Endocrinology and Metabolism

Editorial

Diabetes, obesity and metabolism
Exploring Sex-Specific Mechanisms in Type 2 Diabetes Mellitus by Single-Cell Analysis in Pancreatic Islets: Joonyub Lee; Endocrinol Metab. 2025;40(5):699-701. Published online October 29, 2025; DOI: https://doi.org/10.3803/EnM.2025.2678

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Review Article

Diabetes, obesity and metabolism
Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia: Joonyub Lee, Kun-Ho Yoon; Endocrinol Metab. 2025;40(1):57-63. Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2193

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In East Asians, type 2 diabetes mellitus (T2DM) is primarily characterized by significant defects in insulin secretion and comparatively low insulin resistance. Recently, the prevalence of T2DM has rapidly increased in East Asian countries, including Korea, occurring concurrently with rising obesity rates. This trend has led to an increase in the average body mass index among East Asian T2DM patients, highlighting the influence of insulin resistance in the development of T2DM within this group. Currently, the incidence of T2DM in Korea is declining, which may indicate potential adaptive changes in insulin secretory capacity. This review focuses on the changing epidemiology of T2DM in East Asia, with a particular emphasis on the characteristics of peak functional β-cell mass.

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A phase 1 single and multiple ascending dose study of orforglipron in Japanese participants with type 2 diabetes
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Association of Insulin Resistance with Dysglycemia in Elder Koreans: Age- and Sex-Specific Cutoff Values
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Journal of Personalized Medicine.2025; 15(9): 438. CrossRef
Exploring Sex-Specific Mechanisms in Type 2 Diabetes Mellitus by Single-Cell Analysis in Pancreatic Islets
Joonyub Lee
Endocrinology and Metabolism.2025; 40(5): 699. CrossRef

Original Articles

Miscellaneous
Lipid Variability Induces Endothelial Dysfunction by Increasing Inflammation and Oxidative Stress: Marie Rhee, Joonyub Lee, Eun Young Lee, Kun-Ho Yoon, Seung-Hwan Lee; Endocrinol Metab. 2024;39(3):511-520. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2023.1915

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Background
This study investigates the impact of fluctuating lipid levels on endothelial dysfunction.
Methods
Human aortic and umbilical vein endothelial cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, and 100 μM, and in a variability group alternating between 0 and 100 μM PA every 8 hours for 48 hours. In the lipid variability group, cells were exposed to 100 μM PA during the final 8 hours before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, and cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) levels with dichlorofluorescin diacetate assay; mitochondrial function through oxygen consumption rates via XF24 flux analyzer; and endothelial cell functionality via wound healing and cell adhesion assays. Cell viability was evaluated using the MTT assay.
Results
Variable PA levels significantly upregulated inflammatory genes and adhesion molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic and protein levels in human endothelial cells. Oscillating lipid levels reduced basal respiration, adenosine triphosphate synthesis, and maximal respiration, indicating mitochondrial dysfunction. This lipid variability also elevated ROS levels, contributing to a chronic inflammatory state. Functionally, these changes impaired cell migration and increased monocyte adhesion, and induced endothelial apoptosis, evidenced by reduced cell viability, increased BAX, and decreased BCL2 expression.
Conclusion
Lipid variability induce endothelial dysfunction by elevating inflammation and oxidative stress, providing mechanistic insights into how lipid variability increases cardiovascular risk.

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Frontiers in Endocrinology.2025;[Epub] CrossRef
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Hashum Sum, Alison C. Brewer
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Hygerta Berisha, Reham Hattab, Laura Comi, Claudia Giglione, Silvia Migliaccio, Paolo Magni
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Diabetes, obesity and metabolism
Effectiveness of a Social Networking Site Based Automatic Mobile Message Providing System on Glycemic Control in Patients with Type 2 Diabetes Mellitus: Kyuho Kim, Jae-Seung Yun, Joonyub Lee, Yeoree Yang, Minhan Lee, Yu-Bae Ahn, Jae Hyoung Cho, Seung-Hyun Ko; Endocrinol Metab. 2024;39(2):344-352. Published online December 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1871

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Background
This study investigated the effectiveness of a social networking site (SNS)-based automatic mobile message providing system on glycemic control in patients with type 2 diabetes mellitus (T2DM).
Methods
A 3-month, randomized, open-label, controlled, parallel-group trial was conducted. One hundred and ten participants with T2DM were randomized to a mobile message system (MMS) (n=55) or control group (n=55). The MMS group received protocolbased automated messages two times per day for 10 weeks regarding diabetes self-management through KakaoTalk SNS messenger. The primary outcome was the difference in the change in glycated hemoglobin (HbA1c) levels (%) from baseline to week 12.
Results
HbA1c levels were more markedly decreased in the MMS group (8.4%±0.7% to 8.0%±1.1%) than in the control group (8.5%±0.8% to 8.4%±0.8%), resulting in a significant between-group difference (P=0.027). No differences were observed in changes in fasting glucose levels, lipid profiles, and the number of participants who experienced hypoglycemia, or in changes in lifestyle behavior between groups. However, the self-monitoring of blood glucose frequency was significantly increased in the MMS group compared to the control group (P=0.003). In addition, sleep duration was increased in the MMS group, but was not changed in the control group.
Conclusion
An SNS-based automatic mobile message providing system was effective in improving glycemic control in patients in T2DM. Studies which based on a more individualized protocol, and investigate longer beneficial effect and sustainability will be required in the future.

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Text messaging interventions are associated with reductions in HbA1c among patients with diabetes: a systematic review and meta-analysis
Neda Pirouzmand, Grace S Ko, Lucas C Godoy, Olivia Haldenby, Cynthia A Jackevicius, Ayman Jubran, Candace D McNaughton, Baiju R Shah, Maneesh Sud, Karen Tu, Dennis T Ko
BMJ Open Diabetes Research & Care.2025; 13(6): e005218. CrossRef
Effectiveness of text message-delivered health behaviour intervention on HbA1c change in adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials
Qiumian Hong, Xiaoying Zhang, Mengxi Guo, Zhaoyang Wen, Qing Tang, Jiali Zhou, Peige Song, Xiaolin Wei, Ning Zhang
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Effects of multimodal mobile health interventions on cardiovascular risk factor management in patients with diabetes: a systematic review and meta-analysis
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Miscellaneous
Prediction of Cardiovascular Complication in Patients with Newly Diagnosed Type 2 Diabetes Using an XGBoost/GRU-ODE-Bayes-Based Machine-Learning Algorithm: Joonyub Lee, Yera Choi, Taehoon Ko, Kanghyuck Lee, Juyoung Shin, Hun-Sung Kim; Endocrinol Metab. 2024;39(1):176-185. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1739

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Background
Cardiovascular disease is life-threatening yet preventable for patients with type 2 diabetes mellitus (T2DM). Because each patient with T2DM has a different risk of developing cardiovascular complications, the accurate stratification of cardiovascular risk is critical. In this study, we proposed cardiovascular risk engines based on machine-learning algorithms for newly diagnosed T2DM patients in Korea.
Methods
To develop the machine-learning-based cardiovascular disease engines, we retrospectively analyzed 26,166 newly diagnosed T2DM patients who visited Seoul St. Mary’s Hospital between July 2009 and April 2019. To accurately measure diabetes-related cardiovascular events, we designed a buffer (1 year), an observation (1 year), and an outcome period (5 years). The entire dataset was split into training and testing sets in an 8:2 ratio, and this procedure was repeated 100 times. The area under the receiver operating characteristic curve (AUROC) was calculated by 10-fold cross-validation on the training dataset.
Results
The machine-learning-based risk engines (AUROC XGBoost=0.781±0.014 and AUROC gated recurrent unit [GRU]-ordinary differential equation [ODE]-Bayes=0.812±0.016) outperformed the conventional regression-based model (AUROC=0.723± 0.036).
Conclusion
GRU-ODE-Bayes-based cardiovascular risk engine is highly accurate, easily applicable, and can provide valuable information for the individualized treatment of Korean patients with newly diagnosed T2DM.

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A Novel Approach Utilizing Bagging, Histogram Gradient Boosting, and Advanced Feature Selection for Predicting the Onset of Cardiovascular Diseases
Norma Latif Fitriyani, Muhammad Syafrudin, Nur Chamidah, Marisa Rifada, Hendri Susilo, Dursun Aydin, Syifa Latif Qolbiyani, Seung Won Lee
Mathematics.2025; 13(13): 2194. CrossRef
Development and validation of a machine learning model for cardiovascular disease risk prediction in type 2 diabetes patients
Chunming Xu, Fachao Shi, Wenlong Ding, Cunming Fang, Caoyang Fang
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Jieyun You, Tianwen Wei, Yue Yu, Jing Huang, Yuxiao Sun, Wei Guo, Qi Zhang
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Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study: Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee, Committee of Big Data, Korean Endocrine Society; Endocrinol Metab. 2023;38(5):525-537. Published online September 7, 2023; DOI: https://doi.org/10.3803/EnM.2023.1765

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Background
This study investigated the risk of cause-specific mortality according to glucose tolerance status in elderly South Koreans.
Methods
A total of 1,292,264 individuals aged ≥65 years who received health examinations in 2009 were identified from the National Health Information Database. Participants were classified as normal glucose tolerance, impaired fasting glucose, newly-diagnosed diabetes, early diabetes (oral hypoglycemic agents ≤2), or advanced diabetes (oral hypoglycemic agents ≥3 or insulin). The risk of system-specific and disease-specific deaths was estimated using multivariate Cox proportional hazards analysis.
Results
During a median follow-up of 8.41 years, 257,356 deaths were recorded. Diabetes was associated with significantly higher risk of all-cause mortality (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.57 to 1.60); death due to circulatory (HR, 1.49; 95% CI, 1.46 to 1.52), respiratory (HR, 1.51; 95% CI, 1.47 to 1.55), and genitourinary systems (HR, 2.22; 95% CI, 2.10 to 2.35); and neoplasms (HR, 1.30; 95% CI, 1.28 to 1.32). Diabetes was also associated with a significantly higher risk of death due to ischemic heart disease (HR, 1.70; 95% CI, 1.63 to 1.76), cerebrovascular disease (HR, 1.46; 95% CI, 1.41 to 1.50), pneumonia (HR, 1.69; 95% CI, 1.63 to 1.76), and acute or chronic kidney disease (HR, 2.23; 95% CI, 2.09 to 2.38). There was a stepwise increase in the risk of death across the glucose spectrum (P for trend <0.0001). Stroke, heart failure, or chronic kidney disease increased the risk of all-cause mortality at every stage of glucose intolerance.
Conclusion
A dose-dependent association between the risk of mortality from various causes and severity of glucose tolerance was noted in the elderly population.

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Kyung‐Hun Sung, Jin Yu, Seyoon Kim, Mee Kyoung Kim, Yong‐Moon Mark Park, Kyungdo Han, Seung‐Hwan Lee
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Joonyub Lee, Seung-Hwan Lee, Mee-Kyoung Kim, Hyuk-Sang Kwon, Jae-Seung Yun, Yeoree Yang, Kun-Ho Yoon, Jae-Hyoung Cho, Chi-Un Pae, Kyungdo Han, Jang Won Son
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Peter S. Hamblin, Anthony W. Russell, Stella Talic, Sophia Zoungas
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Yanling Yang, Zhigu Liu, Beisi Lin, Yintong Huang, Hongrong Deng, Xubin Yang, Longyi Zeng, Jinhua Yan, Wen Xu
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Effect of glucose variability on the mortality of adults aged 75 years and over during the first year of the COVID-19 pandemic
Miguel A. Salinero-Fort, F. Javier San Andrés-Rebollo, Juan Cárdenas-Valladolid, José Mostaza, Carlos Lahoz, Fernando Rodriguez-Artalejo, Paloma Gómez-Campelo, Pilar Vich-Pérez, Rodrigo Jiménez-García, José M. de-Miguel-Yanes, Javier Maroto-Rodriguez, Bel
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Joonyub Lee, Kun‐Ho Yoon
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Jae-Seung Yun, Kyungdo Han, Bongseong Kim, Seung-Hyun Ko, Hyuk-Sang Kwon, Yu-Bae Ahn, Yong-Moon Mark Park, Seung-Hwan Lee
Diabetes Research and Clinical Practice.2024; 217: 111876. CrossRef
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Response

Diabetes, Obesity and Metabolism
Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes (Endocrinol Metab 2022;37:641-51, Han-sang Baek et al.): Han-sang Baek, Ji-Yeon Park, Jin Yu, Joonyub Lee, Yeoree Yang, Jeonghoon Ha, Seung Hwan Lee, Jae Hyoung Cho, Dong-Jun Lim, Hun-Sung Kim; Endocrinol Metab. 2022;37(6):945-946. Published online December 2, 2022; DOI: https://doi.org/10.3803/EnM.2022.602

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Young patients with type 2 diabetes have high relative risks for complications in a country with middle-high sociodemographic index, similarly to those countries with high index
Gergő A. Molnár, Zoltán Kiss, István Wittmann
Frontiers in Endocrinology.2025;[Epub] CrossRef
Differences in cardiovascular disease incidence according to changes in obesity status in young diabetic patients
Do Kyeong Song, Yeon-Ah Sung, Young Sun Hong, Min-ho Kim, Hyejin Lee
Cardiovascular Diabetology – Endocrinology Reports.2025;[Epub] CrossRef

Original Article

Diabetes, Obesity and Metabolism
Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes: Han-sang Baek, Ji-Yeon Park, Jin Yu, Joonyub Lee, Yeoree Yang, Jeonghoon Ha, Seung Hwan Lee, Jae Hyoung Cho, Dong-Jun Lim, Hun-Sung Kim; Endocrinol Metab. 2022;37(4):641-651. Published online August 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1501

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Background
The prevalence of young-onset diabetes (YOD) has been increasing worldwide. As the incidence of YOD increases, it is necessary to determine the characteristics of YOD and the factors that influence its development and associated complications.
Methods
In this retrospective study, we recruited patients who were diagnosed with type 2 diabetes mellitus between June 2001 and December 2021 at a tertiary hospital. The study population was categorized according to age: YOD (age <40 years), middle-age-onset diabetes (MOD, 40≤ age <65 years), and late-onset diabetes (LOD, age ≥65 years). We examined trends in glycemic control by analyzing fasting glucose levels during the first year in each age group. A Cox proportional-hazards model was used to determine the relative risk of developing complications according to glycemic control trends.
Results
The fasting glucose level at the time of diagnosis was highest in the YOD group (YOD 149±65 mg/dL; MOD 143±54 mg/dL; and LOD 140±55 mg/dL; p=0.009). In the YOD group, glucose levels decreased at 3 months, but increased by 12 months. YOD patients and those with poor glycemic control in the first year were at a higher risk of developing complications, whereas the risk in patients with LOD was not statistically significant.
Conclusion
YOD patients had higher glucose levels at diagnosis, and their glycemic control was poorly maintained. As poor glycemic control can influence the development of complications, especially in young patients, intensive treatment is necessary for patients with YOD.

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