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Kun-Ho Yoon  (Yoon KH) 33 Articles
Complications
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Diabetic Ketoacidosis as an Effect of Sodium-Glucose Cotransporter 2 Inhibitor: Real World Insights
Han-Sang Baek, Chaiho Jeong, Yeoree Yang, Joonyub Lee, Jeongmin Lee, Seung-Hwan Lee, Jae Hyoung Cho, Tae-Seo Sohn, Hyun-Shik Son, Kun-Ho Yoon, Eun Young Lee
Diabetes Metab J. 2024;48(6):1169-1175.   Published online June 10, 2024
DOI: https://doi.org/10.4093/dmj.2024.0036
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  • 1 Web of Science
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AbstractAbstract PDFPubReader   ePub   
One of the notable adverse effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor is diabetic ketoacidosis (DKA) often characterized by euglycemia. In this retrospective review of patients with DKA from 2015 to 2023, 21 cases of SGLT2 inhibitorassociated DKA were identified. Twelve (57.1%) exhibited euglycemic DKA (euDKA) while nine (42.9%) had hyperglycemic DKA (hyDKA). More than 90% of these cases were patients with type 2 diabetes mellitus. Despite similar age, sex, body mass index, and diabetes duration, individuals with hyDKA showed poorer glycemic control and lower C-peptide levels compared with euDKA. Renal impairment and acidosis were worse in the hyDKA group, requiring hemodialysis in two patients. Approximately one-half of hyDKA patients had concurrent hyperosmolar hyperglycemic state. Common symptoms included nausea, vomiting, general weakness, and dyspnea. Seizure was the initial manifestation of DKA in two cases. Infection and volume depletion were major contributors, while carbohydrate restriction and inadequate insulin treatment also contributed to SGLT2 inhibitor-associated DKA. Despite their beneficial effects, clinicians should be vigilant for SGLT2 inhibitor risk associated with DKA.

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  • Dapagliflozin/Empagliflozin/Ertugliflozin

    Reactions Weekly.2025; 2042(1): 142.     CrossRef
  • Diabetes mellitus im Alter
    Andrej Zeyfang, Jürgen Wernecke, Anke Bahrmann
    Diabetologie und Stoffwechsel.2024; 19(S 02): S226.     CrossRef
Drug/Regimen
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Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial
Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon, the Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) study investigators
Diabetes Metab J. 2024;48(5):915-928.   Published online April 23, 2024
DOI: https://doi.org/10.4093/dmj.2023.0259
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.
Drug Regimen
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Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension
Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon
Diabetes Metab J. 2023;47(6):808-817.   Published online September 26, 2023
DOI: https://doi.org/10.4093/dmj.2022.0387
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  • 2 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Citations

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  • Clinical-economic assessment of the potential contribution of evogliptin to achieving the targets of the Federal project «Fight against diabetes mellitus» and reduction of population mortality
    N. N. Avxentyev, A. S. Makarov, I. A. Karpova, V. V. Yavlyanskaya
    Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice.2025; (4): 55.     CrossRef
  • Design, synthesis, and biological evaluation of quinazolinone-dihydropyrimidinone as a potential anti-diabetic agent via GLUT4 translocation stimulation
    Arvind Kumar Jaiswal, Ajay Kishor Kushawaha, Pawan kumar, Alisha Ansari, Nikita Chhikara, Hemlata bhatt, Sarita Katiyar, Ishbal Ahmad, Abhijit Deb Choudhury, Rabi Sankar Bhatta, Akhilesh K. Tamrakar, Koneni V. Sashidhara
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  • Efficacy and safety of dapagliflozin add‐on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled study
    In‐Kyung Jeong, Kyung Mook Choi, Kyung Ah Han, Kyoung‐Ah Kim, In Joo Kim, Seung Jin Han, Won Young Lee, Soon Jib Yoo
    Diabetes, Obesity and Metabolism.2024; 26(11): 5065.     CrossRef
Others
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Opening the Precision Diabetes Care through Digital Healthcare
Joonyub Lee, Jin Yu, Kun-Ho Yoon
Diabetes Metab J. 2023;47(3):307-314.   Published online March 29, 2023
DOI: https://doi.org/10.4093/dmj.2022.0386
  • 10,889 View
  • 332 Download
  • 1 Web of Science
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AbstractAbstract PDFPubReader   ePub   
The national healthcare systems of every country in the world cannot sustain the rise in healthcare expenditure caused by chronic diseases and their complications. To sustain the national healthcare system, a novel system should be developed to improve the quality of care and minimize healthcare costs. For 20 years, our team developed patient-communicating digital healthcare platforms and proved their efficacy. National scale randomized control trials are underway to systematically measure the efficacy and economic benefits of this digital health care system. Precision medicine aims to maximize effectiveness of disease management by considering individual variability. Digital health technologies enable precision medicine at a reasonable cost that was not available before. The government launched the “National Integrated Bio-big Data Project” which will collect diverse health data from the participants. Individuals will share their health information to physicians or researchers at their will by gateway named “My-Healthway.’ Taken together, now we stand in front of the evolution of medical care, so-called “Precision medicine.” led by various kinds of technologies and a huge amount of health information exchange. We should lead these new trends as pioneers, not as followers, to establish and implement the best care for our patients that can help them to withstand their devastating diseases.

Citations

Citations to this article as recorded by  
  • Social determinants of health and type 2 diabetes in Asia
    Kyunghun Sung, Seung‐Hwan Lee
    Journal of Diabetes Investigation.2025;[Epub]     CrossRef
  • Technological Innovations Transforming Diabetes Care in Practice
    Shinae Kang
    The Journal of Korean Diabetes.2024; 25(2): 57.     CrossRef
  • Islet transplantation in Korea
    Joonyub Lee, Kun‐Ho Yoon
    Journal of Diabetes Investigation.2024; 15(9): 1165.     CrossRef
Basic Research
Differentiation of Microencapsulated Neonatal Porcine Pancreatic Cell Clusters in Vitro Improves Transplant Efficacy in Type 1 Diabetes Mellitus Mice
Gyeong-Jin Cheon, Heon-Seok Park, Eun-Young Lee, Min Jung Kim, Young-Hye You, Marie Rhee, Ji-Won Kim, Kun-Ho Yoon
Diabetes Metab J. 2022;46(5):677-688.   Published online February 7, 2022
DOI: https://doi.org/10.4093/dmj.2021.0202
  • 6,109 View
  • 288 Download
  • 2 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Neonatal porcine pancreatic cell clusters (NPCCs) have been proposed as an alternative source of β cells for islet transplantation because of their low cost and growth potential after transplantation. However, the delayed glucose lowering effect due to the immaturity of NPCCs and immunologic rejection remain as a barrier to NPCC’s clinical application. Here, we demonstrate accelerated differentiation and immune-tolerant NPCCs by in vitro chemical treatment and microencapsulation.
Methods
NPCCs isolated from 3-day-old piglets were cultured in F-10 media and then microencapsulated with alginate on day 5. Differentiation of NPCCs is facilitated by media supplemented with activin receptor-like kinase 5 inhibitor II, triiodothyronine and exendin-4 for 2 weeks. Marginal number of microencapsulated NPCCs to cure diabetes with and without differentiation were transplanted into diabetic mice and observed for 8 weeks.
Results
The proportion of insulin-positive cells and insulin mRNA levels of NPCCs were significantly increased in vitro in the differentiated group compared with the undifferentiated group. Blood glucose levels decreased eventually after transplantation of microencapsulated NPCCs in diabetic mice and normalized after 7 weeks in the differentiated group. In addition, the differentiated group showed nearly normal glucose tolerance at 8 weeks after transplantation. In contrast, neither blood glucose levels nor glucose tolerance were improved in the undifferentiated group. Retrieved graft in the differentiated group showed greater insulin response to high glucose compared with the undifferentiated group.
Conclusion
in vitro differentiation of microencapsulated immature NPCCs increased the proportion of insulin-positive cells and improved transplant efficacy in diabetic mice without immune rejection.

Citations

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  • Dual-targeted nano-encapsulation of neonatal porcine islet-like cell clusters with triiodothyronine-loaded bifunctional polymersomes
    Sang Hoon Lee, Minse Kim, Eun-Jin Lee, Sun Mi Ahn, Yu-Rim Ahn, Jaewon Choi, Jung-Taek Kang, Hyun-Ouk Kim
    Discover Nano.2024;[Epub]     CrossRef
  • Long‐term efficacy of encapsulated xenogeneic islet transplantation: Impact of encapsulation techniques and donor genetic traits
    Heon‐Seok Park, Eun Young Lee, Young‐Hye You, Marie Rhee, Jong‐Min Kim, Seong‐Soo Hwang, Poong‐Yeon Lee
    Journal of Diabetes Investigation.2024; 15(6): 693.     CrossRef
Metabolic Risk/Epidemiology
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Short-Term Effects of the Internet-Based Korea Diabetes Prevention Study: 6-Month Results of a Community-Based Randomized Controlled Trial
Jin-Hee Lee, Sun-Young Lim, Seon-Ah Cha, Chan-Jung Han, Ah Reum Jung, Kook-Rye Kim, Kun-Ho Yoon, Seung-Hyun Ko
Diabetes Metab J. 2021;45(6):960-965.   Published online March 17, 2021
DOI: https://doi.org/10.4093/dmj.2020.0225
  • 7,495 View
  • 174 Download
  • 9 Web of Science
  • 10 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The aims of this study were to determine the short-term effectiveness of an internet-based lifestyle modification (LSM) program in preventing the onset of type 2 diabetes mellitus (T2DM) in prediabetes patients in community settings. A total of 415 subjects who were diagnosed with prediabetes were randomly assigned to the LSM and standard management (SM) groups. After the 6-month intervention, the LSM group had a statistically significant reduction in body weight, body mass index compared to the SM group participants. In the LSM group, blood glucose levels were significantly decreased after intervention and the clinical improvement effect was evident in the group that achieved the target weight loss of 5% or more of the initial weight for 6 months. Internet-based 6-month-intensive LSM programs conducted by public health center personnel are an effective way to provide lifestyle intervention programs and encourage maintenance of healthy behaviors in subjects with a high risk of T2DM in community settings.

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  • 2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
    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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    Tanja Fredensborg Holm, Flemming Witt Udsen, Iben Engelbrecht Giese, Kristine Færch, Morten Hasselstrøm Jensen, Bernt Johan von Scholten, Stine Hangaard
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    Eun Young Lee, Seon-Ah Cha, Jae-Seung Yun, Sun-Young Lim, Jin-Hee Lee, Yu-Bae Ahn, Kun-Ho Yoon, Min Kyung Hyun, Seung-Hyun Ko
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Drug/Regimen
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A Century of Progress in Diabetes Care with Insulin: A History of Innovations and Foundation for the Future
Seung-Hwan Lee, Kun-Ho Yoon
Diabetes Metab J. 2021;45(5):629-640.   Published online September 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0163
  • 13,482 View
  • 619 Download
  • 20 Web of Science
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The year 2021 marks the 100th anniversary of the discovery of insulin, which has greatly changed the lives of people with diabetes and become a cornerstone of advances in medical science. A rapid bench-to-bedside application of the lifesaving pancreatic extract and its immediate commercialization was the result of a promising idea, positive drive, perseverance, and collaboration of Banting and colleagues. As one of the very few proteins isolated in a pure form at that time, insulin also played a key role in the development of important methodologies and in the beginning of various fields of modern science. Since its discovery, insulin has evolved continuously to optimize the care of people with diabetes. Since the 1980s, recombinant DNA technology has been employed to engineer insulin analogs by modifying their amino acid sequence, which has resulted in the production of insulins with various profiles that are currently used. However, unmet needs in insulin treatment still exist, and several forms of future insulins are under development. In this review, we discuss the past, present, and future of insulin, including a history of ceaseless innovations and collective intelligence. We believe that this story will be a solid foundation and an unerring guide for the future.

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Guideline/Fact Sheet
Article image
2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim, Sang Youl Rhee, You-Bin Lee, Sang-Man Jin, Jae Hyeon Kim, Chong Hwa Kim, Dae Jung Kim, SungWan Chun, Eun-Jung Rhee, Hyun Min Kim, Hyun Jung Kim, Donghyun Jee, Jae Hyun Kim, Won Seok Choi, Eun-Young Lee, Kun-Ho Yoon, Seung-Hyun Ko, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2021;45(4):461-481.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0156
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

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Drug/Regimen
Article image
Effect of Dapagliflozin as an Add-on Therapy to Insulin on the Glycemic Variability in Subjects with Type 2 Diabetes Mellitus (DIVE): A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study
Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon
Diabetes Metab J. 2021;45(3):339-348.   Published online May 28, 2020
DOI: https://doi.org/10.4093/dmj.2019.0203
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.

Methods

In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).

Results

At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P<0.001), glycated albumin (−3.94%±2.55% vs. −0.67%±2.48%, P<0.001), and CGM-derived mean glucose (−41.6±39.2 mg/dL vs. 1.1±46.2 mg/dL, P<0.001) levels were observed in the dapagliflozin group compared with the placebo group. SD and MAGE were significantly decreased in the dapagliflozin group, but not in the placebo group. However, the difference in ΔSD and ΔMAGE failed to reach statistical significance between two groups. No significant differences in the incidence of safety endpoints were observed between the two groups.

Conclusion

Dapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.

Citations

Citations to this article as recorded by  
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Independent Impact of Diabetes on the Severity of Coronavirus Disease 2019 in 5,307 Patients in South Korea: A Nationwide Cohort Study (Diabetes Metab J 2020;44:737-46)
Sun Joon Moon, Eun-Jung Rhee, Won-Young Lee, Kun-Ho Yoon
Diabetes Metab J. 2020;44(6):942-943.   Published online December 23, 2020
DOI: https://doi.org/10.4093/dmj.2020.0266
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COVID-19
Article image
Independent Impact of Diabetes on the Severity of Coronavirus Disease 2019 in 5,307 Patients in South Korea: A Nationwide Cohort Study
Sun Joon Moon, Eun-Jung Rhee, Jin-Hyung Jung, Kyung-Do Han, Sung-Rae Kim, Won-Young Lee, Kun-Ho Yoon
Diabetes Metab J. 2020;44(5):737-746.   Published online October 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0141
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Inconsistent results have been observed regarding the independent effect of diabetes on the severity of coronavirus disease 2019 (COVID-19). We conducted a nationwide population-based cohort study to evaluate the relationship between diabetes and COVID-19 severity in South Korea.
Methods
Patients with laboratory-confirmed COVID-19 aged ≥30 years were enrolled and medical claims data were obtained from the Korean Health Insurance Review and Assessment Service. Hospitalization, oxygen treatment, ventilator application, and mortality were assessed as severity outcomes. Multivariate logistic regression analyses were performed after adjusting for age, sex, and comorbidities.
Results
Of 5,307 COVID-19 patients, the mean age was 56.0±14.4 years, 2,043 (38.5%) were male, and 770 (14.5%) had diabetes. The number of patients who were hospitalized, who received oxygen, who required ventilator support, and who died was 4,986 (94.0%), 884 (16.7%), 121 (2.3%), and 211 (4.0%), respectively. The proportion of patients with diabetes in the abovementioned outcome groups was 14.7%, 28.1%, 41.3%, 44.6%, showing an increasing trend according to outcome severity. In multivariate analyses, diabetes was associated with worse outcomes, with an adjusted odds ratio (aOR) of 1.349 (95% confidence interval [CI], 1.099 to 1.656; P=0.004) for oxygen treatment, an aOR of 1.930 (95% CI, 1.276 to 2.915; P<0.001) for ventilator use, and an aOR of 2.659 (95% CI, 1.896 to 3.729; P<0.001) for mortality.
Conclusion
Diabetes was associated with worse clinical outcomes in Korean patients with COVID-19, independent of other comorbidities. Therefore, patients with diabetes and COVID-19 should be treated with caution.

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Complications
Article image
Differences in Clinical Outcomes between Patients with and without Hypoglycemia during Hospitalization: A Retrospective Study Using Real-World Evidence
Jeongmin Lee, Tong Min Kim, Hyunah Kim, Seung-Hwan Lee, Jae Hyoung Cho, Hyunyong Lee, Hyeon Woo Yim, Kun-Ho Yoon, Hun-Sung Kim
Diabetes Metab J. 2020;44(4):555-565.   Published online May 8, 2020
DOI: https://doi.org/10.4093/dmj.2019.0064
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Some patients admitted to hospitals for glycemic control experience hypoglycemia despite regular meals and despite adhering to standard blood glucose control protocols. Different factors can have a negative impact on blood glucose control and prognosis after discharge. This study investigated risk factors for hypoglycemia and its effects on glycemic control during the hospitalization of patients in the general ward.

Methods

This retrospective study included patients who were admitted between 2009 and 2018. Patients were provided regular meals at fixed times according to ideal body weights during hospitalization. We categorized the patients into two groups: those with and those without hypoglycemia during hospitalization.

Results

Of the 3,031 patients, 379 experienced at least one episode of hypoglycemia during hospitalization (HYPO group). Hypoglycemia occurred more frequently particularly in cases of premixed insulin therapy. Compared with the control group, the HYPO group was older (61.0±16.8 years vs. 59.1±16.5 years, P=0.035), with more females (60.4% vs. 49.6%, P<0.001), lower body mass index (BMI) (23.5±4.2 kg/m2 vs. 25.1±4.4 kg/m2, P<0.001), and higher prevalence of type 1 diabetes mellitus (6.1% vs. 2.6%, P<0.001), They had longer hospital stay (11.1±13.5 days vs. 7.6±4.6 days, P<0.001). After discharge the HYPO group had lower glycosylated hemoglobin reduction rate (−2.0%±0.2% vs. −2.5%±0.1%, P=0.003) and tended to have more frequent cases of cardiovascular disease.

Conclusion

Hypoglycemia occurred more frequently in older female patients with lower BMI and was associated with longer hospital stay and poorer glycemic control after discharge. Therefore, clinicians must carefully ensure that patients do not experience hypoglycemia during hospitalization.

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Drug/Regimen
Use of SGLT-2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Abdominal Obesity: An Asian Perspective and Expert Recommendations
Wayne Huey-Herng Sheu, Siew Pheng Chan, Bien J. Matawaran, Chaicharn Deerochanawong, Ambrish Mithal, Juliana Chan, Ketut Suastika, Chin Meng Khoo, Huu Man Nguyen, Ji Linong, Andrea Luk, Kun-Ho Yoon
Diabetes Metab J. 2020;44(1):11-32.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2019.0208
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AbstractAbstract PDFPubReader   

The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM.

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    Kyoung Hwa Ha, Dae Jung Kim, Yong Jun Choi
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    Rongfeng Han, Yang Zhang, Xia Jiang
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    Ayako Nagayama, Kenji Ashida, Miki Watanabe, Kanoko Moritaka, Aya Sonezaki, Yoichiro Kitajima, Hirokazu Takahashi, Satoko Yoshinobu, Shimpei Iwata, Junichi Yasuda, Nao Hasuzawa, Shuichi Ozono, Seiichi Motomura, Masatoshi Nomura
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    Hayato Tanabe, Hiroaki Masuzaki, Michio Shimabukuro
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  • SGLT2 Inhibitors as Add-On Therapy to Metformin for People with Type 2 Diabetes: A Review of Placebo-Controlled Trials in Asian versus Non-Asian Patients


    André J Scheen
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    Yoshifumi Saisho
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Clinical Diabetes & Therapeutics
Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
Hae Kyung Yang, Seung-Hwan Lee, Juyoung Shin, Yoon-Hee Choi, Yu-Bae Ahn, Byung-Wan Lee, Eun Jung Rhee, Kyung Wan Min, Kun-Ho Yoon
Diabetes Metab J. 2019;43(3):287-301.   Published online December 20, 2018
DOI: https://doi.org/10.4093/dmj.2018.0054
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin.

Methods

A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24.

Results

The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups.

Conclusion

In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.

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  • The effect of acarbose on inflammatory cytokines and adipokines in adults: a systematic review and meta-analysis of randomized clinical trials
    Ali Mohammadian, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Niloufar Rasaei, Hossein Bahari, Samira Rastgoo, Reza Bagheri, Farideh Shiraseb, Omid Asbaghi
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    Elnaz Golalipour, Dorsa Hosseininasab, Mahlagha Nikbaf-Shandiz, Niloufar Rasaei, Hossein Bahari, Mahya Mehri Hajmir, Samira Rastgoo, Farideh Shiraseb, Omid Asbaghi
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    Choong Whan Lee, Byoung Hoon You, Sreymom Yim, Seung Yon Han, Hee-Sung Chae, Mingoo Bae, Seo-Yeon Kim, Jeong-Eun Yu, Jieun Jung, Piseth Nhoek, Hojun Kim, Han Seok Choi, Young-Won Chin, Hyun Woo Kim, Young Hee Choi
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  • The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials
    Mohsen Yousefi, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Samira Rastgoo, Reza Bagher, Alireza Khadem, Farideh Shiraseb, Omid Asbaghi
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  • A systematic review, meta-analysis, dose-response, and meta-regression of the effects of acarbose intake on glycemic markers in adults
    Sina Raissi Dehkordi, Naseh Pahlavani, Mahlagha Nikbaf-Shandiz, Reza Bagheri, Niloufar Rasaei, Melika Darzi, Samira Rastgoo, Hossein Bahari, Farideh Shiraseb, Omid Asbaghi
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Complications
Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus
Yeoree Yang, Eun-Young Lee, Jae-Hyoung Cho, Yong-Moon Park, Seung-Hyun Ko, Kun-Ho Yoon, Moo-Il Kang, Bong-Yun Cha, Seung-Hwan Lee
Diabetes Metab J. 2018;42(6):496-512.   Published online September 28, 2018
DOI: https://doi.org/10.4093/dmj.2018.0026
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus.

Methods

In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements.

Results

A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%).

Conclusion

CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

Citations

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  • Intensified glycemic control by HbA1c for patients with coronary heart disease and Type 2 diabetes: a review of findings and conclusions
    Jingyang Chen, Dong Yin, Kefei Dou
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
  • Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis
    Hyunah Kim, Da Young Jung, Seung-Hwan Lee, Jae-Hyoung Cho, Hyeon Woo Yim, Hun-Sung Kim
    Journal of Korean Medical Science.2023;[Epub]     CrossRef
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    Haejung Lee, Gaeun Park, Ah Reum Khang
    Asian Nursing Research.2023; 17(5): 259.     CrossRef
  • The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study
    Natsumi Matsuoka-Uchiyama, Haruhito A. Uchida, Shugo Okamoto, Yasuhiro Onishi, Katsuyoshi Katayama, Mariko Tsuchida-Nishiwaki, Hidemi Takeuchi, Rika Takemoto, Yoshiko Hada, Ryoko Umebayashi, Naoko Kurooka, Kenji Tsuji, Jun Eguchi, Hirofumi Nakajima, Kenic
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    Xiaochun Zhang, Xue Yang, Bao Sun, Chunsheng Zhu
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    Yun-Ru Lai, Chih-Cheng Huang, Wen-Chan Chiu, Rue-Tsuan Liu, Nai-Wen Tsai, Hung-Chen Wang, Wei-Che Lin, Ben-Chung Cheng, Yu-Jih Su, Chih-Min Su, Sheng-Yuan Hsiao, Pei-Wen Wang, Jung-Fu Chen, Cheng-Hsien Lu
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Epidemiology
Serum Betatrophin Concentrations and the Risk of Incident Diabetes: A Nested Case-Control Study from Chungju Metabolic Disease Cohort
Seung-Hwan Lee, Marie Rhee, Hyuk-Sang Kwon, Yong-Moon Park, Kun-Ho Yoon
Diabetes Metab J. 2018;42(1):53-62.   Published online November 3, 2017
DOI: https://doi.org/10.4093/dmj.2018.42.1.53
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AbstractAbstract PDFPubReader   
Background

Betatrophin is a newly identified hormone derived from the liver and adipose tissue, which has been suggested to regulate glucose and lipid metabolism. Circulating levels of betatrophin are altered in various metabolic diseases, although the results are inconsistent. We aimed to examine whether betatrophin is a useful biomarker in predicting the development of diabetes.

Methods

A nested case-control study was performed using a prospective Chungju Metabolic disease Cohort Study. During a 4-year follow-up period, we analyzed 167 individuals who converted to diabetes and 167 non-converters, who were matched by age, sex, and body mass index. Serum betatrophin levels were measured by an ELISA (enzyme-linked immunosorbent assay).

Results

Baseline serum betatrophin levels were significantly higher in the converter group compared to the non-converter group (1,315±598 pg/mL vs. 1,072±446 pg/mL, P<0.001). After adjusting for age, sex, body mass index, fasting plasma glucose, systolic blood pressure, total cholesterol, and family history of diabetes, the risk of developing diabetes showed a stepwise increase across the betatrophin quartile groups. Subjects in the highest baseline quartile of betatrophin levels had more than a threefold higher risk of incident diabetes than the subjects in the lowest quartile (relative risk, 3.275; 95% confidence interval, 1.574 to 6.814; P=0.010). However, no significant relationships were observed between serum betatrophin levels and indices of insulin resistance or β-cell function.

Conclusion

Circulating levels of betatrophin could be a potential biomarker for predicting new-onset diabetes. Further studies are needed to understand the underlying mechanism of this association.

Citations

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  • Maternal and cord blood betatrophin (angiopoietin‐like protein 8) in pregnant women with gestational diabetes and normoglycemic controls: A systematic review, meta‐analysis, and meta‐regression
    Faustino R. Pérez‐López, Junhua Yuan, Manuel Sánchez‐Prieto, María T. López‐Baena, Gonzalo R. Pérez‐Roncero, Seshadri Reddy Varikasuvu
    Diabetes/Metabolism Research and Reviews.2023;[Epub]     CrossRef
  • Evaluation of Adiponectin and ANGPTL8 in Women With Metabolic Syndrome in the Madinah Region of Saudi Arabia
    Walaa Mohammedsaeed, Ahmed Ahmed, Nada Alharbi, Amjaad Aljohani, Razan Alruwaithi, Reem Alharbi, Shatha Alahmadi
    Cureus.2023;[Epub]     CrossRef
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    Hassan Tavassoli, Ali Heidarianpour
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    Leonardo Catalano-Iniesta, Virginia Sánchez Robledo, María Carmen Iglesias-Osma, Amparo Galán Albiñana, Sixto Carrero, Enrique J. Blanco, Marta Carretero-Hernández, José Carretero, María José García-Barrado
    Journal of Clinical Medicine.2020; 9(2): 512.     CrossRef
  • Higher circulating levels of ANGPTL8 are associated with body mass index, triglycerides, and endothelial dysfunction in patients with coronary artery disease
    Reza Fadaei, Hossein Shateri, Johanna K. DiStefano, Nariman Moradi, Mohammad Mohammadi, Farzad Emami, Hassan Aghajani, Nasrin Ziamajidi
    Molecular and Cellular Biochemistry.2020; 469(1-2): 29.     CrossRef
  • Effects of a diet with or without physical activity on angiopoietin-like protein 8 concentrations in overweight/obese patients with newly diagnosed type 2 diabetes: a randomized controlled trial
    Hao Hu, Guoyue Yuan, Xinchen Wang, Jin Sun, Zhaohua Gao, Tingting Zhou, Wenwen Yin, Ruonan Cai, Xing Ye, Zhaoling Wang
    Endocrine Journal.2019; 66(1): 89.     CrossRef
  • The potential role of angiopoietin-like protein-8 in type 2 diabetes mellitus: a possibility for predictive diagnosis and targeted preventive measures?
    Yasmine Amr Issa, Samar Samy Abd ElHafeez, Noha Gaber Amin
    EPMA Journal.2019; 10(3): 239.     CrossRef
  • A Short Review on ANGPTL-8 as an Important Regulator in Diabetes
    Maryam Esfahani, Mohammad Taghi Goodarzi
    Avicenna Journal of Medical Biochemistry.2019; 7(2): 61.     CrossRef
Others
Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD
So-Hyun Lee, Marie Rhee, Ji-Won Kim, Kun-Ho Yoon
Diabetes Metab J. 2017;41(5):405-416.   Published online September 5, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.5.405
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

To develop surrogate insulin-producing cells for diabetes therapy, adult stem cells have been identified in various tissues and studied for their conversion into β-cells. Pancreatic progenitor cells are derived from the endodermal epithelium and formed in a manner similar to gut progenitor cells. Here, we generated insulin-producing cells from the intestinal epithelial cells that induced many of the specific pancreatic transcription factors using adenoviral vectors carrying three genes: PMB (pancreatic and duodenal homeobox 1 [Pdx1], V-maf musculoaponeurotic fibrosarcoma oncogene homolog A [MafA], and BETA2/NeuroD).

Methods

By direct injection into the intestine through the cranial mesenteric artery, adenoviruses (Ad) were successfully delivered to the entire intestine. After virus injection, we could confirm that the small intestine of the mouse was appropriately infected with the Ad-Pdx1 and triple Ad-PMB.

Results

Four weeks after the injection, insulin mRNA was expressed in the small intestine, and the insulin gene expression was induced in Ad-Pdx1 and Ad-PMB compared to control Ad-green fluorescent protein. In addition, the conversion of intestinal cells into insulin-expressing cells was detected in parts of the crypts and villi located in the small intestine.

Conclusion

These data indicated that PMB facilitate the differentiation of mouse intestinal cells into insulin-expressing cells. In conclusion, the small intestine is an accessible and abundant source of surrogate insulin-producing cells.

Citations

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  • Stem Cells Reprogramming in Diabetes Mellitus and Diabetic Complications: Recent Advances
    Hafez R. Madkor, Mostafa K. Abd El-Aziz, Mostafa S. Abd El-Maksoud, Islam M. Ibrahim, Fares E.M. Ali
    Current Diabetes Reviews.2025;[Epub]     CrossRef
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    Kelvin Baafi, John C. March
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    Lubov Borisovna Mitrofanova, Anastasia Arkadyevna Perminova, Daria Viktorovna Ryzhkova, Anna Andreyevna Sukhotskaya, Vladimir Gireyevich Bairov, Irina Leorovna Nikitina
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    Tae-young Lee, In-Su Cho, Narayan Bashyal, Francisco J Naya, Ming-Jer Tsai, Jeong Seon Yoon, Jung-Mi Choi, Chang-Hwan Park, Sung-Soo Kim, Haeyoung Suh-Kim
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    Youngsun Lee, Hye Young Choi, Ara Kwon, Hyeyeon Park, Mi-Hyun Park, Ji-Won Kim, Min Jung Kim, Yong-Ou Kim, Sungwook Kwak, Soo Kyung Koo
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Others
Exenatide versus Insulin Lispro Added to Basal Insulin in a Subgroup of Korean Patients with Type 2 Diabetes Mellitus
Kun-Ho Yoon, Elise Hardy, Jenny Han
Diabetes Metab J. 2017;41(1):69-74.   Published online December 26, 2016
DOI: https://doi.org/10.4093/dmj.2017.41.1.69
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AbstractAbstract PDFPubReader   
Background

The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations.

Methods

We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine.

Results

Exenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment.

Conclusion

This analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.

Citations

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    Ju-Ming Lu
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    Inkuk Lee, Eun Seok Kang
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    Hyun Jin Kim
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    Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
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    Hyun Jin Kim, Seok O Park, Seung-Hyun Ko, Sang Youl Rhee, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Byung-Wan Lee, Jin Hwa Kim, Kyung Mook Choi
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    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
    The Korean Journal of Internal Medicine.2017; 32(6): 967.     CrossRef
  • Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
    Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
    Diabetes & Metabolism Journal.2017; 41(5): 337.     CrossRef
  • Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
    Diabetes & Metabolism Journal.2017; 41(5): 367.     CrossRef
Clinical Care/Education
Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment
Yeoree Yang, Jeong-Ah Shin, Hae Kyung Yang, Seung-Hwan Lee, Seung-Hyun Ko, Yu-Bae Ahn, Kun-Ho Yoon, Jae-Hyoung Cho
Diabetes Metab J. 2016;40(6):454-462.   Published online October 11, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.6.454
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AbstractAbstract PDFPubReader   
Background

There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin.

Methods

In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT.

Results

Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group.

Conclusion

Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Citations

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  • Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries
    Gregory R. Fulcher, Shahid Akhtar, Saleh J. Al-Jaser, Johan Medina, Mafauzy Mohamed, Nemencio A. Nicodemus, Anne Helene Olsen, Kiran P. Singh, Adri Kok
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    Takahisa Hirose, Ching-Chu Chen, Kyu Jeung Ahn, Jacek Kiljański
    Diabetes Therapy.2019; 10(3): 805.     CrossRef
  • Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
    Diabetes & Metabolism Journal.2017; 41(5): 367.     CrossRef
  • Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017
    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
    The Korean Journal of Internal Medicine.2017; 32(6): 967.     CrossRef
Complications
Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes
Jae-Seung Yun, Seung-Hyun Ko, Sun-Hye Ko, Ki-Ho Song, Ki-Dong Yoo, Kun-Ho Yoon, Yong-Moon Park, Yu-Bae Ahn
Diabetes Metab J. 2015;39(6):498-506.   Published online July 8, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.6.498
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AbstractAbstract PDFPubReader   
Background

To investigate whether a history of prior cardiovascular disease (CVD) is associated with severe hypoglycemia (SH) in patients with type 2 diabetes.

Methods

We conducted a prospective cohort study from January 2001 to December 2012 with a median follow-up time of 9.5 years (5,814 person-years). Patients aged 25 to 75 years with type 2 diabetes and without chronic kidney disease were enrolled (n=894), and 624 patients completed follow-up. SH was defined as hypoglycemic episodes requiring hospitalization or medical care in an emergency department. We used the Cox proportional hazards regression analysis to test associations between SH episodes and potential explanatory variables.

Results

Among the 624 participants who completed follow-up, 60 patients (9.6%) had previous CVD. Compared to patients without CVD, patients with previous CVD were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline. During follow-up, 62 patients (9.9%) experienced at least one SH episode (incidence of 1.33 per 100 patient-years). The development of SH was associated with a history of CVD (hazard ratio, 1.99; 95% confidence interval, 1.07 to 3.72; P=0.031) after adjusting for sex, age, diabetic duration, hypertension, hemoglobin A1c levels, diabetic complications, cardiovascular autonomic neuropathy, and insulin use.

Conclusion

A history of CVD was an independent risk factor for the development of SH in patients with type 2 diabetes mellitus. For patients with CVD, modulation of glycemic targets and diabetic education for the prevention of hypoglycemia should be implemented.

Citations

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Effects of 6-Month Sitagliptin Treatment on Insulin and Glucagon Responses in Korean Patients with Type 2 Diabetes Mellitus
Hae Kyung Yang, Borami Kang, Seung-Hwan Lee, Hun-Sung Kim, Kun-Ho Yoon, Bong-Yun Cha, Jae-Hyoung Cho
Diabetes Metab J. 2015;39(4):335-341.   Published online July 17, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.4.335
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AbstractAbstract PDFPubReader   
Background

This study aimed to evaluate the effect of sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, on insulin secretion and glucagon suppression in Korean subjects with type 2 diabetes mellitus.

Methods

Twenty-four subjects underwent a 75-g oral glucose tolerance test (OGTT) before and after 6 months of sitagliptin treatment. Sitagliptin, insulin, and sulfonylurea were withdrawn for 3 days before OGTT to eliminate any acute effects on β-cell insulin or α-cell glucagon secretion. Venous samples were drawn five times during each OGTT to measure plasma glucose, insulin, and glucagon. Indices on insulin secretion and resistance were calculated.

Results

Early phase insulin secretion, measured by the insulinogenic index significantly increased after 6 months of sitagliptin treatment, especially in the higher baseline body mass index group and higher baseline glycosylated hemoglobin (HbA1c) group. There were no significant differences in the insulin resistance indices before and after sitagliptin treatment. Although no significant differences were observed in the absolute levels of glucagon and the glucagon-to-insulin ratio, there was a significant reduction in the percentile change of glucagon-to-insulin ratio at 30- and 120-minute during the OGTT.

Conclusion

Although the HbA1c level did not decrease significantly after 6 months of sitagliptin treatment, an increase in insulin secretion and reduction in early phase postprandial plasma glucagon-to-insulin ratio excursion was confirmed in Korean subjects with type 2 diabetes.

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
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Efficacy of the Smartphone-Based Glucose Management Application Stratified by User Satisfaction
Hun-Sung Kim, Wona Choi, Eun Kyoung Baek, Yun A Kim, So Jung Yang, In Young Choi, Kun-Ho Yoon, Jae-Hyoung Cho
Diabetes Metab J. 2014;38(3):204-210.   Published online June 17, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.3.204
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AbstractAbstract PDFPubReader   
Background

We aimed to assess the efficacy of the smartphone-based health application for glucose control and patient satisfaction with the mobile network system used for glucose self-monitoring.

Methods

Thirty-five patients were provided with a smartphone device, and self-measured blood glucose data were automatically transferred to the medical staff through the smartphone application over the course of 12 weeks. The smartphone user group was divided into two subgroups (more satisfied group vs. less satisfied group) based on the results of questionnaire surveys regarding satisfaction, comfort, convenience, and functionality, as well as their willingness to use the smartphone application in the future. The control group was set up via a review of electronic medical records by group matching in terms of age, sex, doctor in charge, and glycated hemoglobin (HbA1c).

Results

Both the smartphone group and the control group showed a tendency towards a decrease in the HbA1c level after 3 months (7.7%±0.7% to 7.5%±0.7%, P=0.077). In the more satisfied group (n=27), the HbA1c level decreased from 7.7%±0.8% to 7.3%±0.6% (P=0.001), whereas in the less satisfied group (n=8), the HbA1c result increased from 7.7%±0.4% to 8.1%±0.5% (P=0.062), showing values much worse than that of the no-smartphone control group (from 7.7%±0.5% to 7.7%±0.7%, P=0.093).

Conclusion

In addition to medical feedback, device and network-related patient satisfaction play a crucial role in blood glucose management. Therefore, for the smartphone app-based blood glucose monitoring to be effective, it is essential to provide the patient with a well-functioning high quality tool capable of increasing patient satisfaction and willingness to use.

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Statin Discontinuation after Achieving a Target Low Density Lipoprotein Cholesterol Level in Type 2 Diabetic Patients without Cardiovascular Disease: A Randomized Controlled Study
Seung-Hwan Lee, Hyuk-Sang Kwon, Yong-Moon Park, Seung-Hyun Ko, Yoon-Hee Choi, Kun-Ho Yoon, Yu-Bae Ahn
Diabetes Metab J. 2014;38(1):64-73.   Published online February 19, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.1.64
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AbstractAbstract PDFPubReader   
Background

This study investigated the rate of relapse of dyslipidemia and the factors which could predict relapse following a short-term statin discontinuation after achieving a target low density lipoprotein cholesterol (LDL-C) level in type 2 diabetic patients without cardiovascular disease (CVD).

Methods

Ninety-nine subjects on rosuvastatin treatment and whose LDL-C level was lower than 100 mg/dL were randomly assigned to discontinue or maintain statin treatment at a 2:1 ratio. The subjects were followed-up after 10 weeks. A relapse of dyslipidemia was defined as a reascent of LDL-C level to greater than 100 mg/dL.

Results

The statin discontinuation group had a significant rate of relapse compared to the maintenance group (79% vs. 3%, respectively). Pretreatment and baseline lipid levels, their ratios, and hemoglobin A1c level were significantly different between the relapse and nonrelapse groups. The pretreatment and baseline lipid profiles and their ratios were independently associated with relapse. The pretreatment LDL-C level was the most useful parameter for predicting a relapse, with a cutoff of 123 mg/dL. During the follow-up period, no CVD event was noted.

Conclusion

The relapse rate of dyslipidemia was high when statins were discontinued in type 2 diabetic patients without CVD. Statin discontinuation should be considered carefully based on the pretreatment lipid profiles of patients.

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Pattern of Stress-Induced Hyperglycemia according to Type of Diabetes: A Predator Stress Model
Jin-Sun Chang, Young-Hye You, Shin-Young Park, Ji-Won Kim, Hun-Sung Kim, Kun-Ho Yoon, Jae-Hyoung Cho
Diabetes Metab J. 2013;37(6):475-483.   Published online December 12, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.6.475
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AbstractAbstract PDFPubReader   
Background

We aimed to quantify stress-induced hyperglycemia and differentiate the glucose response between normal animals and those with diabetes. We also examined the pattern in glucose fluctuation induced by stress according to type of diabetes.

Methods

To load psychological stress on animal models, we used a predator stress model by exposing rats to a cat for 60 minutes and measured glucose level from the beginning to the end of the test to monitor glucose fluctuation. We induced type 1 diabetes model (T1D) for ten Sprague-Dawley rats using streptozotocin and used five Otsuka Long-Evans Tokushima Fatty rats as obese type 2 diabetes model (OT2D) and 10 Goto-Kakizaki rats as nonobese type 2 diabetes model (NOT2D). We performed the stress loading test in both the normal and diabetic states and compared patterns of glucose fluctuation among the three models. We classified the pattern of glucose fluctuation into A, B, and C types according to speed of change in glucose level.

Results

Increase in glucose, total amount of hyperglycemic exposure, time of stress-induced hyperglycemia, and speed of glucose increase were significantly increased in all models compared to the normal state. While the early increase in glucose after exposure to stress was higher in T1D and NOT2D, it was slower in OT2D. The rate of speed of the decrease in glucose level was highest in NOT2D and lowest in OT2D.

Conclusion

The diabetic state was more vulnerable to stress compared to the normal state in all models, and the pattern of glucose fluctuation differed among the three types of diabetes. The study provides basic evidence for stress-induced hyperglycemia patterns and characteristics used for the management of diabetes patients.

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  • Stress hyperglycemia as first sign of asymptomatic type 1 diabetes: an instructive case
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Predictive Clinical Parameters and Glycemic Efficacy of Vildagliptin Treatment in Korean Subjects with Type 2 Diabetes
Jin-Sun Chang, Juyoung Shin, Hun-Sung Kim, Kyung-Hee Kim, Jeong-Ah Shin, Kun-Ho Yoon, Bong-Yun Cha, Ho-Young Son, Jae-Hyoung Cho
Diabetes Metab J. 2013;37(1):72-80.   Published online February 15, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.1.72
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AbstractAbstract PDFPubReader   
Background

The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes.

Methods

In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics.

Results

Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (ΔHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment.

Conclusion

Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.

Citations

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  • Predictive clinical parameters for the hemoglobin A1c-lowering effect of vildagliptin in Japanese patients with type 2 diabetes
    Yukihiro Bando, Masayuki Yamada, Keiko Aoki, Hideo Kanehara, Azusa Hisada, Kazuhiro Okafuji, Daisyu Toya, Nobuyoshi Tanaka
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    Jun Sung Moon, Kyu Chang Won
    Diabetes & Metabolism Journal.2013; 37(1): 36.     CrossRef
Effects of a 6-Month Exenatide Therapy on HbA1c and Weight in Korean Patients with Type 2 Diabetes: A Retrospective Cohort Study
Juyoung Shin, Jin-Sun Chang, Hun-Sung Kim, Sun-Hee Ko, Bong-Yun Cha, Ho-Young Son, Kun-Ho Yoon, Jae-Hyoung Cho
Diabetes Metab J. 2012;36(5):364-370.   Published online October 18, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.5.364
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AbstractAbstract PDFPubReader   
Background

While many studies have shown the good efficacy and safety of exenatide in patients with diabetes, limited information is available about exenatide in clinical practice in Korean populations. Therefore, this retrospective cohort study was designed to analyze the effects of exenatide on blood glucose level and body weight in Korean patients with type 2 diabetes mellitus.

Methods

We reviewed the records of the patients with diabetes who visited Seoul St. Mary's Hospital and for whom exenatide was prescribed from June 2009 to October 2011. After excluding subjects based on their race/ethnicity, medical history, whether or not they changed more than 2 kinds of oral hypoglycemic agents with exenatide treatment, loss to follow-up, or whether they stopped exenatide therapy within 6 months, a total of 52 subjects were included in the final analysis.

Results

The mean glycated hemoglobin (HbA1c) level and weight remarkably decreased from 8.5±1.7% to 6.7±1.0% (P<0.001) and from 82.3±15.8 kg to 78.6±16.3 kg (P<0.001), respectively. The multiple regression analysis indicated that the reduction in HbA1c level was significantly associated with a shorter duration of diabetes, a higher baseline HbA1c level, and greater weight reduction, whereas weight loss had no significant correlation with other factors. No severe adverse events were observed.

Conclusion

These results suggest that a 6-month exenatide injection therapy significantly improved patients' HbA1c levels and body weights without causing serious adverse effects in Korean patients with type 2 diabetes.

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Low Density Lipoprotein Cholesterol Target Goal Attainment Rate and Physician Perceptions about Target Goal Achievement in Korean Patients with Diabetes
Jenie Yoonoo Hwang, Chang Hee Jung, Woo Je Lee, Cheol Young Park, Sung Rae Kim, Kun-Ho Yoon, Moon Kyu Lee, Sung Woo Park, Joong-Yeol Park
Diabetes Metab J. 2011;35(6):628-636.   Published online December 26, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.6.628
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AbstractAbstract PDFPubReader   
Background

This study aims to investigate the discrepancy between clinicians' perceptions and actual achievement rates of low density lipoprotein cholesterol (LDL-C) in Korean patients with diabetes according to updated American Diabetes Association (ADA)/American College of Cardiology Foundation (ACC) recommendations.

Methods

This is a multi-center, retrospective, non-interventional, observational study. Diabetic patients aged 18 years or older were eligible if they had been diagnosed with hypercholesterolemia or were receiving a lipid-lowering therapy between May 2010 and August 2010. The information was obtained by reviewing medical records and using a self-completed questionnaire to examine physician perceptions.

Results

A total of 2,591 subjects who satisfied the inclusion criteria were enrolled. Highest-risk and high-risk patients accounted for 61.9% and 38.1% of the patients, respectively. Although most (96.3%) underwent a statin monotherapy or a statin-based combination therapy, just 47.4% of patients attained the LDL-C target. However, the physicians' perceptions on target achievement rate (70.6%) were different from the actual results (47.4%). Many patients (65.3%) remained on the starting doses of statins, despite evidence of poor achievement of lipid goals.

Conclusion

Only less than half of patients with diabetes attained the LDL-C goal. The surveys showed that poor physician performance might be due to the lack of recognition on ADA/ACC consensus causing a low LDL-C target attainment rate. Therefore, changes in doctor perception are needed to attain target LDL-C level and reduce cardiovascular risk in Korean patients with diabetes.

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    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Article image
2011 Clinical Practice Guidelines for Type 2 Diabetes in Korea
Seung-Hyun Ko, Sung-Rea Kim, Dong-Joon Kim, Seung-Joon Oh, Hye-Jin Lee, Kang-Hee Shim, Mi-Hye Woo, Jun-Young Kim, Nan-Hee Kim, Jae-Taik Kim, Chong Hwa Kim, Hae Jin Kim, In-Kyung Jeong, Eun-Kyung Hong, Jae-Hyoung Cho, Ji-Oh Mok, Kun-Ho Yoon
Diabetes Metab J. 2011;35(5):431-436.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.431
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AbstractAbstract PDFPubReader   

As in other countries, type 2 diabetes is major health concern in Korea. A dramatic increase in the prevalence of type 2 diabetes and its chronic complications has led to an increase in health costs and economic burdens. Early detection of high risk individuals, hidden diabetic patients, and improvement in the quality of care for the disease are the first steps to mitigate the increase in prevalence. The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the '3rd Clinical Practice Guidelines' at the end of 2010. In the guidelines, the committee recommended active screening of high risk individuals for early detection and added the hemoglobin A1c level to the diagnostic criteria for type 2 diabetes based on clinical studies performed in Korea. Furthermore, the committee members emphasized that integrating patient education and self-management is an essential part of care. The drug treatment algorithm based on the degree of hyperglycemia and patient characteristics were also updated.

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Glucolipotoxicity in Pancreatic β-Cells
Ji-Won Kim, Kun-Ho Yoon
Diabetes Metab J. 2011;35(5):444-450.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.444
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AbstractAbstract PDFPubReader   

The recent epidemic of type 2 diabetes in Asia differs from that reported in other regions of the world in several key areas: it has evolved over a much shorter time, in an earlier stage of life, and in people with lower body mass indices. These phenotypic characteristics of patients strongly suggest that insulin secretory defects may perform a more important function in the development and progression of diabetes. A genetic element clearly underlies β-cell dysfunction and insufficient β-cell mass; however, a number of modifiable factors are also linked to β-cell deterioration, most notably chronic hyperglycemia and elevated free fatty acid (FFA) levels. Neither glucose nor FFAs alone cause clinically meaningful β-cell toxicity, especially in patients with normal or impaired glucose tolerance. Thus the term "glucolipotoxicity" is perhaps more appropriate in describing the phenomenon. Several mechanisms have been proposed to explain glucolipotoxicity-induced β-cell dysfunction and death, but its major factors appear to be depression of key transcription factor gene expression by altered intracellular energy metabolism and oxidative stress. Therefore, stabilization of metabolic changes induced by glucolipotoxicity in β-cells represents a new avenue for the treatment of type 2 diabetes mellitus.

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Management of Blood Pressure in Patients with Type 2 Diabetes Mellitus: A Nationwide Survey in Korean
Mi Hae Seo, Woo Je Lee, Cheol Young Park, Sung Rae Kim, Joong Yeol Park, Kun-Ho Yoon, Moon Kyu Lee, Sung Woo Park
Diabetes Metab J. 2011;35(4):348-353.   Published online August 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.4.348
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AbstractAbstract PDFPubReader   
Background

Hypertension is common in patients with type 2 diabetes, affecting up to 60% of patients. The Korean Diabetes Association performed a nationwide survey about prevalence, awareness and control of hypertension among diabetic Koreans.

Methods

The current survey included 3,859 diabetic patients recruited from 43 hospitals in Korea. Age, gender, height, weight and blood pressure (BP) were measured by standard methods. Data on fasting plasma glucose, glycosylated hemoglobin (HbA1c), awareness of hypertension, and compliance of antihypertensive medication were collected via interview and reviewed using patient medical records.

Results

A total of 57.5% of all patients were >60 years old. Their mean HbA1c was 7.6±1.5%. Among antihypertensive medication users, 39.9% had <130 mm Hg and <80 mm Hg, whereas 60.1% had ≥130 mm Hg or ≥80 mm Hg. The answer "BP is under good control" was given by 75.1% of the antihypertensive medication users. Out of these patients, 26.4% had <130 mm Hg and <80 mm Hg, whereas 73.6% had ≥130 mm Hg or ≥80 mm Hg. A total of 75.5% of antihypertensive medication users answered that they had taken their antihypertensive medication every day for the past 2 weeks. "Forgetfulness" was most frequently the reason of non-compliance for patients that did not take their antihypertensive medication regularly.

Conclusion

Approximately one third of the patients with diabetes were found to reach target blood pressure control in the 43 hospitals across Korea. Stricter control is needed to reduce severe complications of diabetes in Korea.

Citations

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Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells
Young-Hye You, Dong-Sik Ham, Heon-Seok Park, Marie Rhee, Ji-Won Kim, Kun-Ho Yoon
Diabetes Metab J. 2011;35(2):119-129.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.119
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AbstractAbstract PDFPubReader   
Background

A limitation in the number of insulin-producing pancreatic beta-cells is a special feature of diabetes. The identification of alternative sources for the induction of insulin-producing surrogate beta-cells is a matter of profound importance. PDX-1/VP16, BETA2/NeuroD, and MafA overexpression have been shown to influence the differentiation and proliferation of pancreatic stem cells. However, few studies have been conducted using adult animal pancreatic stem cells.

Methods

Adult pig pancreatic cells were prepared from the non-endocrine fraction of adult pig pancreata. Porcine neonatal pancreas cell clusters (NPCCs) were prepared from neonatal pigs aged 1-2 days. The dispersed pancreatic cells were infected with PDX-1/VP16, BETA2/NeuroD, and MafA adenoviruses. After infection, these cells were transplanted under the kidney capsules of normoglycemic nude mice.

Results

The adenovirus-mediated overexpression of PDX-1, BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in adult pig pancreatic cells. Immunocytochemistry revealed that the number of insulin-positive cells in NPCCs and adult pig pancreatic cells was approximately 2.6- and 1.1-fold greater than those in the green fluorescent protein control group, respectively. At four weeks after transplantation, the relative volume of insulin-positive cells in the grafts increased in the NPCCs, but not in the adult porcine pancreatic cells.

Conclusion

These data indicate that PDX-1, BETA2/NeuroD, and MafA facilitate the beta-cell differentiation of NPCCs, but not adult pig pancreatic cells. Therefore PDX-1, BETA2/NeuroD, and MafA-induced NPCCs can be considered good sources for the induction of pancreatic beta-cells, and may also have some utility in the treatment of diabetes.

Citations

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Repeated Gene Transfection Impairs the Engraftment of Transplanted Porcine Neonatal Pancreatic Cells
Min Koo Seo, Cheng-Lin Sun, Ji-Won Kim, Kun-Ho Yoon, Suk Kyeong Lee
Diabetes Metab J. 2011;35(1):72-79.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.72
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AbstractAbstract PDFPubReader   
Background

Previously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF) gene in an Epstein-Barr virus (EBV)-based plasmid (pEBVHGF) showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.

Methods

Neonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.

Results

Re-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF).

Conclusion

For clinical application of transfected neonatal porcine pancreatic cells, further studies are required to develop methods of overcoming the damage for the cells caused by repeated transfection and to re-aggregate them into islet-like structures.

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Ubiquitous Diabetes Management System via Interactive Communication Based on Information Technologies: Clinical Effects and Perspectives
Jae-Hyoung Cho, Hun-Sung Kim, Jae-Hoon Han, Jin-Hee Lee, Jeong-Ah Oh, Yoon-Hee Choi, Kun-Ho Yoon
Korean Diabetes J. 2010;34(5):267-273.   Published online October 31, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.5.267
  • 4,681 View
  • 30 Download
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AbstractAbstract PDFPubReader   

New diabetes management systems based on interactive communication have been introduced recently, accompanying rapid advances in information technology; these systems are referred to as "ubiquitous diabetes management systems." In such ubiquitous systems, patients and medical teams can communicate via Internet or telecommunications, with patients uploading their glucose data and personal information, and medical teams sending optimal feedback. Clinical evidence from both long-term and short-term trials has been reported by some researchers. Such systems appear to be effective not only in reducing the levels of HbA1c but also in stabilizing glucose control. However, most notably, evidence for the cost-effectiveness of such a system should be demonstrated before it can be propagated out to the general population in actual clinical practice. To establish a cost-effective model, various types of clinical decision supporting software designed to reduce the labor time of physicians must first be developed. A number of sensors and devices for monitoring patients' data are expected to be available in the near future; thus, methods for automatic interconnections between devices and web charts were also developed. Further investigations to demonstrate the clinical outcomes of such a system should be conducted, hopefully leading to a new paradigm of diabetes management.

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