Diabetes & Metabolism Journal

Original Article

Drug/Regimen
Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial: Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon, the Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) study investigators; Received August 7, 2023 Accepted November 30, 2023 Published online April 23, 2024; DOI: https://doi.org/10.4093/dmj.2023.0259 [Epub ahead of print]

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Abstract PDF: Background
Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Brief Report

Metabolic Risk/Epidemiology
Trends in the Prevalence of Obesity and Its Phenotypes Based on the Korea National Health and Nutrition Examination Survey from 2007 to 2017 in Korea: Sang Ouk Chin, You-Cheol Hwang, Hong-Yup Ahn, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung; Diabetes Metab J. 2022;46(5):808-812. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0226

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This study used data from the Korea National Health and Nutrition Examination Survey IV–VII from 2007 to identify the prevalence of obesity and its phenotypes (metabolically unhealthy obesity [MUO] and metabolically healthy obesity [MHO]) and their secular changes. The prevalence of obesity in Korea increased with significant secular changes observed (β=0.326, P trend <0.01) between 2007 and 2017, and especially in men (β=0.682, P trend <0.001) but not in women. The changes in the prevalence of obesity during the study period were different between men and women (P=0.001). The prevalence of MUO significantly increased only in men (β=0.565, P trend <0.01), while that of MHO increased only in women (β=0.179, P<0.05), especially in the younger age group (β=0.308, P<0.01).

Citations

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Hormonal Gut–Brain Signaling for the Treatment of Obesity
Eun Roh, Kyung Mook Choi
International Journal of Molecular Sciences.2023; 24(4): 3384. CrossRef
Differences of Regional Fat Distribution Measured by Magnetic Resonance Imaging According to Obese Phenotype in Koreans
Ha-Neul Choi, Hyunjung Lim, Young-Seol Kim, Sang-Youl Rhee, Jung-Eun Yim
Metabolic Syndrome and Related Disorders.2022; 20(10): 551. CrossRef

Original Articles

Metabolic Risk/Epidemiology
Increased Visit-to-Visit Liver Enzyme Variability Is Associated with Incident Diabetes: A Community-Based 12-Year Prospective Cohort Study: Kyuhoon Bang, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung, You-Cheol Hwang; Diabetes Metab J. 2021;45(6):890-898. Published online March 17, 2021; DOI: https://doi.org/10.4093/dmj.2020.0208

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub: Background
Fatty liver and/or increased liver enzyme values have been reported to be associated with incident diabetes. We sought to determine whether increased visit-to-visit liver enzyme variability is associated with incident diabetes.
Methods
Study participants were recruited from the Korean Genome and Epidemiologic Study (KoGES). A total of 4,151 people aged 40 to 69 years was recruited and tested every 2 years for up to 12 years. Visit-to-visit aspartate aminotransferase (AST) and alanine aminotransferase (ALT) variability was evaluated in first the 6-year period through the use of various variability measurements: standard deviation (SD), average successive variability, coefficient of variation (CV), and variation independent of mean (VIM). Oral glucose tolerance test was performed at every visit.
Results
During the 6-year follow‐up appointments, 13.0% (538/4,151) of people developed incident diabetes. Visit-to-visit AST variability was associated with an increased risk of diabetes independent of conventional risk factors for diabetes (hazard ratio per 1-SD increment [95% confidence interval]: 1.06 [1.00 to 1.11], 1.12 [1.04 to 1.21], and 1.13 [1.04 to 1.22] for SD, CV, and VIM, respectively; all P<0.05); however, no such associations were observed in the visit-to-visit ALT variability. According to alcohol consumption status, both AST and ALT variability were independent predictors for incident diabetes in subjects with heavy alcohol consumption; however, neither AST nor ALT variability was associated with diabetes risk in subjects who did not drink alcohol heavily.
Conclusion
Visit-to-visit liver enzyme variability is an independent predictor of incident diabetes. Such association was more evident in those who consumed significant amounts of alcohol.

Clinical Diabetes & Therapeutics
Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus: You-Cheol Hwang, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung; Diabetes Metab J. 2019;43(5):582-589. Published online January 16, 2019; DOI: https://doi.org/10.4093/dmj.2018.0124

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Background

The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy.

Methods

This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks.

Results

After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation.

Conclusion

A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Citations

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Yura Kang, Jung Mi Park, Sang-Hak Lee
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Maya R Chilbert, Dylan VanDuyn, Sara Salah, Collin M Clark, Qing Ma
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Ezetimibe and diabetes mellitus:a new strategy for lowering cholesterol
V.A. Serhiyenko, A.A. Serhiyenko
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2022; 18(5): 302. CrossRef
The Effect of Rosuvastatin on Plasma/Serum Levels of High-Sensitivity C-Reactive Protein, Interleukin-6, and D-Dimer in People Living with Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis
Akililu Alemu Ashuro, Yin-Guang Fan, Yuan-Sheng Fu, Dong-Sheng Di, Napoleon Bellua Sam, Hai-Feng Pan, Dong-Qing Ye
AIDS Research and Human Retroviruses.2021; 37(11): 821. CrossRef
Comparison of the Efficacy and Safety of Rosuvastatin/Ezetimibe Combination Therapy and Rosuvastatin Monotherapy on Lipoprotein in Patients With Type 2 Diabetes: Multicenter Randomized Controlled Study
Jiwoo Lee, You-Cheol Hwang, Woo Je Lee, Jong Chul Won, Kee-Ho Song, Cheol-Young Park, Kyu Jeung Ahn, Joong-Yeol Park
Diabetes Therapy.2020; 11(4): 859. CrossRef
Comparison of Renal Effects of Ezetimibe–Statin Combination versus Statin Monotherapy: A Propensity-Score-Matched Analysis
Jaehyun Bae, Namki Hong, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Yong-ho Lee
Journal of Clinical Medicine.2020; 9(3): 798. CrossRef
Combined use of rosuvastatin and ezetimibe improves hepatic steatosis in patients with dyslipidemia
Won Dong Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seung Up Kim
European Journal of Gastroenterology & Hepatology.2020; 32(12): 1538. CrossRef
Influence of rosuvastatin dose on total fatty acids and free fatty acids in plasma
Cristian I. Ciucanu, Sonia Olariu, Daliborca C. Vlad, Victor Dumitraşcu
Medicine.2020; 99(48): e23356. CrossRef
The effect of switching from statin-monotherapy to statin/ezetimibe combination therapy on lipid profiles in patients with type 2 diabetes and dyslipidemia: a multicenter open-label study (EUCLID)
Mitsuhide Takeshita, Atsushi Tanaka, Atsushi Kawaguchi, Keiko Sato, Shigeru Toyoda, Teruo Inoue, Koichi Node
Vascular Failure.2020; 4(1): 22. CrossRef
Response: Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2019;43:582–9)
You-Cheol Hwang
Diabetes & Metabolism Journal.2019; 43(6): 915. CrossRef
Letter: Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2019;43:582–9)
Tae Seo Sohn
Diabetes & Metabolism Journal.2019; 43(6): 909. CrossRef
Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes
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Nutrients.2019; 11(9): 2022. CrossRef

Clinical Diabetes and Therapeutics
Hospital-Based Korean Diabetes Prevention Study: A Prospective, Multi-Center, Randomized, Open-Label Controlled Study: Sang Youl Rhee, Suk Chon, Kyu Jeung Ahn, Jeong-Taek Woo; Diabetes Metab J. 2019;43(1):49-58. Published online November 2, 2018; DOI: https://doi.org/10.4093/dmj.2018.0033

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Background

The prevalence of diabetes mellitus (DM) continues to increase, and the disease burden is the highest of any medical condition in Korea. However, large-scale clinical studies have not yet conducted to establish the basis for diabetes prevention in Korea.

Methods

The hospital-based Korean Diabetes Prevention Study (H-KDPS) is a prospective, multi-center, randomized, open-label controlled study conducted at university hospitals for the purpose of gathering data to help in efforts to prevent type 2 DM. Ten university hospitals are participating, and 744 subjects will be recruited. The subjects are randomly assigned to the standard care group, lifestyle modification group, or metformin group, and their clinical course will be observed for 36 months.

Results

All intervention methodologies were developed, validated, and approved by Korean Diabetes Association (KDA) multi-disciplinary team members. The standard control group will engage in individual education based on the current KDA guidelines, and the lifestyle modification group will participate in a professionally guided healthcare intervention aiming for ≥5% weight loss. The metformin group will begin dosing at 250 mg/day, increasing to a maximum of 1,000 mg/day. The primary endpoint of this study is the cumulative incidence of DM during the 3 years after randomization.

Conclusion

The H-KDPS study is the first large-scale clinical study to establish evidence-based interventions for the prevention of type 2 DM in Koreans. The evidence gathered by this study will be useful for enhancing the health of Koreans and improving the stability of the Korean healthcare system (Trial registration: CRIS KCT0002260, NCT02981121).

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Joon Ha, Stephanie T. Chung, Max Springer, Joon Young Kim, Phil Chen, Aaryan Chhabra, Melanie G. Cree, Cecilia Diniz Behn, Anne E. Sumner, Silva A. Arslanian, Arthur S. Sherman
American Journal of Physiology-Endocrinology and Metabolism.2024; 326(4): E454. CrossRef
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Impaired fasting glucose levels in overweight or obese subjects for screening of type 2 diabetes in Korea
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The Korean Journal of Internal Medicine.2021; 36(2): 382. CrossRef
Development and Validation of a Deep Learning Based Diabetes Prediction System Using a Nationwide Population-Based Cohort
Sang Youl Rhee, Ji Min Sung, Sunhee Kim, In-Jeong Cho, Sang-Eun Lee, Hyuk-Jae Chang
Diabetes & Metabolism Journal.2021; 45(4): 515. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
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Diabetes & Metabolism Journal.2021; 45(6): 960. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Seung-Hyun Ko
The Journal of Korean Diabetes.2021; 22(4): 244. CrossRef
Optimal fasting plasma glucose and haemoglobin A1c levels for screening of prediabetes and diabetes according to 2‐hour plasma glucose in a high‐risk population: The Korean Diabetes Prevention Study
Seon‐Ah Cha, Suk Chon, Jae‐Seung Yun, Sang Youl Rhee, Sun‐Young Lim, Kun‐Ho Yoon, Yu‐Bae Ahn, Seung‐Hyun Ko, Jeong‐Taek Woo, Jin‐Hee Lee
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Risk Factors for the Progression of Intima-Media Thickness of Carotid Arteries: A 2-Year Follow-Up Study in Patients with Newly Diagnosed Type 2 Diabetes: Sang Ouk Chin, Jin Kyung Hwang, Sang Youl Rhee, Suk Chon, You-Cheol Hwang, Seungjoon Oh, Kyu Jeung Ahn, Ho Yeon Chung, Jeong-taek Woo, Sung-Woon Kim, Young Seol Kim, Ja-Heon Kang, In-Kyung Jeong; Diabetes Metab J. 2013;37(5):365-374. Published online October 17, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.5.365

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Background

Intima-media thickness (IMT) of the carotid arteries is known to have a positive correlation with the risk of cardiovascular disease. This study was designed to identify risk factors affecting the progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM).

Methods

Patients with newly diagnosed T2DM with carotid IMT measurements were enrolled, and their clinical data and carotid IMT results at baseline and 2 years later were compared.

Results

Of the 171 patients, 67.2% of males and 50.8% of females had abnormal baseline IMT of the left common carotid artery. At baseline, systolic blood pressure, body mass index and smoking in male participants, and fasting plasma glucose and glycated hemoglobin levels in females were significantly higher in patients with abnormal IMT than in those with normal IMT. Low density lipoprotein cholesterol (LDL-C) levels in males and high density lipoprotein cholesterol (HDL-C) levels in females at the 2-year follow-up were significantly different between the nonprogression and the progression groups. Reduction of the United Kingdom Prospective Diabetes Study (UKPDS) 10-year coronary heart disease (CHD) risk score after 2 years was generally higher in the nonprogression group than the progression group.

Conclusion

LDL-C levels in males and HDL-C levels in females at the 2-year follow-up were significantly different between participants with and without progression of carotid IMT. Furthermore, a reduction in the UKPDS 10-year CHD risk score appeared to delay the advancement of atherosclerosis. Therefore, the importance of establishing the therapeutic goal of lipid profiles should be emphasized to prevent the progression of carotid IMT in newly diagnosed T2DM patients.

Citations

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Comparison of the Effectiveness of Low Carbohydrate Versus Low Fat Diets, in Type 2 Diabetes: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Tanefa A. Apekey, Maria J. Maynard, Monia Kittana, Setor K. Kunutsor
Nutrients.2022; 14(20): 4391. CrossRef
Nomogram Based on Risk Factors for Type 2 Diabetes Mellitus Patients with Coronary Heart Disease

Rong Shi, Birong Wu, Zheyun Niu, Hui Sun, Fan Hu
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 5025. CrossRef
HMGA1 Mediated High-Glucose-Induced Vascular Smooth Muscle Cell Proliferation in Diabetes Mellitus: Association Between PI3K/Akt Signaling and HMGA1 Expression
Qinghai Zhang, Ling Chen, Zhibo Zhao, Ying Wu, Jing Zhong, Gebo Wen, Renxian Cao, Xuyu Zu, Jianghua Liu
DNA and Cell Biology.2018; 37(4): 389. CrossRef
Relationship between frequency of hypoglycemic episodes and changes in carotid atherosclerosis in insulin-treated patients with type 2 diabetes mellitus
Tomoya Mita, Naoto Katakami, Toshihiko Shiraiwa, Hidenori Yoshii, Nobuichi Kuribayashi, Takeshi Osonoi, Hideaki Kaneto, Keisuke Kosugi, Yutaka Umayahara, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
Scientific Reports.2017;[Epub] CrossRef
Impact of carotid atherosclerosis detection on physician and patient behavior in the management of type 2 diabetes mellitus: a prospective, observational, multicenter study
In-Kyung Jeong, Sin-Gon Kim, Dong Hyeok Cho, Chong Hwa Kim, Chul Sik Kim, Won-Young Lee, Kyu-Chang Won, Doo-Man Kim
BMC Cardiovascular Disorders.2016;[Epub] CrossRef
The effect of fibroblast growth factors and advanced glycation end-products on the intima-media complex thickness in patients with coronary heart disease and type 2 diabetes
Ekaterina Vladimirovna Ivannikova, Victor Yurievich Kalashnikov, Olga Mikhailovna Smirnova, Alexander Borisovich Kuznetsov, Сергей Anatolievich Terekhin, Alexander Viktorovich Il'in
Diabetes mellitus.2014; 17(2): 47. CrossRef

Safety and Efficacy of Modern Insulin Analogues: Hye Jin Yoo, Keun Yong Park, Kang Seo Park, Kyu Jeung Ahn, Kyung Wan Min, Jeong Hyun Park, Sang Ah Chang, Bong Soo Cha, Dong-Jun Kim, Yong Seong Kim, Tae Keun Oh, Suk Chon, Il Seong Nam-Goong, Mi Jin Kim, Hye-Soon Kim, Young Sik Choi, You Hern Ahn, Sora Lee, Sei Hyun Baik; Diabetes Metab J. 2013;37(3):181-189. Published online June 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.3.181

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Background

A1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart.

Methods

Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints.

Results

Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7±15.9 to 72.5±13.5) while the mean body weight was slightly increased (0.6±3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%±2.2%, 2.5±4.7 mmol/L, and 4.0±6.4 mmol/L, respectively.

Conclusion

The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

Citations

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Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
The Korean Journal of Internal Medicine.2017; 32(6): 967. CrossRef
Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
Diabetes & Metabolism Journal.2017; 41(5): 367. CrossRef
An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial
Gyuri Kim, Ji Cheol Bae, Byoung Kee Yi, Kyu Yeon Hur, Dong Kyung Chang, Moon-Kyu Lee, Jae Hyeon Kim, Sang-Man Jin
BMC Medical Informatics and Decision Making.2017;[Epub] CrossRef
Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes
Gyuri Kim, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
Yonsei Medical Journal.2016; 57(6): 1395. CrossRef
Avoiding or coping with severe hypoglycemia in patients with type 2 diabetes
Jae-Seung Yun, Seung-Hyun Ko
The Korean Journal of Internal Medicine.2015; 30(1): 6. CrossRef
Clinical Characteristics of Patients Responding to Once-Daily Basal Insulin Therapy in Korean Subjects with Type 2 Diabetes
Sun Ok Song, You-Cheol Hwang, Kyu-Jeung Ahn, Bong Soo Cha, Young Duk Song, Dae Wook Lee, Byung-Wan Lee
Diabetes Therapy.2015; 6(4): 547. CrossRef
The optimal morning:evening ratio in total dose of twice‐daily biphasic insulin analogue in poorly controlled Type 2 diabetes: a 24‐week multi‐centre prospective, randomized controlled, open‐labelled clinical study
C. H. Jung, J.‐Y. Park, J. H. Cho, K.‐H. Yoon, H. K. Yang, Y.‐H. Lee, B. S. Cha, B.‐W. Lee
Diabetic Medicine.2014; 31(1): 68. CrossRef
The glycemic efficacies of insulin analogue regimens according to baseline glycemic status in Korean patients with type 2 diabetes: sub‐analysis from the A 1 chieve ® study
Y.‐C. Hwang, J. G. Kang, K. J. Ahn, B. S. Cha, S.‐H. Ihm, S. Lee, M. Kim, B.‐W. Lee
International Journal of Clinical Practice.2014; 68(11): 1338. CrossRef
Letter: Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study (Diabetes Metab J2013;37:117-24)
Byung-Wan Lee
Diabetes & Metabolism Journal.2013; 37(3): 212. CrossRef

Prevalence of Chronic Complications in Korean Patients with Type 2 Diabetes Mellitus Based on the Korean National Diabetes Program: Sang Youl Rhee, Suk Chon, Mi Kwang Kwon, Ie Byung Park, Kyu Jeung Ahn, In Ju Kim, Sung-Hoon Kim, Hyoung Woo Lee, Kyung Soo Koh, Doo Man Kim, Sei Hyun Baik, Kwan Woo Lee, Moon Suk Nam, Yong Soo Park, Jeong-taek Woo, Young Seol Kim; Diabetes Metab J. 2011;35(5):504-512. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.504

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Background

The Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years.

Methods

This study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics.

Results

Among the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects.

Conclusion

The prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females.

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Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies: Suk Chon, Moon Chan Choi, Yun Jung Lee, You Cheol Hwang, In-Kyung Jeong, Seungjoon Oh, Kyu Jeung Ahn, Ho Yeon Chung, Jeong-Taek Woo, Sung-Woon Kim, Jin-Woo Kim, Young Seol Kim; Diabetes Metab J. 2011;35(1):80-85. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.80

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Abstract PDF PubReader

Background

Type B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.

Methods

To evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.

Results

In the patient's pre-treatment serum IgG, the binding of ¹²⁵I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10^-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.

Conclusion

We treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

Citations

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Systematic Review—Type B Insulin Resistance With Isolated Hypoglycemia and Suppressed Insulin
Natasha Brown, Marianne S Elston
The Journal of Clinical Endocrinology & Metabolism.2024; 109(4): 936. CrossRef
Type B insulin resistance syndrome: a systematic review
Luizianne Mariano Martins, Virgínia Oliveira Fernandes, Manuela Montenegro Dias de Carvalho, Daniel Duarte Gadelha, Paulo Cruz de Queiroz, Renan Magalhães Montenegro
Archives of Endocrinology and Metabolism.2020;[Epub] CrossRef
Autoimmune hypoglycemia
Marina Y. Yukina, Diana A. Davtyan, Ekaterina A. Troshina, Nurana F. Nuralieva
Obesity and metabolism.2018; 15(3): 9. CrossRef
Unique pharmacology of a novel allosteric agonist/sensitizer insulin receptor monoclonal antibody
Simon A. Hinke, Anne M. Cieniewicz, Thomas Kirchner, Katharine D'Aquino, Rupesh Nanjunda, Jason Aligo, Robert Perkinson, Philip Cooper, Ken Boayke, Mark L. Chiu, Steve Jarantow, Eilyn R. Lacy, Yin Liang, Dana L. Johnson, Jean M. Whaley, Russell B. Lingham
Molecular Metabolism.2018; 10: 87. CrossRef
Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study
Joanna Klubo-Gwiezdzinska, Maria Lange, Elaine Cochran, Robert K. Semple, Cornelia Gewert, Rebecca J. Brown, Phillip Gorden
Diabetes Care.2018; 41(11): 2353. CrossRef
Hypoinsulinemic Hypoglycemia Followed By The Onset Of Severe Insulin Resistance With Hyperglycemia And Circulating Anti-Insulin Receptor Antibodies In A Patient Suffering Systemic Lupus Erythematosus: A Case Report And Literature Review
Guillermo Martínez de Pinillos, Mariana Tomé, María M. Viloria, Joaquín Bobillo, María V. Cózar
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The treatment of hyperinsulinemic hypoglycaemia in adults: an update
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Immunosuppressive Therapy in Treatment of Refractory Hypoglycemia in Type B Insulin Resistance: A Case Report
Lavanya Viswanathan, Imali Sirisena
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反復する低血糖発作を契機に発見されたインスリン受容体異常症B型の1例(A case of type B insulin resistance presenting as recurrent hypoglycemia)
杉本龍 (Ryu Sugimoto), 髙木誠 (Makoto Takaki), 前原潤一 (Junichi Maehara), 具嶋泰弘 (Yasuhiro Gushima)
Nihon Kyukyu Igakukai Zasshi: Journal of Japanese Association for Acute Medicine.2017; 28(3): 100. CrossRef
Type B insulin resistance syndrome
Devina L. Willard, Mary Stevenson, Devin Steenkamp
Current Opinion in Endocrinology, Diabetes & Obesity.2016; 23(4): 318. CrossRef
Antibody-Mediated Insulin Resistance: When Insulin and Insulin Receptor Act as Autoantigens in Humans
Christelle Liminet, Julien Vouillarmet, Karim Chikh, Emmanuel Disse
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The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis
Adel A.A. Ismail
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Type B insulin-resistance syndrome presenting as autoimmune hypoglycemia, associated with systemic lupus erythematosus and interstitial lung disease
Seon Mee Kang, Heung Yong Jin, Kyung Ae Lee, Ji Hyun Park, Hong Sun Baek, Tae Sun Park
The Korean Journal of Internal Medicine.2013; 28(1): 98. CrossRef
Treatment of recurrent hypoglycemia with plasmapheresis and steroid in nondiabetic patient
Mustafa Kulaksızoglu, Mustafa Sait Gonen, Levent Kebapcilar, Fatih Sahin, Fatih Demirci, Ali Topcu
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The effect of hyperglycemia and hypoglycemia on glucose transport and expression of glucose transporters in human lymphocytes B and T: An in vitro study
Bożenna Oleszczak, Leszek Szablewski, Monika Pliszka
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The effect of glucose concentrations in the medium on expression of insulin receptors in human lymphocytes B and T: anin vitrostudy
Bożenna Oleszczak, Leszek Szablewski, Monika Pliszka
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Fulminant Type 1 diabetes in a pregnant woman as an initial manifestation of the insulin autoimmune syndrome
H. S. Kim, T.‐Y. Lee, E. Y. Kim, J. H. Choi, S. Y. Kim, Y.‐C. Hwang, J.‐H. Kang, K. J. Ahn, H. Y. Chung, I.‐K. Jeong
Diabetic Medicine.2012; 29(10): 1335. CrossRef
A Case of the Type B Insulin Resistance Syndrome with Chronic Hepatitis B
Hyun Seok Choi, Byoung Ho Choi, Seok Hoo Jeong, Shung Han Choi, Dong Su Shin, Sei hyun Kim, Young Sil Eom, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Ki Young Lee
Endocrinology and Metabolism.2011; 26(4): 360. CrossRef

Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study: Kun Ho Yoon, Jeong Ah Shin, Hyuk Sang Kwon, Seung Hwan Lee, Kyung Wan Min, Yu Bae Ahn, Soon Jib Yoo, Kyu Jeung Ahn, Sung Woo Park, Kwan Woo Lee, Yeon Ah Sung, Tae Sun Park, Min Seon Kim, Yong Ki Kim, Moon Suk Nam, Hye Soon Kim, Ie Byung Park, Jong Suk Park, Jeong Taek Woo, Ho Young Son; Diabetes Metab J. 2011;35(1):26-33. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.26

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Background

Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.

Methods

We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.

Results

HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.

Conclusion

The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

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The Changes in Early Phase Insulin Secretion in Newly Diagnosed, Drug Naive Korean Prediabetes Subjects: Sang Youl Rhee, Joo Young Kim, Suk Chon, You Cheol Hwang, In Kyung Jeong, Seungjoon Oh, Kyu Jeung Ahn, Ho Yeon Chung, Jeong-taek Woo, Sung Woon Kim, Jin-Woo Kim, Young Seol Kim; Korean Diabetes J. 2010;34(3):157-165. Published online June 30, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.3.157

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Abstract PDF PubReader

Background

There have been no systematic observations regarding changes in early phase insulin secretion among Korean prediabetes and early stage type 2 diabetes mellitus (T2DM) patients.

Methods

We conducted 75-g oral glucose tolerance tests (OGTT) in 873 subjects with suspected abnormal glucose tolerance. All subjects were diagnosed as having normal glucose tolerance (NGT), prediabetes (preDM), or T2DM according to the OGTT results and the insulin secretory and insulin resistance indices of each subject were calculated. Additionally, we analyzed the changes in early phase insulin secretion according to changes in fasting (Glc₀), post-prandial (Glc₁₂₀) glucose and HbA1c (A1c) levels.

Results

As compared to subjects with NGT, the insulin secretory indices of the preDM and T2DM subjects progressively declined, and the insulin resistance indices were progressively aggravated. Early phase insulin secretion decreased rapidly according to the increments of Glc₀, Glc₁₂₀ and A1c, and these changes were most prominent in the NGT stage. Compared to the control group, the early phase insulin secretion levels of the preDM or T2DM subjects were less than 50% when Glc₀ was over 100 mg/dL, Glc₁₂₀ was over 145 mg/dL, and A1c was over 5.8%.

Conclusion

This study suggests that progressive beta cell dysfunction in Koreans may be initiated and rapidly aggravated during the period generally designated as 'normal.'

Citations

Citations to this article as recorded by

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Xueli Cai, Lili Xia, Yuesong Pan, Dian He, Huiping Zhu, Tiemin Wei, Yan He
Diabetology & Metabolic Syndrome.2019;[Epub] CrossRef
Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism
Mi Kyung Kwak, Jee Yang Lee, Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh
Journal of Clinical Medicine.2019; 8(12): 2194. CrossRef
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Reviews

Insulin Resistance During Pregnancy.: Kyu Jeung Ahn; Korean Diabetes J. 2009;33(2):77-82. Published online April 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.2.77

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Abstract PDF: Pregnancy is a complex metabolic state involving dramatic alterations in the hormonal or cytokine environments (increases in estrogen, progesterone, prolactin, cortisol, human chorionic gonadotropin, placental growth hormone and human placental lactogen, TNF-alpha, resistin, leptin, and a decrease in adiponectin) as well as an increasing burden of fuel utilization by the conceptus. Metabolically, the first trimester is characterized by increased insulin sensitivity and lipogenesis. The second and third trimesters, in contrast, are characterized by insulin resistance and increased lipolysis.

Stem Cell and Diabetes.: Kyu Jeung Ahn; Korean Diabetes J. 2001;25(3):179-183. Published online June 1, 2001

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Abstract PDF: No abstract available.

Original Articles

Critical Factors Determined Islet Graft Function In Canine Islet Autotransplantation.: Tae Young Yang, In Kyung Jeong, Seung Hoon Oh, Sang Hoon Lee, Dong Jun Kim, Jong Ryul Hahm, Byung Joon Kim, Kyu Jeung Ahn, Sung Joo Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2000;24(2):170-179. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Islet cell transplantation is an attractive alternative to whole organ pancreas transplantation, since it is clearly safer and simpler surgical procedure for the reciplents. However, several obstacles still remain, because the free islets appear to be more susceptible to non-specific inflammatory damage or immune mediated destruction than islets in an intact pancreas. Therefore, the purpose of this study is to examine the functional outcome of islet autograft and the factors related to the islets graft survival in mongrel dogs. METHODS: Twelve adult mongrel dogs weighting 12~16 kg were used for the experiment of total pancratectomy and islet autotransplantation. The islets were properly isolated by a modified Recordi method. The obtained islets were further purified by centrifugation on discontinuous gradients using cell separation system (Model 2991, Cobe, Lakewood Colo). After the heparization(50U/kg), the islets were injected slowly into the liver through the portal vain for 30 minutes. The post-transplantation intravenous glucose tolerence test (IVGTT) with glucose disappearance rate (K), liver function test (LFT), fasting plasma glucose (FPG) ware measured periodically. RESULTS: I) The median of Ks were 1.3%/min (range 0.3~2.1) and the lEq/kg (150 m equivalents/kg of recipient body weight) was 3520 (range 1350-6550). The Ks in recipients with high lEq/kg (> or =5,000) were significantly higher than those in recipients with low lEq/kg (<5,000)(r=0.78, p<0.05). 2) The islet cell viability were estimated to be 95% and the median of the required insulin dosage for the maintenance of normal FPG were 0.7 (range 0~1.6) U/kg/day, The insulin requirement correlated well with the level of lEq/kg (r=-0.90, p<0.01). 3) The median of the volume of the transplanted pancreatic islet cell were 2.1 mL (range 0.7~5.0) and the purity was 60k (range 10~95), The portal pressure gradients of during the transplant procedure were 4.0(range 0.5~12.0) cmH20. The portal pressure gradients in recipients with high purity were significantly lower than those in recipients with low purity (r=-0,80, p<0,05). CONCLUSIONS: In this study, we confirmed that autotransplantation of islet cell on the pancreatectomized dogs can render nearly normoglycemia, and transplanted islet mass was most critical factor to successful autotransplantation in canine model.

Mutations in Hepatocyte Nuclear Factor-la in Early-Onset Type 2 Diabetes Mellitus in Korea.: Kyoung Ah Kim, Myung Shik Lee, Kyu Jeung Ahn, Jae Hoon Chung, Yong Ki Min, Moon Kyu Lee, Ki Up Lee, Ghi Su Kim, Kyoung Ho Suk, Dae Yeun Hwang, Kwang Won Kim; Korean Diabetes J. 1999;23(6):793-802. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 2 diabetes mellitus is a heterogeneous disorder caused by the unfavorable combination of genetic and environmental factors. Maturity-onset diabetes of the young (MODY) is a rare form of familial type 2 diabetes mellitus characterized by an early onset, and it is appearance in at least three consecutive generations, consistent with an autosomal dominant mode of inheritance. It accounts for 1~3% of type 2 diabetes mellitus cases. As of today, five different MODY genes have been identified. In 1996, Yamagata et al. reported that MODY3 and MODY 1 were caused by mutations in hepatocyte nuclear factor (HNF) la and 4a, respectively. Furthermore, there have been reports that HNF-la gene mutation could be a cause of early-onset type 2 diabetes mellitus with familial history, although these patients do not fulfill the clinical criteria of MODY. Therefore, the purpose of this study was to examine the mutation of HNF-la gene in early-onset type 2 diabetes mellitus in Korean subjects. METHODS: Sixteen cases of early-onset type 2 diabetes mellitus with familial history were included in the study. Five of these subjects were MODY patients according to our revised criteria. DNA was isolated from peripheral blood. The 10 exons and flanking introns of the HNF-1 a gene were amplified by polymerase chain reaction (PCR). The PCR products were sequenced using an AmpliTaq FS Dye Terminator Cycle Sequencing Kit (Perkin-Elmer Applied Biosystems). RESULT: Mutation in the HNF-la gene was identified in 1 of the 16 patients. It was a hitherto unreported novel missense mutation, R263L. This mutation co-segregated with type 2 diabetes mellitus or impaired glucose tolerance in his family and was not found in family members with normal glucose tolerance. CONCLUSION: Findings from this study suggests that MODY3 caused by mutation of HNF-la gene is also present in early onset type 2 diabetic of Korean subjects. This is the first time that HNF-la mutation causing MODY was identified in Korea.

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