Diabetes & Metabolism Journal

Original Articles

Others
Efficacy and Safety of HD-6277, a Novel G Protein-Coupled Receptor 40 Agonist, in Individuals with Type 2 Diabetes Mellitus: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 2 Clinical Trial: Yong-ho Lee, Kyung Wan Min, Jun Hwa Hong, Soo Lim, Jae Myung Yu, Choon Hee Chung, Jun Sung Moon, Jong Chul Won, Chul Woo Ahn, Jie-Eun Lee, Tae Nyun Kim, Byung-Wan Lee; Received July 17, 2025 Accepted October 11, 2025 Published online December 19, 2025; DOI: https://doi.org/10.4093/dmj.2025.0528 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
This study assessed the efficacy and safety of HD-6277, a novel oral G protein-coupled receptor 40 (GPR40) agonist in adults with inadequate control of type 2 diabetes mellitus (T2DM).
Methods
This double-blind, randomized, placebo-controlled phase 2 trial recruited 112 individuals aged 18–75 years with T2DM and glycosylated hemoglobin (HbA1c) levels between 7.0% and 10.0% while on diet and exercise alone for at least 8 weeks before screening. Parallel-group randomized trials of HD-6277 (50 and 100 mg groups vs. placebo) were conducted for 12 weeks. The primary outcome was the change in HbA1c levels from baseline to week 12. Secondary outcomes included changes in HbA1c, fasting plasma glucose (FPG), postprandial glucose, insulin, glycoalbumin, and C-peptide at weeks 4, 8, and 12.
Results
At week 12, HD-6277 at 50 and 100 mg demonstrated statistically significant reductions in HbA1c compared to placebo, with least square (LS) mean differences of –0.73% (95% confidence interval [CI], –1.11 to –0.35; P=0.0002) and –0.85% (95% CI, –1.21 to –0.50; P<0.0001), respectively. Both doses also produced clinically meaningful reductions in FPG. Additionally, HD- 6277 at 100 mg significantly increased the insulinogenic index compared to placebo, with an LS mean difference of 1.91 (95% CI, 0.34 to 3.48; P=0.0175). No clinically relevant treatment-related adverse events were observed.
Conclusion
HD-6277 at 50 and 100 mg improved glycemic control and was well-tolerated in adults with T2DM inadequately managed with diet and exercise. GPR40 agonists may offer a promising new therapeutic option for T2DM.

Guideline/Statement/Fact Sheet
2025 Clinical Practice Guidelines for Diabetes Management in Korea: Recommendation of the Korean Diabetes Association: Shinae Kang, Seon Mee Kang, Jong Han Choi, Seung-Hyun Ko, Bo Kyung Koo, Hyuk-Sang Kwon, Mi Kyung Kim, Sang Yong Kim, Soo-Kyung Kim, Young-eun Kim, Eun Sook Kim, Jae Hyeon Kim, Chong Hwa Kim, Ji Min Kim, Hae Jin Kim, Min Kyong Moon, Sun Joon Moon, Jun Sung Moon, Joon Ho Moon, Se Hee Min, Jung Hwan Park, Jaehyun Bae, Keeho Song, Ji Yoon Ahn, Jae-Seung Yun, Woo Je Lee, You-Bin Lee, Suk Chon, Eonju Jeon, Sang-Man Jin, Eugene Han, You-Cheol Hwang, Jae Hyun Bae, YoonJu Song, Jeong Hyun Lim, Jae Won Cho, Ji Yeon Choi, Yong Hee Hong, Jieun Lee, Sung Eun Kim, Ji Yun Noh, Bong-Soo Cha, Byung-Wan Lee; Diabetes Metab J. 2025;49(4):582-783. Published online July 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0469

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Impact of smart watch mobile application on the risk treatment of type 2 diabetes mellitus (iSMART-DM)
Min Kyoung Jang, Yun Kyung Cho, Jung Yoon Moon, Se Hee Min, Ju Hee Hwang, Chang Hee Jung
Primary Care Diabetes.2026; 20(1): 47. CrossRef
Efficacy and safety of adding a fourth oral antidiabetic drug versus metformin dose escalation in patients with type 2 diabetes inadequately controlled on triple oral combination therapy (EFFORT): A 24‐week, randomized, open‐label, multicenter trial
So Ra Kim, Jun Hwa Hong, Sin Gon Kim, Soo‐Kyung Kim, Hyuk‐Sang Kwon, Jun Sung Moon, Jung Hwan Park, Jae Myung Yu, Bong‐Soo Cha, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2026;[Epub] CrossRef
Glucagon-like Peptide-1 Receptor Agonists and Gastrointestinal Neoplasms
Yu Jin Kim, Jaehyun Bae
Journal of Digestive Cancer Research.2025; 13(2): 99. CrossRef
Is the next STEP on the BPROAD to intensive blood pressure lowering for all type 2 diabetic patients?: consensus statements from the Korean Society of Hypertension
Eun Mi Lee, In-Jeong Cho, Hae Jin Kim, Dae-Hee Kim, Hae-Young Lee, Sungha Park, Sang-Hyun Ihm
Clinical Hypertension.2025;[Epub] CrossRef
Lifestyle prescriptions for diabetes management in primary care: a narrative review
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Efficacy and safety of combining empagliflozin in people with type 2 diabetes mellitus uncontrolled with metformin and sitagliptin: A randomised, double‐blind, multicentre, therapeutic confirmatory phase 3 clinical trial
Seung‐Hwan Lee, Kyung Ah Han, Eun‐Gyoung Hong, Jun Goo Kang, Choon Hee Chung, Jong Chul Won, Eon Ju Jeon, Jung‐Hwan Cho, Ho Chan Cho, Sin Gon Kim, Eun Seok Kang, So Hun Kim, Hae Jin Kim, In‐Kyung Jeong, Sung Wan Chun, Young Min Cho
Diabetes, Obesity and Metabolism.2025;[Epub] CrossRef
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Pharmacotherapy
Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP): Nam Hoon Kim, Soo Lim, In-Kyung Jeong, Eun-Jung Rhee, Jun Sung Moon, Ohk-Hyun Ryu, Hyuk-Sang Kwon, Jong Chul Won, Sang Soo Kim, Sang Yong Kim, Bon Jeong Ku, Heung Yong Jin, Sin Gon Kim, Bong-Soo Cha, on Behalf of Investigators of ENVELOP Study; Diabetes Metab J. 2025;49(2):225-234. Published online January 6, 2025; DOI: https://doi.org/10.4093/dmj.2024.0238

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Background
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Citations

Citations to this article as recorded by

Reverse translational approach to clarify the strong potency of enavogliflozin, a novel sodium-glucose cotransporter 2 inhibitor
Sun-Hwa Park, Hye-Young Ji, Ji-Soo Choi, Kyung Seok Oh, Jihoon Lee, Minyeong Pang, Im-Sook Song, Joon Seok Park
The Journal of Pharmacology and Experimental Therapeutics.2025; 392(8): 103650. CrossRef

Guideline/Fact Sheet
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 Youl Rhee, Hae Jin Kim, Hyun Min Kim, Jung Hae Ko, Nam Hoon Kim, Chong Hwa Kim, Jeeyun Ahn, Tae Jung Oh, Soo-Kyung Kim, Jaehyun Kim, Eugene Han, Sang-Man Jin, Jaehyun Bae, Eonju Jeon, Ji Min Kim, Seon Mee Kang, Jung Hwan Park, Jae-Seung Yun, Bong-Soo Cha, Min Kyong Moon, Byung-Wan Lee; Diabetes Metab J. 2024;48(4):546-708. Published online July 26, 2024; DOI: https://doi.org/10.4093/dmj.2024.0249

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Editorial

Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?: Il Rae Park, Jun Sung Moon; Diabetes Metab J. 2024;48(3):387-389. Published online May 22, 2024; DOI: https://doi.org/10.4093/dmj.2024.0168

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Original Articles

Drug Regimen
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study: Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(6):818-825. Published online November 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0171

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Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

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Drug Regimen
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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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.

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Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice.2025; (4): 55. CrossRef
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Editorial

Navigating the Seas of Glycemic Control: The Role of Continuous Glucose Monitoring in Type 1 Diabetes Mellitus: Jun Sung Moon; Diabetes Metab J. 2023;47(3):345-346. Published online May 26, 2023; DOI: https://doi.org/10.4093/dmj.2023.0125

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Original Article

Drug/Regimen
Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance: Jun Sung Moon, Nam Hoon Kim, Jin Oh Na, Jae Hyoung Cho, In-Kyung Jeong, Soon Hee Lee, Ji-Oh Mok, Nan Hee Kim, Dong Jin Chung, Jinhong Cho, Dong Woo Lee, Sun Woo Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(1):82-91. Published online June 20, 2022; DOI: https://doi.org/10.4093/dmj.2021.0356

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Background
To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus.
Methods
This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed.
Results
The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a “responder” to empagliflozin therapy.
Conclusion
Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

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Response

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study (Diabetes Metab J 2021;45:675-83): Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin; Diabetes Metab J. 2022;46(1):162-163. Published online January 27, 2022; DOI: https://doi.org/10.4093/dmj.2021.0331

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Special Editorial

Drug/Regimen
The History of Insulin Therapy in Korea: Jun Sung Moon, Jong Chul Won, Young Min Cho; Diabetes Metab J. 2021;45(5):623-628. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0171

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Response

Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus (Diabetes Metab J 2021;45:109-14): Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Jae-Han Jeon, Mi Kyung Kim, Keun-Gyu Park; Diabetes Metab J. 2021;45(2):279-280. Published online March 25, 2021; DOI: https://doi.org/10.4093/dmj.2020.0300

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Short Communication

COVID-19
Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus: Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Yin Young Lee, Nan Hee Cho, Ji-Hyun Lee, Jae-Han Jeon, Yeon-Kyung Choi, Mi Kyung Kim, Keun-Gyu Park; Diabetes Metab J. 2021;45(1):109-114. Published online December 4, 2020; DOI: https://doi.org/10.4093/dmj.2020.0226

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub

This study investigated the impact of social distancing due to coronavirus disease 2019 (COVID-19) on glycemic control in people with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the change in glycosylated hemoglobin level (ΔHbA1c) in people with T2DM who undertook social distancing because of COVID-19. We compared the ΔHbA1c between COVID-19 and non-COVID-19 cohorts that were enrolled at the same time of year. The ΔHbA1c of the COVID-19 cohort was significantly higher than that of two non-COVID-19 cohorts. Subgroup analysis according to age and baseline HbA1c level showed that social distancing significantly increased the mean HbA1c level of participants of <50 years. The ΔHbA1c of participants of <50 years and with HbA1c <7.0% in the COVID-19 cohort showed larger changes than other subgroups. In adjusted model, adjusted ΔHbA1c levels in the COVID-19 cohort remained significantly higher than those in the two other cohorts. Social distancing negatively impacts blood glucose control in people with T2DM, especially those who are younger and have good blood glucose control.

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Response

Response: The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study (Diabetes Metab J 2020;44:405–13): Seung Min Chung, June Hong Ahn, Jun Sung Moon; Diabetes Metab J. 2020;44(4):625-626. Published online August 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0167

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Risk factors and outcomes associated with diabetes mellitus in COVID-19 patients: a meta-analytic synthesis of observational studies
Upasna Gaba, Mohammad Altamish, Md Azharuddin, Mohammad Adil, Pinaki Ghosh, Bishal Gyawali, Yogesh Yadav, Manju Sharma
Journal of Diabetes & Metabolic Disorders.2022; 21(2): 1395. CrossRef
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Melina Farshbafnadi, Sara Kamali Zonouzi, Mohammadmahdi Sabahi, Mahsa Dolatshahi, Mohammad Hadi Aarabi
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Original Articles

Drug/Regimen
Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study: Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Kim, Hye Soon Kim, Il Seong Nam-Goong, Eun Sook Kim, Jin Ook Chung, Dong-Hyeok Cho, Chang Won Lee, Young Il Kim, Dong Jin Chung, Kyu Chang Won, In Joo Kim, Tae Sun Park, Duk Kyu Kim, Hosang Shon; Diabetes Metab J. 2021;45(5):675-683. Published online August 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0107

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub

Background

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Methods

From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.

Results

In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.

Conclusion

This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Citations

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Efficacy and safety of adding a fourth oral antidiabetic drug versus metformin dose escalation in patients with type 2 diabetes inadequately controlled on triple oral combination therapy (EFFORT): A 24‐week, randomized, open‐label, multicenter trial
So Ra Kim, Jun Hwa Hong, Sin Gon Kim, Soo‐Kyung Kim, Hyuk‐Sang Kwon, Jun Sung Moon, Jung Hwan Park, Jae Myung Yu, Bong‐Soo Cha, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2026;[Epub] CrossRef
Empagliflozin-based quadruple oral therapy for type 2 diabetes: a prospective cohort study
Fatemeh Moosaie, Shiva Abedinzadeh, Soghra Rabizadeh, Kimia Daneshvar, Mohammadamin Noorafrooz, Fatemeh Alsadat Mojtahedi, Niloofar Deravi, Seyede Marzie Fatemi Abhari, Akam Ramezani, Alipasha Meysamie, Marzieh Hajibabaei, Sahar Karimpour Reyhan, Mahsa Ab
Scientific Reports.2025;[Epub] CrossRef
Estimating Type 2 Diabetes Prevalence: A Model of Drug Consumption Data
Rita Oliveira, Matilde Monteiro-Soares, José Pedro Guerreiro, Rúben Pereira, António Teixeira-Rodrigues
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Nadia Gul, Inayat Ur Rehman, Yasar shah, Arbab Muhammad Ali, Zahid Ali, Omer Shehzad, Khang Wen Goh, Long Chiau Ming, Amal K. Suleiman, Nimesh Lageju
PLOS ONE.2024; 19(11): e0311435. CrossRef
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Covid-19
The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea: Mi Kyung Kim, Jae-Han Jeon, Sung-Woo Kim, Jun Sung Moon, Nan Hee Cho, Eugene Han, Ji Hong You, Ji Yeon Lee, Miri Hyun, Jae Seok Park, Yong Shik Kwon, Yeon-Kyung Choi, Ki Tae Kwon, Shin Yup Lee, Eon Ju Jeon, Jin-Woo Kim, Hyo-Lim Hong, Hyun Hee Kwon, Chi Young Jung, Yin Young Lee, Eunyeoung Ha, Seung Min Chung, Jian Hur, June Hong Ahn, Na-young Kim, Shin-Woo Kim, Hyun Ha Chang, Yong Hoon Lee, Jaehee Lee, Keun-Gyu Park, Hyun Ah Kim, Ji-Hyun Lee; Diabetes Metab J. 2020;44(4):602-613. Published online August 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0146

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Abstract PDF Supplementary Material PubReader ePub

Background

Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes.

Methods

We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group.

Results

Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease.

Conclusion

DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

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Response

Response: Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports (Diabetes Metab J 2020;44:349–53): Na-young Kim, Eunyeong Ha, Jun Sung Moon, Yong-Hoon Lee, Eun Young Choi; Diabetes Metab J. 2020;44(3):484-485. Published online June 29, 2020; DOI: https://doi.org/10.4093/dmj.2020.0129; [Original]

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Original Article

Complications
The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study: Seung Min Chung, Yin Young Lee, Eunyeong Ha, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee, Jian Hur, Kyung Soo Hong, Jong Geol Jang, Hyun Jung Jin, Eun Young Choi, Kyeong-Cheol Shin, Jin Hong Chung, Kwan Ho Lee, June Hong Ahn, Jun Sung Moon; Diabetes Metab J. 2020;44(3):405-413. Published online May 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0105

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Background

To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM.

Methods

This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group.

Results

After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of ≥70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045).

Conclusion

The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.

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Brief Report

Complications
Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports: Na-young Kim, Eunyeong Ha, Jun Sung Moon, Yong-Hoon Lee, Eun Young Choi; Diabetes Metab J. 2020;44(2):349-353. Published online April 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0091

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Since the first case was contracted by coronavirus disease-19 (COVID-19) in Daegu, Korea in February 2020, about 6,800 cases and 130 deaths have been reported on April 9, 2020. Recent studies have reported that patients with diabetes showed higher mortality and they had a worse prognosis than the group without diabetes. In poorly controlled patients with diabetes, acute hyperglycemic crises such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) also might be precipitated by COVID-19. Thus, intensive monitoring and aggressive supportive care should be needed to inadequately controlled patients with diabetes and COVID-19 infection. Here, we report two cases of severe COVID-19 patients with acute hyperglycemic crises in Korea.

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Review

Basic Research
The Role of CD36 in Type 2 Diabetes Mellitus: β-Cell Dysfunction and Beyond: Jun Sung Moon, Udayakumar Karunakaran, Elumalai Suma, Seung Min Chung, Kyu Chang Won; Diabetes Metab J. 2020;44(2):222-233. Published online April 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0053

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Abstract PDF PubReader ePub

Impaired β-cell function is the key pathophysiology of type 2 diabetes mellitus, and chronic exposure of nutrient excess could lead to this tragedy. For preserving β-cell function, it is essential to understand the cause and mechanisms about the progression of β-cells failure. Glucotoxicity, lipotoxicity, and glucolipotoxicity have been suggested to be a major cause of β-cell dysfunction for decades, but not yet fully understood. Fatty acid translocase cluster determinant 36 (CD36), which is part of the free fatty acid (FFA) transporter system, has been identified in several tissues such as muscle, liver, and insulin-producing cells. Several studies have reported that induction of CD36 increases uptake of FFA in several cells, suggesting the functional interplay between glucose and FFA in terms of insulin secretion and oxidative metabolism. However, we do not currently know the regulating mechanism and physiological role of CD36 on glucolipotoxicity in pancreatic β-cells. Also, the downstream and upstream targets of CD36 related signaling have not been defined. In the present review, we will focus on the expression and function of CD36 related signaling in the pancreatic β-cells in response to hyperglycemia and hyperlipidemia (ceramide) along with the clinical studies on the association between CD36 and metabolic disorders.

Citations

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Letter

Letter: Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study (Diabetes Metab J 2019;43:640–8): Jun Sung Moon; Diabetes Metab J. 2019;43(6):911-912. Published online December 26, 2019; DOI: https://doi.org/10.4093/dmj.2019.0207

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Brief Report

Complications
Short-Term Walking Outcomes in Diabetic and Non-Diabetic Unilateral Transtibial Amputees: Dong Gyu Kwak, Jeong-Yong Hur, Jun Sung Moon, Min Cheol Chang; Diabetes Metab J. 2020;44(4):614-618. Published online November 4, 2019; DOI: https://doi.org/10.4093/dmj.2019.0080

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This study compared short-term walking outcomes in diabetic amputees after prosthesis fitting compared to that in non-diabetic amputees. We retrospectively investigated walking outcomes at 3 months after starting gait training with a prosthesis. Forty-four unilateral transtibial amputees with (n=18) and without diabetes (n=26) were included. At 3 months after gait training with a prosthesis, only 2/18 (11.1%) and 3/18 (16.7%) diabetic amputees were capable of independent outdoor and indoor walking without cane, respectively. However, 21/26 (80.8%) and 24/26 (92.3%) non-diabetic amputees were capable of independent outdoor and indoor walking without cane, respectively. With assistance of cane, most of non-diabetic amputees (n=24, 92.3%) were capable of walking in both outdoor and indoor but only seven (38.9%) and nine (50.0%) diabetic amputees were capable, respectively. Thus, short-term walking outcome were poor in transtibial amputee with diabetes compare to those without diabetes, and these results suggest intensive rehabilitation would be needed to them.

Citations

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Angular Kinematics at Minimum Toe Clearance in People With Transtibial Amputation Using Articulated and Nonarticulated Prosthesis
Mauricio Riveras, Matthew Oldfield, Paola Catalfamo-Formento
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Naoki Suzuki, Midori Miyagi, Yoshihito Furusawa, Takahiro Miura, Takumi Agarie, Yuki Imaizumi, Chihiro Nakazawa, Tamao Takahashi, Keisuke Obata, Yumi Izumiyama, Kazunori Nishijima, Hiroyuki Miyauchi, Naoya Iwata, Tomoe Sobu, Yusuke Sekiguchi, Kota Ataka,
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Short Communication

Epidemiology
Low-Normal Free Thyroxine Levels in Euthyroid Male Are Associated with Prediabetes: Sung Woo Kim, Jae-Han Jeon, Jun Sung Moon, Eon Ju Jeon, Mi-Kyung Kim, In-Kyu Lee, Jung Beom Seo, Keun-Gyu Park; Diabetes Metab J. 2019;43(5):718-726. Published online March 19, 2019; DOI: https://doi.org/10.4093/dmj.2018.0222

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Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.

Citations

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Hypothyroidism: playing the cardiometabolic risk concerto
George J. Kahaly, Youshuo Liu, Luca Persani
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Original Article

Islet Studies and Transplantation
Myricetin Protects Against High Glucose-Induced β-Cell Apoptosis by Attenuating Endoplasmic Reticulum Stress via Inactivation of Cyclin-Dependent Kinase 5: Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Jae-Han Jeon, Nam Doo Kim, Keun-Gyu Park, Kyu Chang Won, Jaechan Leem, In-Kyu Lee; Diabetes Metab J. 2019;43(2):192-205. Published online January 16, 2019; DOI: https://doi.org/10.4093/dmj.2018.0052

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Background

Chronic hyperglycemia has deleterious effects on pancreatic β-cell function and turnover. Recent studies support the view that cyclin-dependent kinase 5 (CDK5) plays a role in β-cell failure under hyperglycemic conditions. However, little is known about how CDK5 impair β-cell function. Myricetin, a natural flavonoid, has therapeutic potential for the treatment of type 2 diabetes mellitus. In this study, we examined the effect of myricetin on high glucose (HG)-induced β-cell apoptosis and explored the relationship between myricetin and CDK5.

Methods

To address this question, we subjected INS-1 cells and isolated rat islets to HG conditions (30 mM) in the presence or absence of myricetin. Docking studies were conducted to validate the interaction between myricetin and CDK5. Gene expression and protein levels of endoplasmic reticulum (ER) stress markers were measured by real-time reverse transcription polymerase chain reaction and Western blot analysis.

Results

Activation of CDK5 in response to HG coupled with the induction of ER stress via the down regulation of sarcoendoplasmic reticulum calcium ATPase 2b (SERCA2b) gene expression and reduced the nuclear accumulation of pancreatic duodenal homeobox 1 (PDX1) leads to β-cell apoptosis. Docking study predicts that myricetin inhibit CDK5 activation by direct binding in the ATP-binding pocket. Myricetin counteracted the decrease in the levels of PDX1 and SERCA2b by HG. Moreover, myricetin attenuated HG-induced apoptosis in INS-1 cells and rat islets and reduce the mitochondrial dysfunction by decreasing reactive oxygen species production and mitochondrial membrane potential (Δψm) loss.

Conclusion

Myricetin protects the β-cells against HG-induced apoptosis by inhibiting ER stress, possibly through inactivation of CDK5 and consequent upregulation of PDX1 and SERCA2b.

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Corrigendum

Corrigendum: Hemorheologic Alterations in Patients with Type 2 Diabetes Mellitus Presented with an Acute Myocardial Infarction: Kyu-Hwan Park, Ung Kim, Kang-Un Choi, Jong-Ho Nam, Jung-Hee Lee, Chan-Hee Lee, Jang-Won Son, Jong-Seon Park, Dong-Gu Shin, Kyu-Chang Won, Jun Sung Moon, Yu Kyung Kim, Jang-Soo Suh; Diabetes Metab J. 2018;42(3):254-254. Published online June 19, 2018; DOI: https://doi.org/10.4093/dmj.2018.0096

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Original Articles

Epidemiology
The Changes of Trends in the Diagnosis and Treatment of Diabetic Foot Ulcer over a 10-Year Period: Single Center Study: Choong Hee Kim, Jun Sung Moon, Seung Min Chung, Eun Jung Kong, Chul Hyun Park, Woo Sung Yoon, Tae Gon Kim, Woong Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Diabetes Metab J. 2018;42(4):308-319. Published online April 27, 2018; DOI: https://doi.org/10.4093/dmj.2017.0076

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Background

This study aims to describe the trends in the severity and treatment modality of patients with diabetic foot ulcer (DFU) at a single tertiary referral center in Korea over the last 10 years and compare the outcomes before and after the introduction of a multidisciplinary diabetic foot team.

Methods

In this retrospective observational study, electronic medical records of patients from years 2002 to 2015 at single tertiary referral center were reviewed. Based on the year of first admission, patients were assigned to a group either before or after the year 2012, the year the diabetes team launched.

Results

Of the 338 patients with DFU, 229 were first admitted until the year 2011 (group A), while 109 were first admitted since the year 2012 (group B). Mean age was higher in group B, and ulcer size was larger than those of group A. Whereas duration of diabetes was longer in group B, glycemic control was improved (mean glycosylated hemoglobin, 9.48% vs. 8.50%). The proportion of minor lower extremity amputation (LEA) was increased, but length of hospital stay was decreased (73.7±79.6 days vs. 39.8±36.9 days). As critical ischemic limb increased, the proportion of major LEA was not decreased.

Conclusion

Improved glycemic control, multidisciplinary strategies with prompt surgical treatment resulted in reduced length of hospital stay, but these measures did not reduce major LEAs. The increase in critical ischemic limb may have played a role in the unexpected outcome, and may suggest the need for increased vascular intervention strategies in DFU treatment.

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Others
Hemorheologic Alterations in Patients with Type 2 Diabetes Mellitus Presented with an Acute Myocardial Infarction: Kyu-Hwan Park, Ung Kim, Kang-Un Choi, Jong-Ho Nam, Jung-Hee Lee, Chan-Hee Lee, Jang-Won Son, Jong-Seon Park, Dong-Gu Shin, Kyu-Chang Won, Jun Sung Moon, Yu Kyung Kim, Jang-Soo Suh; Diabetes Metab J. 2018;42(2):155-163. Published online March 21, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.155

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Background

Hemorheologic indices are known to be related to vascular complications in variable clinical settings. However, little is known about the associations between hemorheologic parameters and acute myocardial infarction (AMI) in type 2 diabetes mellitus (T2DM). The purpose of this study was to demonstrate the changes of hemorheologic environment inside of blood using hemorheologic parameters, especially the elongation index (EI) and critical shear stress (CSS) in diabetics with versus without AMI.

Methods

A total of 195 patients with T2DM were enrolled. Patients were divided into the study group with AMI (AMI+, n=77) and control group (AMI−, n=118) who had no history of coronary artery disease. Hemorheologic parameters such as EI and CSS were measured and compared between the two groups.

Results

The EI was lower (30.44%±1.77% in AMI+ and 31.47%±1.48% in AMI−, P<0.001) but the level of CSS was higher (316.13±108.20 mPa in AMI+ and 286.80±85.34 mPa in AMI−, P=0.040) in the AMI+. The CSS was significantly related to the erythrocyte sedimentation rate (R²=0.497, P<0.001) and use of dipeptidyl peptidase-4 inhibitors (R²=0.574, P=0.048).

Conclusion

Diabetics with AMI resulted in adverse hemorheologic changes with lower EI and higher CSS compared to diabetic subjects without AMI. Evaluation of the hemorheologic parameters may provide valuable supplementary information for managing patients with AMI and T2DM.

Citations

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Effects of dapagliflozin on cardiac function and short-term prognosis of patients with both acute myocardial infarction and type 2 diabetes mellitus
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Clinical Care/Education
Patient Understanding of Hypoglycemia in Tertiary Referral Centers: Nan Hee Cho, Nam Kyung Kim, Eugene Han, Jun Hwa Hong, Eon Ju Jeon, Jun Sung Moon, Mi Hae Seo, Ji Eun Lee, Hyun-Ae Seo, Mi-Kyung Kim, Hye Soon Kim; Diabetes Metab J. 2018;42(1):43-52. Published online February 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.1.43

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Background

Hypoglycemia is an important complication in the treatment of patients with diabetes. We surveyed the insight by patients with diabetes into hypoglycemia, their hypoglycemia avoidance behavior, and their level of worry regarding hypoglycemia.

Methods

A survey of patients with diabetes, who had visited seven tertiary referral centers in Daegu or Gyeongsangbuk-do, Korea, between June 2014 and June 2015, was conducted. The survey contained questions about personal history, symptoms, educational experience, self-management, and attitudes about hypoglycemia.

Results

Of 758 participants, 471 (62.1%) had experienced hypoglycemia, and 250 (32.9%) had experienced hypoglycemia at least once in the month immediately preceding the study. Two hundred and forty-two (31.8%) of the participants had received hypoglycemia education at least once, but only 148 (19.4%) knew the exact definition of hypoglycemia. Hypoglycemic symptoms identified by the participants were dizziness (55.0%), sweating (53.8%), and tremor (40.8%). They mostly chose candy (62.1%), chocolate (37.7%), or juice (36.8%) as food for recovering hypoglycemia. Participants who had experienced hypoglycemia had longer duration of diabetes and a higher proportion of insulin usage. The mean scores for hypoglycemia avoidance behavior and worry about hypoglycemia were 21.2±10.71 and 23.38±13.19, respectively. These scores tended to be higher for participants with higher than 8% of glycosylated hemoglobin, insulin use, and experience of emergency room visits.

Conclusion

Many patients had experienced hypoglycemia and worried about it. We recommend identifying patients that are anxious about hypoglycemia and educating them about what to do when they develop hypoglycemic symptoms, especially those who have a high risk of hypoglycemia.

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Severe hypoglycemia and the risk of end stage renal disease in type 2 diabetes
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Response: Patient Understanding of Hypoglycemia in Tertiary Referral Centers (Diabetes Metab J 2018;42:43-52)
Nan Hee Cho, Hye Soon Kim
Diabetes & Metabolism Journal.2018; 42(2): 175. CrossRef
Letter: Patient Understanding of Hypoglycemia in Tertiary Referral Centers (Diabetes Metab J 2018;42:43-52)
Jae-Han Jeon
Diabetes & Metabolism Journal.2018; 42(2): 173. CrossRef

Editorial

Obesity and Metabolic Syndrome
Simple Screening Using Ultrasonography for Prediction of Gestational Diabetes Mellitus: Seung Min Chung, Jun Sung Moon; Diabetes Metab J. 2017;41(6):438-439. Published online December 19, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.6.438

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Letter

Letter: Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging (Diabetes Metab J 2016;40:140-6): Jun Sung Moon; Diabetes Metab J. 2016;40(3):248-249. Published online April 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.3.248

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Editorial

Complications
Role of Bilirubin in Diabetic Vascular Complications: Can Bilirubin Predict More than Just Liver Disease?: Jun Sung Moon; Diabetes Metab J. 2015;39(5):384-386. Published online October 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.5.384

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Review

Pancreatic α-Cell Dysfunction in Type 2 Diabetes: Old Kids on the Block: Jun Sung Moon, Kyu Chang Won; Diabetes Metab J. 2015;39(1):1-9. Published online February 16, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.1.1

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Type 2 diabetes (T2D) has been known as 'bi-hormonal disorder' since decades ago, the role of glucagon from α-cell has languished whereas β-cell taking center stage. Recently, numerous findings indicate that the defects of glucagon secretion get involve with development and exacerbation of hyperglycemia in T2D. Aberrant α-cell responses exhibit both fasting and postprandial states: hyperglucagonemia contributes to fasting hyperglycemia caused by inappropriate hepatic glucose production, and to postprandial hyperglycemia owing to blunted α-cell suppression. During hypoglycemia, insufficient counter-regulation response is also observed in advanced T2D. Though many debates still remained for exact mechanisms behind the dysregulation of α-cell in T2D, it is clear that the blockade of glucagon receptor or suppression of glucagon secretion from α-cell would be novel therapeutic targets for control of hyperglycemia. Whereas there have not been remarkable advances in developing new class of drugs, currently available glucagon-like peptide-1 and dipeptidyl peptidase-IV inhibitors could be options for treatment of hyperglucagonemia. In this review, we focus on α-cell dysfunction and therapeutic potentials of targeting α-cell in T2D.

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Original Articles

Predicting Mortality of Critically Ill Patients by Blood Glucose Levels: Byung Sam Park, Ji Sung Yoon, Jun Sung Moon, Kyu Chang Won, Hyoung Woo Lee; Diabetes Metab J. 2013;37(5):385-390. Published online October 17, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.5.385

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Background

The aim of this study is to observe the outcome of critically ill patients in relation to blood glucose level at admission and to determine the optimal range of blood glucose at admission predicting lower hospital mortality among critically ill patients.

Methods

We conducted a retrospective cohort study of a total 1,224 subjects (males, 798; females, 426) admitted to intensive care unit (ICU) from 1 January 2009 to 31 December 2010. Blood glucose levels at admission were categorized into four groups (group 1, <100 mg/dL; group 2, 100 to 199 mg/dL; group 3, 200 to 299 mg/dL; and group 4, ≥300 mg/dL).

Results

Among 1,224 patients, 319 patients were already known diabetics, and 296 patients died in ICU. Five hundred fifty-seven subjects received insulin therapy, and 118 received oral hypoglycemic agents. The overall mortality rate was 24.2% (296 patients). The causes of death and mortality rates of diabetic patients were not different from nondiabetic subjects. The mortality curve showed J shape, and there were significant differences in mortality between the groups of blood glucose levels at admission. Group 2 had the lowest mortality rate (P<0.05).

Conclusion

These results suggest that serum glucose levels upon admission into ICU is associated with clinical outcomes in ICU patients. Blood glucose level between 100 and 199 mg/dL at the time of ICU admission could predict lower hospital mortality among critically ill patients.

Citations

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The Role of Skeletal Muscle in Development of Nonalcoholic Fatty Liver Disease: Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Diabetes Metab J. 2013;37(4):278-285. Published online August 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.4.278

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Background

Nonalcoholic fatty liver disease (NAFLD) is closely correlated with abnormal accumulation of visceral fat, but the role of skeletal muscle remains unclear. The aim of this study was to elucidate the role of skeletal muscle in development of NAFLD.

Methods

Among 11,116 subjects (6,242 males), we examined the effects of skeletal muscle mass and visceral fat area (VFA, by bioelectric impedance analysis) on NAFLD using by the fatty liver index (FLI).

Results

Of the total subjects (9,565 total, 5,293 males) included, 1,848 were classified as having NALFD (FLI ≥60). Body mass index, lipid profile, fasting plasma glucose, hemoglobin A1c, prevalence of type 2 diabetes (DM), hypertension (HTN), and metabolic syndrome were higher in males than females, but FLI showed no significant difference. The low FLI group showed the lowest VFA and highest skeletal muscle mass of all the groups. Skeletal muscle to visceral fat ratio (SVR) and skeletal muscle index had inverse correlations with FLI, when adjusted for age and gender. In multivariate regression analysis, SVR was negatively associated with FLI. Among SVR quartiles, the highest quartile showed very low risk of NAFLD when adjusted for age, gender, lipid profile, DM, HTN, and high sensitivity C-reactive protein from the lowest quartiles (odds ratio, 0.037; 95% confidence interval, 0.029 to 0.049).

Conclusion

Skeletal muscle mass was inversely associated with visceral fat area, and higher skeletal muscle mass may have a beneficial effect in preventing NAFLD. These results suggest that further studies are needed to ameliorate or slow the progression of sarcopenia.

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The Relationship between Metformin and Cancer in Patients with Type 2 Diabetes: Hyun Hee Chung, Jun Sung Moon, Ji Sung Yoon, Hyoung Woo Lee, Kyu Chang Won; Diabetes Metab J. 2013;37(2):125-131. Published online April 16, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.2.125

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Abstract PDF PubReader ePub

Background

Recently, several studies reported that the cancer incidence in type 2 diabetes patients is higher than in the general population. Although a number of risks are shared between cancer and diabetes patients, there have been few studies of its correlation. We evaluated the influences of several factors including low density lipoprotein cholesterol (LDL-C), albuminuria and use of metformin on the risk of cancer in patients with type 2 diabetes.

Methods

We enrolled 1,320 patients with at least 5 years of follow-up and 73 patients were diagnosed with cancer during this period. The associations of the risk factors with cancer incidence were evaluated by multiple regression analysis. The subjects were placed into two subgroups based on metformin dosage (<1,000 mg/day, ≥1,000 mg/day) and we compared cancer incidence using analysis of covariance.

Results

LDL-C and albuminuria were not significantly correlated with cancer risk. In contrast, metformin showed a reverse correlation with cancer risk (P=0.006; relative risk, 0.574). In the metformin nonadministration group, smoking, male gender, and high triglyceride levels tended to be contributing factors without statistical significance. Cancer occurence was lower in the low dose metformin group (less than 1,000 mg/day) (P=0.00).

Conclusion

These results suggest that the administration of low dose metformin in patients with type 2 diabetes may be associated with a reduced risk of cancer.

Citations

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Diagnostic Accuracy of 64-Slice MDCT Coronary Angiography for the Assessment of Coronary Artery Disease in Korean Patients with Type 2 Diabetes: Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Ihn-Ho Cho, Hyoung Woo Lee; Diabetes Metab J. 2013;37(1):54-62. Published online February 15, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.1.54

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Background

A 64-slice multidetector computed tomography (MDCT) is well known to be a useful noninvasive form of angiography for the general population, but not for certain patients with diabetes. The aim of this study was to investigate the diagnostic accuracy and usefulness of 64-slice MDCT coronary angiography for detecting coronary artery disease in Korean patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 240 patients were included, 74 of whom had type 2 diabetes (M:F=40:33; 41.8±9.5 years). We compared significant coronary stenosis (>50% luminal narrowing) in MDCT with invasive coronary angiography (ICA) by segment, artery, and patient. We also evaluated the influence of obesity and coronary calcium score on MDCT accuracy.

Results

Of the 4,064 coronary segments studied, 4,062 segments (T2DM=1,109) were assessed quantitatively by both MDCT and ICA, and 706 segments (T2DM=226) were detected as a significant lesion by ICA in all patients. Sensitivity, specificity, as well as positive and negative predictive values for the presence of significant stenosis in T2DM were: by segment, 89.4%, 96.4%, 85.8%, and 97.4%, respectively; by artery (n=222), 95.1%, 92.9%, 94.4%, and 93.8%, respectively; by patients (n=74), 98.4%, 100.0%, 98.4%, and 90.0%, respectively. Regardless of presence of diabetes, there was no significant difference in diagnostic accuracy. Obesity (≥25 kg/m²) and coronary calcium score did not also affect the diagnostic accuracy of MDCT.

Conclusion

The 64-slice MDCT coronary angiography was found to have similar diagnostic accuracy with ICA, regardless of diabetes. These results suggest MDCT may be helpful to reduce unnecessary invasive studies for patients with diabetes.

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Editorial

The Efficacy of Vildagliptin in Korean Patients with Type 2 Diabetes: Jun Sung Moon, Kyu Chang Won; Diabetes Metab J. 2013;37(1):36-39. Published online February 15, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.1.36

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Citations

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The effect of glargine versus glimepiride on pancreatic β-cell function in patients with type 2 diabetes uncontrolled on metformin monotherapy: open-label, randomized, controlled study
Jun Sung Moon, Kyoung Soo Ha, Ji Sung Yoon, Hyoung Woo Lee, Hyun Chul Lee, Kyu Chang Won
Acta Diabetologica.2014; 51(2): 277. CrossRef

Original Article

The Combination of Fasting Plasma Glucose and Glycosylated Hemoglobin as a Predictor for Type 2 Diabetes in Korean Adults.: Chan Hee Lee, Woo Jin Chang, Hyun Hee Chung, Hyun Jung Kim, Sang Hyun Park, Jun Sung Moon, Ji Eun Lee, Ji Sung Yoon, Kyung Ah Chun, Kyu Chang Won, Ihn Ho Cho, Hyoung Woo Lee; Korean Diabetes J. 2009;33(4):306-314. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.306

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Abstract PDF

BACKGROUND
The oral glucose tolerance test (OGTT) for detection of diabetes is difficult to perform in clinical settings. The aim of this study is to evaluate the performance of a more practical detection test, combined fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), as a predictor of diabetes mellitus (DM) in a Korean sample. METHODS: We examined 2,045 (M = 1,276, mean age = 47.8 +/- 9.0 yrs) medical check-up program participants between January 2002 to December 2003. FPG, HbA1c and a number of other biochemical tests were performed at baseline and four after years after initial screening. Patients who originally presented with diabetes were excluded. The characteristics of newly-diagnosed DM patients and non-diabetic patients were compared. RESULTS: The incidence of newly diagnosed diabetes was 1.6% (32/2,045) after four years of follow up. The subjects in the DM group were older, had higher levels of SBP, DBP, FPG, HbA1c, triglyceride, HDL cholesterol, GGT and LDH (P < 0.05). In multivariate logistic regression analysis, FPG (odds ratio [OR] 1.124) and HbA1c (OR 4.794) were significantly correlated with onset of diabetes (P < 0.05). The interaction parameter between FPG and HbA1c was more than 1.0, indicating that the two effects are synergistic. The predictive cut-off values of HbA1c and FPG were 5.35% (area under curve [AUC] = 0.944) and 102.5 mg/dL (AUC = 0.930), respectively. CONCLUSION: The combination of HbA1c above 5.35% and FPG above 102.5 mg/dL predicted the onset of diabetes in a Korean sample. These results suggest that the combination of FPG and HbA1c may be useful for predicting progression to type 2 diabetes in east Asians.

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Hyeongsu Kim, Minjung Lee, Haejoon Kim, Kunsei Lee, Sounghoon Chang, Vitna Kim, Jun Pyo Myong, Soyoun Jeon
Asian Nursing Research.2013; 7(2): 67. CrossRef
Impact of HbA1c Criterion on the Detection of Subjects with Increased Risk for Diabetes among Health Check-Up Recipients in Korea
Hong-Kyu Kim, Sung-Jin Bae, Jaeone Choe
Diabetes & Metabolism Journal.2012; 36(2): 151. CrossRef
The Utility of HbA1c as a Diagnostic Criterion of Diabetes
Hee-Jung Kim, Eun Young Choi, Eal Whan Park, Yoo Seock Cheong, Hong-Yoen Lee, Ji Hyun Kim
Korean Journal of Family Medicine.2011; 32(7): 383. CrossRef
Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus
Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim
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Optimal range of HbA1c for the prediction of future diabetes: A 4-year longitudinal study
Ji Cheol Bae, Eun Jung Rhee, Won Young Lee, Se Eun Park, Cheol Young Park, Ki Won Oh, Sung Woo Park, Sun Woo Kim
Diabetes Research and Clinical Practice.2011; 93(2): 255. CrossRef
The Combination of Fasting Plasma Glucose and Glycosylated Hemoglobin as a Predictor for Type 2 Diabetes in Korean Adults (Korean Diabetes J 33(4):306-314, 2009)
Soo Lim
Korean Diabetes Journal.2009; 33(5): 448. CrossRef
The Combination of Fasting Plasma Glucose and Glycosylated Hemoglobin as a Predictor for Type 2 Diabetes in Korean Adults (Korean Diabetes J 33(4):306-314, 2009)
Chan Hee Lee, Hyoung Woo Lee
Korean Diabetes Journal.2009; 33(5): 451. CrossRef

Letter

Relationship Between Serum Bilirubin Levels and Coronary Atherosclerosis in Patients with Type 2 Diabetes.: Jun Sung Moon, Kyu Chang Won; Korean Diabetes J. 2008;32(5):464-466. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.464

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Original Articles

Relationship Between Serum Bilirubin Levels and Coronary Atherosclerosis in Patients with Type 2 Diabetes.: Jun Sung Moon, Woo Jin Chang, Chan Hee Lee, Ji Eun Lee, Kyung Ah Chun, Ji Sung Yoon, Ihn Ho Cho, Hyoung Woo Lee, Kyu Chang Won; Korean Diabetes J. 2008;32(4):338-345. Published online August 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.4.338

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Abstract PDF

BACKGROUND
Lipid oxidation and formation of oxygen radicals have been identified to be the important factors of atherogenesis. Because bilirubin, a potent physiological antioxidant inhibits lipid oxidation, it is suggested that low serum concentrations of bilirubin is associated with atherosclerosis. The aim of this study was to evaluate the relationship between bilirubin levels and coronary atherosclerosis. METHODS: The coronary calcium score (CCS) of 172 subjects (male 63, mean age 60.5 +/- 1.0) with type 2 diabetes were evaluated in Yeungnam University Hospital between January 2005 and February 2007. The subjects were divided into two groups with CCS 10 as the cut off. RESULTS: Higher CCS was significantly associated with lower bilirubin (P < 0.05), but after adjusted with age, no longer correlation were seen (P = 0.121). To determine the relationship between subclinical coronary atherosclerosis and bilirubin, the subjects with previous history of cardiovascular disease were excluded. In 138 subjects (male 54, mean age 58.4 +/- 1.1), higher CCS was significantly associated with lower levels of bilirubin. After adjusted with age, duration of diabetes, and history of hypertension, CCS was also inversely related with bilirubin (P < 0.05). CONCLUSION: These results suggest that lower levels of bilirubin might be considered as a risk factor of coronary artery disease, especially in type 2 diabetics without cardiovascular disease.

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Jun-Ho Lee, Ji-Won Yoon, Bong-Ki Kim, Hee-Bok Park, Kyu-Sang Lim, Ji-Hyuk Kim
Korean Journal of Poultry Science.2022; 49(4): 255. CrossRef
Correlation of Serum Bilirubin Levels in Type 2 Diabetes Mellitus Patients with and without Diabetic Retinopathy
Johncy John, Gajaraj Tulsidas Naik, Suria C. Rashmi, Sheetal Vaijanath Zille, Swetha Sampangi Iyer, Meghana Neeralagi, Asma M.K
Journal of Evolution of Medical and Dental Sciences.2021; 10(45): 4013. CrossRef
Association of SNPs in the UGT1A gene cluster with total bilirubin and mortality in the Diabetes Heart Study
Amanda J. Cox, Maggie C.-Y. Ng, Jianzhao Xu, Carl D. Langefeld, Kenneth L. Koch, Paul A. Dawson, J. Jeffrey Carr, Barry I. Freedman, Fang-Chi Hsu, Donald W. Bowden
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Byoung Hyun Park, Hye Jung Nho, Chung Gu Cho
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Kiwoong Yu, Cheolhwan Kim, Eunju Sung, Hocheol Shin, Hyewon Lee
Korean Journal of Family Medicine.2011; 32(6): 327. CrossRef
The Relationship among Homocysteine, Bilirubin, and Diabetic Retinopathy
Ho Chan Cho
Diabetes & Metabolism Journal.2011; 35(6): 595. CrossRef
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Soo Lim
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Prevalence of Diabetic Retinopathy in Diabetics Who are Positive for GAD Autoantibody.: Seon Joong Moon, Chan Hee Lee, Jun Sung Moon, Hee Jung Moon, Ji Eun Lee, Kyung Ah Chun, Ji Sung Yoon, Ihn Ho Cho, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2007;31(5):429-434. Published online September 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.5.429

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Abstract PDF

BACKGROUND
Diabetic retinopathy is a leading cause of adult blindness. Some patients show early development and progression of diabetic retinopathy despite of apparently good glycemic control. This is suggesting the involvement of other contributing factors. Recent studies have shown that retinopathy and GAD autoantibody (GADA) show an inverse relationship immunologically. This study is designed to investigate the clinical manifestation of diabetes who are positive for GADA and the relationship between GADA and diabetic retinopathy. METHODS: Type 1 diabetic patients & LADA patients who had visited Yeungnam university Medical Center from 1988 to 2005 were involved. We reviewed the pathologic and laboratory records of these patients and investigated the development of diabetic microvascular complications. RESULTS: Compared with patients who had GADA negative diabetes, patients with GADA positive diabetes had lower prevalence of diabetic retinopathy (GADA negative subject: 25.8% vs. GADA positive subject: 9.6%, P < 0.05). CONCLUSION: We confirmed that diabetic retinopathy and GADA showed an inverse relationship. It seems quite probable that GADA may contribute to the prevention of retinopathy. Further research should be needed concerning the effect of GADA on diabetic retinopathy.

Citations

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Chronic Complications in Adult Diabetic Patients with and without GAD Antibody
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Korean Diabetes Journal.2009; 33(2): 124. CrossRef

gamma-glutamylcysteine Synthetase (gamma-GCS) mRNA Expression in INS-1 Cells and Patients with Type 2 Diabetes Mellitus.: Jae Hong Kim, Chan Hee Lee, Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2007;31(4):302-309. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.302

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Abstract PDF: BACKGROUND
Hyperglycemia is a well-recognized pathogenic factor of long term complications in diabetes mellitus and hyperglycemia also generates reactive oxygen species (ROS) in beta cells when ROS accumulate in excess for prolonged periods of time, they cause chronic oxidative stress and adverse effects. Unfortunately, the islet contacts low capacity of endogenous antioxidant effects. But, gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for glutathione synthesis, is well represented in islets. METHODS: This study is to evaluate the changes in the activity of gamma-GCS, glutathione in beta-cells exposed to high glucose, in pancreatic tissue of OLETF (Otsuka Long Evans Tokushima Fatty) and LETO (Long-Evans Tokushima Otsuka) rats, in leukocytes from patients with Korean type 2 DM (T2DM) and to disclose the effects of high blood glucose on this impairment in patients with T2DM. We divided our patients into 3 groups by HbA1c (controls: n = 20, well controls diabetes: n=24, poorly controlled diabetes: n = 36). RESULTS: We observed that decreased glutathione level, gamma-GCS expression, glucose-stimulated (GSIS) and increased intracellular peroxide level in the INS-1 cells exposed to 30 mM glucose condition. Also decreased glutathione level at erythrocytes, gamma-GCS expression at leukocytes and increased oxidized LDL, MDA (malondialdehyde) level at plasma from patients with T2DM compared to controls (esp, poorly controlled patients). CONCLUSION: These results suggest that insufficient antioxidant defenses by the glutathione pathway may be one of the factors responsible for development of complications in T2DM.

Oxidative Stress of INS-1 Cell, HIT-T15 Cell and Rat Islet Cell as a Mechanism of Glucose Toxicity.: Mi Jung Eun, Kyu Chang Won, Jun Sung Moon, Sun Jung Mun, Ji Eun Lee, Ji Sung Yoon, Kyung Ah Chun, Ihn Ho Cho, Hyoung Woo Lee; Korean Diabetes J. 2005;29(5):393-400. Published online September 1, 2005

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Abstract PDF: BACKGOUND: Chronic hyperglycemia is the proximate cause of many complications of diabetes. The beta cells in type 2 diabetes are also adversely affected by chronic hyperglycemia, with this relentless deterioration in cell function, due to constant exposure to supraphysiologic concentrations of glucose, is termed glucose toxicity; however, the mechanism of glucose toxicity is uncertain. The purpose of this study was to determine whether prolonged exposure of pancreatic islets to supraphysiologic glucose concentration disrupts the intracellular balance between reactive oxygen species(ROS) and antioxidant enzyme; thereby, causing defective insulin secretion. METHODS: HIT-T15 cells were treated with H2O2(20, 50 and 100micrometer) directly added to the culture media, and then intracellular peroxide and insulin mRNA were then measured. The effects of H2O2 on the total peroxide level and insulin secretion were also examined. Isolated pancreatic islet cells from Wistar and 2 beta cell lines (INS-1, HIT-T15) were cultured in either a glucose or ribose (5.6, 11.1, 22.2, 30 and 50mM) containing culture media for 72hours. The intracellular peroxide was measured using flow cytometry and glucose stimulated insulin secretion(GSIS). RESULTS: The intracellular peroxide levels due to H2O2 in HIT-T15 cells were higher with a high concentration of H2O2, and the insulin mRNA in HIT-T15 cells decreased when the cells are treated with a high concentration H2O2. The insulin mRNA of the HIT-T15 cells cultured in a high concentration of ribose was lower than of those cultured in a low concentration of glucose. INS-1, HIT-T15 and rat islet cells, cultured for 72 hours, had progressively greater peroxide levels with higher concentrations of both glucose and ribose. The GSIS in the cells cultured in high concentrations of both glucose and ribose were decreased. CONCLUSION: These results suggest only one potential central mechanism for glucose toxicity in beta cells, this being the formation of excess ROS.

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