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10 "Jang Won Son"
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Original Articles
Cardiovascular Risk/Epidemiology
Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study
Ye Seul Yang, Nam Hoon Kim, Jong Ha Baek, Seung-Hyun Ko, Jang Won Son, Seung-Hwan Lee, Sang Youl Rhee, Soo-Kyung Kim, Tae Seo Sohn, Ji Eun Jun, In-Kyung Jeong, Chong Hwa Kim, Keeho Song, Eun-Jung Rhee, Junghyun Noh, Kyu Yeon Hur, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2024;48(2):279-289.   Published online January 26, 2024
DOI: https://doi.org/10.4093/dmj.2023.0225
  • 1,158 View
  • 163 Download
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD.
Methods
We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study.
Results
Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users.
Conclusion
The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.

Citations

Citations to this article as recorded by  
  • Enhancing Patient Outcomes: Prioritizing SGLT2is and GLP-1RAs in Diabetes with CVD
    Gwanpyo Koh
    Diabetes & Metabolism Journal.2024; 48(2): 208.     CrossRef
Drug Regimen
Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial
Kyung Ah Han, Yong Hyun Kim, Doo Man Kim, Byung Wan Lee, Suk Chon, Tae Seo Sohn, In Kyung Jeong, Eun-Gyoung Hong, Jang Won Son, Jae Jin Nah, Hwa Rang Song, Seong In Cho, Seung-Ah Cho, Kun Ho Yoon
Diabetes Metab J. 2023;47(6):796-807.   Published online February 9, 2023
DOI: https://doi.org/10.4093/dmj.2022.0315
  • 40,101 View
  • 576 Download
  • 4 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500).
Results
Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated.
Conclusion
Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials
    Young Sang Lyu, Sangmo Hong, Si Eun Lee, Bo Young Cho, Cheol-Young Park
    Cardiovascular Diabetology.2024;[Epub]     CrossRef
  • A 52‐week efficacy and safety study of enavogliflozin versus dapagliflozin as an add‐on to metformin in patients with type 2 diabetes mellitus: ENHANCE‐M extension study
    Tae Seo Sohn, Kyung‐Ah Han, Yonghyun Kim, Byung‐Wan Lee, Suk Chon, In‐Kyung Jeong, Eun‐Gyoung Hong, Jang Won Son, JaeJin Na, Jae Min Cho, Seong In Cho, Wan Huh, Kun‐Ho Yoon
    Diabetes, Obesity and Metabolism.2024;[Epub]     CrossRef
  • The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium‐glucose cotransporter‐2 inhibitor, in type 2 diabetes
    Sae Im Jeong, Mu Seong Ban, Jun‐Gi Hwang, Min‐Kyu Park, Soo Lim, Sejoong Kim, Soon Kil Kwon, Yoonjin Kim, Jae Min Cho, Jae Jin Na, Wan Huh, Jae‐Yong Chung
    Diabetes, Obesity and Metabolism.2024;[Epub]     CrossRef
  • Role of novel sodium glucose co-transporter-2 inhibitor enavogliflozin in type-2 diabetes: A systematic review and meta-analysis
    Deep Dutta, B.G. Harish, Beatrice Anne, Lakshmi Nagendra
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(8): 102816.     CrossRef
  • Characteristics of the Latest Therapeutic Agent for Diabetes
    Nuri Yun
    The Journal of Korean Diabetes.2023; 24(3): 148.     CrossRef
  • Prospects of using sodium-glucose co-transporter-2 (SGLT-2) inhibitors in patients with metabolic-associated fatty liver disease (MAFLD)
    Iryna Kostitska, Nadia Protas, Liliia Petrovska
    Diabetes Obesity Metabolic Syndrome.2023; (5): 8.     CrossRef
  • Navigating the Future of Diabetes Treatment with New Drugs: Focusing on the Possibilities and Prospects of Enavogliflozin
    Sang Youl Rhee
    Diabetes & Metabolism Journal.2023; 47(6): 769.     CrossRef
Review
Guideline/Fact Sheet
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
  • 24,045 View
  • 1,630 Download
  • 122 Web of Science
  • 141 Crossref
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.

Citations

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    Journal of Diabetes Research.2024; 2024: 1.     CrossRef
  • Efficacy and Safety of Once-Weekly Semaglutide Versus Once-Daily Sitagliptin as Metformin Add-on in a Korean Population with Type 2 Diabetes
    Byung-Wan Lee, Young Min Cho, Sin Gon Kim, Seung-Hyun Ko, Soo Lim, Amine Dahaoui, Jin Sook Jeong, Hyo Jin Lim, Jae Myung Yu
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    Diabetes Care.2023; 46(5): 959.     CrossRef
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    Jin Yu, Raeun Kim, Jiwon Shinn, Man Young Park, Hun-Sung Kim
    Cardiovascular Prevention and Pharmacotherapy.2023; 5(2): 61.     CrossRef
  • Comparison of the effects of gemigliptin versus glimepiride on cardiac function in patients with type 2 diabetes uncontrolled with metformin: The gemi‐heart study
    Seung Min Chung, Jun Sung Moon, Jun Hwa Hong, In‐Chang Hwang, Soo Lim
    Diabetes, Obesity and Metabolism.2023; 25(8): 2181.     CrossRef
  • The era of continuous glucose monitoring and its expanded role in type 2 diabetes
    Jin Yu, Jae‐Hyoung Cho, Seung‐Hwan Lee
    Journal of Diabetes Investigation.2023; 14(7): 841.     CrossRef
  • Impact of continuous glucose monitoring on glycemic control and its derived metrics in type 1 diabetes: a longitudinal study
    So Hyun Cho, Seohyun Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Impact of mental disorders on the risk of heart failure among Korean patients with diabetes: a cohort study
    Tae Kyung Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
  • Asia-Pacific consensus recommendations for application of continuous glucose monitoring in diabetes management
    Alice P.S. Kong, Soo Lim, Seung-Hyun Yoo, Linong Ji, Liming Chen, Yuqian Bao, Ester Yeoh, Siew-Pheng Chan, Chih-Yuan Wang, Viswanathan Mohan, Neale Cohen, Margaret J. McGill, Stephen M. Twigg
    Diabetes Research and Clinical Practice.2023; 201: 110718.     CrossRef
  • Chronic disease management program applied to type 2 diabetes patients and prevention of diabetic complications: a retrospective cohort study using nationwide data
    Min Kyung Hyun, Jang Won Lee, Seung-Hyun Ko
    BMC Public Health.2023;[Epub]     CrossRef
  • Fatty Liver & Diabetes Statistics in Korea: Nationwide Data 2009 to 2017
    Eugene Han, Kyung-Do Han, Yong-ho Lee, Kyung-Soo Kim, Sangmo Hong, Jung Hwan Park, Cheol-Young Park
    Diabetes & Metabolism Journal.2023; 47(3): 347.     CrossRef
  • Opening the Precision Diabetes Care through Digital Healthcare
    Joonyub Lee, Jin Yu, Kun-Ho Yoon
    Diabetes & Metabolism Journal.2023; 47(3): 307.     CrossRef
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Original Article
Guideline/Fact Sheet
Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status
Chan-Hee Jung, Jang Won Son, Shinae Kang, Won Jun Kim, Hun-Sung Kim, Hae Soon Kim, Mihae Seo, Hye-Jung Shin, Seong-Su Lee, Su Jin Jeong, Yongin Cho, Seung Jin Han, Hyang Mi Jang, Mira Rho, Shinbi Lee, Mihyun Koo, Been Yoo, Jung-Wha Moon, Hye Young Lee, Jae-Seung Yun, Sun Young Kim, Sung Rae Kim, In-Kyung Jeong, Ji-Oh Mok, Kun Ho Yoon
Diabetes Metab J. 2021;45(1):1-10.   Published online January 13, 2021
DOI: https://doi.org/10.4093/dmj.2020.0254
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data.
Methods
This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated.
Results
In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes.
Conclusion
The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

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Review
Drug/Regimen
Comprehensive Review of Current and Upcoming Anti-Obesity Drugs
Jang Won Son, Sungrae Kim
Diabetes Metab J. 2020;44(6):802-818.   Published online December 23, 2020
DOI: https://doi.org/10.4093/dmj.2020.0258
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AbstractAbstract PDFPubReader   ePub   
Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.

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Original Article
Epidemiology
Changing Clinical Characteristics according to Insulin Resistance and Insulin Secretion in Newly Diagnosed Type 2 Diabetic Patients in Korea
Jang Won Son, Cheol-Young Park, Sungrae Kim, Han-Kyu Lee, Yil-Seob Lee
Diabetes Metab J. 2015;39(5):387-394.   Published online October 22, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.5.387
  • 3,820 View
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AbstractAbstract PDFPubReader   
Background

The role of increased insulin resistance in the pathogenesis of type 2 diabetes has been emphasized in Asian populations. Thus, we evaluated the proportion of insulin resistance and the insulin secretory capacity in patients with early phase type 2 diabetes in Korea.

Methods

We performed a cross-sectional analysis of 1,314 drug-naive patients with newly diagnosed diabetes from primary care clinics nationwide. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index to measure insulin resistance, which was defined as a HOMA-IR ≥2.5. Insulin secretory defects were classified based on fasting plasma C-peptide levels: severe (<1.1 ng/mL), moderate (1.1 to 1.7 ng/mL) and mild to non-insulin secretory defect (≥1.7 ng/mL).

Results

The mean body mass index (BMI) was 25.2 kg/m2; 77% of patients had BMIs >23.0 kg/m2. Up to 50% of patients had central obesity based on their waist circumference (≥90 cm in men and 85 cm in women), and 70.6% had metabolic syndrome. Overall, 59.5% of subjects had insulin resistance, and 20.2% demonstrated a moderate to severe insulin secretory defect. Among those with insulin resistance, a high proportion of subjects (79.0%) had a mild or no insulin secretory defect. Only 2.6% of the men and 1.9% of the women had both insulin resistance and a moderate to severe insulin secretory defect.

Conclusion

In this study, patients with early phase type 2 diabetes demonstrated increased insulin resistance, but preserved insulin secretion, with a high prevalence of obesity and metabolic syndrome.

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Reviews
Clinical Care/Education
Dipeptidyl Peptidase 4 Inhibitors and the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: A Tale of Three Studies
Jang Won Son, Sungrae Kim
Diabetes Metab J. 2015;39(5):373-383.   Published online October 22, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.5.373
  • 4,615 View
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  • 31 Web of Science
  • 28 Crossref
AbstractAbstract PDFPubReader   

Dipeptidyl peptidase 4 (DPP4) inhibitors have been touted as promising antihyperglycemic agents due to their beneficial effects on glycemia without inducing hypoglycemia or body weight gain and their good tolerability. Beyond their glucose-lowering effects, numerous clinical trials and experimental studies have suggested that DPP4 inhibitors may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms or involving other substrates. Since 2008, regulatory agencies have required an assessment of cardiovascular disease (CVD) safety for the approval of all new anti-hyperglycemic agents, including incretin-based therapies. Three large prospective DPP4 inhibitor trials with cardiovascular (CV) outcomes have recently been published. According to the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR-TIMI 53) and EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE) trials, DPP4 inhibitors, including saxagliptin and alogliptin, did not appear to increase the risk of CV events in patients with type 2 diabetes and established CVD or high risk factors. Unexpectedly, saxagliptin significantly increased the risk of hospitalization for heart failure by 27%, a finding that has not been explained and that requires further exploration. More recently, the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) trial demonstrated the CV safety of sitagliptin, including assessments of the primary composite CV endpoint and hospitalization for heart failure in patients with type 2 diabetes and established CVD. The CV outcomes of an ongoing linagliptin trial are expected to provide new evidence about the CV effects of a DPP4-inhibitor in patients with type 2 diabetes.

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Clinical Implications of Serum Biomarkers in Diabetic Cardiovascular Complications.
Jang Won Son, Hyuk Sang Kwon
Korean Diabetes J. 2009;33(5):363-372.   Published online October 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.5.363
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AbstractAbstract PDF
Diabetes is associated with increased risk of cardiovascular disease, with atherosclerosis responsible for most associated morbidity and mortality. Atherosclerosis often causes acute thrombotic events through plaque rupture and formation of platelet-rich thrombi. The principal clinical manifestations of atherosclerosis are coronary artery disease, ischemic stroke, and peripheral arterial disease. Endothelial dysfunction, oxidative stress, and low-grade inflammation are key features in the pathophysiology of atherosclerosis.
Case Report
A Case of Diabetic Ketoacidosis in a GAD Antibody-positive Diabetes Patients who Recently Experienced Hyperglycemic Hyperosmolar State.
Jang Won Son, Seok Hong Lee, Jung Ahn Lee, Jaetaek Kim, Yeon Sahng Oh, Soon Hyun Shinn
Korean Diabetes J. 2005;29(3):267-270.   Published online May 1, 2005
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AbstractAbstract PDF
The term latent autoimmune diabetes in adults(LADA) was introduced to define adult diabetic patients who initially do not require insulin, but they have the immune markers of type 1 diabetes and in a number of cases, these patients progress to insulin dependency. LADA patients have several features of classic type 1 diabetes in addition to islet cell antibody positivity, including high rates of HLA-DR3 and DR4. We describe here a case of a patient with a diagnosis of LADA who, having been diagnosed with type 2 diabetes, was affected with diabetic ketoacidosis. In April 2000, a 65-year-old man was admitted to Chung-Ang University Hospital due to his decreased cognitive ability. The patient was diagnosed with type 2 diabetes 30-years ago and he was diagnosed 6-month ago as being in a hyperglycemic hyperosmolar state. He was positive for antibodies against GAD(anti-GAD, 31U/mL). His weight was 70kg, height 167cm, BMI 25 kg/m2 and the blood pressure was 86/52mmHg. No abnormalities on the physical examination were found. His acid-base balance was pH 6.937, serum bicarbonate 2.2mmol/L and the anion gap 38; he also had a strong positive reaction for ketones in his urine and serum. During half a year, the fasting C-peptide level decreased from 0.65nmol/L to 0.13nmol/L, which means the rapid progression of beta-cell destruction. Intensive treatment of LADA with insulin may improve this type of patients' quality of life, and so potentially save the beta-cell function and perhaps lessening the risk of a hyperglycemic crisis
Original Article
Study on the Methylglyoxal-induced Apoptosis in Bovine Retinal Pericytes.
Jaetaek Kim, Seok Hong Lee, Jang Won Son, Jeong An Lee, Yeon Sahng Oh, Soon Hyun Shinn
Korean Diabetes J. 2004;28(3):199-207.   Published online June 1, 2004
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AbstractAbstract PDF
BACKGROUND
One of the histopathological hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that this pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal(MGO), a reactive alpha-dicarbonyl compound of glucose metabolism, on the apoptotic cell death in retinal pericytes. METHODS: Primary cultures of retinal pericytes were prepared from isolated bovine retinal microvessels. The cells were incubated under normoglycemic conditions after treatment with 200-800muM methylglyoxal for 6 hours. The cell viability was assessed using the MTT assay. The apoptosis and intracellular reactive oxygen species(ROS) generation were measured using an ELISA kit and flow cytometry, respectively. The NF-kappaB activation was detected by immunocytochemistry. RESULTS: MGO produced a progressive cytotoxic effect on the retinal pericytes. An analysis of the internucleosomal DNA fragmentation by ELISA showed that MGO(200 to 800muM) induced apoptosis in a concentration-dependent manner. ROS were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. The NF-kappaB activation and increased caspase-3 activity were detected. The apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. CONCLUSION: These results suggest that the elevated MGO levels observed in diabetes may cause apoptosis in the retinal pericytes through an oxidative stress mechanism, and suggests that the nuclear activation of NF-kappaB is involved in the apoptotic process.

Diabetes Metab J : Diabetes & Metabolism Journal