Endocrinology and Metabolism

Original Articles

Steatotic Liver Disease Subtypes and Advanced Fibrosis as Independent Predictors of Ischemic Stroke in Type 2 Diabetes Mellitus: Myunghwa Jang, Gyuri Kim, Kyu-na Lee, Rosa Oh, So Hyun Cho, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Kyungdo Han, Jae Hyeon Kim; Received November 15, 2025 Accepted February 13, 2026 Published online May 18, 2026; DOI: https://doi.org/10.3803/EnM.2025.2792 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Although type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with an increased risk of ischemic stroke, the extent to which steatotic liver disease (SLD) subtypes and advanced liver fibrosis confer additional risk in individuals with T2DM remains unclear. We aimed to investigate the association of SLD categories and/or advanced liver fibrosis with ischemic stroke risk among patients with T2DM.
Methods
A total of 2,220,249 patients with T2DM were classified into five groups: no steatosis, MASLD, MASLD with other combined disease, metabolic dysfunction and alcohol-related steatotic liver disease (MetALD), and alcohol-related liver disease (ALD) with metabolic dysfunction (MD). SLD was defined using a fatty liver index (FLI) of ≥30, and advanced fibrosis was defined by a BARD score of ≥2.
Results
Over a median follow-up of 11 years, 135,482 ischemic strokes (6.10%) occurred. Compared with no steatosis, adjusted hazard ratios (aHRs) for stroke were higher in MASLD (aHR, 1.10; 95% confidence interval [CI], 1.08 to 1.11), MASLD with combined disease (aHR, 1.14; 95% CI, 1.12 to 1.17), MetALD (aHR, 1.13; 95% CI, 1.11 to 1.16), and ALD with MD (aHR, 1.32; 95% CI, 1.27 to 1.37). Advanced fibrosis progressively increased stroke risk compared with non-SLD and non-fibrotic SLD. Compared with the FLI <30 group, those with FLI 30–60 and ≥60 showed increased aHRs for stroke. Very heavy drinking was associated with a further increase in risk compared with non-drinking.
Conclusion
In patients with T2DM, all SLD categories and advanced liver fibrosis were associated with an increased risk of ischemic stroke. Very heavy alcohol consumption was generally associated with a higher stroke risk across FLI categories.

Impact of Fatty Liver Index on Cardiovascular Disease and Mortality across Alcohol Consumption Levels in Young Adults: Byung-Hun Han, Joonyub Lee, Hun-Sung Kim, Jae-Hyoung Cho, Kyungdo Han, Seung-Hwan Lee; Received October 13, 2025 Accepted January 22, 2026 Published online March 30, 2026; DOI: https://doi.org/10.3803/EnM.2025.2710 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The fatty liver index (FLI) is widely used as a surrogate marker for metabolic dysfunction-associated steatotic liver disease, but its predictive value among individuals who consume alcohol remains uncertain. We aimed to investigate the association between FLI and the risk of cardiovascular disease (CVD) and mortality in young adults by alcohol consumption status.
Methods
Using the Korean National Health Information Database, we identified 6,487,686 individuals aged 20–39 years who underwent health examinations between 2009 and 2012. FLI was calculated using body mass index, waist circumference, triglycerides, and γ-glutamyl transferase, and categorized as <30, 30–59, or ≥60. Alcohol consumption was classified as non-drinking, mild, moderate, or heavy using sex-specific thresholds. Risks of CVD—including myocardial infarction (MI) and stroke—and all-cause mortality were evaluated using multivariable Cox proportional hazards models.
Results
During a mean follow-up of 13.3 years, 49,399 MI, 29,842 stroke, and 53,330 deaths were identified. The risk of CVD and mortality increased stepwise across higher FLI categories in all alcohol consumption groups. Compared with participants with FLI <30, the adjusted hazard ratios (95% confidence intervals [CIs]) for composite outcome among those with FLI ≥60 were 1.72 (95% CI, 1.67 to 1.77) in non-drinkers, 1.41 (95% CI, 1.38 to 1.43) in mild drinkers, 1.19 (95% CI, 1.15 to 1.24) in moderate drinkers, and 1.20 (95% CI, 1.12 to 1.30) in heavy drinkers. The association was strongest among non-drinkers (P for interaction <0.0001).
Conclusion
FLI is a useful and practical indicator for predicting CVD and mortality in young adults, regardless of alcohol intake, with the highest predictive performance in non-drinkers.

Sex Disparity in Suicide Mortality among Patients with Type 2 Diabetes: A Nationwide Population-Based Cohort Study: Chaiho Jeong, Bongseong Kim, Dae Jong Oh, Tae-Seo Sohn, Kyungdo Han, Hyuk-Sang Kwon; Received September 16, 2025 Accepted November 24, 2025 Published online March 19, 2026; DOI: https://doi.org/10.3803/EnM.2025.2669 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Suicide represents a major public health concern in Korea. Patients with type 2 diabetes mellitus (T2DM) are at higher risk for psychological distress and suicide. Although the male-to-female suicide mortality ratio in the general population has remained about 2.3, the specific differences in suicide mortality by sex among individuals with T2DM are not well characterized.
Methods
We performed a nationwide cohort study utilizing the Korean National Health Insurance Service database, identifying 2,526,769 adults with T2DM who underwent health screening from 2015 to 2016. Participants were monitored until the occurrence of suicide or the study endpoint.
Results
During a median follow-up of 6.0 years, 5,584 suicide deaths occurred (0.30% in men vs. 0.10% in women). Men exhibited a significantly elevated risk of suicide mortality compared to women (adjusted hazard ratio [HR], 2.88; 95% confidence interval [CI], 2.66 to 3.12). The largest disparity was observed in the ≥80 age group (HR, 3.60; 95% CI, 2.88 to 4.51). However, this sex disparity in suicide mortality was reduced among current smokers and heavy alcohol consumers. Among non-smokers, the HR comparing men to women was 3.51 (95% CI, 3.22 to 3.83), while among current smokers, it was 1.73 (95% CI, 1.40 to 2.14). Similarly, the HR among non-drinkers was 3.04 (95% CI, 2.79 to 3.31), compared with 1.36 (95% CI, 0.85 to 2.18) among heavy drinkers.
Conclusion
Men with T2DM had a significantly higher risk of suicide mortality than women, exceeding the sex disparity seen in the general population, with the gap further influenced by age and lifestyle factors.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
The Severity of Diabetes and the Risk of Diabetic Foot Amputation: A National Cohort Study: Jin Yu, Ji-Hyun Kim, Bongseong Kim, Kyungdo Han, Seung Hwan Lee, Mee Kyoung Kim; Endocrinol Metab. 2025;40(4):574-582. Published online April 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2266

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Background
This study aimed to assess whether markers of diabetes severity could serve as predictors for foot amputation risk among patients with type 2 diabetes mellitus.
Methods
We analyzed data from the nationally representative Korean National Health Insurance System database, tracking 2,544,077 patients with type 2 diabetes mellitus who participated in routine health check-ups between 2009 and 2012, with followup extending through the end of 2018. The parameters used to define the diabetes severity score encompassed diabetes duration, insulin usage, the number of oral glucose-lowering medications, the presence of chronic kidney disease, diabetic retinopathy, and cardiovascular disease. Each factor was assigned one point, yielding a cumulative severity score ranging from 0 to 6.
Results
The risk of diabetic foot amputation was predominantly predicted by insulin therapy, diabetic retinopathy, and a prolonged duration of diabetes. The hazard ratios for foot amputation increased with the severity score as follows: 2.31 (95% confidence interval [CI], 2.15 to 2.47) for a score of 1, 4.73 (95% CI, 4.42 to 5.07) for a score of 2, 8.86 (95% CI, 8.24 to 9.53) for a score of 3, 16.95 (95% CI, 15.60 to 18.4) for a score of 4, 23.98 (95% CI, 21.25 to 27.05) for a score of 5, and 37.87 (95% CI, 28.93 to 49.57) for a score of 6.
Conclusion
Specific markers of advanced diabetes effectively identified patients at an elevated risk for diabetic foot amputation.

Citations

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Costos directos y determinantes de las amputaciones en pacientes diabéticos en un hospital de Nicaragua en el año 2024.
Sidley Irania Hurtado Alvarado, Sheila Karina Valdivia Quiroz
Revista Multidisciplinaria Voces de América y el Caribe.2026; 3(1): 12. CrossRef
Nationwide Big Data Studies of Endocrine Diseases Using the Korean National Health Information Database: Research Trends and Standardization of Operational Definitions
Sun Wook Cho, Jung Hee Kim, Kyoung Jin Kim, Beom-Jun Kim, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2026; 41(1): 86. CrossRef
Cardiovascular outcomes with thiazolidinediones and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus undergoing peripheral artery revascularization
Ji Woong Roh, Jimin Jeon, Joonsang Yoo, Minyoul Baik, Seok-Jae Heo, Deok-Kyu Cho, Jinkwon Kim
Diabetes Research and Clinical Practice.2026; 236: 113281. CrossRef
Diabetes progression and its association with fracture risk in type 2 diabetes
Bongsung Kim, Kyu-Na Lee, Kyungdo Han, Mee Kyoung Kim
Osteoporosis International.2026;[Epub] CrossRef
Development, validation, and pilot implementation of a prognostic model to predict future foot complications among people with diabetes recently discharged from hospital
Surain B. Roberts, Anne Löffler, Dhanesh Ramachandram, Javier Garay-Fernandez, Maia Norman, Conrad Pow, Fahad Razak, Amol A. Verma, Charles de Mestral
Journal of Clinical Epidemiology.2026; 195: 112295. CrossRef
Hemoglobin-albumin-lymphocyte-platelet score associated with diabetic foot severity, unlike modified systemic immune-inflammatory index and modified systemic inflammatory response index
Weiyu Pan, Zhaoyuan Nie, Qizhi Tang, Ling Zhao
Frontiers in Endocrinology.2026;[Epub] CrossRef
Diabetes Progression and Its Impact on Kidney Cancer Risk: Insights From a Longitudinal Korean Cohort Study
Jin Yu, Bongseong Kim, Kyungdo Han, Mee Kyoung Kim
The Journal of Clinical Endocrinology & Metabolism.2025; 111(1): e125. CrossRef
Association of high-density lipoprotein-related inflammatory indicators with diabetic foot ulcer in patients with diabetes: a population-based study
Renhe Deng, Ruyi Tao, Huiyi Luo, Yueqi Gu, Mengyu Yang, Chaoqi Yin
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef

Namgok Lecture 2024

Hypothalamus and pituitary gland Big Data Articles (National Health Insurance Service Database)
Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data: Sangmo Hong, Kyungdo Han, Cheol-Young Park; Endocrinol Metab. 2025;40(1):1-9. Published online February 4, 2025; DOI: https://doi.org/10.3803/EnM.2024.2285

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Acromegaly is a rare endocrine disorder caused by excessive growth hormone secretion. Its low prevalence poses challenges in studying its long-term prognosis and systemic effects. To address this research gap, we conducted five studies using nationwide cohort data from the Korean National Health Insurance Database (NHID). This review consolidates the findings of these studies, which examined various long-term effects of acromegaly. The results demonstrated significant associations between acromegaly and increased mortality, a higher prevalence of mortality, cardiovascular outcomes, neurodegenerative diseases, depression, end-stage kidney disease, respiratory complications, specifically bronchiectasis, spine & hip fracture, and malignancy. These findings highlight the critical need for early diagnosis, comprehensive care, and long-term monitoring, and underscore the importance of a multidisciplinary approach in managing acromegaly.

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Growth Hormone and IGF-1 Actions in the Brain and Neuropsychiatric Diseases
Manuel H. Aguiar-Oliveira, Margaret C. S. Boguszewski, Diego L. Rovaris, Jose Donato
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Cardiovascular Effects of Growth Hormone: From Deficiency to Acromegaly
Negarsadat Neshat, Parth Adrejiya, Zain Muhammad Khan, William H. Frishman, Wilbert S. Aronow
Cardiology in Review.2026;[Epub] CrossRef
Risk of cerebrovascular and cardiovascular events in acromegaly: a systematic review and meta-analysis
Yongyan Wang, Ning Li, Yugeng Li, Jitao Zhang
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Nationwide Big Data Studies of Endocrine Diseases Using the Korean National Health Information Database: Research Trends and Standardization of Operational Definitions
Sun Wook Cho, Jung Hee Kim, Kyoung Jin Kim, Beom-Jun Kim, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2026; 41(1): 86. CrossRef
Recent progress in the understanding of psychological complications of acromegaly: toward a longitudinal clinical phenotype
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Pituitary.2026;[Epub] CrossRef
Osteometabolic complications in patients with secreting pituitary adenomas: Is there an impact of gender?
Luigi di Filippo, Matteo Acanfora, Simona Bolamperti, Umberto Terenzi, Maristella Bonomo, Andrea Giustina
Pituitary.2026;[Epub] CrossRef
Acromegaly complications: an update
Andrea Giustina, Maria Fleseriu
The Journal of Clinical Endocrinology & Metabolism.2026; 111(Supplement): S51. CrossRef
Bidirectional interactions between sleep and metabolism: mechanisms and therapeutic implications for insulin resistance

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Bayar Qasim, Sardar Arif, Ashur Izac, Halder Abozait, Rende Kochary
Medicine International.2025; 6(1): 1. CrossRef
Why Acromegaly Dies: A Systematic Review
Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed
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Original Articles

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Time to Insulin Therapy and Severe Hypoglycemia in Korean Adults Initially Diagnosed with Type 2 Diabetes: A Nationwide Study: You-Bin Lee, Kyungdo Han, Bongsung Kim, So Hee Park, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim, Sang-Man Jin; Endocrinol Metab. 2025;40(3):421-433. Published online February 4, 2025; DOI: https://doi.org/10.3803/EnM.2024.2082

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Abstract PDF Supplementary Material PubReader ePub: Background
We examined the distribution of time to insulin therapy (TIT) post-diabetes diagnosis and the hazard of severe hypoglycemia (SH) according to TIT in Korean adults initially diagnosed with type 2 diabetes (T2D) and who progressed to insulin therapy.
Methods
Using data from the Korean National Health Insurance Service (2002 to 2018), we selected adult incident insulin users (initially diagnosed as T2D) who underwent health examinations between 2009 and 2012. The hazards of SH, recurrent SH, and problematic hypoglycemia were analyzed according to groups categorized using the TIT and clinical risk factors for SH (TIT ≥5 years with risk factors, TIT ≥5 years without risk factors, 3 ≤TIT <5 years, 1 ≤TIT <3 years, and TIT <1 year).
Results
Among 41,637 individuals, 14,840 (35.64%) and 10,587 (25.43%) initiated insulin therapy within <5 and <3 years postdiabetes diagnosis, respectively. During a median 6.53 years, 3,406 SH events occurred. Compared to individuals with TIT ≥5 years and no risk factor for SH, individuals with TIT <3 years had higher outcome hazards in a graded manner (adjusted hazard ratio [95% confidence intervals] for any SH: 1.117 [0.967 to 1.290] in those with 3 ≤TIT <5 years; 1.459 [1.284 to 1.657] in those with 1 ≤ TIT <3 years; and 1.515 [1.309 to 1.754] in those with TIT <1 year). This relationship was more pronounced in the non-obese subpopulation.
Conclusion
Among adults who progressed to insulin therapy after being diagnosed with T2D, a shorter TIT was not uncommon and may predict an increased risk of SH, particularly in non-obese patients.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Risk of Diabetes Mellitus in Adults with Intellectual Disabilities: A Nationwide Cohort Study: Hye Yeon Koo, In Young Cho, Yoo Jin Um, Yong-Moon Mark Park, Kyung Mee Kim, Chung Eun Lee, Kyungdo Han; Endocrinol Metab. 2025;40(1):103-111. Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2126

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Abstract PDF Supplementary Material PubReader ePub: Background
Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations.
Methods
This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID.
Results
Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001).
Conclusion
Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

Diabetes, obesity and metabolism
Impact of Chronic Kidney Disease and Gout on End-Stage Renal Disease in Type 2 Diabetes: Population-Based Cohort Study: Inha Jung, Da Young Lee, Seung Min Chung, So Young Park, Ji Hee Yu, Jun Sung Moon, Ji A Seo, Kyungdo Han, Nan Hee Kim; Endocrinol Metab. 2024;39(5):748-757. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.2020

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Background
We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status.
Methods
Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m²) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD⁻Gout⁻, CKD⁻ Gout⁺, CKD⁺Gout⁻, and CKD⁺Gout⁺. Patients with incident ESRD were followed up until December 2018.
Results
Among 847,884 patients, 11,825 (1.4%) experienced progression to ESRD. ESRD incidence increased in the following order: 0.77 per 1,000 person-years (PY) in the CKD⁻Gout⁻ group, 1.34/1,000 PY in the CKD⁻Gout⁺ group, 8.20/1,000 PY in the CKD⁺Gout⁻ group, and 23.06/1,000 PY in the CKD⁺Gout⁺ group. The presence of gout modified the ESRD risk in a status-dependent manner. Hazard ratios (HR) were 1.49 (95% confidence interval [CI], 1.32 to 1.69) and 2.24 (95% CI, 2.09 to 2.40) in patients without and with CKD, respectively, indicating a significant interaction (P<0.0001). The CKD⁺Gout⁺ group had a markedly higher risk of developing ESRD (HR, 18.9; 95% CI, 17.58 to 20.32) than the reference group (CKD⁻Gout⁻).
Conclusion
Gout substantially enhances the risk of ESRD, even in the absence of CKD. Concurrent CKD and gout synergistically increase the risk of ESRD. Therefore, physicians should carefully screen for hyperuricemia to prevent progression to ESRD.

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Undescribed phenylspirodrimane dimers with anti-gouty activity from the coral-derived fungus Stachybotrys chartarum
Shuang Lin, Yi-Fan Geng, Hanxiao Zeng, Zixue Chai, Baolei Fan, Jun-Cheng Su, Yonghui Zhang, Zhengxi Hu
Phytochemistry.2026; 248: 114891. CrossRef
Gout in the era of multimorbidity: pathogenesis, systemic comorbidities, and evolving therapeutic strategies
Phillip J Kim, Jihun Kang, Jesang Yu, Geun-Tae Kim, Yunkyung Kim
Kosin Medical Journal.2026; 41(1): 26. CrossRef
Heterogeneity in the development of diabetes-related complications: narrative review of the roles of ancestry and geographical determinants
Andrea O. Y. Luk, Yingnan Fan, Baoqi Fan, Edith W. K. Chow, Tony C. K. O
Diabetologia.2025; 68(11): 2386. CrossRef
Relationship between the Chinese visceral adiposity index and gout in individuals with type 2 diabetes mellitus: a cross-sectional population-based study
Ningyu Cai, Mengdie Chen, Ping Feng, Yiyun Wang, Xianping Zhu, Qidong Zheng
Frontiers in Nutrition.2025;[Epub] CrossRef

Review Article

Diabetes, obesity and metabolism
Epidemiology and Trends of Obesity and Bariatric Surgery in Korea: Kyungdo Han, Jin-Hyung Jung, Su-Min Jeong, Mee Kyoung Kim; Endocrinol Metab. 2024;39(5):678-685. Published online August 2, 2024; DOI: https://doi.org/10.3803/EnM.2024.2056

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The prevalence of obesity in Korea has steadily increased over the past decade, reaching 38.4% in 2021. Notably, the rate of class II– III obesity, defined as a body mass index (BMI) of 30 kg/m² or higher, exceeded 7% in the same year. Since January 2019, the National Health Insurance Service (NHIS) has provided coverage for bariatric surgery (BS) for eligible patients. Coverage is available for individuals with a BMI of 35 kg/m² or higher, or those with a BMI of 30 kg/m² or higher who also have obesity-related comorbidities. Additionally, partial reimbursement is offered for BS in patients with type 2 diabetes mellitus who have BMI values between 27.5 and 30 kg/m². From 2019 to 2022, the NHIS recorded 9,080 BS procedures, with sleeve gastrectomy being the most commonly performed. The average percentage of weight loss 198±99.7 days post-surgery was 17.9%, with 80.0% of patients losing more than 10% of their body weight. This article presents the trends in obesity and BS in Korea.

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Original Articles

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Association between Smoking Status and the Risk of Hip Fracture in Patients with Type 2 Diabetes: A Nationwide Population-Based Study: Se-Won Lee, Jun-Young Heu, Ju-Yeong Kim, Jinyoung Kim, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2023;38(6):679-689. Published online December 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1760

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Background
Limited longitudinal evidence exists regarding the potential association between smoking status and hip fracture among individuals with type 2 diabetes. We investigated this association using large-scale, nationwide cohort data for the Korean population.
Methods
This nationwide cohort study included 1,414,635 adults aged 40 and older who received Korean National Health Insurance Service health examinations between 2009 and 2012. Subjects with type 2 diabetes were categorized according to their smoking status, amount smoked (pack-years), number of cigarettes smoked per day, and duration of smoking. The results are presented as hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between smoking status parameters and risk of hip fracture in multivariable Cox proportional hazard regression analysis.
Results
Compared with never-smokers, an increased adjusted HR (aHR) for hip fracture was observed in current smokers (1.681; 95% CI, 1.578 to 1.791), and a comparable aHR for hip fracture was found in former smokers (1.065; 95% CI, 0.999 to 1.136). For former smokers who had smoked 20 pack-years or more, the risk was slightly higher than that for never-smokers (aHR, 1.107; 95% CI, 1.024 to 1.196). The hip fracture risk of female former smokers was similar to that of female current smokers, but the hip fracture risk in male former smokers was similar to that of male never-smokers.
Conclusion
Smoking is associated with an increased risk of hip fracture in patients with type 2 diabetes. Current smokers with diabetes should be encouraged to quit smoking because the risk of hip fracture is greatly reduced in former smokers.

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Hip fractures and type 2 diabetes in the elderly: Risk factors analysis of the Nedices cohort
Federico Hawkins Carranza, Cristina Martín-Arriscado Arroba, Arturo Corbatón-Anchuelo, Guillermo Martínez Díaz-Guerra, Félix Bermejo Pareja
Diabetes & Metabolism.2025; 51(4): 101656. CrossRef
Bone Health in Type 1 and Type 2 Diabetes: Pathophysiological Mechanisms, Clinical Implications, and Management Strategies
Hermine Carine Pouabe Epse Bodah, Suraiya Rahman Shifa, Sara Saleh, Tuba Abeer Hashmi, Tuleen Al Shawa, Badreshiya Kajal Akshaykumar, Nabeel Sufwan, Rajvinder Kaur, Andrii Shevchuk, Usman Ul Haq, Manju Rai
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Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
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; Endocrinol Metab. 2023;38(6):770-781. Published online November 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1726

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Background
Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population.
Methods
Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model.
Results
During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m², and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death.
Conclusion
Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

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Latent class analysis of association between occupational hazard factors and gamma-glutamyltransferase in automobile manufacturing workers: a cross-sectional study
Huixia Ji, Dandan Liu, Ye Chen
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Association of Serum Gamma-Glutamyltransferase with In-hospital Heart Failure in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
An-Cheng Hou, Jian-Tong Hou, Wei-Ning Zhou, Yan-Jin Wei, Zhi-Hong Ou, Cun-Fei Liu
Reviews in Cardiovascular Medicine.2025;[Epub] CrossRef
The J-shaped relationship between the gamma-glutamyltransferase to high-density lipoprotein cholesterol ratio and mortality risk in U.S. adults
Shujuan Qiu, Chunlei Li, Zhentao Guo
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Association between the levels of gamma-glutamyl transpeptidase and the risk of stroke: systematic review and meta-analysis
Gustavo Adolfo Vásquez-Tirado, Stefany M. Nieto-Rivera, Claudia Vanessa Quispe-Castañeda, Edinson Dante Meregildo-Rodríguez, Leslie Jacqueline Liñán-Díaz, Wilson Marcial Guzmán-Aguilar
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Serum gamma-glutamyl transferase level is associated with the risk of pancreatic cystic neoplasms: A nationwide retrospective cohort study
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Interplay of serum biomarkers bilirubin and γ-glutamyltranspeptidase in predicting cardiovascular complications in type-2 diabetes mellitus
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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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Inverse association between obesity and suicidal death risk
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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, 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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Xi Yang, Hannah L. Nathan, Ebruba E. Oyekan, Tim I. M. Korevaar, Doaa Ahmed, Katherine Pacifico, Aisha Hameed, Manju Chandiramani, Anita Banerjee, Caroline Ovadia
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Friederike Weschenfelder, Barbara Dusek, Heinke Adamczewski, Dietmar Weber, Matthias Kaltheuner, Yvonne Heimann, Tanja Groten
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Ho Yeon Kim, Ki Hoon Ahn, Geum Joon Cho, Soon-Cheol Hong, Min-Jeong Oh, Hai-Joong Kim
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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
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Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Association of High-Density Lipoprotein Cholesterol Phenotypes with the Risk of Cardiovascular Diseases and Mortality: A Cohort Study in Korea: Ga Eun Nam, Youn Huh, Jin-Hyung Jung, Kyungdo Han, Seon Mee Kim, on Behalf of the Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity; Endocrinol Metab. 2022;37(2):261-271. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1259

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Background
We investigated whether low high-density lipoprotein cholesterol (HDL-C) and isolated and non-isolated low HDL-C levels are associated with the risk of cardiovascular diseases and all-cause mortality among Korean adults.
Methods
We included 8,665,841 individuals aged ≥20 years who had undergone a health examination provided by the Korean National Health Insurance Service (NHIS) in 2009 and were followed up until the end of 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for study outcomes were calculated using multivariable Cox proportional hazard regression analysis.
Results
During the 8.2 years of mean follow-up, myocardial infarction (MI), stroke, and all-cause mortality occurred in 81,431, 110,996, and 244,309 individuals, respectively. After adjusting for confounding variables (model 3), individuals with low HDL-C and lower HDL quartiles were associated with significantly increased risks of all three outcomes, compared to those with normal HDL-C and highest HDL-C quartile (all P<0.001), respectively. HRs for incident MI (1.28; 95% CI, 1.26 to 1.30), stroke (1.13; 95% CI, 1.11 to 1.15), and all-cause mortality (1.07; 95% CI, 1.05 to 1.08) increased in the non-isolated low HDL-C group compared to the normal HDL-C group. Isolated low HDL-C also showed an increase in the HRs of incident stroke (1.06; 95% CI, 1.04 to 1.08) and all-cause mortality (1.30; 95% CI, 1.28 to 1.32).
Conclusion
Low HDL-C and non-isolated low HDL-C were associated with increased risk of MI, stroke, and all-cause mortality, and isolated low HDL-C was associated with incident stroke and all-cause mortality risk.

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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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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)
Graves’ Disease and the Risk of End-Stage Renal Disease: A Korean Population-Based Study: Yoon Young Cho, Bongseong Kim, Dong Wook Shin, Hye Ryoun Jang, Bo-Yeon Kim, Chan-Hee Jung, Jae Hyeon Kim, Sun Wook Kim, Jae Hoon Chung, Kyungdo Han, Tae Hyuk Kim; Endocrinol Metab. 2022;37(2):281-289. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1333

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Background
Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed.
Methods
This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles.
Results
Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD.
Conclusion
This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

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Kidney diseases and the thyroid: interactions and consequences
Gabriela Brenta
Nature Reviews Endocrinology.2026; 22(4): 228. CrossRef
The Association between Impaired Sensitivity to Thyroid Hormones and Hyperhomocysteinemia in Euthyroid Individuals: Mediating Role of Creatinine
婧煜胡
Advances in Clinical Medicine.2026; 16(03): 1680. CrossRef
Chronic Kidney Disease and Thyroid Hormones
Yuan Cheng, Haofei Hu, Wangyang Li, Sheng Nie, Shiyu Zhou, Yuna Chen, Tao Cao, Hong Xu, Bicheng Liu, Chunbo Chen, Huafeng Liu, Qiongqiong Yang, Hua Li, Yaozhong Kong, Guisen Li, Yan Zha, Ying Hu, Gang Xu, Yongjun Shi, Yilun Zhou, Guobin Su, Ying Tang, Men
The Journal of Clinical Endocrinology & Metabolism.2025; 110(8): e2446. CrossRef
Significance of pathological changes and chemokine expression in various organs in a Graves’ disease animal model
Yang Yang, Chen Hui
Journal of Molecular Histology.2025;[Epub] CrossRef
Renal function changes in patients with subclinical hyperthyroidism: a novel postulated mechanism
Magdy Mohamed Allam, Hanaa Tarek El-Zawawy, Tarek Hussein El-Zawawy
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Effect of Hyperthyroidism on Preventing Renal Insufficiency
Tae Yong Kim
Endocrinology and Metabolism.2022; 37(2): 220. CrossRef
Effects and Clinical Value of Peritoneal Dialysis on Water and Water Balance, Adverse Reactions, Quality of Life, and Clinical Prognosis in Patients with Decompensated Chronic Nephropathy: A Systematic Review and Meta-Analysis
Xichao Wang, Miaomiao Zhang, Na Sun, Wenxiu Chang, Gang Chen
Computational and Mathematical Methods in Medicine.2022; 2022: 1. 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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Ocular motor cranial neuropathy and risk of thyroid cancer: A Korean population-based study
Jaeryung Kim, Kyung-Ah Park, Kyungdo Han, Jin-Hyung Jung, Sei Yeul Oh, Soolienah Rhiu, Xing Xiong,
PLOS ONE.2025; 20(3): e0319872. CrossRef
Association between serum lipid and papillary thyroid cancer: a retrospective study in China
Zike Zhang, Xingyu Lan, Long You, Dongsheng Han, Hui Tang, Ying Zhao, Xiao Hu
PeerJ.2025; 13: e19644. CrossRef
Association between total cholesterol levels and all-cause mortality among newly diagnosed patients with cancer
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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Association between organophosphate flame retardant exposure and lipid metabolism: data from the 2013–2014 National Health and Nutrition Examination Survey
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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Low serum total cholesterol levels predict inferior prognosis of patients with POEMS syndrome
Jue Zhang, Ting Zhang, Ye Yao, Xuxing Shen, Yuanyuan Jin, Run Zhang, Lijuan Chen
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Lipoprotein alterations in endocrine disorders - a review of the recent developments in the field
Michal Olejarz, Ewelina Szczepanek-Parulska, Marek Ruchala
Frontiers in Endocrinology.2024;[Epub] CrossRef
Associations Between Metabolic Obesity Phenotypes and Pathological Characteristics of Papillary Thyroid Carcinoma
Xiuyun Li, Xiujuan Zhang, Li Sun, Lulu Yang, Qihang Li, Zhixiang Wang, Yafei Wu, Ling Gao, Jiajun Zhao, Qingling Guo, Meng Zhou
Endocrine Practice.2024; 30(7): 624. CrossRef
Analysis of risk factors for papillary thyroid carcinoma and the association with thyroid function indicators
Jianning Liu, Zhuoying Feng, Ru Gao, Peng Liu, Fangang Meng, Lijun Fan, Lixiang Liu, Yang Du
Frontiers in Endocrinology.2024;[Epub] CrossRef
Carbohydrate, Lipid, and Apolipoprotein Biomarkers in Blood and Risk of Thyroid Cancer: Findings from the AMORIS Cohort
Xue Xiao, Yi Huang, Fetemeh Sadeghi, Maria Feychting, Niklas Hammar, Fang Fang, Zhe Zhang, Qianwei Liu
Cancers.2023; 15(2): 520. CrossRef
Altered serum lipid levels are associated with prognosis of diffuse large B cell lymphoma and influenced by utility of rituximab
Fei Wang, Luo Lu, HuiJuan Chen, Yanhua Yue, Yanting Sun, Feng Yan, Bai He, Rongrong Lin, Weiying Gu
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
Trends in Endocrinology & Metabolism.2023; 34(5): 303. CrossRef
Low Serum Cholesterol Level Is a Significant Prognostic Factor That Improves CLL-IPI in Chronic Lymphocytic Leukaemia
Rui Gao, Kaixin Du, Jinhua Liang, Yi Xia, Jiazhu Wu, Yue Li, Bihui Pan, Li Wang, Jianyong Li, Wei Xu
International Journal of Molecular Sciences.2023; 24(8): 7396. CrossRef
Do metabolic factors increase the risk of thyroid cancer? a Mendelian randomization study
Weiwei Liang, FangFang Sun
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Assessment of causal association between differentiated thyroid cancer and disordered serum lipid profile: a Mendelian randomization study
Qiang Ma, Yu Li, Lijuan An, Liang Guo, Xiaokang Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Risk factors and diagnostic prediction models for papillary thyroid carcinoma
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

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Hip Fracture Risk According to Diabetic Kidney Disease Phenotype in a Korean Population: Seung Eun Lee, Juhwan Yoo, Kyoung-Ah Kim, Kyungdo Han, Han Seok Choi; Endocrinol Metab. 2022;37(1):148-158. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1315

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Background
Diabetic kidney disease (DKD) is associated with an elevated risk of fractures. However, little is known about the association between proteinuric or non-proteinuric DKD and the risk of hip fracture. Thus, we investigated the incidence of hip fractures among Korean adults with type 2 diabetes mellitus (T2DM) stratified by DKD phenotype.
Methods
In this retrospective cohort study using the Korean National Health Insurance Service database, patients with T2DM who received at least one general health checkup between 2009 and 2012 were followed until the date of hip fracture, death, or December 31, 2018. We classified the DKD phenotype by proteinuria and estimated glomerular filtration rate (eGFR), as follows: no DKD (PU⁻GFR⁻), proteinuric DKD with normal eGFR (PU⁺GFR⁻), non-proteinuric DKD with reduced eGFR (PU⁻GFR⁺), and proteinuric DKD with reduced eGFR (PU⁺GFR⁺)
Results
The cumulative incidence of hip fractures was highest in the PU⁺GFR⁺ group, followed by the PU⁻GFR⁺ group and the PU⁺GFR⁻ group. After adjustment for confounding factors, the hazard ratio (HR) for hip fracture was still highest in the PU⁺GFR⁺ group. However, the PU⁺GFR⁻ group had a higher HR for hip fracture than the PU⁻GFR⁺ group (PU⁺GFR⁺ : HR, 1.69; 95% confidence interval [CI], 1.57 to 1.81; PU⁺GFR⁻ : HR, 1.37; 95% CI, 1.30 to 1.46; PU⁻GFR⁺ : HR, 1.20; 95% CI, 1.16 to 1.24 using the PU⁻GFR⁻ group as the reference category).
Conclusion
The present study demonstrated that DKD was significantly associated with a higher risk of hip fracture, with proteinuria as a major determinant.

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Bone Mineral Density and the Risk of Fracture According to eGFR in Postmenopausal Women
Minsang Kim, Kyungdo Han, Jin Kyung Kwon, Jae-ik Oh, Jinsun Lee, Jung Hun Koh, Min Woo Kang, Jeong Min Cho, Semin Cho, Seong Geun Kim, Sehyun Jung, Hyuk Huh, Soojin Lee, Eunjeong Kang, Yaerim Kim, Kwon Wook Joo, Dong Ki Kim, Sehoon Park
Journal of the American Society of Nephrology.2026; 37(5): 984. CrossRef
Diabetes progression and its association with fracture risk in type 2 diabetes
Bongsung Kim, Kyu-Na Lee, Kyungdo Han, Mee Kyoung Kim
Osteoporosis International.2026;[Epub] CrossRef
Associations Between Renal Dysfunction Subtypes and Vertebral Fracture in Patients with Type 2 Diabetes: A Longitudinal Study
Nandong Hu, Yiping Zhang, Zicheng Wei, Rui Yu, Yingying Zhang, Xiao Chen
Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 1915. CrossRef
Risk of fracture with sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes: an updated meta-analysis of randomized controlled trials
Mahdieh Khoshzaban Banisi
International Journal of Physiology, Pathophysiology and Pharmacology.2025; 17(3): 61. CrossRef
Proteinuria screening and risk of bone fracture: a retrospective cohort study using a nationwide population-based database
Akira Okada, Akira Honda, Hideaki Watanabe, Yusuke Sasabuchi, Shotaro Aso, Kayo Ikeda Kurakawa, Masaomi Nangaku, Toshimasa Yamauchi, Hideo Yasunaga, Hirotaka Chikuda, Takashi Kadowaki, Satoko Yamaguchi
Clinical Kidney Journal.2024;[Epub] CrossRef
Fracture risks associated with sodium-glucose cotransporter-2 inhibitors in type 2 diabetes patients across eGFR and albuminuria categories: A population-based study in Hong Kong
David Tak Wai Lui, Tingting Wu, Eric Ho Man Tang, Ivan Chi Ho Au, Chi Ho Lee, Yu Cho Woo, Kathryn Choon Beng Tan, Carlos King Ho Wong
Diabetes Research and Clinical Practice.2023; 197: 110576. CrossRef
Diagnose und Management der Osteoporose bei Diabetes mellitus (Update 2023)
Christian Muschitz, Alexandra Kautzky-Willer, Yvonne Winhofer, Martina Rauner, Judith Haschka, Daniel Cejka, Robert Wakolbinger-Habel, Peter Pietschmann
Wiener klinische Wochenschrift.2023; 135(S1): 207. CrossRef
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Seung Eun Lee, Juhwan Yoo, Bong-Seong Kim, Kyoung-Ah Kim, Kyungdo Han, Han Seok Choi
Archives of Osteoporosis.2023;[Epub] CrossRef
Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea
Seung Eun Lee, Juhwan Yoo, Han Seok Choi, Kyungdo Han, Kyoung-Ah Kim
Diabetes & Metabolism Journal.2023; 47(4): 523. CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Risk of Diabetes in Subjects with Positive Fecal Immunochemical Test: A Nationwide Population-Based Study: Kwang Woo Kim, Hyun Jung Lee, Kyungdo Han, Jung Min Moon, Seung Wook Hong, Eun Ae Kang, Jooyoung Lee, Hosim Soh, Seong-Joon Koh, Jong Pil Im, Joo Sung Kim; Endocrinol Metab. 2021;36(5):1069-1077. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1119

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Background
Positive fecal immunochemical test (FIT) results have been recently suggested as a risk factor for systemic inflammation. Diabetes induces inflammation in the gastrointestinal tract via several ways. We investigated the association between FIT results and the incidence of diabetes.
Methods
A total of 7,946,393 individuals aged ≥50 years from the National Cancer Screening Program database who underwent FIT for colorectal cancer (CRC) screening from 2009 to 2012 were enrolled. The primary outcome was newly diagnosed diabetes based on the International Classification of Disease 10th revision codes and administration of anti-diabetic medication during the follow-up period.
Results
During a mean follow-up of 6.5 years, the incidence rates of diabetes were 11.97, 13.60, 14.53, and 16.82 per 1,000 personyears in the FIT negative, one-positive, two-positive, and three-positive groups, respectively. The hazard ratios (HRs) for the incidence of diabetes were 1.14 (95% confidence interval [CI], 1.12 to 1.16; HR, 1.21; 95% CI, 1.16 to 1.27; and HR, 1.40; 95% CI, 1.28 to 1.55) in the one-positive, two-positive, and three-positive FIT groups compared with the FIT negative group, respectively. The effect was consistent in individuals with normal fasting blood glucose (adjusted HR 1.55 vs. 1.14, P for interaction <0.001).
Conclusion
Positive FIT results were associated with a significantly higher risk of diabetes, suggesting that the FIT can play a role not only as a CRC screening tool, but also as a surrogate marker of systemic inflammation; thus, increasing the diabetes risk.

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Uncovering a dose-response relationship between positive fecal immunochemical test (FIT) and all-cause, cardiovascular and cancer-related mortality
Chi Pang Wen, Min Kuang Tsai, June Han Lee, Hung Yi Chiou, Christopher Wen, Ta-Wei David Chu, Chien Hua Chen
European Journal of Internal Medicine.2024; 120: 69. CrossRef
Risk of Cancers Proximal to the Colon in Fecal Immunochemical Test Positive Screenees in a Colorectal Cancer Screening Program
Willemijn de Klaver, Manon van der Vlugt, Manon C.W. Spaander, Patrick M. Bossuyt, Evelien Dekker
Gastroenterology.2024; 167(4): 788. CrossRef
Systematic review: Mortality associated with raised faecal immunochemical test and positive faecal occult blood results
Francesca Ligori Malcolm, Anjali K. D. S. Yapa, Zhen Yu Wong, Alastair James Morton, Colin Crooks, Joe West, Ayan Banerjea, David Humes
Alimentary Pharmacology & Therapeutics.2024; 60(7): 840. CrossRef
Faecal haemoglobin concentrations are associated with all-cause mortality and cause of death in colorectal cancer screening
Lasse Kaalby, Ulrik Deding, Issam Al-Najami, Gabriele Berg-Beckhoff, Thomas Bjørsum-Meyer, Tinne Laurberg, Aasma Shaukat, Robert J. C. Steele, Anastasios Koulaouzidis, Morten Rasmussen, Morten Kobaek-Larsen, Gunnar Baatrup
BMC Medicine.2023;[Epub] CrossRef
Positive Results from the Fecal Immunochemical Test Can Be Related to Dementia: A Nationwide Population-Based Study in South Korea
Yu Kyung Jun, Seung Woo Lee, Kwang Woo Kim, Jung Min Moon, Seong-Joon Koh, Hyun Jung Lee, Joo Sung Kim, Kyungdo Han, Jong Pil Im
Journal of Alzheimer's Disease.2023; 91(4): 1515. CrossRef
Faecal Haemoglobin Estimated by Faecal Immunochemical Tests—An Indicator of Systemic Inflammation with Real Clinical Potential
Karen N. Barnett, Gavin R. C. Clark, Robert J. C. Steele, Callum G. Fraser
Diagnostics.2021; 11(11): 2093. CrossRef

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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Diabetology & Metabolic Syndrome.2026;[Epub] CrossRef
Impact of cumulative exposure to a high TG to HDL-C ratio on type 2 diabetes risk in young adults
Jung Heo, Byungpyo Kim, Kyungdo Han, Jae-Hyuk Lee, Seo-Young Sohn, Jiyeon Ahn, Whi-An Kwon, Moon Jung Kim, Eun-Young Doo, Min-Kyung Lee
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Min Cheol Chang, Seung Min Chung, Sang Gyu Kwak
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Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study
Byeong Yun Ahn, Bokyung Kim, Sanghyun Park, Sang Gyun Kim, Kyungdo Han, Soo‐Jeong Cho
Cancer.2024; 130(10): 1807. 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
Triglyceride-glucose index is associated with the risk of impaired fasting glucose in Chinese elderly individuals
Jie Liu, Feng Yi, Kai Duan, Haibo Liu
Scientific Reports.2024;[Epub] CrossRef
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
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

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Cardiovascular Outcomes of Obesity According to Menopausal Status: A Nationwide Population-Based Study: Bo Kyung Koo, Sang-Hyun Park, Kyungdo Han, Min Kyong Moon; Endocrinol Metab. 2021;36(5):1029-1041. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1197

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Background
We estimated the effect of obesity on the incidence of cardiovascular disease (CVD) and mortality in women according to menopausal status.
Methods
Women aged 40 to 69 years under routine health check-ups provided by the National Health Insurance Service in 2009 were followed up till 2018 (n=2,208,559).
Results
In premenopausal women, a significant increment of mortality rate was found in underweight and obesity class II (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.31 to 1.67; and HR, 1.25; 95% CI, 1.12 to 1.39) compared to normal body mass index (BMI); overweight and obesity class I did not affect mortality rate. In postmenopausal women, obesity as well as overweight status reduced the risk of mortality compared to normal BMI (HR, 0.86; 95% CI, 0.83 to 0.88; and HR, 0.84; 95% CI, 0.82 to 0.86). By contrast, there was a linear association between CVD and BMI above the normal range irrespective of menopausal status, which was attenuated in diabetic women.
Conclusion
The current study replicated the J-shaped relationship between BMI and mortality, being more prominent in the postmenopausal group. The risk of CVD was linearly increased as BMI was increased above the normal range irrespective of menopausal status.

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Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study: Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park; Endocrinol Metab. 2021;36(3):628-636. Published online May 26, 2021; DOI: https://doi.org/10.3803/EnM.2020.948

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Background
To investigate the clinical characteristics of gestational diabetes mellitus (GDM) in Korea, using a nationwide database.
Methods
We analyzed 417,139 women who gave birth between 2011 and 2015 using the Korean National Health Information Database. They underwent the Korean National Health Screening Program within one year before pregnancy and were not prescribed drugs for diabetes nor diagnosed with diabetes mellitus before 280 days antepartum. Patients with GDM were defined as those who visited the outpatient clinic more than twice with GDM codes.
Results
The prevalence of GDM was 12.70% and increased with increasing maternal age, prepregnancy body mass index (BMI), waist circumference (WC), and fasting plasma glucose (FPG) (P for trend <0.05). As compared with those aged <25 years, the odds ratio for women with GDM aged ≥40 years were 4.804 (95% confidence interval [CI], 4.436 to 5.203) after adjustment for covariates. Women with prepregnancy BMI ≥30 kg/m² were at 1.898 times (95% CI, 1.736 to 2.075) greater risk for GDM than those with prepregnancy BMI <18.5 kg/m². Women with WC of ≥95 cm were at 1.158 times (95% CI, 1.029 to 1.191) greater risk for GDM than women with WC of less than 65 cm. High FPG, high income, smoking, and drinking were associated with an elevated risk of GDM.
Conclusion
The prevalence of GDM in Korean women increased up to 12.70% during 2011 to 2015. These data suggest the importance of GDM screening and prevention in high-risk groups in Korea.

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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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Clinical Study Big Data Articles (National Health Insurance Service Database)
Variabilities in Weight and Waist Circumference and Risk of Myocardial Infarction, Stroke, and Mortality: A Nationwide Cohort Study: Da Hye Kim, Ga Eun Nam, Kyungdo Han, Yang-Hyun Kim, Kye-Yeung Park, Hwan-Sik Hwang, Byoungduck Han, Sung Jung Cho, Seung Jin Jung, Yeo-Joon Yoon, Yong Kyun Roh, Kyung Hwan Cho, Yong Gyu Park; Endocrinol Metab. 2020;35(4):933-942. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.871

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Abstract PDF Supplementary Material PubReader ePub

Background
Evidence regarding the association between variabilities in obesity measures and health outcomes is limited. We aimed to examine the association between variabilities in obesity measures and cardiovascular outcomes and all-cause mortality.
Methods
We identified 4,244,460 individuals who underwent health examination conducted by the Korean National Health Insurance Service during 2012, with ≥3 anthropometric measurements between 2009 and 2012. Variabilities in body weight (BW) and waist circumference (WC) were assessed using four indices including variability independent of the mean (VIM). We performed multivariable Cox proportional hazards regression analyses.
Results
During follow-up of 4.4 years, 16,095, 18,957, and 30,200 cases of myocardial infarction (MI), stroke, and all-cause mortality were recorded. Compared to individuals with the lowest quartiles, incrementally higher risks of study outcomes and those of stroke and all-cause mortality were observed among individuals in higher quartiles of VIM for BW and VIM for WC, respectively. The multivariable adjusted hazard ratios and 95% confidence intervals comparing the highest versus lowest quartile groups of VIM for BW were 1.17 (1.12 to 1.22) for MI, 1.20 (1.16 to 1.25) for stroke, and 1.66 (1.60 to 1.71) for all-cause mortality; 1.07 (1.03 to 1.12) for stroke and 1.29 (1.25 to 1.33) for all-cause mortality regarding VIM for WC. These associations were similar with respect to the other indices for variability.
Conclusion
This study revealed positive associations between variabilities in BW and WC and cardiovascular outcomes and allcause mortality. Our findings suggest that variabilities in obesity measures are associated with adverse health outcomes in the general population.

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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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Clinical Study
Impact of the Dynamic Change of Metabolic Health Status on the Incident Type 2 Diabetes: A Nationwide Population-Based Cohort Study: Jung A Kim, Da Hye Kim, Seon Mee Kim, Yong Gyu Park, Nan Hee Kim, Sei Hyun Baik, Kyung Mook Choi, Kyungdo Han, Hye Jin Yoo; Endocrinol Metab. 2019;34(4):406-414. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.406

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Background

Metabolically healthy obese (MHO) is regarded as a transient concept. We examined the effect of the dynamic change of metabolic health status on the incidence of type 2 diabetes mellitus (T2DM) both in obese and normal weight individuals.

Methods

We analyzed 3,479,514 metabolically healthy subjects aged over 20 years from the Korean National Health Screening Program, who underwent health examination between 2009 and 2010, with a follow-up after 4 years. The relative risk for T2DM incidence until the December 2017 was compared among the four groups: stable metabolically healthy normal weight (MHNW), unstable MHNW, stable MHO, and unstable MHO.

Results

During the 4 years, 11.1% of subjects in the MHNW group, and 31.5% in the MHO group converted to a metabolically unhealthy phenotype. In the multivariate adjusted model, the unstable MHO group showed the highest risk of T2DM (hazard ratio [HR], 4.67; 95% confidence interval [CI], 4.58 to 4.77). The unstable MHNW group had a higher risk of T2DM than stable MHO group ([HR, 3.23; 95% CI, 3.16 to 3.30] vs. [HR, 1.81; 95% CI, 1.76 to 1.85]). The stable MHO group showed a higher risk of T2DM than the stable MHNW group. The influence of the transition into a metabolically unhealthy phenotype on T2DM incidence was greater in subjects with aged <65 years, women, and those with weight gain.

Conclusion

Metabolically healthy phenotype was transient both in normal weight and obese individuals. Maintaining metabolic health was critical for the prevention of T2DM, irrespective of their baseline body mass index.

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Obesity and Metabolism
Comparison of the Effects of Ezetimibe-Statin Combination Therapy on Major Adverse Cardiovascular Events in Patients with and without Diabetes: A Meta-Analysis: Namki Hong, Yong-ho Lee, Kenichi Tsujita, Jorge A. Gonzalez, Christopher M. Kramer, Tomas Kovarnik, George N. Kouvelos, Hiromichi Suzuki, Kyungdo Han, Chan Joo Lee, Sung Ha Park, Byung-Wan Lee, Bong-Soo Cha, Eun Seok Kang; Endocrinol Metab. 2018;33(2):219-227. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.219

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Background

Ezetimibe-statin combination therapy has been found to reduce low density lipoprotein cholesterol levels and the risk of major adverse cardiovascular events (MACEs) in large trials. We sought to examine the differential effect of ezetimibe on MACEs when added to statins according to the presence of diabetes.

Methods

Randomized clinical trials with a sample size of at least 50 participants and at least 24 weeks of follow-up that compared ezetimibe-statin combination therapy with a statin- or placebo-controlled arm and reported at least one MACE, stratified by diabetes status, were included in the meta-analysis and meta-regression.

Results

A total of seven trials with 28,191 enrolled patients (mean age, 63.6 years; 75.1% men; 7,298 with diabetes [25.9%]; mean follow-up, 5 years) were analysed. MACEs stratified by diabetes were obtained from the published data (two trials) or through direct contact (five trials). No significant heterogeneity was observed among studies (I²=14.7%, P=0.293). Ezetimibe was associated with a greater reduction of MACE risk in subjects with diabetes than in those without diabetes (pooled relative risk, 0.84 vs. 0.93; P_{heterogeneity}=0.012). In the meta-regression analysis, the presence of diabetes was associated with a greater reduction of MACE risk when ezetimibe was added to statins (β=0.87, P=0.038).

Conclusion

Ezetimibe-statin combination therapy was associated with greater cardiovascular benefits in patients with diabetes than in those without diabetes. Our findings suggest that ezetimibe-statin combination therapy might be a useful strategy in patients with diabetes at a residual risk of MACEs.

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Association between Body Weight Changes and Menstrual Irregularity: The Korea National Health and Nutrition Examination Survey 2010 to 2012: Kyung Min Ko, Kyungdo Han, Youn Jee Chung, Kun-Ho Yoon, Yong Gyu Park, Seung-Hwan Lee; Endocrinol Metab. 2017;32(2):248-256. Published online June 23, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.248

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Background

Menstrual irregularity is an indicator of endocrine disorders and reproductive health status. It is associated with various diseases and medical conditions, including obesity and underweight. We aimed to assess the association between body weight changes and menstrual irregularity in Korean women.

Methods

A total of 4,621 women 19 to 54 years of age who participated in the 2010 to 2012 Korea National Health and Nutrition Examination Survey were included in this study. Self-reported questionnaires were used to collect medical information assessing menstrual health status and body weight changes. Odds ratios (ORs) and 95% confidence interval (CI) were calculated to evaluate the association between body weight changes and menstrual irregularity.

Results

Significantly higher ORs (95% CI) were observed in the association between menstrual irregularity and both weight loss (OR, 1.74; 95% CI, 1.22 to 2.48) and weight gain (OR, 1.45; 95% CI, 1.13 to 1.86) after adjusting for age, body mass index, current smoking, heavy alcohol drinking, regular exercise, calorie intake, education, income, metabolic syndrome, age of menarche, parity, and stress perception. Of note, significant associations were only observed in subjects with obesity and abdominal obesity, but not in non-obese or non-abdominally obese subjects. U-shaped patterns were demonstrated in both obese and abdominally obese subjects, indicating that greater changes in body weight are associated with higher odds of menstrual irregularity.

Conclusion

We found a U-shaped pattern of association between body weight changes and menstrual irregularity among obese women in the general Korean population. This result indicates that not only proper weight management but also changes in body weight may influence the regulation of the menstrual cycle.

Citations

Citations to this article as recorded by

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