presenting to A Tertiary Care Hospital
    Niktash Khan Hadi, Muhammad Salman Aamir, Tahir Ghaffar, Sulaiman Khan, Siraj ul Islam, Shafiullah Khan, Nizamuddin ., Muhammad Ali
    Pakistan Journal of Health Sciences.2023; : 84.     CrossRef
Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance
Tae Jung Oh, Se Hee Min, Chang Ho Ahn, Eun Ky Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho
Diabetes Metab J. 2015;39(2):147-153.   Published online March 9, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.147
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AbstractAbstract PDFPubReader   
Background

Subjects with normal glucose tolerance (NGT) who have a high 1-hour postload plasma glucose level (≥155 mg/dL; NGT 1 hour-high) have been shown to be at higher risk for type 2 diabetes than subjects with NGT 1 hour-low postload plasma glucose level (<155 mg/dL). We compared β-cell function in subjects with NGT 1 hour-high, NGT 1 hour-low, and impaired glucose tolerance (IGT).

Methods

We classified subjects into NGT 1 hour-low (n=149), NGT 1 hour-high (n=43), and IGT (n=52). The β-cell function was assessed based on insulinogenic index (IGI), oral disposition index (DI), and insulin secretion-sensitivity index-2 (ISSI-2).

Results

Insulin sensitivity was comparable between the subjects with NGT 1 hour-high and NGT 1 hour-low. The β-cell function with/without adjusting insulin sensitivity was significantly different among the three groups. The IGI (pmol/mmol) was 116.8±107.3 vs. 64.8±47.8 vs. 65.8±80.6 (P=0.141), oral DI was 3.5±4.2 vs. 1.8±1.4 vs. 1.8±3.1 (P<0.001), and ISSI-2 was 301.2±113.7 vs. 213.2±67.3 vs. 172.5±87.5 (P<0.001) in NGT 1 hour-low, NGT 1 hour-high, and IGT, respectively. Post hoc analyses revealed that oral DI and ISSI-2 were significantly different between NGT 1 hour-low and NGT 1 hour-high but comparable between NGT 1 hour-high and IGT.

Conclusion

Among Korean subjects with NGT, those who have a higher 1-hour postload glucose level have a compromised insulin-sensitivity adjusted β-cell function to a similar degree as IGT subjects.

Citations

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    Chiara M.A. Cefalo, Alessia Riccio, Teresa Vanessa Fiorentino, Elena Succurro, Gaia Chiara Mannino, Maria Perticone, Angela Sciacqua, Francesco Andreozzi, Giorgio Sesti
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    Min Jin Lee, Ji Hyun Bae, Ah Reum Khang, Dongwon Yi, Joo Yeon Kim, Su Hyun Kim, Dong Hee Kim, Dasol Kang, Sujin Park, Yun Kyung Jeon, Sang Soo Kim, Bo Hyun Kim, Mi Sook Yun, Yang Ho Kang
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    Tae Jung Oh, Soo Lim, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Young Min Cho, Kyong Soo Park, HakChul Jang, Nam H. Cho
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    Martin Buysschaert, Michael Bergman, Donald Yanogo, Ram Jagannathan, Benoit Buysschaert, Vanessa Preumont
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  • Response: Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance (Diabetes Metab J2015;39:147-53)
    Tae Jung Oh, Se Hee Min, Chang Ho Ahn, Eun Ky Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho
    Diabetes & Metabolism Journal.2015; 39(3): 270.     CrossRef
  • Letter: Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance (Diabetes Metab J2015;39:147-53)
    Hee Kyung Kim
    Diabetes & Metabolism Journal.2015; 39(3): 268.     CrossRef
Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody
Yul Hwangbo, Jin Taek Kim, Eun Ky Kim, Ah Reum Khang, Tae Jung Oh, Hak Chul Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Young Min Cho
Diabetes Metab J. 2012;36(2):136-143.   Published online April 17, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.2.136
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AbstractAbstract PDFPubReader   
Background

Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in β-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes.

Methods

We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics.

Results

The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups.

Conclusion

The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

Citations

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Carotid Intimal-Medial Thickness Is Not Increased in Women with Previous Gestational Diabetes Mellitus
Yun Hyi Ku, Sung Hee Choi, Soo Lim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Hak Chul Jang
Diabetes Metab J. 2011;35(5):497-503.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.497
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AbstractAbstract PDFPubReader   
Background

Gestational diabetes mellitus (GDM) is known to increase the risk of cardiovascular diseases. Measuring the carotid artery intimal-medial thickness (CIMT) is a non-invasive technique used to evaluate early atherosclerosis and to predict future cardiovascular diseases. We examined the association between CIMT and cardiovascular risk factors in young Korean women with previous GDM.

Methods

One hundred one women with previous GDM and 19 women who had normal pregnancies (NP) were recruited between 1999 and 2002. At one year postpartum, CIMT was measured using high-resolution B-mode ultrasonography, and oral glucose tolerance tests were performed. Fasting glucose, glycated hemoglobin A1c (HbA1c), insulin levels and lipid profiles were also measured. CIMTs in the GDM and NP groups were compared, and the associations between CIMT and cardiovascular risk factors were analyzed in the GDM group.

Results

CIMT results of the GDM group were not significantly different from those of the NP group (GDM, 0.435±0.054 mm; NP, 0.460±0.046 mm; P=0.069). In the GDM group, a higher HbA1c was associated with an increase in CIMT after age adjustment (P=0.011). CIMT results in the group with HbA1c >6.0% were higher than those of the normal HbA1c (HbA1c ≤6.0%) (P=0.010). Nine of the patients who are type 2 diabetes mellitus converters within one year postpartum but showed no significant difference in CIMT results compared to NP group.

Conclusion

Higher HbA1c is associated with an increase in CIMT in women with previous GDM. However, CIMT at one year postpartum was not increased in these women compared to that in NP women.

Citations

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  • Women with a history of gestational diabetes mellitus present an accumulation of cardiovascular risk factors at age 46—A birth cohort study
    Evi Bakiris, Kaisu Luiro, Jari Jokelainen, Laure Morin‐Papunen, Sirkka Keinänen‐Kiukaanniemi, Kari Kaikkonen, Terhi Piltonen, Juha S. Tapanainen, Juha Auvinen
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Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones
Kyeong Won Lee, Yun Hyi Ku, Min Kim, Byung Yong Ahn, Sung Soo Chung, Kyong Soo Park
Diabetes Metab J. 2011;35(4):340-347.   Published online August 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.4.340
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AbstractAbstract PDFPubReader   
Background

Sulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic β-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor γ (PPARγ), one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARγ transcriptional activity and on the glucose uptake via PPARγ.

Methods

Transcription reporter assays using Cos7 cells were performed to determine if specific sulfonylureas stimulate PPARγ transactivation. Glimepiride, gliquidone, and glipizide (1 to 500 µM) were used as treatment, and rosiglitazone at 1 and 10 µM was used as a control. The effects of sulfonylurea and rosiglitazone treatments on the transcriptional activity of endogenous PPARγ were observed. In addition, 3T3-L1 adipocytes were treated with rosiglitazone (10 µM), glimepiride (100 µM) or both to verify the effect of glimepiride on rosiglitazone-induced glucose uptake.

Results

Sulfonylureas, including glimepiride, gliquidone and glipizide, increased PPARγ transcriptional activity, gliquidone being the most potent PPARγ agonist. However, no additive effects were observed in the presence of rosiglitazone. When rosiglitazone was co-treated with glimepiride, PPARγ transcriptional activity and glucose uptake were reduced compared to those after treatment with rosiglitazone alone. This competitive effect of glimepiride was observed only at high concentrations that are not achieved with clinical doses.

Conclusion

Sulfonylureas like glimepiride, gliquidone and glipizide increased the transcriptional activity of PPARγ. Also, glimepiride was able to reduce the effect of rosiglitazone on PPARγ agonistic activity and glucose uptake. However, the competitive effect does not seem to occur at clinically feasible concentrations.

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Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea
Jin Taek Kim, Tae Jung Oh, Ye An Lee, Jun Ho Bae, Hyo Jeong Kim, Hye Seung Jung, Young Min Cho, Kyong Soo Park, Soo Lim, Hak Chul Jang, Hong Kyu Lee
Diabetes Metab J. 2011;35(2):166-172.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.166
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AbstractAbstract PDFPubReader   
Background

To investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects.

Methods

We analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009.

Results

A total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users.

Conclusion

We identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.

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The Search for Genetic Risk Factors of Type 2 Diabetes Mellitus
Kyong Soo Park
Diabetes Metab J. 2011;35(1):12-22.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.12
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AbstractAbstract PDFPubReader   

Type 2 diabetes mellitus (T2DM) is caused by complex interplay between multiple genetic and environmental factors. The three major approaches used to identify the genetic susceptibility include candidate gene approach, familial linkage analysis and genome- wide association analysis. Recent advance in genome-wide association studies have greatly improved our understanding of the pathophysiology of T2DM. As of the end of 2010, there are more than 40 confirmed T2DM-associated genetic loci. Most of the T2DM susceptibility genes were implicated in decreased β-cell function. However, these genetic variations have a modest effect and their combination only explains less than 10% of the T2DM heritability. With the advent of the next-generation sequencing technology, we will soon identify rare variants of larger effect as well as causal variants. These advances in understanding the genetics of T2DM will lead to the development of new therapeutic and preventive strategies and individualized medicine.

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A Survey on Ubiquitous Healthcare Service Demand among Diabetic Patients
Soo Lim, So-Youn Kim, Jung Im Kim, Min Kyung Kwon, Sei Jin Min, Soo Young Yoo, Seon Mee Kang, Hong Il Kim, Hye Seung Jung, Kyong Soo Park, Jun Oh Ryu, Hayley Shin, Hak Chul Jang
Diabetes Metab J. 2011;35(1):50-57.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.50
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AbstractAbstract PDFPubReader   
Background

Advanced information technology can be used when developing diagnostic and treatment strategies to provide better care for diabetic patients. However, the levels of need and demand for the use of technological advances have not been investigated in diabetic patients. We proposed and developed an individualized, ubiquitous (U)-healthcare service using advanced information technology for more effective glucose control. Prior to our service initiation, we surveyed patient needs and other pertinent information.

Methods

During August 2009, we conducted a 34-item questionnaire survey among patients with diabetes who were older than 40 years in two certain hospitals in Korea.

Results

The mean age of the 228 participants was 61.2±9 years, and males made up 49.1% of the sample. Seventy-one percent replied that they wanted individualized healthcare service, and they also wanted their health information to be delivered through mobile devices such as a cellular phone or a personal digital assistant (40.4%). Most patients had never heard of U-healthcare services (81.1%); however, after explaining the concept, 71.1% of participants responded that they would use the service if it was provided. Despite their willingness, participants were concerned about technical difficulty in using the service (26.3%) as well as the cost of the service (29.8%).

Conclusion

The current study suggests that more than 70% of diabetic patients are interested in using U-healthcare services. To encourage widespread use, the application program or device of U-healthcare services should be simple, easy to use and affordable while also including a policy for the protection of private information.

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Insulin Secretion and Incretin Hormone Concentration in Women with Previous Gestational Diabetes Mellitus
Sung Hoon Yu, Bongjun Cho, Yejin Lee, Eunhye Kim, Sung Hee Choi, Soo Lim, Ka Hee Yi, Young Joo Park, Kyong Soo Park, Hak Chul Jang
Diabetes Metab J. 2011;35(1):58-64.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.58
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AbstractAbstract PDFPubReader   
Background

We examined the change in the levels of incretin hormone and effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) on insulin secretion in women with previous gestational diabetes (pGDM).

Methods

A 75-g oral glucose tolerance test (OGTT) was conducted on 34 women with pGDM. In addition, 11 women with normal glucose tolerance, matched for age, height and weight, were also tested. The insulin, GIP, GLP-1, and glucagon concentrations were measured, and their anthropometric and biochemical markers were also measured.

Results

Among 34 women with pGDM, 18 had normal glucose tolerance, 13 had impaired glucose tolerance (IGT) and 1 had diabetes. No significant differences were found in GLP-1 concentration between the pGDM and control group. However, a significantly high level of glucagon was present in the pGDM group at 30 minutes into the OGTT. The GIP concentration was elevated at 30 minutes and 60 minutes in the pGDM group. With the exception of the 30-minute timepoint, women with IGT had significantly high blood glucose from 0 to 120 minutes. However, there was no significant difference in insulin or GLP-1 concentration. The GIP level was significantly high from 0 to 90 minutes in patients diagnosed with IGT.

Conclusion

GLP-1 secretion does not differ between pGDM patients and normal women. GIP was elevated, but that does not seem to induce in increase in insulin secretion. Therefore, we conclude that other factors such as heredity and environment play important roles in the development of type 2 diabetes.

Citations

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Polymorphisms of the Reg1α Gene and Early Onset Type 2 Diabetes in the Korean Population
Bo Kyung Koo, Young Min Cho, Kuchan Kimm, Jong-Young Lee, Bermseok Oh, Byung Lae Park, Hyun Sub Cheong, Hyoung Doo Shin, Kyung Soo Ko, Sang Gyu Park, Hong Kyu Lee, Kyong Soo Park
Korean Diabetes J. 2010;34(4):229-236.   Published online August 31, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.4.229
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AbstractAbstract PDFPubReader   
Background

The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1α is homologous with murine Reg1, we investigated whether common variants in Reg1α are associated with type 2 diabetes in the Korean population.

Methods

We sequenced the Reg1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects.

Results

No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009).

Conclusion

Polymorphisms in the Reg1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.

Citations

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  • A Novel Variant Of Regenerating Iα Gene (REG) In Type II Diabetics Among Pakistani Targeted Population
    Sadaf Saleem, Saeeda Baig, Sadia Farrukh, Mazhar Shafiq
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Type 1 Diabetes
Article image
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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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.

Diabetes Metab J : Diabetes & Metabolism Journal
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