Diabetes & Metabolism Journal

Brief Reports

Technology/Device
Effectiveness of the Stage 4 Smart Insulin Pen DIA:CONN P8 for Glycemic Control in a Real-World Setting: So Yoon Kwon, Hyoseon Kwak, Jae Hyeon Kim; Received February 11, 2025 Accepted March 23, 2025 Published online September 3, 2025; DOI: https://doi.org/10.4093/dmj.2025.0112 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: This study evaluated whether a stage 4 smart insulin pen (SIP) provides superior glycemic control compared with a traditional insulin pen (TIP) in individuals with intensively insulin-treated diabetes. Forty-two adults with continuous glucose monitoring (CGM), multiple daily insulin injections, and no prior SIP use were included. After diabetes self-management education (DSME), the SIP group (n=21) initiated SIP, whereas the TIP group (n=21) continued their usual regimens. Glycemic metrics were assessed using CGM before and 2 weeks after DSME. Both groups demonstrated significant improvements in glycemic outcomes. However, SIP users exhibited superior improvements in the percentage of time in range, percentage of time below range (%TBR) <70 mg/dL, %TBR <54 mg/dL, and glycemic risk index compared with TIP users (between-group difference [BD] 11.0%, P=0.046; BD –2.6%, P=0.024; BD –0.9%, P=0.027; BD –18.2, P=0.022, respectively). These findings suggest that SIP, with its bolus calculation and CGM integration, is associated with improved glycemic outcomes in adults with intensively insulin-treated diabetes.

Technology/Device
Effectiveness of Predicted Low-Glucose Suspend Pump Technology in the Prevention of Hypoglycemia in People with Type 1 Diabetes Mellitus: Real-World Data Using DIA:CONN G8: Jee Hee Yoo, Ji Yoon Kim, Jae Hyeon Kim; Diabetes Metab J. 2025;49(1):144-149. Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0039

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We evaluated the effectiveness of the predictive low-glucose suspend (PLGS) algorithm in the DIA:CONN G8. Forty people with type 1 diabetes mellitus (T1DM) who used a DIA:CONN G8 for at least 2 months with prior experience using pumps without and with PLGS were retrospectively analyzed. The objective was to assess the changes in time spent in hypoglycemia (percent of time below range [%TBR]) before and after using PLGS. The mean age, sensor glucose levels, glucose threshold for suspension, and suspension time were 31.1±22.8 years, 159.7±23.2 mg/dL, 81.1±9.1 mg/dL, and 111.9±79.8 min/day, respectively. Overnight %TBR <70 mg/dL was significantly reduced after using the algorithm (differences=0.3%, from 1.4%±1.5% to 1.1%±1.2%, P=0.045). The glycemia risk index (GRI) improved significantly by 4.2 (from 38.8±20.9 to 34.6±19.0, P=0.002). Using the PLGS did not result in a change in the hyperglycemia metric (all P>0.05). Our findings support the PLGS in DIA:CONN G8 as an effective algorithm to improve night-time hypoglycemia and GRI in people with T1DM.

Citations

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Scoping review of subcutaneous glucose monitoring techniques
Eva Hrubá, Jan Kubíček, Martin Augustynek
Measurement.2026; 261: 119940. CrossRef
Current Status of Continuous Glucose Monitoring Use in South Korean Type 1 Diabetes Mellitus Population–Pronounced Age-Related Disparities: Nationwide Cohort Study
Ji Yoon Kim, Seohyun Kim, Jae Hyeon Kim
Diabetes & Metabolism Journal.2025; 49(5): 1040. CrossRef

Original Articles

Type 1 Diabetes
Optimal Coefficient of Variance Threshold to Minimize Hypoglycemia Risk in Individuals with Well-Controlled Type 1 Diabetes Mellitus: Jee Hee Yoo, Seung Hee Yang, Sang-Man Jin, Jae Hyeon Kim; Diabetes Metab J. 2024;48(3):429-439. Published online March 4, 2024; DOI: https://doi.org/10.4093/dmj.2023.0083

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Background
This study investigated the optimal coefficient of variance (%CV) for preventing hypoglycemia based on real-time continuous glucose monitoring (rt-CGM) data in people with type 1 diabetes mellitus (T1DM) already achieving their mean glucose (MG) target.
Methods
Data from 172 subjects who underwent rt-CGM for at least 90 days and for whom 439 90-day glycemic profiles were available were analyzed. Receiver operator characteristic analysis was conducted to determine the cut-off value of %CV to achieve time below range (%TBR)^{<54 mg/dL} <1 and =0.
Results
Overall mean glycosylated hemoglobin was 6.8% and median %TBR^{<54 mg/dL} was 0.2%. MG was significantly higher and %CV significantly lower in profiles achieving %TBR^{<54 mg/dL} <1 compared to %TBR^{<54 mg/dL} ≥1 (all P<0.001). The cut-off value of %CV for achieving %TBR^{<54 mg/dL} <1 was 37.5%, 37.3%, and 31.0%, in the whole population, MG >135 mg/dL, and ≤135 mg/dL, respectively. The cut-off value for %TBR^{<54 mg/dL}=0% was 29.2% in MG ≤135 mg/dL. In profiles with MG ≤135 mg/dL, 94.2% of profiles with a %CV <31 achieved the target of %TBR^{<54 mg/dL} <1, and 97.3% with a %CV <29.2 achieved the target of %TBR<54 mg/ dL=0%. When MG was >135 mg/dL, 99.4% of profiles with a %CV <37.3 achieved %TBR^{<54 mg/dL} <1.
Conclusion
In well-controlled T1DM with MG ≤135 mg/dL, we suggest a %CV <31% to achieve the %TBR^{<54 mg/dL} <1 target. Furthermore, we suggest a %CV <29.2% to achieve the target of %TBR^{<54 mg/dL} =0 for people at high risk of hypoglycemia.

Citations

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Glycemic variability before and during Ramadan fasting among adults with type 2 diabetes and hepatic cirrhosis: a prospective paired cohort using real‑time CGM
Sarah Firdausa, Irsan Hasan, Dicky L. Tahapary, Ignatius Bima Prasetya, Suharko Soebardi, Cleopas Martin Rumende, Hamzah Shatri, Cosphiadi Irawan, Wismandari Wisnu
Diabetes Research and Clinical Practice.2026; 231: 112955. CrossRef
Plasma C-Peptide Level and Continuous Glucose Monitoring-Derived Coefficient of Variation as a Predictable Risk Factor for Hypoglycemia in Koreans with Diabetes
Seung-Hyun Ko
Endocrinology and Metabolism.2025; 40(2): 198. CrossRef
Time in tight range and time in range for predicting the achievement of typical glucose management indicator and HbA1c targets
Seohyun Kim, Sang Ho Park, Jin A. Lee, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Sang-Man Jin
Diabetologia.2025; 68(8): 1674. CrossRef
Associations of time in tight range, time in range, and glycated hemoglobin with albuminuria in type 1 diabetes: A cross-sectional study
Ji Yoon Kim, Seohyun Kim, Sang Ho Park, Jin A Lee, So Hyun Cho, Rosa Oh, Myunghwa Jang, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Sang-Man Jin
Diabetes Research and Clinical Practice.2025; 226: 112325. CrossRef
When would I be surprised? Variability in predicted probability of survival for being “surprised” and “not surprised” to the surprise question
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Drug/Regimen
Efficacy and Safety of IDegAsp in a Real-World Korean Population with Type 2 Diabetes Mellitus: Shinae Kang, Yu-Bae Ahn, Tae Keun Oh, Won-Young Lee, Sung Wan Chun, Boram Bae, Amine Dahaoui, Jin Sook Jeong, Sungeun Jung, Hak Chul Jang; Diabetes Metab J. 2024;48(5):929-936. Published online February 27, 2024; DOI: https://doi.org/10.4093/dmj.2023.0297

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Background
This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp.
Methods
This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106).
Results
In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. –0.51%, P<0.001; 5.21 mg/dL vs. –23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods.
Conclusion
In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.

Citations

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Switching to insulin degludec/aspart penfill reusable cartridges in patients with type 2 diabetes mellitus: real-life outcomes
Sezin Dogan Çakır, Hatice Deniz Yücel, Zeynep Akgül Kızılçay, Mine Adaş
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef
Efficacy and safety of insulin degludec/aspart in patients with type 2 and type 1 diabetes mellitus: real-world evidence from Indonesia
Hendra Zufry, Krishna Wardhana Sucipto, Agustia Sukri Ekadamayanti, Qanita Iqbal
Frontiers in Endocrinology.2025;[Epub] CrossRef
Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing
Yiming Wu, Junqing Zhang, Ang Li
Diabetes Therapy.2024; 15(12): 2515. CrossRef

Review

Cardiovascular Risk/Epidemiology
Intensified Multifactorial Intervention in Patients with Type 2 Diabetes Mellitus: Takayoshi Sasako, Toshimasa Yamauchi, Kohjiro Ueki; Diabetes Metab J. 2023;47(2):185-197. Published online January 12, 2023; DOI: https://doi.org/10.4093/dmj.2022.0325

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In the management of diabetes mellitus, one of the most important goals is to prevent its micro- and macrovascular complications, and to that end, multifactorial intervention is widely recommended. Intensified multifactorial intervention with pharmacotherapy for associated risk factors, alongside lifestyle modification, was first shown to be efficacious in patients with microalbuminuria (Steno-2 study), then in those with less advanced microvascular complications (the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care [ADDITION]-Europe and the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases [J-DOIT3]), and in those with advanced microvascular complications (the Nephropathy In Diabetes-Type 2 [NID-2] study and Diabetic Nephropathy Remission and Regression Team Trial in Japan [DNETT-Japan]). Thus far, multifactorial intervention led to a reduction in cardiovascular and renal events, albeit not necessarily significant. It should be noted that not only baseline characteristics but also the control status of the risk factors and event rates during intervention among the patients widely varied from one trial to the next. Further evidence is needed for the efficacy of multifactorial intervention in a longer duration and in younger or elderly patients. Moreover, now that new classes of antidiabetic drugs are available, it should be addressed whether strict and safe glycemic control, alongside control of other risk factors, could lead to further risk reductions in micro- and macrovascular complications, thereby decreasing all-cause mortality in patients with type 2 diabetes mellitus.

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Zhanpeng He, Hui Cheng, Zhihui Jia, Zimin Niu, Yu Ting Li, Wenyong Huang, Vivian Yawei Guo, Zhiran Su, Yao Jie Xie, Jie Shen, Harry HX Wang
Journal of Diabetes Investigation.2025; 16(5): 884. CrossRef
Thiamine and METTL14 in Diabetes Management with Intensive Insulin Therapy
Miaoguan Peng, Yingying Zhang, Xiaoshi Weng, Jianfeng Wu, Taizhen Luo, Yanmei Dong, Shiyun Wen, Naifeng Liang, Liangying Zhong, Yaojie Zhai, Yijuan Xie, Yingjun Xie, Yuyi Chen
Biomedicines.2025; 13(4): 980. CrossRef
Kidney Disease: Improving Global Outcomes Summit Recommendations on Implementation of Diabetes Management in CKD: From Primary to Data-Driven Collaborative Care
Philip Kam-Tao Li, Michael Cheung, Kai-Ming Chow, Maria Kwan Wa Leung, Lee-Ling Lim, Juliana N.M. Lui, Andrea O.Y. Luk, Jo-Anne Manski-Nankervis, Samuel Seidu, Nikhil Tandon, Adrian Liew, Peter Lin, Fei Chau Pang, Na Tian, Kohjiro Ueki, Martin C.S. Wong,
Kidney International Reports.2025; 10(8): 2551. CrossRef
Comparative Pharmacological and Pharmaceutical Perspectives on Antidiabetic Therapies in Humans, Dogs, and Cats
Iljin Kim, Jang-Hyuk Yun
Pharmaceutics.2025; 17(9): 1098. CrossRef
Diabetic retinopathy as a sentinel of systemic vascular dysfunction: Shared molecular mechanisms with cardiovascular disease
Ting Wang, Hongyu Li, Chuyao Wang, Xiuyun Li, Aijun Deng, Xinwei Jiao
Experimental Eye Research.2025; 261: 110644. CrossRef
Effect of a Multifactorial Intervention on Retinopathy in People With Type 2 Diabetes
Takayoshi Sasako, Kohjiro Ueki, Kengo Miyoshi, Kana Miyake, Tomohisa Aoyama, Yukiko Okazaki, Naoki Ishizuka, Toshimasa Yamauchi, Mitsuhiko Noda, Takashi Kadowaki, Masakazu Haneda, Yasunori Iwashima, Mizuho Okada, Toshihiro Suda, Naoki Tamasawa, Makoto Dai
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Original Articles

Type 1 Diabetes
Performance of Fast-Acting Aspart Insulin as Compared to Aspart Insulin in Insulin Pump for Managing Type 1 Diabetes Mellitus: A Meta-Analysis: Deep Dutta, Ritin Mohindra, Kunal Mahajan, Meha Sharma; Diabetes Metab J. 2023;47(1):72-81. Published online June 24, 2022; DOI: https://doi.org/10.4093/dmj.2022.0035

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Background
No meta-analysis has analysed efficacy and safety of fast-acting aspart insulin (FIAsp) with insulin pump in type 1 diabetes mellitus (T1DM).
Methods
Electronic databases were searched for randomised controlled trials (RCTs) involving T1DM patients on insulin pump receiving FIAsp in intervention arm, and placebo/active comparator insulin in control arm. Primary outcome was to evaluate changes in 1- and 2-hour post-prandial glucose (1hPPG and 2hPPG). Secondary outcomes were to evaluate alterations in percentage time with blood glucose <3.9 mmol/L (hypoglycaemia), time in range (TIR) blood glucose 3.9 to 10 mmol/L, insulin requirements and adverse events.
Results
Data from four RCTs involving 640 patients was analysed. FIAsp use in insulin pump was associated with significantly greater lowering of 1hPPG (mean difference [MD], –1.35 mmol/L; 95% confidence interval [CI], –1.72 to –0.98; P<0.01; I²=63%) and 2hPPG (MD, –1.19 mmol/L; 95% CI, –1.38 to –1.00; P<0.01; I²=0%) as compared to controls. TIR was comparable among groups (MD, 1.06%; 95% CI, –3.84 to 5.96; P=0.67; I²=70%). Duration of blood glucose <3.9 mmol/L was lower in FIAsp group, approaching significance (MD, –0.91%; 95% CI, –1.84 to 0.03; P=0.06; I²=0%). Total hypoglycaemic episodes (risk ratio [RR], 1.35; 95% CI, 0.55 to 3.31; P=0.51; I²=0%), severe hypoglycaemia (RR, 2.26; 95% CI, 0.77 to 6.66; P=0.14), infusion site reactions (RR, 1.35; 95% CI, 0.63 to 2.93; P=0.77; I²=0%), and treatment-emergent adverse events (RR, 1.13; 95% CI, 0.80 to 1.60; P=0.50; I²=0%) were comparable.
Conclusion
FIAsp use in insulin pump is associated with better post-prandial glycaemic control with no increased hypoglycaemia or glycaemic variability.

Citations

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A Pilot Study Evaluating Meal Timing, Macronutrient Composition, and Faster-Acting Insulin Aspart Versus Insulin Aspart on Postprandial Glycemia with the Medtronic Advanced Hybrid Closed-Loop System
Dale J. Morrison, Melissa H. Lee, Sara Vogrin, Declan Hennessy, Emma Netzer, Hannah M. Jones, Lesley Robinson, Carmel E. Smart, Natalie Kurtz, Anirban Roy, Benyamin Grosman, David O’Neal
Diabetes Technology & Therapeutics.2026; 28(1): 38. CrossRef
Tips for successful use of commercial automated insulin delivery systems: An expert paper of the Italian working group on diabetes and technology
Sergio Di Molfetta, Antonio Rossi, Roberta Assaloni, Roberto Franceschi, Valeria Grancini, Vincenzo Guardasole, Andrea Enzo Scaramuzza, Antonietta Maria Scarpitta, Maddalena Trombetta, Angela Zanfardino, Riccardo Candido, Angelo Avogaro, Valentino Cherubi
Diabetes Research and Clinical Practice.2025; 223: 112117. CrossRef
Glycemic Management Across the Lifespan for People With Type 1 Diabetes: A Clinical Practice Guideline
Ilana J. Halperin, Brandy Wicklow, Shazhan Amed, Alanna Chambers, Charlotte Courage, Elizabeth Cummings, Patricia Kirkland, Dylan MacKay, Meranda Nakhla, Zubin Punthakee, Paul M. Ryan, Lindsay Sawatsky, Peter A. Senior, Bikrampal S. Sidhu, Alanna Weisman
Canadian Journal of Diabetes.2025; 49(1): 5. CrossRef
Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials
Mohamed Saad Rakab, Rahma Mogahed Rateb, Basel Hatem Elsalakawi, Bashar M. Al Zoubi, Abubakar Nazir, Mutaz Moath Abu-Laila, Abdelrahman Sherif Ghanem, Alaa Maamoun, Mohab Mattar, Basma Ataallah, Brian T. Layden, Abeer M. Mahmoud
Frontiers in Endocrinology.2025;[Epub] CrossRef
Burden and Coping Strategies of Hypoglycemia in People with Diabetes
Aris Liakos, Thomas Karagiannis, Ioannis Avgerinos, Apostolos Tsapas, Eleni Bekiari
Current Diabetes Reviews.2024;[Epub] CrossRef
Ultrafast-acting insulin: pharmacological properties and their impact on clinical aspects
L. A. Suplotova, A. Sh. Tilkiyan
Meditsinskiy sovet = Medical Council.2024; (13): 146. CrossRef
Unveiling the Spectrum of Glucose Variability: A Novel Perspective on FreeStyle Libre Monitoring Data
Adrian H. Heald, Mike Stedman, John Warner-Levy, Lleyton Belston, Angela Paisley, Aleksandra Jotic, Nebojsa Lalic, Martin Gibson, Hellena H. Habte-Asres, Martin Whyte, Angus Forbes
Diabetes Therapy.2024; 15(12): 2475. CrossRef
Efficacy and Safety of Ultra-rapid Lispro Insulin in Managing Type-1 and Type-2 Diabetes: A Systematic Review and Meta-Analysis
Deep Dutta, Lakshmi Nagendra, Saptarshi Bhattacharya, Meha Sharma
Indian Journal of Endocrinology and Metabolism.2023; 27(6): 467. CrossRef

Metabolic Risk/Epidemiology
Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus: Soyeon Kang, Yong-Moon Park, Dong Jin Kwon, Youn-Jee Chung, Jeong Namkung, Kyungdo Han, Seung-Hyun Ko; Diabetes Metab J. 2022;46(4):578-591. Published online January 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0135

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Background
Estrogen promotes glucose homeostasis, enhances insulin sensitivity, and maintains counterregulatory responses in recurrent hypoglycemia in women of reproductive age. Postmenopausal women with type 2 diabetes mellitus (T2DM) might be more vulnerable to severe hypoglycemia (SH) events. However, the relationship between reproductive factors and SH occurrence in T2DM remains unelucidated.
Methods
This study included data on 181,263 women with postmenopausal T2DM who participated in a national health screening program from January 1 to December 31, 2009, obtained using the Korean National Health Insurance System database. Outcome data were obtained until December 31, 2018. Associations between reproductive factors and SH incidence were assessed using Cox proportional hazards models.
Results
During the mean follow-up of 7.9 years, 11,279 (6.22%) postmenopausal women with T2DM experienced SH episodes. A longer reproductive life span (RLS) (≥40 years) was associated with a lower SH risk compared to a shorter RLS (<30 years) (adjusted hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.69 to 0.80; P for trend <0.001) after multivariable adjustment. SH risk decreased with every 5-year increment of RLS (with <30 years as a reference [adjusted HR, 0.91; 95% CI, 0.86 to 0.95; P=0.0001 for 30−34 years], [adjusted HR, 0.80; 95% CI, 0.76 to 0.84; P<0.001 for 35−39 years], [adjusted HR, 0.74; 95% CI, 0.68 to 0.81; P<0.001 for ≥40 years]). The use of hormone replacement therapy (HRT) was associated with a lower SH risk than HRT nonuse.
Conclusion
Extended exposure to endogenous ovarian hormone during lifetime may decrease the number of SH events in women with T2DM after menopause.

Citations

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Defining Continuous Glucose Monitor Time in Range in a Large, Community-Based Cohort Without Diabetes
Nicole L Spartano, Naznin Sultana, Honghuang Lin, Huimin Cheng, Sophia Lu, David Fei, Joanne M Murabito, Maura E Walker, Howard A Wolpert, Devin W Steenkamp
The Journal of Clinical Endocrinology & Metabolism.2025; 110(4): 1128. CrossRef
Associations of acrylamide biomarkers with reproductive lifespan: A cross-sectional study in U.S. women
Junying Li, Chen Chen, Xing Dong, Yushan Cao, Zhuo Bao, Yixuan Liu, Jinxiang Yan, Pei Zhang, Yongzhen Guo, Xianxu Zeng
Food and Chemical Toxicology.2025; 202: 115500. CrossRef
Supporting women with diabetes experiencing menopause: A workshop to co‐design research recommendations for improving the understanding of and support for women with diabetes experiencing menopause
Steven Parks, Nia Otake John, Anna Morris, Kamini Shah, Elizabeth Eves, Dawn Adams, Eleanor Barry, Vicki Causer, Rachel Churm, Sahir Ahmed‐Evans, Alex Vienne Haggett, Reena Patel, Rita Forde, Rebecca Reynolds
Diabetic Medicine.2025;[Epub] CrossRef
Association between serum copper level and reproductive health of Women in the United States: a cross-sectional study
Yi Yuan, Tong-Yu Peng, Guang-Yuan Yu, Zhao Zou, Meng-Ze Wu, Ruofei Zhu, Shuang Wu, Zi Lv, Su-Xin Luo
International Journal of Environmental Health Research.2024; 34(6): 2441. CrossRef
Reproductive Lifespan and Motor Progression of Parkinson’s Disease
Ruwei Ou, Qianqian Wei, Yanbing Hou, Lingyu Zhang, Kuncheng Liu, Junyu Lin, Tianmi Yang, Jing Yang, Zheng Jiang, Wei Song, Bei Cao, Huifang Shang
Journal of Clinical Medicine.2022; 11(20): 6163. CrossRef
Menopause and development of Alzheimer’s disease: Roles of neural glucose metabolism and Wnt signaling
Paulina Villaseca, Pedro Cisternas, Nibaldo C. Inestrosa
Frontiers in Endocrinology.2022;[Epub] CrossRef

Review

Technology/Device
Current Advances of Artificial Pancreas Systems: A Comprehensive Review of the Clinical Evidence: Sun Joon Moon, Inha Jung, Cheol-Young Park; Diabetes Metab J. 2021;45(6):813-839. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0177

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Since Banting and Best isolated insulin in the 1920s, dramatic progress has been made in the treatment of type 1 diabetes mellitus (T1DM). However, dose titration and timely injection to maintain optimal glycemic control are often challenging for T1DM patients and their families because they require frequent blood glucose checks. In recent years, technological advances in insulin pumps and continuous glucose monitoring systems have created paradigm shifts in T1DM care that are being extended to develop artificial pancreas systems (APSs). Numerous studies that demonstrate the superiority of glycemic control offered by APSs over those offered by conventional treatment are still being published, and rapid commercialization and use in actual practice have already begun. Given this rapid development, keeping up with the latest knowledge in an organized way is confusing for both patients and medical staff. Herein, we explore the history, clinical evidence, and current state of APSs, focusing on various development groups and the commercialization status. We also discuss APS development in groups outside the usual T1DM patients and the administration of adjunct agents, such as amylin analogues, in APSs.

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Original Article

Drug/Regimen
Efficacy and Safety of Self-Titration Algorithms of Insulin Glargine 300 units/mL in Individuals with Uncontrolled Type 2 Diabetes Mellitus (The Korean TITRATION Study): A Randomized Controlled Trial: Jae Hyun Bae, Chang Ho Ahn, Ye Seul Yang, Sun Joon Moon, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2022;46(1):71-80. Published online June 16, 2021; DOI: https://doi.org/10.4093/dmj.2020.0274

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Background
To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM).
Methods
In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without noct urnal hypoglycemia at week 12.
Results
Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014).
Conclusion
The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).

Citations

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Review

Type 1 Diabetes
Non-Insulin Antidiabetes Treatment in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis: Xiaoling Cai, Chu Lin, Wenjia Yang, Lin Nie, Linong Ji; Diabetes Metab J. 2021;45(3):312-325. Published online March 15, 2021; DOI: https://doi.org/10.4093/dmj.2020.0171

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In order to evaluate the efficacy and side effects of the non-insulin antidiabetes medications as an adjunct treatment in type 1 diabetes mellitus (T1DM), we conducted systematic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between the date of inception and March 2020 to produce a systematic review and meta-analysis. Overall, 57 studies were included. Compared with placebo, antidiabetes agents in adjunct to insulin treatment resulted in significant reduction in glycosylated hemoglobin (weighted mean difference [WMD], –0.30%; 95% confidence interval [CI], –0.34 to –0.25%; P<0.01) and body weight (WMD, –2.15 kg; 95% CI, –2.77 to –1.53 kg; P<0.01), and required a significantly lower dosage of insulin (WMD, –5.17 unit/day; 95% CI, –6.77 to –3.57 unit/day; P<0.01). Compared with placebo, antidiabetes agents in adjunct to insulin treatment increased the risk of hypoglycemia (relative risk [RR], 1.04; 95% CI, 1.01 to 1.08; P=0.02) and gastrointestinal side effects (RR, 1.99; 95% CI, 1.61 to 2.46; P<0.01) in patients with T1DM. Compared with placebo, the use of non-insulin antidiabetes agents in addition to insulin could lead to glycemic improvement, weight control and lower insulin dosage, while they might be associated with increased risks of hypoglycemia and gastrointestinal side effects in patients with T1DM.

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Original Articles

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

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Background

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

Methods

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

Results

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

Conclusion

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

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Drug/Regimen
Switching to Once-Daily Insulin Degludec/Insulin Aspart from Basal Insulin Improves Postprandial Glycemia in Patients with Type 2 Diabetes Mellitus: Randomized Controlled Trial: Kyu Yong Cho, Akinobu Nakamura, Chiho Oba-Yamamoto, Kazuhisa Tsuchida, Shingo Yanagiya, Naoki Manda, Yoshio Kurihara, Shin Aoki, Tatsuya Atsumi, Hideaki Miyoshi; Diabetes Metab J. 2020;44(4):532-541. Published online November 22, 2019; DOI: https://doi.org/10.4093/dmj.2019.0093

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Background

To explore the efficacy and safety of switching from once-daily basal insulin therapy to once-daily pre-meal injection insulin degludec/insulin aspart (IDegAsp) with respect to the glycemic control of participants with type 2 diabetes mellitus (T2DM).

Methods

In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, participants on basal insulin therapy were switched to IDegAsp (IDegAsp group; n=30) or continued basal insulin (Basal group; n=29). The primary endpoint was the superiority of IDegAsp in causing changes in the daily blood glucose profile, especially post-prandial blood glucose concentration after 12 weeks.

Results

Blood glucose concentrations after dinner and before bedtime were lower in the IDegAsp group, and the improvement in blood glucose before bedtime was significantly greater in the IDegAsp group than in the Basal group at 12 weeks (−1.7±3.0 mmol/L vs. 0.3±2.1 mmol/L, P<0.05). Intriguingly, glycemic control after breakfast was not improved by IDegAsp injection before breakfast, in contrast to the favorable effect of injection before dinner on blood glucose after dinner. Glycosylated hemoglobin significantly decreased only in the IDegAsp group (58 to 55 mmol/mol, P<0.05). Changes in daily insulin dose, body mass, and recorded adverse effects, including hypoglycemia, were comparable between groups.

Conclusion

IDegAsp was more effective than basal insulin at reducing blood glucose after dinner and before bedtime, but did not increase the incidence of hypoglycemia. Switching from basal insulin to IDegAsp does not increase the burden on the patient and positively impacts glycemic control in patients with T2DM.

Citations

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Efficacy, safety and treatment satisfaction of transition to a regimen of insulin degludec/aspart: A pilot study
Na Yang, Lu Lv, Shu-Meng Han, Li-Yun He, Zi-Yi Li, Yu-Cheng Yang, Fan Ping, Ling-Ling Xu, Wei Li, Hua-Bing Zhang, Yu-Xiu Li
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Evaluation of pharmacokinetic and pharmacodynamic similarity of an IDegAsp biosimilar versus the originator in healthy Chinese volunteers
Hui Liu, Yang Xiong, Xinlei Chen, Hongling Yu, Li Lan, Wengang He, Wenjia Wang, Yulei Zhuang, Li Deng, Kanghua Huang, Linfeng Guo, Yerong Yu
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Efficacy and safety of iGlarLixi versus IDegAsp in people with type 2 diabetes inadequately controlled with basal insulin: A systematic literature review and network meta‐analysis of non‐Asian studies
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Insulin degludec/insulin aspart (IDegAsp) treatment on glycemic control and weight in patients with insulin experienced uncontrolled type 2 diabetes mellitus: A retrospective observational study
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Clinical Complications
Hypoglycemia and Dementia Risk in Older Patients with Type 2 Diabetes Mellitus: A Propensity-Score Matched Analysis of a Population-Based Cohort Study: Young-Gun Kim, Dong Gyu Park, So Young Moon, Ja Young Jeon, Hae Jin Kim, Dae Jung Kim, Kwan-Woo Lee, Seung Jin Han; Diabetes Metab J. 2020;44(1):125-133. Published online October 23, 2019; DOI: https://doi.org/10.4093/dmj.2018.0260

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Background

Type 2 diabetes mellitus (T2DM) is associated with an increased risk for dementia. The effects of hypoglycemia on dementia are controversial. Thus, we evaluated whether hypoglycemia increases the risk for dementia in senior patients with T2DM.

Methods

We used the Korean National Health Insurance Service Senior cohort, which includes >10% of the entire senior population of South Korea. In total, 5,966 patients who had ever experienced at least one episode of hypoglycemia were matched with those who had not, using propensity score matching. The risk of dementia was assessed through a survival analysis of matched pairs.

Results

Patients with underlying hypoglycemic events had an increased risk for all-cause dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) compared with those who had not experienced a hypoglycemic event (hazard ratio [HR], 1.254; 95% confidence interval [CI], 1.166 to 1.349; P<0.001 for all-cause dementia; HR, 1.264; 95% CI, 1.162 to 1.375; P<0.001 for AD; HR, 1.286; 95% CI, 1.110 to 1.490; P<0.001 for VaD). According to number of hypoglycemic episodes, the HRs of dementia were 1.170, 1.201, and 1.358 in patients with one hypoglycemic episode, two or three episodes, and more than three episodes, respectively. In the subgroup analysis, hypoglycemia was associated with an increased risk for dementia in both sexes with or without T2DM microvascular or macrovascular complications.

Conclusion

Our findings suggest that patients with a history of hypoglycemia have a higher risk for dementia. This trend was similar for AD and VaD, the two most important subtypes of dementia.

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Review

Others
Continuous Glucose Monitoring Sensors for Diabetes Management: A Review of Technologies and Applications: Giacomo Cappon, Martina Vettoretti, Giovanni Sparacino, Andrea Facchinetti; Diabetes Metab J. 2019;43(4):383-397. Published online July 25, 2019; DOI: https://doi.org/10.4093/dmj.2019.0121

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Abstract PDF PubReader ePub

By providing blood glucose (BG) concentration measurements in an almost continuous-time fashion for several consecutive days, wearable minimally-invasive continuous glucose monitoring (CGM) sensors are revolutionizing diabetes management, and are becoming an increasingly adopted technology especially for diabetic individuals requiring insulin administrations. Indeed, by providing glucose real-time insights of BG dynamics and trend, and being equipped with visual and acoustic alarms for hypo- and hyperglycemia, CGM devices have been proved to improve safety and effectiveness of diabetes therapy, reduce hypoglycemia incidence and duration, and decrease glycemic variability. Furthermore, the real-time availability of BG values has been stimulating the realization of new tools to provide patients with decision support to improve insulin dosage tuning and infusion. The aim of this paper is to offer an overview of current literature and future possible developments regarding CGM technologies and applications. In particular, first, we outline the technological evolution of CGM devices through the last 20 years. Then, we discuss about the current use of CGM sensors from patients affected by diabetes, and, we report some works proving the beneficial impact provided by the adoption of CGM. Finally, we review some recent advanced applications for diabetes treatment based on CGM sensors.

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Original Articles

Clinical Diabetes & Therapeutics
Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Korean Patients with Type 2 Diabetes Mellitus in Real-World Clinical Practice: A Ram Hong, Bo Kyung Koo, Sang Wan Kim, Ka Hee Yi, Min Kyong Moon; Diabetes Metab J. 2019;43(5):590-606. Published online February 28, 2019; DOI: https://doi.org/10.4093/dmj.2018.0134

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Abstract PDF Supplementary Material PubReader ePub

Background

This study aimed to evaluate the efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in Korean patients who had inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice.

Methods

We included 410 patients who started SGLT2 inhibitors (empagliflozin or dapagliflozin) as add-on therapy or switch therapy between February 2015 and June 2017. The primary efficacy endpoint was a change in glycosylated hemoglobin (HbA1c) from baseline to week 12. The secondary endpoints were patients achieving HbA1c <7.0% and changes in the fasting plasma glucose (FPG), lipid profiles, body weight, and blood pressure (BP).

Results

The mean HbA1c at baseline was 8.5% (8.6% in the add-on group and 8.4% in the switch group). At week 12, the mean adjusted HbA1c decreased by −0.68% in the overall patients (P<0.001), by −0.94% in the add-on group, and by −0.42% in the switch group. Significant reductions in FPG were also observed both in the add-on group and switch group (−30.3 and −19.8 mg/dL, respectively). Serum triglyceride (−16.5 mg/dL), body weight (−2.1 kg), systolic BP (−4.7 mm Hg), and diastolic BP (−1.3 mm Hg) were significantly improved in the overall patients. Approximately 18.3% of the patients achieved HbA1c <7.0% at week 12. A low incidence of hypoglycemia and genital tract infection was observed (6.3% and 2.2%, respectively).

Conclusion

SGLT2 inhibitors can be a suitable option as either add-on or switch therapy for Korean patients with inadequately controlled T2DM.

Citations

Citations to this article as recorded by

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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.

Citations

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Severe Hypoglycemia Increases Dementia Risk and Related Mortality: A Nationwide, Population-based Cohort Study
Eugene Han, Kyung-do Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Seung-Hyun Ko, Yong-ho Lee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(5): e1976. CrossRef
Severe hypoglycemia as a preventable risk factor for cardiovascular disease in patients with type 2 diabetes mellitus
Soo-Yeon Choi, Seung-Hyun Ko
The Korean Journal of Internal Medicine.2021; 36(2): 263. CrossRef
Severe hypoglycemia and the risk of end stage renal disease in type 2 diabetes
Jae-Seung Yun, Yong-Moon Park, Kyungdo Han, Hyung-Wook Kim, Seon-Ah Cha, Yu-Bae Ahn, Seung-Hyun Ko
Scientific Reports.2021;[Epub] CrossRef
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

Reviews

Clinical Diabetes & Therapeutics
Recent Updates on Type 1 Diabetes Mellitus Management for Clinicians: Ahmed Iqbal, Peter Novodvorsky, Simon R. Heller; Diabetes Metab J. 2018;42(1):3-18. Published online February 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.1.3

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Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that requires life-long administration of insulin. Optimal management of T1DM entails a good knowledge and understanding of this condition both by the physician and the patient. Recent introduction of novel insulin preparations, technological advances in insulin delivery and glucose monitoring, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring and improved understanding of the detrimental effects of hypoglycaemia and hyperglycaemia offer new opportunities and perspectives in T1DM management. Evidence from clinical trials suggests an important role of structured patient education. Our efforts should be aimed at improved metabolic control with concomitant reduction of hypoglycaemia. Despite recent advances, these goals are not easy to achieve and can put significant pressure on people with T1DM. The approach of physicians should therefore be maximally supportive. In this review, we provide an overview of the recent advances in T1DM management focusing on novel insulin preparations, ways of insulin administration and glucose monitoring and the role of metformin or sodium-glucose co-transporter 2 inhibitors in T1DM management. We then discuss our current understanding of the effects of hypoglycaemia on human body and strategies aimed at mitigating the risks associated with hypoglycaemia.

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Clinical Diabetes & Therapeutics
Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association: Hyun Jin Kim, Seok O Park, Seung-Hyun Ko, Sang Youl Rhee, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Byung-Wan Lee, Jin Hwa Kim, Kyung Mook Choi; Diabetes Metab J. 2017;41(6):423-429. Published online December 19, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.6.423

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The glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The cardiovascular safety of GLP-1RAs has been assessed in several randomized clinical trials and systematic reviews. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RA may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA.

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Original Article

Complications
Baseline-Corrected QT (QTc) Interval Is Associated with Prolongation of QTc during Severe Hypoglycemia in Patients with Type 2 Diabetes Mellitus: Seon-Ah Cha, Jae-Seung Yun, Tae-Seok Lim, Yoon-Goo Kang, Kang-Min Lee, Ki-Ho Song, Ki-Dong Yoo, Yong-Moon Park, Seung-Hyun Ko, Yu-Bae Ahn; Diabetes Metab J. 2016;40(6):463-472. Published online October 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.6.463

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Background

We investigated an association between baseline heart rate-corrected QT (QTc) interval before severe hypoglycemia (SH) and prolongation of QTc interval during SH in patients with type 2 diabetes mellitus (T2DM).

Methods

Between January 2004 and June 2014, 208 patients with T2DM, who visited the emergency department because of SH and underwent standard 12-lead electrocardiography within the 6-month period before SH were consecutively enrolled. The QTc interval was analyzed during the incidence of SH, and 6 months before and after SH. QTc intervals of 450 ms or longer in men and 460 ms or longer in women were considered abnormally prolonged.

Results

The mean age and diabetes duration were 68.1±12.1 and 14.1±10.1 years, respectively. The mean QTc intervals at baseline and SH episodes were 433±33 and 460±33 ms, respectively (P<0.001). One hundred and fourteen patients (54.8%) had a prolonged QTc interval during SH. There was a significant decrease in the prolonged QTc interval within 6 months after SH (QTc interval prolongation during SH vs. after recovery, 54.8% vs. 33.8%, P<0.001). The prolonged QTc interval was significantly associated with baseline QTc interval prolongation (odds ratio, 2.92; 95% confidence interval, 1.22 to 6.96; P=0.016) after adjusting for multiple confounders.

Conclusion

A prolonged QTc interval at baseline was significantly associated with prolongation of the QTc interval during SH in patients with T2DM, suggesting the necessity of QTc interval monitoring and attention to those with a prolonged QTc interval to prevent SH.

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Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes
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Review

Complications
Risk Factors and Adverse Outcomes of Severe Hypoglycemia in Type 2 Diabetes Mellitus: Jae-Seung Yun, Seung-Hyun Ko; Diabetes Metab J. 2016;40(6):423-432. Published online October 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.6.423

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Hypoglycemia has been considered as a major barrier to achieving the proper glycemic target in type 2 diabetes mellitus patients. In particular, severe hypoglycemia (SH), which is defined as a hypoglycemic episode requiring the assistance of another person to raise the patient's glucose level, is a serious complication of diabetes because of its possible fatal outcomes. Recently, the recommendations for diabetes care have emphasized a patient-centered approach, considering the individualized patient factors including hypoglycemia. Many studies have been performed which analyzed the risk factors and clinical outcomes for SH. From the studies, researchers recommend that targeting a less stringent glycosylated hemoglobin level and selecting a safer class of drugs for hypoglycemia are appropriate for patients with a high risk of SH. Also, careful clinical attention to prevent hypoglycemia, including intensive education, is necessary to minimize the risk of SH and SH-related fatal outcomes.

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Original Articles

Complications
Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in Patients with Type 2 Diabetes: Seon-Ah Cha, Jae-Seung Yun, Tae-Seok Lim, Seawon Hwang, Eun-Jung Yim, Ki-Ho Song, Ki-Dong Yoo, Yong-Moon Park, Yu-Bae Ahn, Seung-Hyun Ko; Diabetes Metab J. 2016;40(3):202-210. Published online April 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.3.202

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Abstract PDF PubReader ePub

Background

We investigated the association between severe hypoglycemia (SH) and the risk of cardiovascular (CV) or all-cause mortality in patients with type 2 diabetes.

Methods

The study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR), who consecutively enrolled (n=1,260) from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis.

Results

Among the 906 participants (71.9%) who completed follow-up, 85 patients (9.4%) had at least one episode of SH, and 86 patients (9.5%) died (9.1 per 1,000 patient-years). Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P=0.003) and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P=0.002) after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use.

Conclusion

We found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes.

Citations

Citations to this article as recorded by

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Endocrinología, Diabetes y Nutrición (English ed.).2018; 65(8): 451. CrossRef
Time- and frequency-domain measures of heart rate variability predict cardiovascular outcome in patients with type 2 diabetes
Seon-Ah Cha, Yong-Moon Park, Jae-Seung Yun, Seung-Hwan Lee, Yu-Bae Ahn, Sung-Rae Kim, Seung-Hyun Ko
Diabetes Research and Clinical Practice.2018; 143: 159. CrossRef
Newly diagnosed type 2 diabetes in an ethnic minority population: clinical presentation and comparison to other populations
Michael Morkos, Bettina Tahsin, Louis Fogg, Leon Fogelfeld
BMJ Open Diabetes Research & Care.2018; 6(1): e000568. CrossRef
DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular outcomes and mortality
Thomas R. Pieber, Steven P. Marso, Darren K. McGuire, Bernard Zinman, Neil R. Poulter, Scott S. Emerson, Richard E. Pratley, Vincent Woo, Simon Heller, Martin Lange, Kirstine Brown-Frandsen, Alan Moses, Jesper Barner Lekdorf, Lucine Lehmann, Kajsa Kvist,
Diabetologia.2018; 61(1): 58. CrossRef
Intervention effects of Compound Houttuyniae Herba to diabetic renal damage based on SOCS-JAK/STAT negative feedback regulation
Yun Fang, Sai-cong Shao, Hai-ying Wang
Chinese Herbal Medicines.2018; 10(4): 424. CrossRef
Monotherapy in Patients with Type 2 Diabetes Mellitus
Sang Youl Rhee, Hyun Jin Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 349. CrossRef
Monotherapy in patients with type 2 diabetes mellitus
Sang Youl Rhee, Hyun Jin Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 959. CrossRef
Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 947. CrossRef
Cardiovascular effects of dipeptidyl peptidase-4 inhibitor in diabetic patients with and without established cardiovascular disease: a meta-analysis and systematic review
Shishi Xu, Xinyue Zhang, Lizhi Tang, Fang Zhang, Nanwei Tong
Postgraduate Medicine.2017; 129(2): 205. CrossRef
Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 337. CrossRef
Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus
Ying Wang, Xiuru Qi, Chunliang Wang, Danning Zhao, Hongjie Wang, Jianxin Zhang
Biomedical Reports.2017; 6(1): 69. CrossRef
Cardiovascular risk assessment in patients with diabetes
Marcello Casaccia Bertoluci, Viviane Zorzanelli Rocha
Diabetology & Metabolic Syndrome.2017;[Epub] CrossRef
Pathogenetic features of the combined course of arterial hypertension and diabetes mellitus 2 type
O.M. Bilovol, L.R. Bobronnikova, O.V. Al-Trawneh
Shidnoevropejskij zurnal vnutrisnoi ta simejnoi medicini.2017; 2017(1): 4. CrossRef
Risk Factors and Adverse Outcomes of Severe Hypoglycemia in Type 2 Diabetes Mellitus
Jae-Seung Yun, Seung-Hyun Ko
Diabetes & Metabolism Journal.2016; 40(6): 423. CrossRef
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Koutaro Yokote, Yasuo Terauchi, Ichiro Nakamura, Haruko Sugamori
Expert Opinion on Pharmacotherapy.2016; 17(15): 1995. CrossRef
Hypoglycemia: Culprit or Bystander?
You-Cheol Hwang
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Schwere Hypoglykämien erhöhen die Mortalität
E. Fritschka
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Clinical Care/Education
Clinical Characteristics and Metabolic Predictors of Rapid Responders to Dipeptidyl Peptidase-4 Inhibitor as an Add-on Therapy to Sulfonylurea and Metformin: Ye An Kim, Won Sang Yoo, Eun Shil Hong, Eu Jeong Ku, Kyeong Seon Park, Soo Lim, Young Min Cho, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi; Diabetes Metab J. 2015;39(6):489-497. Published online November 27, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.489

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Background

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

Methods

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

Results

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

Conclusion

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

Citations

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A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes
Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
Medicine.2016; 95(44): e5155. CrossRef

Complications
Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes: Jae-Seung Yun, Seung-Hyun Ko, Sun-Hye Ko, Ki-Ho Song, Ki-Dong Yoo, Kun-Ho Yoon, Yong-Moon Park, Yu-Bae Ahn; Diabetes Metab J. 2015;39(6):498-506. Published online July 8, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.498

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Background

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

Methods

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

Results

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

Conclusion

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

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Randomised controlled trial of pharmacist-led patient counselling in controlling hypoglycaemic attacks in older adults with type 2 diabetes mellitus (ROSE-ADAM): A study protocol of the SUGAR intervention
Huda Y. Almomani, Carlos Rodriguez Pascual, Sayer I. Al-Azzam, Keivan Ahmadi
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Jeffrey Freeman
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Young-ung Kim, Yong-joon Shin, Young Woo Cho
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The Korean Journal of Internal Medicine.2018; 33(5): 952. CrossRef
Time- and frequency-domain measures of heart rate variability predict cardiovascular outcome in patients with type 2 diabetes
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Diabetes Research and Clinical Practice.2018; 143: 159. CrossRef
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Mi-Kyung Kim
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Response: Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes (Diabetes Metab J 2015;39:498-506)
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Intensive Individualized Reinforcement Education Is Important for the Prevention of Hypoglycemia in Patients with Type 2 Diabetes: Yun-Mi Yong, Kyung-Mi Shin, Kang-Min Lee, Jae-Young Cho, Sun-Hye Ko, Min-Hyang Yoon, Tae-Won Kim, Jong-Hyun Jeong, Yong-Moon Park, Seung-Hyun Ko, Yu-Bae Ahn; Diabetes Metab J. 2015;39(2):154-163. Published online March 10, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.2.154

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Background

We investigated whether an intensive individualized reinforcement education program could influence the prevention of hypoglycemic events in patients with type 2 diabetes.

Methods

From March 2013 to September 2013, patients aged 35 to 75 years with type 2 diabetes who had not previously participated in diabetes education, and treated with insulin or a sulfonylurea-containing regimen were included in the study. After structured group education, the patients assigned to the intensive individualized education group (IT) were requested to visit for reinforcement. All subjects in the IT were encouraged to self-manage dose adjustments. Participants in both groups (control group [CG, group education only; n=22] and IT [n=24]) attended follow-up visits at 2, 8, 12, and 24 weeks. At each visit, all patients were asked whether they had experienced hypoglycemia.

Results

The total study population consisted of 20 men (43.5%; mean age and diabetic duration of 55.9±11.0 and 5.1±7.3 years, respectively). At 24 weeks, there were no significant differences in hemoglobin A1c values between the CG and IT. The total number of hypoglycemic events per patient was 5.26±6.5 in the CG and 2.58±2.3 times in the IT (P=0.004). Adherence to lifestyle modification including frequency of exercise, self-monitoring of blood glucose, or dietary habit was not significantly different between the groups. However, adherence to hypoglycemia management, especially the dose adjustment of medication, was significantly higher in the IT compared with the CG.

Conclusion

Compared with the structured group education, additional IT resulted in additional benefits in terms of avoidance of hypoglycemia and treating hypoglycemia in patients with type 2 diabetes.

Citations

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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
Diabetes & Metabolism Journal.2025; 49(4): 582. CrossRef
The SUGAR handshake intervention to prevent hypoglycaemia in elderly people with type 2 diabetes: process evaluation within a pragmatic randomised controlled trial
Huda Y. Almomani, Helen M. Ayre, Richard A. Powell, Keivan Armani
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2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang
Diabetes & Metabolism Journal.2024; 48(4): 546. CrossRef
Effectiveness of the SUGAR intervention on hypoglycaemia in elderly patients with type 2 diabetes: A pragmatic randomised controlled trial
Huda Y. Almomani, Carlos Rodriguez Pascual, Paul Grassby, Keivan Ahmadi
Research in Social and Administrative Pharmacy.2023; 19(2): 322. CrossRef
A Cross-Sectional study on risk factors for severe hypoglycemia among Insulin-Treated elderly type 2 diabetes Mellitus (T2DM) patients in Singapore
Michelle Shi Min Ko, Wai Kit Lee, Li Chang Ang, Su-Yen Goh, Yong Mong Bee, Ming Ming Teh
Diabetes Research and Clinical Practice.2022; 185: 109236. CrossRef
Management Status of Patients with Type 2 Diabetes Mellitus at General Hospitals in Korea: A 5-Year Follow-Up Study
Jin Hee Jung, Jung Hwa Lee, Hyang Mi Jang, Young Na, Hee Sun Choi, Yeon Hee Lee, Yang Gyo Kang, Na Rae Kim, Jeong Rim Lee, Bok Rye Song, Kang Hee Sim
The Journal of Korean Diabetes.2022; 23(1): 64. CrossRef
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Rayan Mamoon, Md Y Mamoon, Debbie Hermanstyne, Issac Sachmechi
Cureus.2022;[Epub] CrossRef
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Huda Y. Almomani, Carlos Rodriguez Pascual, Sayer I. Al-Azzam, Keivan Ahmadi
Research in Social and Administrative Pharmacy.2021; 17(5): 885. CrossRef
Severe hypoglycemia as a preventable risk factor for cardiovascular disease in patients with type 2 diabetes mellitus
Soo-Yeon Choi, Seung-Hyun Ko
The Korean Journal of Internal Medicine.2021; 36(2): 263. CrossRef
Type 2 diabetes patients’ views on prevention of hypoglycaemia – a mixed methods study investigating self-management issues and self-identified causes of hypoglycaemia
Stijn Crutzen, Tessa van den Born-Bondt, Petra Denig, Katja Taxis
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Chukwuma Uduku, Valentina Pendolino, Ian Godsland, Nick Oliver, Monika Reddy, Rachael T. Fothergill
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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
Diabetes & Metabolism Journal.2017; 41(5): 367. CrossRef
Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 337. CrossRef
Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
The Korean Journal of Internal Medicine.2017; 32(6): 967. CrossRef
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Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
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Hypoglycemia and Health Costs
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Association between estimated blood glucose levels and glycated hemoglobin levels
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Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea: Chang-Yun Woo, Ji Yun Jeong, Jung Eun Jang, Jaechan Leem, Chang Hee Jung, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Jung Bok Lee, Ki-Up Lee; Diabetes Metab J. 2015;39(2):126-131. Published online March 9, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.2.126

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Background

Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.

Methods

To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.

Results

Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.

Conclusion

The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

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Corrected QT Interval Prolongation during Severe Hypoglycemia without Hypokalemia in Patients with Type 2 Diabetes: Jae Won Beom, Jung Min Kim, Eun Joo Chung, Ju Yeong Kim, Seung Yeong Ko, Sang Don Na, Cheol Hwan Kim, Gun Park, Mi Yeon Kang; Diabetes Metab J. 2013;37(3):190-195. Published online June 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.3.190

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Background

To evaluate the effects of severe hypoglycemia without hypokalemia on the electrocardiogram in patients with type 2 diabetes in real-life conditions.

Methods

Electrocardiograms of adult type 2 diabetic patients during the episodes of severe hypoglycemia and the recovered stage were obtained and analysed between October 1, 2011 and May 31, 2012. Patients who maintained the normal serum sodium and potassium levels during the episodes of severe hypoglycemia were only selected as the subjects of this study. Severe hypoglycemia was defined, in this study, as the condition requiring active medical assistance such as administering carbohydrate when serum glucose level was less than 60 mg/dL.

Results

Nine type 2 diabetes patients (seven men, two women) were included in the study. The mean subject age was 73.2±7.7 years. The mean hemoglobin A1c level was 6.07%±1.19%. The median duration of diabetes was 10 years (range, 3.5 to 30 years). Corrected QT (QTc) intervals were significantly increased during the episodes of severe hypoglycemia compared to the recovered stage (447.6±18.2 ms vs. 417.2±30.6 ms; P<0.05). However, the morphology and the amplitude of the T waves were not changed and ST-segment elevation and/or depression were not found during the episodes of severe hypoglycemia.

Conclusion

In this study, QTc interval prolongation during the episodes of severe hypoglycemia was observed without hypokalemia. Therefore, the distinct alterations in cardiac repolarization during the episodes of severe hypoglycemia may not be associated with hypokalemia.

Citations

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Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes
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Celebrities in the heart, strangers in the pancreatic beta cell: Voltage‐gated potassium channels Kv7.1 and Kv11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes
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Severe Hypoglycemia Is a Serious Complication and Becoming an Economic Burden in Diabetes: Won Chul Ha, Su Jin Oh, Ji Hyun Kim, Jung Min Lee, Sang Ah Chang, Tae Seo Sohn, Hyun Shik Son; Diabetes Metab J. 2012;36(4):280-284. Published online August 20, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.4.280

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Background

The prevalence of hypoglycemia is increasing due to the growing incidence of diabetes and the latest strict guidelines for glycated hemoglobin (HbA1c) levels under 7%. This study examined the clinical characteristics, causal factors, and medical costs of severely hypoglycemic patients in an emergency room (ER) of Uijeongbu St. Mary's Hospital.

Methods

The study consisted of a retrospective analysis of the characteristics, risk factors, and medical costs of 320 severely hypoglycemic patients with diabetes who presented to an ER of Uijeongbu St. Mary's Hospital from January 1, 2006 to December 31, 2009.

Results

Most hypoglycemic patients (87.5%, 280/320) were over 60 years old with a mean age of 69.5±10.9 years and a mean HbA1c level of 6.95±1.46%. Mean serum glucose as noted in the ER was 37.9±34.5 mg/dL. Renal function was decreased, serum creatinine was 2.0±2.1 mg/dL and estimated glomerular filtration rate (eGFR) was 48.0±33.6 mL/min/1.73 m². In addition, hypoglycemic patients typically were taking sulfonylureas or insulin and a variety of other medications, and had a long history of diabetes.

Conclusion

Severe hypoglycemia is frequent in older diabetic patients, subjects with low HbA1c levels, and nephropathic patients. Therefore, personalized attention is warranted, especially in long-term diabetics with multiple comorbidities who may not have been properly educated or may need re-education for hypoglycemia.

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

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Background

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

Methods

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

Results

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

Conclusion

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

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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 ePub

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

Citations to this article as recorded by

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Case Reports

Hypoglycemia due to Focal Nesidioblastosis in a Patient with Type 2 Diabetes Mellitus.: Eun Jung Lee, Kee Ho Song, Suk Kyeong Kim, Seong Hwan Chang, Dong Lim Kim; Korean Diabetes J. 2009;33(3):251-256. Published online June 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.3.251

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Abstract PDF: We report a 45-year-old man with type 2 diabetes who presented with recurrent hypoglycemia. Biochemical and imagingstudies did not show any mass-like lesion in the pancreas, so prednisolone and diazoxide were administered for the treatment of hypoglycemia. However, the hypoglycemia persisted during and after the medical treatment. A selective arterial calcium stimulation test was performed and revealed a suspicious lesion at the head of the pancreas. The patient underwent enucleation of the pancreas head lesion. The lesion was confirmed histologically to be focal nesidioblastosis and surgical resection was successfully performed. The patient showed no hypoglycemic symptoms postoperatively.

A Case of Insulinoma Associated with Type 2 Diabetes Mellitus.: Sung Soo Yoo, Wan Sub Shim, Chul Hyun Kim, Ki Cheol Ha, Seung Min Lye, Eun Joo Kim, So Hun Kim, Seong Bin Hong, Moonsuk Nam, Yong Seong Kim; Korean Diabetes J. 2007;31(6):517-519. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.517

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Abstract PDF: An insulinoma is an endocrine tumor of the pancreas derived from the beta cells with abnormal insulin secretion. An insulinoma is rare, the incidence being estimated at only four per one million person-years. The association of diabetes mellitus and insulinoma is extraordinarily rare, but we should not overlook an insulinoma as a possible cause of hypoglycemia in patients with diabetes mellitus. A 70-year-old diabetic man who had been treated with oral hypoglycemic agents for type 2 diabetes suffered from night sweating for 10 days. Even after he stopped taking his oral hypoglycemic agents, the night sweating continued. The patient was admitted to evaluate the cause of the recurrent hypoglycemic events. After a 72-hour fasting test and selective arterial calcium stimulation test with venous sampling, he was diagnosed with insulinoma accompanied by type 2 diabetes mellitus. In the course of the study, the patient was also incidentally diagnosed with lung cancer.

A Case of Recurrent Hypoglycemic Hemiparesis in an Adult with Type 1 Diabetes Mellitus.: Kyoung Min Kim, Se Hun Kang, Se In Hong, Dong Hyeok Cho, Ho Cheol Kang, Dong Jin Chung, Min Young Chung; Korean Diabetes J. 2006;30(2):136-139. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.136

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Abstract PDF: Transient hypoglycemic hemiparesis is a rare but important presentation of hypoglycemia that is frequently misdiagnosed as stroke. The development of hemiparesis as a result of hypoglycemia was first described in 1928. Thereafter over the years, several cases have been sporadically reported in Korea, but case reports of recurrent hypoglycemic hemiparesis are rare. We recently experienced a case of recurrent hypoglycemic hemiparesis in an adult with type 1 diabetes mellitus. A 30-year-old woman with type 1 diabetes receiving daily multiple subcutaneous insulin injections was admitted with right hemiparesis. She had had admitted with the same symptom and recovered with oral carbohydrates in twice 2 years ago. Her clinical course improved over 2 hours after infusion of dextrose solution. Further investigations such as CT, MRI and MRA revealed no abnormality

A Case of Severe Prolonged Hypoglycemia Caused by Combined Ramipril and Amiloride Treatment in a Nondiabetic Woman.: Min Ho Cho, Dol Mi Kim, Chul Sik Kim, Joug Suk Park, Joo Young Nam, Jin Hyuck Chang, Jina Park, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(6):554-557. Published online December 1, 2004

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Abstract PDF: The relationship between angiotensin converting enzyme inhibition and hypoglycemia remains controversial. An 82-year-old, nondiabetic woman who had taken ramipril 5 mg with amiloride 5 mg for two months was admitted to the hospital because of her altered mentality. Her plasma glucose was 1.5 mmol/L and she regained her consciousness after normalization of the plasma glucose. The recurrent attacks of hypoglycemia ended when she stopped taking ramipril. Her hypoglycemia was thought to result from the combined deficiency of catecholamines and cortisol that was induced by a deficiency of angiotensin II. The glucagoninsensitivity was thought to result from a chronic elevation of bradykinin due to the ACE inhibitor, and the relative hyperinsulinemia was though to be cased by the amiloride.

A Case of Primary Insulin Autoimmune Syndrome in a Patient Suspected of Having an Insulinoma.: Sung Ju Lee, Jee Hyun Kong, Joo Young Nam, Jong Suk Park, Chul Sik Kim, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(1):45-50. Published online February 1, 2004

1,459 View
21 Download

Abstract PDF: Insulin autoimmune syndrome consists of fasting hypoglycemia, hyperinsulinemia and detectable insulin-binding antibodies in patients never been exposed to exogenous insulin. Most affected patients present with other autoimmune disorders, most often Graves' disease. A significant increase in the insulin and C-peptide plasma concentrations and the presence of other anti organ antibodies are also observed. Awareness of insulin autoimmune syndrome hypoglycemia is important as this may produce severe neuroglycopenic symptoms, which may be confused with the presence of an insulinoma. The correct diagnosis is important to avoid unnecessary surgical intervention in patients who are best treated with conservative support, watchful waiting, or in some cases, immunosuppressive therapy. Herein, a case of autoimmune insulin syndrome, suspected as being an insulinoma is reported.

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