Endocrinology and Metabolism

Editorial

Diabetes, obesity and metabolism
Younger-Onset Diabetes: Is the Age of Onset More Important than the Duration of Diabetes?: Mee Kyoung Kim; Endocrinol Metab. 2024;39(1):90-91. Published online February 22, 2024; DOI: https://doi.org/10.3803/EnM.2024.102

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Original Articles

Diabetes, obesity and metabolism
Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis: Mee Kyoung Kim, Kyungdo Han, Hyuk-Sang Kwon, Soon Jib Yoo; Endocrinol Metab. 2023;38(4):426-435. Published online July 20, 2023; DOI: https://doi.org/10.3803/EnM.2023.1737

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Background
The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results.
Methods
This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis.
Results
During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure.
Conclusion
In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.

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Diabetes Duration, Cholesterol Levels, and Risk of Cardiovascular Diseases in Individuals With Type 2 Diabetes
Mee Kyoung Kim, Kyu Na Lee, Kyungdo Han, Seung-Hwan Lee
The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef

Calcium & bone metabolism
Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study: Chaiho Jeong, Jeongmin Lee, Jinyoung Kim, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Tae-Seo Sohn, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek; Endocrinol Metab. 2023;38(2):260-268. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1663

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Background
Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures.
Methods
We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider’s medical specialty, the proximity to the medical center, and financial burdens of treatment.
Results
Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over –2.5, and in five (2.3%) patients due to expected dental procedures.
Conclusion
Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.

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Denosumab

Reactions Weekly.2023; 1963(1): 206. CrossRef

Review Article

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database: Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee; Endocrinol Metab. 2023;38(1):10-24. Published online February 9, 2023; DOI: https://doi.org/10.3803/EnM.2023.102

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The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

Citations

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Associations Between Physical Activity and the Risk of Hip Fracture Depending on Glycemic Status: A Nationwide Cohort Study
Kyoung Min Kim, Kyoung Jin Kim, Kyungdo Han, Yumie Rhee
The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1194. CrossRef
Weight change in patients with new‐onset type 2 diabetes mellitus and its association with remission: Comprehensive real‐world data
Jinyoung Kim, Bongseong Kim, Mee Kyoung Kim, Ki‐Hyun Baek, Ki‐Ho Song, Kyungdo Han, Hyuk‐Sang Kwon
Diabetes, Obesity and Metabolism.2024; 26(2): 567. CrossRef
Diabetes severity and the risk of depression: A nationwide population-based study
Yunjung Cho, Bongsung Kim, Hyuk-Sang Kwon, Kyungdo Han, Mee Kyoung Kim
Journal of Affective Disorders.2024; 351: 694. CrossRef
Information Bias Might Exaggerate Lung Cancer Risk of Patients With Rheumatoid Arthritis
Nobuyuki Horita, Kaoru Takase-Minegishi
Journal of Thoracic Oncology.2024; 19(2): 348. CrossRef
Diabetes Duration, Cholesterol Levels, and Risk of Cardiovascular Diseases in Individuals With Type 2 Diabetes
Mee Kyoung Kim, Kyu Na Lee, Kyungdo Han, Seung-Hwan Lee
The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef
Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up
Ji Young Kang, Kyungdo Han, Seung-Hwan Lee, Mee Kyoung Kim
Respiratory Research.2023;[Epub] CrossRef
Research on obesity using the National Health Information Database: recent trends
Eun-Jung Rhee
Cardiovascular Prevention and Pharmacotherapy.2023; 5(2): 35. CrossRef
Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef
Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis
Mee Kyoung Kim, Kyungdo Han, Hyuk-Sang Kwon, Soon Jib Yoo
Endocrinology and Metabolism.2023; 38(4): 426. CrossRef
Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study
Hwa Young Ahn, Sun Wook Cho, Mi Young Lee, Young Joo Park, Bon Seok Koo, Hang-Seok Chang, Ka Hee Yi
Endocrinology and Metabolism.2023; 38(4): 436. CrossRef
Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case–Control Study from Korea
Hyeree Park, Sun Wook Cho, Sung Ho Lee, Kangmin Kim, Hyun-Seung Kang, Jeong Eun Kim, Aesun Shin, Won-Sang Cho
Thyroid®.2023; 33(12): 1483. CrossRef
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
Endocrinology and Metabolism.2023; 38(5): 525. CrossRef
Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study
Shinje Moon, Sangmo Hong, Kyungdo Han, Cheol-Young Park
European Journal of Endocrinology.2023; 189(3): 363. CrossRef
Cumulative effect of impaired fasting glucose on the risk of dementia in middle-aged and elderly people: a nationwide cohort study
Jin Yu, Kyu-Na Lee, Hun-Sung Kim, Kyungdo Han, Seung-Hwan Lee
Scientific Reports.2023;[Epub] CrossRef
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study
Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun
Endocrinology and Metabolism.2023; 38(6): 770. CrossRef
Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea
Jiwon Kim, Namki Hong, Jimi Choi, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Sin Gon Kim, Cheol Ryong Ku
Endocrinology and Metabolism.2023; 38(6): 690. CrossRef

Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Predicting the Risk of Insulin-Requiring Gestational Diabetes before Pregnancy: A Model Generated from a Nationwide Population-Based Cohort Study in Korea: Seung-Hwan Lee, Jin Yu, Kyungdo Han, Seung Woo Lee, Sang Youn You, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim; Endocrinol Metab. 2023;38(1):129-138. Published online January 27, 2023; DOI: https://doi.org/10.3803/EnM.2022.1609

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Background
The severity of gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. We aimed to generate a risk model for predicting insulin-requiring GDM before pregnancy in Korean women.
Methods
A total of 417,210 women who received a health examination within 52 weeks before pregnancy and delivered between 2011 and 2015 were recruited from the Korean National Health Insurance database. The risk prediction model was created using a sample of 70% of the participants, while the remaining 30% were used for internal validation. Risk scores were assigned based on the hazard ratios for each risk factor in the multivariable Cox proportional hazards regression model. Six risk variables were selected, and a risk nomogram was created to estimate the risk of insulin-requiring GDM.
Results
A total of 2,891 (0.69%) women developed insulin-requiring GDM. Age, body mass index (BMI), current smoking, fasting blood glucose (FBG), total cholesterol, and γ-glutamyl transferase were significant risk factors for insulin-requiring GDM and were incorporated into the risk model. Among the variables, old age, high BMI, and high FBG level were the main contributors to an increased risk of insulin-requiring GDM. The concordance index of the risk model for predicting insulin-requiring GDM was 0.783 (95% confidence interval, 0.766 to 0.799). The validation cohort’s incidence rates for insulin-requiring GDM were consistent with the risk model’s predictions.
Conclusion
A novel risk engine was generated to predict insulin-requiring GDM among Korean women. This model may provide helpful information for identifying high-risk women and enhancing prepregnancy care.

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Establishment and validation of a nomogram to predict the neck contracture after skin grafting in burn patients: A multicentre cohort study
Rui Li, Yangyang Zheng, Xijuan Fan, Zilong Cao, Qiang Yue, Jincai Fan, Cheng Gan, Hu Jiao, Liqiang Liu
International Wound Journal.2023; 20(9): 3648. CrossRef
Predicting the Need for Insulin Treatment: A Risk-Based Approach to the Management of Women with Gestational Diabetes Mellitus
Anna S. Koefoed, H. David McIntyre, Kristen S. Gibbons, Charlotte W. Poulsen, Jens Fuglsang, Per G. Ovesen
Reproductive Medicine.2023; 4(3): 133. CrossRef
Prepregnancy Glucose Levels Within Normal Range and Its Impact on Obstetric Complications in Subsequent Pregnancy: A Population Cohort Study
Ho Yeon Kim, Ki Hoon Ahn, Geum Joon Cho, Soon-Cheol Hong, Min-Jeong Oh, Hai-Joong Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef
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
Endocrinology and Metabolism.2023; 38(5): 525. CrossRef
The CHANGED Score—A New Tool for the Prediction of Insulin Dependency in Gestational Diabetes
Paul Rostin, Selina Balke, Dorota Sroka, Laura Fangmann, Petra Weid, Wolfgang Henrich, Josefine Theresia Königbauer
Journal of Clinical Medicine.2023; 12(22): 7169. CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Cumulative Exposure to High γ-Glutamyl Transferase Level and Risk of Diabetes: A Nationwide Population-Based Study: Ji-Yeon Park, Kyungdo Han, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim, Seung-Hwan Lee; Endocrinol Metab. 2022;37(2):272-280. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1416

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Background
Elevated γ-glutamyl transferase (γ-GTP) level is associated with metabolic syndrome, impaired glucose tolerance, and insulin resistance, which are risk factors for type 2 diabetes. We aimed to investigate the association of cumulative exposure to high γ-GTP level with risk of diabetes.
Methods
Using nationally representative data from the Korean National Health Insurance system, 346,206 people who were free of diabetes and who underwent 5 consecutive health examinations from 2005 to 2009 were followed to the end of 2018. High γ-GTP level was defined as those in the highest quartile, and the number of exposures to high γ-GTP level ranged from 0 to 5. Hazard ratio (HR) and 95% confidence interval (CI) for diabetes were analyzed using the multivariable Cox proportional-hazards model.
Results
The mean follow-up duration was 9.2±1.0 years, during which 15,183 (4.4%) patients developed diabetes. There was a linear increase in the incidence rate and the risk of diabetes with cumulative exposure to high γ-GTP level. After adjusting for possible confounders, the HR of diabetes in subjects with five consecutive high γ-GTP levels were 2.60 (95% CI, 2.47 to 2.73) in men and 3.05 (95% CI, 2.73 to 3.41) in women compared with those who never had a high γ-GTP level. Similar results were observed in various subgroup and sensitivity analyses.
Conclusion
There was a linear relationship between cumulative exposure to high γ-GTP level and risk of diabetes. Monitoring and lowering γ-GTP level should be considered for prevention of diabetes in the general population.

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Validation of Estimated Small Dense Low-Density Lipoprotein Cholesterol Concentration in a Japanese General Population
Keisuke Endo, Ryo Kobayashi, Makito Tanaka, Marenao Tanaka, Yukinori Akiyama, Tatsuya Sato, Itaru Hosaka, Kei Nakata, Masayuki Koyama, Hirofumi Ohnishi, Satoshi Takahashi, Masato Furuhashi
Journal of Atherosclerosis and Thrombosis.2023;[Epub] CrossRef
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study
Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun
Endocrinology and Metabolism.2023; 38(6): 770. CrossRef
Elevated gamma‐glutamyl transferase to high‐density lipoprotein cholesterol ratio has a non‐linear association with incident diabetes mellitus: A second analysis of a cohort study
Haofei Hu, Yong Han, Mijie Guan, Ling Wei, Qijun Wan, Yanhua Hu
Journal of Diabetes Investigation.2022; 13(12): 2027. CrossRef
Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio: A valuable predictor of type 2 diabetes mellitus incidence
Wangcheng Xie, Bin Liu, Yansong Tang, Tingsong Yang, Zhenshun Song
Frontiers in Endocrinology.2022;[Epub] CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Repeated Low High-Density Lipoprotein Cholesterol and the Risk of Thyroid Cancer: A Nationwide Population- Based Study in Korea: Jinyoung Kim, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2022;37(2):303-311. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1332

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Background
High-density lipoprotein cholesterol (HDL-C) plays an important role in the reverse cholesterol transport pathway and prevents atherosclerosis-mediated disease. It has also been suggested that HDL-C may be a protective factor against cancer. However, an inverse correlation between HDL-C and cancer has not been established, and few studies have explored thyroid cancer.
Methods
The study participants received health checkups provided by the Korean National Health Insurance Service from 2009 to 2013 and were followed until 2019. Considering the variability of serum HDL-C level, low HDL-C level was analyzed by grouping based on four consecutive health checkups. The data analysis was performed using univariate and multivariate Cox proportional hazard regression models.
Results
A total of 3,134,278 total study participants, thyroid cancer occurred in 16,129. In the crude model, the hazard ratios for the association between repeatedly measured low HDL-C levels and thyroid cancer were 1.243, 1.404, 1.486, and 1.680 (P for trend <0.01), respectively, which were significant even after adjusting for age, sex, lifestyle factors, and metabolic diseases. The subgroup analysis revealed that low HDL-C levels likely had a greater impact on the group of patients with central obesity (P for interaction= 0.062), high blood pressure (P for interaction=0.057), impaired fasting glucose (P for interaction=0.051), and hyperlipidemia (P for interaction=0.126).
Conclusion
Repeatedly measured low HDL-C levels can be considered a risk factor for cancer as well as vascular disease. Low HDL-C levels were associated with the risk of thyroid cancer, and this correlation was stronger in a metabolically unhealthy population.

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Seohyun Kim, Gyuri Kim, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
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Fu-Jen Cheng, Kai-Fan Tsai, Kuo-Chen Huang, Chia-Te Kung, Wan-Ting Huang, Huey-Ling You, Shau-Hsuan Li, Chin-Chou Wang, Wen-Chin Lee, Hsiu-Yung Pan
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Jue Zhang, Ting Zhang, Ye Yao, Xuxing Shen, Yuanyuan Jin, Run Zhang, Lijuan Chen
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Annals of Hematology.2023; 102(2): 393. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
High-density lipoprotein cholesterol and carcinogenesis
Meijuan Tan, Shijie Yang, Xiequn Xu
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International Journal of Molecular Sciences.2023; 24(8): 7396. CrossRef
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Weiwei Liang, FangFang Sun
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Qiang Ma, Yu Li, Lijuan An, Liang Guo, Xiaokang Liu
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Xiaowen Zhang, Yuyang Ze, Jianfeng Sang, Xianbiao Shi, Yan Bi, Shanmei Shen, Xinlin Zhang, Dalong Zhu
Frontiers in Endocrinology.2022;[Epub] CrossRef
Exposure to multiple trace elements and thyroid cancer risk in Chinese adults: A case-control study
Jia-liu He, Hua-bing Wu, Wen-lei Hu, Jian-jun Liu, Qian Zhang, Wei Xiao, Ming-jun Hu, Ming Wu, Fen Huang
International Journal of Hygiene and Environmental Health.2022; 246: 114049. CrossRef

Review Article

Diabetes, Obesity and Metabolism
Recent Updates to Clinical Practice Guidelines for Diabetes Mellitus: Jin Yu, Seung-Hwan Lee, Mee Kyoung Kim; Endocrinol Metab. 2022;37(1):26-37. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.105

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Guidelines for the management of patients with diabetes have become an important part of clinical practice that improve the quality of care and help establish evidence-based medicine in this field. With rapidly accumulating evidence on various aspects of diabetes care, including landmark clinical trials of treatment agents and newer technologies, timely updates of the guidelines capture the most current state of the field and present a consensus. As a leading academic society, the Korean Diabetes Association publishes practice guidelines biennially and the American Diabetes Association does so annually. In this review, we summarize the key changes suggested in the most recent guidelines. Some of the important updates include treatment algorithms emphasizing comorbid conditions such as atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease in the selection of anti-diabetic agents; wider application of continuous glucose monitoring (CGM), insulin pump technologies and indices derived from CGM such as time in range; more active screening of subjects at high-risk of diabetes; and more detailed individualization in diabetes care. Although there are both similarities and differences among guidelines and some uncertainty remains, these updates provide a good approach for many clinical practitioners who are battling with diabetes.

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Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Frequency of Exposure to Impaired Fasting Glucose and Risk of Mortality and Cardiovascular Outcomes: Seung-Hwan Lee, Kyungdo Han, Hyuk-Sang Kwon, Mee Kyoung Kim; Endocrinol Metab. 2021;36(5):1007-1015. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1218

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Background
Metabolic abnormalities, such as impaired fasting glucose (IFG), are dynamic phenomena; however, it is unclear whether the timing of IFG exposure and cumulative exposure to IFG are related to cardiovascular disease (CVD) and mortality risk.
Methods
Data were extracted from a nationwide population-based cohort in South Korea for adults (n=2,206,679) who were free of diabetes and had 4 years of consecutive health examination data. Fasting blood glucose levels of 100 to 125 mg/dL were defined as IFG, and the number of IFG diagnoses for each adult in the 4-year period was tabulated as the IFG exposure score (range, 0 to 4). Adults with persistent IFG for the 4-year period received a score of 4.
Results
The median follow-up was 8.2 years. There were 24,820 deaths, 13,502 cases of stroke, and 13,057 cases of myocardial infarction (MI). IFG exposure scores of 1, 2, 3, and 4 were associated with all-cause mortality (multivariable-adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.08 to 1.15; aHR, 1.16; 95% CI, 1.12 to 1.20; aHR, 1.20; 95% CI, 1.15 to 1.25; aHR, 1.18; 95% CI, 1.11 to 1.25, respectively) compared with an IFG exposure score of 0. Adjusting for hypertension and dyslipidemia attenuated the slightly increased risk of MI or stroke associated with high IFG exposure scores, but significant associations for allcause mortality remained.
Conclusion
The intensity of IFG exposure was associated with an elevated risk of all-cause mortality, independent of cardiovascular risk factors. The association between IFG exposure and CVD risk was largely mediated by the coexistence of dyslipidemia and hypertension.

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A nationwide cohort study on diabetes severity and risk of Parkinson disease
Kyungdo Han, Bongsung Kim, Seung Hwan Lee, Mee Kyoung Kim
npj Parkinson's Disease.2023;[Epub] CrossRef
Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up
Ji Young Kang, Kyungdo Han, Seung-Hwan Lee, Mee Kyoung Kim
Respiratory Research.2023;[Epub] CrossRef
Construction and Validation of a Model for Predicting Impaired Fasting Glucose Based on More Than 4000 General Population
Cuicui Wang, Xu Zhang, Chenwei Li, Na Li, Xueni Jia, Hui Zhao
International Journal of General Medicine.2023; Volume 16: 1415. CrossRef
Factors Affecting High Body Weight Variability
Kyungdo Han, Mee Kyoung Kim
Journal of Obesity & Metabolic Syndrome.2023; 32(2): 163. CrossRef
Exposure to perfluoroalkyl and polyfluoroalkyl substances and risk of stroke in adults: a meta-analysis
Min Cheol Chang, Seung Min Chung, Sang Gyu Kwak
Reviews on Environmental Health.2023;[Epub] CrossRef
Cumulative effect of impaired fasting glucose on the risk of dementia in middle-aged and elderly people: a nationwide cohort study
Jin Yu, Kyu-Na Lee, Hun-Sung Kim, Kyungdo Han, Seung-Hwan Lee
Scientific Reports.2023;[Epub] CrossRef
A Longitudinal Retrospective Observational Study on Obesity Indicators and the Risk of Impaired Fasting Glucose in Pre- and Postmenopausal Women
Myung Ji Nam, Hyunjin Kim, Yeon Joo Choi, Kyung-Hwan Cho, Seon Mee Kim, Yong-Kyun Roh, Kyungdo Han, Jin-Hyung Jung, Yong-Gyu Park, Joo-Hyun Park, Do-Hoon Kim
Journal of Clinical Medicine.2022; 11(10): 2795. CrossRef
Current Trends of Big Data Research Using the Korean National Health Information Database
Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee
Diabetes & Metabolism Journal.2022; 46(4): 552. CrossRef
Lipid cutoffs for increased cardiovascular disease risk in non-diabetic young people
Mee Kyoung Kim, Kyungdo Han, Hun-Sung Kim, Kun-Ho Yoon, Seung-Hwan Lee
European Journal of Preventive Cardiology.2022; 29(14): 1866. CrossRef
Low-Density Lipoprotein Cholesterol Level, Statin Use and Myocardial Infarction Risk in Young Adults
Heekyoung Jeong, Kyungdo Han, Soon Jib Yoo, Mee Kyoung Kim
Journal of Lipid and Atherosclerosis.2022; 11(3): 288. CrossRef
Additive interaction of diabetes mellitus and chronic kidney disease in cancer patient mortality risk
Seohyun Kim, Gyuri Kim, Jae Hyeon Kim
Scientific Reports.2022;[Epub] CrossRef

Bone Metabolism
Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: Jeonghoon Ha, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Seung Hyun Ko, Moo Il Kang, Sung Dae Moon, Ki-Hyun Baek; Endocrinol Metab. 2021;36(4):895-903. Published online August 9, 2021; DOI: https://doi.org/10.3803/EnM.2021.1026

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Background
Prospective comparative studies on the effects of various antidiabetic agents on bone metabolism are limited. This study aimed to assess changes in bone mass and biochemical bone markers in postmenopausal patients with type 2 diabetes mellitus (T2DM).
Methods
This prospective, multicenter, open-label, comparative trial included 264 patients with T2DM. Patients who had received a metformin, or sulfonylurea/metformin combination (Group 1); a thiazolidinedione combination (Group 2); a dipeptidyl peptidase-4 inhibitor (gemigliptin) combination (Group 3); or an sodium-glucose cotransporter 2 inhibitor (empagliflozin) combination (Group 4) were prospectively treated for 12 months; bone mineral density (BMD) and bone turnover marker (BTM) changes were evaluated.
Results
The femoral neck BMD percentage changes were −0.79%±2.86% (Group 1), −2.50%±3.08% (Group 2), −1.05%±2.74% (Group 3), and −1.24%±2.91% (Group 4) (P<0.05). The total hip BMD percentage changes were −0.57%±1.79% (Group 1), −1.74%±1.48% (Group 2), −0.75%±1.87% (Group 3), and −1.27%±1.72% (Group 4) (P<0.05). Mean serum BTM (C-terminal type 1 collagen telopeptide and procollagen type 1 amino-terminal propeptide) levels measured during the study period did not change over time or differ between groups.
Conclusion
Significant bone loss in the femoral neck and total hip was associated with thiazolidinedione combination regimens. However, bone loss was not significantly associated with combination regimens including gemigliptin or empagliflozin. Caution should be exercised during treatment with antidiabetic medications that adversely affect the bone in patients with diabetes at a high risk of bone loss.

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Lili Huang, Wei Zhong, Xinghuan Liang, Huijuan Wang, Shi-en Fu, Zuojie Luo
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A multicentre, double‐blind, placebo‐controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add‐on therapy in type 2 diabetic patients treated with metformin and dapagliflozin
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Complementary effects of dapagliflozin and lobeglitazone on metabolism in a diet-induced obese mouse model
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Clinical Study Big Data Articles (National Health Insurance Service Database)
Cumulative Exposure to Metabolic Syndrome Components and the Risk of Dementia: A Nationwide Population-Based Study: Yunjung Cho, Kyungdo Han, Da Hye Kim, Yong-Moon Park, Kun-Ho Yoon, Mee Kyoung Kim, Seung-Hwan Lee; Endocrinol Metab. 2021;36(2):424-435. Published online April 14, 2021; DOI: https://doi.org/10.3803/EnM.2020.935

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Background
Metabolic disturbances are modifiable risk factors for dementia. Because the status of metabolic syndrome (MetS) and its components changes over time, we aimed to investigate the association of the cumulative exposure to MetS and its components with the risk of dementia.
Methods
Adults (n=1,492,776; ≥45-years-old) who received health examinations for 4 consecutive years were identified from a nationwide population-based cohort in Korea. Two exposure-weighted scores were calculated: cumulative number of MetS diagnoses (MetS exposure score, range of 0 to 4) and the composite of its five components (MetS component exposure score, range of 0 to 20). Hazard ratio (HR) and 95% confidence interval (CI) values for dementia were analyzed using the multivariable Cox proportional-hazards model.
Results
Overall, 47.1% of subjects were diagnosed with MetS at least once, and 11.5% had persistent MetS. During the mean 5.2 years of follow-up, there were 7,341 cases (0.5%) of incident dementia. There was a stepwise increase in the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia with increasing MetS exposure score and MetS component exposure score (each P for trend <0.0001). The HR of all-cause dementia was 2.62 (95% CI, 1.87 to 3.68) in subjects with a MetS component exposure score of 20 compared with those with a score of 0. People fulfilling only one MetS component out of 20 already had an approximately 40% increased risk of all-cause dementia and Alzheimer’s disease.
Conclusion
More cumulative exposure to metabolic disturbances was associated with a higher risk of dementia. Of note, even minimal exposure to MetS components had a significant effect on the risk of dementia.

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Association between metabolic syndrome and risk of incident dementia in UK Biobank
Danial Qureshi, Jennifer Collister, Naomi E. Allen, Elżbieta Kuźma, Thomas Littlejohns
Alzheimer's & Dementia.2024; 20(1): 447. CrossRef
Cumulative exposure to metabolic syndrome affects the risk of psoriasis differently according to age group: a nationwide cohort study in South Korea
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Electroacupuncture stimulation improves cognitive ability and regulates metabolic disorders in Alzheimer’s disease model mice: new insights from brown adipose tissue thermogenesis
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Investigating the nexus of metabolic syndrome, serum uric acid, and dementia risk: a prospective cohort study
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Clustering of Cardiometabolic Risk Factors and Dementia Incidence in Older Adults: A Cross-Country Comparison in England, the United States, and China
Panagiota Kontari, Chris Fife-Schaw, Kimberley Smith, Lewis A Lipsitz
The Journals of Gerontology: Series A.2023; 78(6): 1035. CrossRef
Predicting the Risk of Insulin-Requiring Gestational Diabetes before Pregnancy: A Model Generated from a Nationwide Population-Based Cohort Study in Korea
Seung-Hwan Lee, Jin Yu, Kyungdo Han, Seung Woo Lee, Sang Youn You, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim
Endocrinology and Metabolism.2023; 38(1): 129. CrossRef
Metabolic syndrome and the risk of postoperative delirium and postoperative cognitive dysfunction: a multi-centre cohort study
Insa Feinkohl, Jürgen Janke, Arjen J.C. Slooter, Georg Winterer, Claudia Spies, Tobias Pischon
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Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study
Marcos D. Machado-Fragua, Séverine Sabia, Aurore Fayosse, Céline Ben Hassen, Frank van der Heide, Mika Kivimaki, Archana Singh-Manoux
BMC Medicine.2023;[Epub] CrossRef
Cumulative effect of impaired fasting glucose on the risk of dementia in middle-aged and elderly people: a nationwide cohort study
Jin Yu, Kyu-Na Lee, Hun-Sung Kim, Kyungdo Han, Seung-Hwan Lee
Scientific Reports.2023;[Epub] CrossRef
Early metabolic impairment as a contributor to neurodegenerative disease: Mechanisms and potential pharmacological intervention
Walaa Fakih, Ralph Zeitoun, Ibrahim AlZaim, Ali H. Eid, Firas Kobeissy, Khaled S. Abd‐Elrahman, Ahmed F. El‐Yazbi
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Association of Metabolic Syndrome With Incident Dementia: Role of Number and Age at Measurement of Components in a 28-Year Follow-up of the Whitehall II Cohort Study
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Risk of Neurodegenerative Diseases in Patients With Acromegaly
Sangmo Hong, Kyungdo Han, Kyung-Soo Kim, Cheol-Young Park
Neurology.2022;[Epub] CrossRef

Clinical Study
Predicting the Development of Myocardial Infarction in Middle-Aged Adults with Type 2 Diabetes: A Risk Model Generated from a Nationwide Population-Based Cohort Study in Korea: Seung-Hwan Lee, Kyungdo Han, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim; Endocrinol Metab. 2020;35(3):636-646. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.704

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Background
Most of the widely used prediction models for cardiovascular disease are known to overestimate the risk of this disease in Asians. We aimed to generate a risk model for predicting myocardial infarction (MI) in middle-aged Korean subjects with type 2 diabetes.
Methods
A total of 1,272,992 subjects with type 2 diabetes aged 40 to 64 who received health examinations from 2009 to 2012 were recruited from the Korean National Health Insurance database. Seventy percent of the subjects (n=891,095) were sampled to develop the risk prediction model, and the remaining 30% (n=381,897) were used for internal validation. A Cox proportional hazards regression model and Cox coefficients were used to derive a risk scoring system. Twelve risk variables were selected, and a risk nomogram was created to estimate the 5-year risk of MI.
Results
During 7.1 years of follow-up, 24,809 cases of MI (1.9%) were observed. Age, sex, smoking status, regular exercise, body mass index, chronic kidney disease, duration of diabetes, number of anti-diabetic medications, fasting blood glucose, systolic blood pressure, total cholesterol, and atrial fibrillation were significant risk factors for the development of MI and were incorporated into the risk model. The concordance index for MI prediction was 0.682 (95% confidence interval [CI], 0.678 to 0.686) in the development cohort and 0.669 (95% CI, 0.663 to 0.675) in the validation cohort.
Conclusion
A novel risk engine was generated for predicting the development of MI among middle-aged Korean adults with type 2 diabetes. This model may provide useful information for identifying high-risk patients and improving quality of care.

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A literature review of quality assessment and applicability to HTA of risk prediction models of coronary heart disease in patients with diabetes
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Diabetes Research and Clinical Practice.2024; 209: 111574. CrossRef
Predicting the Risk of Insulin-Requiring Gestational Diabetes before Pregnancy: A Model Generated from a Nationwide Population-Based Cohort Study in Korea
Seung-Hwan Lee, Jin Yu, Kyungdo Han, Seung Woo Lee, Sang Youn You, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim
Endocrinology and Metabolism.2023; 38(1): 129. CrossRef
Factors Affecting High Body Weight Variability
Kyungdo Han, Mee Kyoung Kim
Journal of Obesity & Metabolic Syndrome.2023; 32(2): 163. CrossRef
Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study
Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Sang Min Lee, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki Won Oh, Sung Rae Cho, Young-Hoon Jeong, Eun-Jung Rhee
Endocrinology and Metabolism.2023; 38(5): 568. CrossRef
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Yichen Jin, Ziyuan Xu, Yuting Zhang, Yue Zhang, Danyang Wang, Yangyang Cheng, Yaguan Zhou, Muhammad Fawad, Xiaolin Xu
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Assessing the Validity of the Criteria for the Extreme Risk Category of Atherosclerotic Cardiovascular Disease: A Nationwide Population-Based Study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
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Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality
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Effects of exercise initiation and smoking cessation after new-onset type 2 diabetes mellitus on risk of mortality and cardiovascular outcomes
Mee Kyoung Kim, Kyungdo Han, Bongsung Kim, Jinyoung Kim, Hyuk-Sang Kwon
Scientific Reports.2022;[Epub] CrossRef
Current Trends of Big Data Research Using the Korean National Health Information Database
Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee
Diabetes & Metabolism Journal.2022; 46(4): 552. CrossRef
Lipid cutoffs for increased cardiovascular disease risk in non-diabetic young people
Mee Kyoung Kim, Kyungdo Han, Hun-Sung Kim, Kun-Ho Yoon, Seung-Hwan Lee
European Journal of Preventive Cardiology.2022; 29(14): 1866. CrossRef
Low-Density Lipoprotein Cholesterol Level, Statin Use and Myocardial Infarction Risk in Young Adults
Heekyoung Jeong, Kyungdo Han, Soon Jib Yoo, Mee Kyoung Kim
Journal of Lipid and Atherosclerosis.2022; 11(3): 288. CrossRef
Nonalcoholic fatty liver disease and the risk of insulin-requiring gestational diabetes
Sang Youn You, Kyungdo Han, Seung-Hawn Lee, Mee Kyoung Kim
Diabetology & Metabolic Syndrome.2021;[Epub] CrossRef

Clinical Study
Consistency of the Glycation Gap with the Hemoglobin Glycation Index Derived from a Continuous Glucose Monitoring System: Han Na Joung, Hyuk-Sang Kwon, Ki-Hyun Baek, Ki-Ho Song, Mee Kyoung Kim; Endocrinol Metab. 2020;35(2):377-383. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.377

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Background
Discordances between glycated hemoglobin (HbA1c) levels and glycemic control are common in clinical practice. We aimed to investigate the consistency of the glycation gap with the hemoglobin glycation index (HGI).
Methods
From 2016 to 2019, 36 patients with type 2 diabetes were enrolled. HbA1c, glycated albumin (GA), and fasting blood glucose levels were simultaneously measured and 72-hour continuous glucose monitoring (CGM) was performed on the same day. Repeated tests were performed at baseline and 1 month later, without changing patients’ diabetes management. The HGI was calculated as the difference between the measured HbA1c and the predicted HbA1c that was derived from CGM. The glycation gap was calculated as the difference between the measured and GA-based predicted HbA1c levels.
Results
Strong correlations were found between the mean blood glucose (MBG)-based HGI and the prebreakfast glucose-based HGI (r=0.867, P<0.001) and between the glycation gap and the MBG-based HGI (r=0.810, P<0.001). A close correlation was found between the MBG-based HGI at baseline and that after 1 month (r=0.729, P<0.001), with a y-intercept of 0 and a positive slope.
Conclusion
The HGI and glycation gap were highly reproducible, and the magnitudes of repeated determinations were closely correlated. Patients with similar mean glucose levels may have significantly different HbA1c levels.

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Klara R Klein, Edward Franek, Steven Marso, Thomas R Pieber, Richard E Pratley, Amoolya Gowda, Kajsa Kvist, John B Buse
BMJ Open Diabetes Research & Care.2021; 9(2): e002339. CrossRef

Review Article

Obesity and Metabolism
Effects of Cardiovascular Risk Factor Variability on Health Outcomes: Seung-Hwan Lee, Mee Kyoung Kim, Eun-Jung Rhee; Endocrinol Metab. 2020;35(2):217-226. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.217

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Innumerable studies have suggested “the lower, the better” for cardiovascular risk factors, such as body weight, lipid profile, blood pressure, and blood glucose, in terms of health outcomes. However, excessively low levels of these parameters cause health problems, as seen in cachexia, hypoglycemia, and hypotension. Body weight fluctuation is related to mortality, diabetes, obesity, cardiovascular disease, and cancer, although contradictory findings have been reported. High lipid variability is associated with increased mortality and elevated risks of cardiovascular disease, diabetes, end-stage renal disease, and dementia. High blood pressure variability is associated with increased mortality, myocardial infarction, hospitalization, and dementia, which may be caused by hypotension. Furthermore, high glucose variability, which can be measured by continuous glucose monitoring systems or self-monitoring of blood glucose levels, is associated with increased mortality, microvascular and macrovascular complications of diabetes, and hypoglycemic events, leading to hospitalization. Variability in metabolic parameters could be affected by medications, such as statins, antihypertensives, and hypoglycemic agents, and changes in lifestyle patterns. However, other mechanisms modify the relationships between biological variability and various health outcomes. In this study, we review recent evidence regarding the role of variability in metabolic parameters and discuss the clinical implications of these findings.

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Original Article

Clinical Study
Comparison of Natural Course between Thyroid Cancer Nodules and Thyroid Benign Nodules: Kyun-Jin Yun, Jeonghoon Ha, Min-Hee Kim, Ye Young Seo, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek; Endocrinol Metab. 2019;34(2):195-202. Published online June 24, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.195

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Background

The natural course of thyroid cancer nodules and benign nodules is different. This study was to compare the changes in size between thyroid cancer nodules and thyroid benign nodules. The risk factors associated with the changes of thyroid cancer nodules were assessed.

Methods

This study contains retrospective observational and prospective analysis. A total of 113 patients with 120 nodules were recruited in the cancer group, and 116 patients with 119 nodules were enrolled in the benign group. Thyroid ultrasonography was performed at least two times at more than 1-year interval.

Results

The mean follow-up durations were 29.5±18.8 months (cancer group) and 31.9±15.8 months (benign group) (P=0.32). The maximum diameter change in length was 0.36±0.97 mm/year in the cancer group and –0.04±0.77 mm/year in the benign group (P<0.01). The volume was significantly increased in the cancer group compared with the benign group (0.06±0.18 mL/year vs. 0.004±0.05 mL/year, respectively, P<0.01; 26.9%±57.9%/year vs. 1.7%±26.0%/year, P<0.01). Initial maximum diameter (β=0.02, P<0.01) and initial volume (β=0.13, P<0.01) were significantly associated with volume change (mL)/year. Initial maximum standardized uptake value did not predict the nodule growth.

Conclusion

It is suggested that thyroid cancer nodules progress rapidly compared with benign nodules. Initial size and volume of nodule were independent risk factors for cancer nodule growth.

Citations

Citations to this article as recorded by

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