Endocrinology and Metabolism

Original Article

Impact of Tumor Bilaterality and Multifocality in Predicting Recurrence of Papillary Thyroid Carcinoma: A Retrospective Cohort Study: Eunji Kim, Jun Hyun Park, Ji-Young Park, Jin Hyang Jung, Sang-Woo Lee; Received August 14, 2025 Accepted November 26, 2025 Published online March 4, 2026; DOI: https://doi.org/10.3803/EnM.2025.2607 [Epub ahead of print]

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Abstract PDF: Background
This study investigated the prognostic value of bilaterality and multifocality in papillary thyroid carcinoma (PTC) recurrence, aiming to inform optimal surgical strategies.
Methods
In this retrospective cohort, 1,966 patients who underwent total thyroidectomy for PTC (2011–2014) were categorized into four groups according to tumor multifocality and bilaterality confirmed by postoperative histopathology: group 1, unilateral solitary; group 2, unilateral multifocal; group 3, bilateral solitary; group 4, bilateral multifocal. Clinicopathologic features and clinical outcomes were compared across these groups.
Results
Group 4 exhibited the highest prevalence of BRAFV600E positivity, nodal metastases, and recurrence. Both bilaterality and multifocality were associated with more aggressive clinicopathologic characteristics. Recurrence risk increased with the number of tumor foci, with the odds ratio (OR) significantly elevated for more than five foci. Satellite pattern was strongly linked to recurrence (OR, 19.49; P<0.001). While tumor multifocality (≥5 foci) and bilaterality were associated with recurrence in univariate analyses, these associations were not independent after adjustment. Kaplan-Meier analysis demonstrated the lowest recurrence-free survival (RFS) in group 4. Patients with bilateral disease had significantly lower RFS than those with unilateral disease (P=0.003), whereas multifocality did not significantly affect RFS compared to solitary disease (P=0.095).
Conclusion
Tumor bilaterality, multifocality (≥5 foci), and satellite pattern were associated with aggressive features and higher recurrence risk. Although not independent predictors, these factors may serve as useful surrogate markers of aggressive disease biology and help guide personalized surgical strategies in patients with PTC.

Namgok Lecture 2025

Mineral, bone & muscle
Current Knowledge on Atypical Parathyroid Tumors and Emerging Strategies for Risk Stratification: Hye-Sun Park, Milim Kim, Jong Ju Jeong, Namki Hong, Yumie Rhee; Endocrinol Metab. 2026;41(1):14-25. Published online January 7, 2026; DOI: https://doi.org/10.3803/EnM.2025.2846

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Abstract PDF PubReader ePub: Atypical parathyroid tumors (APTs) are an uncommon subset of parathyroid neoplasms that carry substantial clinical relevance because of their histological and clinical resemblance to parathyroid cancer. Despite this importance, the diagnosis of APTs remains persistently challenging, even for experienced pathologists. Their histopathological features overlap extensively with those of parathyroid cancer, and at present, no specific immunohistochemical markers are available that can reliably distinguish between these entities. Moreover, the clinical manifestations of APTs are indistinguishable from those of parathyroid adenomas or true parathyroid cancer. A major concern is the uncertain malignant potential of APTs, which contributes to difficulties in prognostic prediction and the absence of standardized surveillance guidelines. Although most published studies suggest a benign clinical course for the majority of APTs, these conclusions are frequently limited by relatively short follow-up durations. This limitation is underscored by several case reports describing recurrence or metastatic disease in patients initially diagnosed with APTs, subsequently prompting reclassification as parathyroid cancer. Recent advances in molecular technologies, particularly RNA sequencing and genomic profiling, have facilitated novel approaches to risk assessment and prognostic evaluation in APTs. This review aims to provide a comprehensive overview of the diagnosis, clinical manifestations, and current molecular strategies used to assess the malignant potential of APTs.

Original Article

Global Burden of Early-Onset Cancers Attributable to Metabolic Risk Factors from 1990 to 2021 and Projections to 2040: Wenmei Qiao, Kaijian Zhou, Liang He, Jiahui Guo, Qiqiang Guo, Jing Zhang, Yongze Li; Received July 24, 2025 Accepted October 21, 2025 Published online January 5, 2026; DOI: https://doi.org/10.3803/EnM.2025.2577 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Early-onset cancers (diagnosed in individuals under 50 years of age) are increasingly contributing to the global cancer burden. Among the known contributors, specific metabolic risk factors—namely high body mass index (BMI) and high fasting plasma glucose (FPG)—have emerged as significant determinants. This study assessed the global burden of early-onset cancers attributable to these two metabolic risk factors and projected their trends through 2040.
Methods
Using data from the Global Burden of Disease 2021 study, we analyzed mortality, disability-adjusted life years (DALYs), and estimated annual percentage changes for early-onset cancers linked to metabolic risk factors, stratified by age, sex, and sociodemographic index (SDI). Future trends were projected based on these data.
Results
In 2021, the two metabolic risk factors (high FPG and high BMI) together accounted for 34,112 (95% uncertainty interval [UI], 15,037 to 54,888) deaths and 1,691,418 (95% UI, 762,923 to 2,698,657) DALYs from early-onset cancers, corresponding to mortality and DALY rates of 0.9 (95% UI, 0.4 to 1.4) and 42.8 (95% UI, 19.3 to 68.3) per 100,000 population, respectively. Between 1990 and 2021, both mortality and DALY rates rose significantly, with the greatest increases observed in individuals aged 30–34 years and in low-middle SDI regions. High FPG and high BMI were the leading contributors, with colorectal cancer showing the highest burden and liver cancer the most rapid growth. While high BMI predominated in most SDI regions, high FPG was more prominent in low-SDI countries, particularly among females. Projections indicate a continued rise in mortality and DALY rates through 2040.
Conclusion
High BMI and high FPG are major contributors to the global burden of early-onset cancers, with marked sex and socioeconomic disparities necessitating targeted interventions. Urgent strategies are required to mitigate metabolic risks and enhance early cancer detection, especially among vulnerable populations.

Review Article

Thyroid
Diagnostic Challenges, Prognostic Assessment, and Treatment Strategies in High-Grade Differentiated Thyroid Carcinoma: Chan Kwon Jung, Agnes Stephanie Harahap; Endocrinol Metab. 2025;40(6):830-850. Published online December 11, 2025; DOI: https://doi.org/10.3803/EnM.2025.2725

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Abstract PDF PubReader ePub: High-grade differentiated thyroid carcinoma (HGDTC) is a recently codified entity in the 2022 World Health Organization Classification of Endocrine Tumors, defined by a mitotic count of ≥5 mitoses per 2 mm² and/or tumor necrosis in a carcinoma that retains papillary, follicular, or oncocytic differentiation without anaplastic morphology. Although uncommon, HGDTC presents significant diagnostic and therapeutic challenges. This review summarizes current evidence regarding histopathologic recognition, molecular features, prognostic determinants, and evolving treatment paradigms. Particular attention is given to pattern-specific pitfalls such as high-grade papillary thyroid carcinoma, the diffuse sclerosing subtype, and the prognostic influence of the invasion phenotype (encapsulated versus infiltrative). Subcentimeter papillary carcinomas exhibiting increased mitotic activity alone should not be overinterpreted as HGDTC. An integrated, stepwise approach is proposed to enhance diagnostic reproducibility, refine risk stratification, and optimize multidisciplinary management in clinical practice.

Original Articles

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Joint Associations of the Geriatric Nutrition Risk Index and Frailty with All-Cause and Cause-Specific Mortality in Diabetes Patients: A Prospective Cohort Study: Chenke Gu, Qiuyue Jia, Youxiang Wang, Weikang Li, Suying Ding, Jingfeng Chen; Endocrinol Metab. 2025;40(6):916-927. Published online November 17, 2025; DOI: https://doi.org/10.3803/EnM.2025.2441

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Abstract PDF Supplementary Material PubReader ePub: Background
This study investigated the independent and joint impacts of the geriatric nutritional risk index (GNRI) and frailty index (FI) on all-cause and cause-specific mortality in patients with diabetes.
Methods
This study included 1,790 National Health and Nutrition Examination Survey participants between 1999 and 2018. GNRI and FI were used to assess patients with diabetes, who were categorized into low GNRI and high GNRI groups, as well as low FI and high FI groups, to evaluate older adults’ nutritional status. These groups were combined into four categories. Weighted Cox proportional hazards models, Kaplan-Meier survival curves, and restricted cubic spline regression models were applied to assess the independent and joint associations of GNRI and FI with all-cause and cause-specific mortality in patients with diabetes.
Results
The median follow-up period was 100 months, during which 720 deaths occurred. An independent linear dose-response relationship between GNRI, FI, and all-cause mortality risk was observed. The combination of low GNRI and high FI was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.65; 95% confidence interval [CI], 1.02 to 2.68) for the low GNRI+low FI group, 2.03 (95% CI, 1.61 to 2.55) for the high GNRI+high FI group, and 3.65 (95% CI, 2.38 to 5.58) for the low GNRI+high FI group. Stratified analysis (reference: high GNRI+low FI group) showed an increased mortality risk among men in the low GNRI+high FI group.
Conclusion
The combination of low GNRI and high FI was independently and jointly associated with increased risk of all-cause, cardiovascular disease, diabetes, and hypertension mortality, particularly among men.

A Nomogram for End-Stage Renal Disease Prediction in Patients with Type 2 Diabetes Mellitus: A Nationwide Cohort Study in Korea: Inha Jung, Bong-Seong Kim, So Young Park, Da Young Lee, Ji Hee Yu, Ji A Seo, Kyung-Do Han, Nan Hee Kim; Received July 22, 2025 Accepted September 18, 2025 Published online November 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2570 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Despite the rising incidence of end-stage renal disease (ESRD) among individuals with type 2 diabetes mellitus (T2DM) in Korea, no predictive model or nomogram has been developed using a nationwide cohort. In this study, we developed a nomogram to predict the long-term risk of ESRD in patients with T2DM using a large-scale, population-based Korean database.
Methods
Using the Korean National Health Insurance Database, patients with T2DM who underwent health examinations between 2015 and 2016 were assigned as development (n=1,744,277) and validation (n=747,407) cohorts. New ESRD cases were identified using codes for renal replacement therapy. A Cox proportional hazards regression model was used to derive a risk-scoring system, and 13 variables were selected. A risk score nomogram was then created to estimate the risk of ESRD.
Results
In the development cohort, 8,631 patients with T2DM developed ESRD during a follow-up period of 4.8±0.9 years. After multivariable adjustment, significant predictors of ESRD included male sex, current smoking, physical inactivity, low income, low body mass index, hypertension, low-density lipoprotein cholesterol ≥160 mg/dL, chronic kidney disease, insulin use, and longer duration of T2DM. A final nomogram incorporating 13 variables was developed to estimate the individual probability of ESRD. The concordance index for ESRD prediction in the validation cohort was 0.906 (95% confidence interval, 0.9 to 0.912).
Conclusion
This 13-variable nomogram provides a simple tool for identifying patients with T2DM at high risk of ESRD and may aid in early intervention.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Impact of Glucose Metabolism Status on the Association between Apolipoprotein A-I and Ischemic Risk in Patients with Coronary Artery Disease: A Large-Sample Cohort Study: Kailun Yan, Jiawen Li, Kexin Zhang, Menglu Liu, Pei Zhu, Xiaofang Tang, Deshan Yuan, Yuejin Yang, Runlin Gao, Jinqing Yuan, Xueyan Zhao; Endocrinol Metab. 2025;40(6):904-915. Published online November 7, 2025; DOI: https://doi.org/10.3803/EnM.2025.2407

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Abstract PDF Supplementary Material PubReader ePub: Background
Apolipoprotein A-I (ApoA-I) is a key cardioprotective lipoprotein. Nevertheless, it remains unclear how ApoA-I relates to ischemic risk across glucose metabolism statuses in patients with coronary artery disease (CAD). This study investigated whether glucose metabolism status influences the association between ApoA-I and ischemic risk in CAD patients.
Methods
This cohort study included 10,724 consecutive CAD patients undergoing percutaneous coronary intervention, who were classified into diabetes mellitus (DM), pre-DM, and normal glucose regulation (NGR) groups. The primary clinical endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, revascularization, and stroke.
Results
Of the 10,232 patients ultimately included, 2,139 (20.9%) experienced MACCE over 5 years. A significant interaction was observed between ApoA-I levels and glucose metabolism status (P for interaction=0.041). In the DM group, an L-shaped association between ApoA-I and MACCE was found, with lower ApoA-I levels linked to a higher risk of MACCE (P for non-linearity= 0.044). Multivariate Cox regression analysis showed that patients in the lowest quintile of ApoA-I had a 1.327-fold increased risk of MACCE compared to those at the lowest risk (hazard ratio, 1.327; 95% confidence interval, 1.097 to 1.604). However, no significant association was observed in the pre-DM or NGR groups (both P>0.05).
Conclusion
This large-scale, 5-year follow-up study is the first to demonstrate that lower ApoA-I levels are associated with increased MACCE risk in CAD patients with DM, highlighting the potential value of ApoA-I in risk stratification and as a therapeutic target.

Review Articles

Mineral, bone & muscle
Incorporating Artificial Intelligence into Fracture Risk Assessment: Using Clinical Imaging to Predict the Unpredictable: Sung Hye Kong; Endocrinol Metab. 2025;40(4):499-507. Published online August 4, 2025; DOI: https://doi.org/10.3803/EnM.2025.2518

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Abstract PDF PubReader ePub

Artificial intelligence (AI) is increasingly being explored as a complementary tool to traditional fracture risk assessment methods. Conventional approaches, such as bone mineral density measurement and established clinical risk calculators, provide populationlevel stratification but often fail to capture the structural nuances of bone fragility. Recent advances in AI—particularly deep learning techniques applied to imaging—enable opportunistic screening and individualized risk estimation using routinely acquired radiographs and computed tomography (CT) data. These models demonstrate improved discrimination for osteoporotic fracture detection and risk prediction, supporting applications such as time-to-event modeling and short-term prognosis. CT- and radiograph-based models have shown superiority over conventional metrics in diverse cohorts, while innovations like multitask learning and survival plots contribute to enhanced interpretability and patient-centered communication. Nevertheless, challenges related to model generalizability, data bias, and automation bias persist. Successful clinical integration will require rigorous external validation, transparent reporting, and seamless embedding into electronic medical systems. This review summarizes recent advances in AI-driven fracture assessment, critically evaluates their clinical promise, and outlines a roadmap for translation into real-world practice.

Citations

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Thyroid
The Initial Risk Stratification System for Differentiated Thyroid Cancer: Key Updates in the 2024 Korean Thyroid Association Guideline: Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Jeongmin Lee, Dong-Jun Lim, Chan Kwon Jung, Young Joo Park, on Behalf of the Korean Thyroid Association Clinical Guideline Committee; Endocrinol Metab. 2025;40(3):357-384. Published online June 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2465

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In 2024, the Korean Thyroid Association (KTA) introduced a revised Risk Stratification System (K-RSS) for differentiated thyroid cancer, building upon the modified RSS (M-RSS) proposed by the American Thyroid Association in 2015. The K-RSS emphasizes the cumulative impact of coexisting clinical and pathological features, acknowledging that multiple intermediate-risk factors collectively indicate a higher recurrence risk. Histologic classification follows the 2022 World Health Organization classification, consolidating encapsulated follicular-patterned thyroid carcinomas, including invasive encapsulated follicular variant papillary thyroid carcinoma, follicular thyroid carcinoma, and oncocytic carcinoma of the thyroid gland, and stratifying them by the extent of capsular and vascular invasion. High-grade thyroid carcinoma is newly included. Updated criteria for tumor size and extrathyroidal extension (ETE) represent another significant change. BRAF^V600E-mutated papillary thyroid carcinomas measuring 1 to 2 cm are now considered lower risk than previously classified in the M-RSS, while encapsulated follicular-patterned tumors larger than 4 cm are considered higher risk. Both minimal ETE and gross ETE confined to the strap muscles have been downgraded to low and intermediate risk, respectively. These changes are accompanied by updates regarding molecular profiling and surgical margin status. Collectively, these updates aim to minimize overtreatment in low-risk patients, while ensuring intensified management for those at higher risk.

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Who Really Needs RAI Ablation Therapy for Low-to-Intermediate Risk Differentiated Thyroid Cancer? Insights from the IoN Trial
Young Joo Park
Clinical Thyroidology®.2025; 37(9): 323. CrossRef
From Classification to Personalization: Advances in Thyroid Cancer Risk Stratification Systems
Mijin Kim, Bo Hyun Kim
Endocrinology and Metabolism.2025; 40(5): 689. CrossRef
Thyroglobulin Cutoffs after Total Thyroidectomy Without Radioiodine in Low- to Intermediate-Risk Thyroid Cancer: A Multicenter Cohort Study
Mijin Kim, Eun Kyung Lee, Kyeong Jin Kim, Soo Myoung Shin, Jinsun Jang, Je Yoon Shin, Meihua Jin, Ja Seong Bae, Kwangsoon Kim, Won Gu Kim, Min Ji Jeon, Seung Heon Kang, Hee Kyung Kim, Jee Hee Yoon, Yea Eun Kang, Hwa Young Ahn, Young Joo Park, Bo Hyun Kim
Thyroid®.2025;[Epub] CrossRef
Diagnostic Challenges, Prognostic Assessment, and Treatment Strategies in High-Grade Differentiated Thyroid Carcinoma
Chan Kwon Jung, Agnes Stephanie Harahap
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Original Article

Diabetes, obesity and metabolism
Fatty Liver Index Dynamics as a Predictor of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus and Non-Cirrhotic Livers: Eun-Hee Cho, Min Gu Kang, Chang Hun Lee, Shinyoung Oh, Chen Shen, Ha Ram Oh, Young Ran Park, Hyun Lee, Jong Seung Kim, Ji Hyun Park; Endocrinol Metab. 2025;40(6):883-892. Published online May 29, 2025; DOI: https://doi.org/10.3803/EnM.2024.2286

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Abstract PDF Supplementary Material PubReader ePub: Background
Type 2 diabetes mellitus (T2DM) is a significant risk factor for hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease; however, surveillance strategies for patients with T2DM, especially without cirrhosis, are inadequate. This study examined whether the fatty liver index (FLI) and its dynamic changes can effectively identify patients with T2DM at increased risk for HCC.
Methods
Data from 92,761 individuals with T2DM aged 40 to 79 who underwent two health screenings (2012 to 2015) were analyzed. The FLI, calculated using waist circumference, body mass index, triglycerides, and gamma-glutamyl transferase, was used to stratify patients by baseline FLI and FLI changes between screenings. HCC cases were identified via International Classification of Diseases codes and reimbursement records (2016 to 2020).
Results
Patients with baseline FLI of 30 to 59.9 had a 1.90-fold higher risk (P<0.01) and those with FLI ≥60 had a 2.94-fold higher risk (P<0.01) of developing HCC compared to those with FLI <30. An increase in FLI from <30 to ≥30 resulted in a 2.10-fold higher risk of HCC (P<0.01), while a reduction in FLI from ≥30 to <30 led to a 0.64-fold lower risk (P=0.03). Protective benefits of FLI reduction took approximately 3 years to manifest.
Conclusion
Baseline and dynamic monitoring of FLI effectively identified HCC risk in T2DM patients with non-cirrhotic livers, supporting early detection and intervention.

Review Article

Diabetes, obesity and metabolism
Prevalence and Current Status of Cardiometabolic Risk Factors in Korean Adults Based on Fact Sheets 2024: Eun-Jung Rhee; Endocrinol Metab. 2025;40(2):174-184. Published online April 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2398

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Korea has entered ‘super-aged’ society in 2025 with the proportion of people 65 years or older exceeding 20% as of the end of the year 2024. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. According to data from 2022, the overall prevalence of obesity reached 38.4%, marking a continued upward trend, based on National Health Insurance medical checkup data. In the combined data of 2021 to 2022, the prevalence of diabetes was 15.5% in Koreans older than 30 years according to the Diabetes Fact Sheet 2024 published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2022 was 30% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2022 was 40.9% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations in 2024.

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High incidence of eating disorders in individuals with type 2 diabetes and their association with cardiovascular and mortality risks
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Eun-Jung Rhee
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2024 Cardio-cerebrovascular disease fact sheet in Korea
Kyungdo Han, Jin-Hyung Jung, Sang-Suk Choi, Seung-Hyun Ko
Cardiovascular Prevention and Pharmacotherapy.2025; 7(3): 85. CrossRef
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Rishibha Kaushik, B. P. Priyadarshi, Lalit Kumar, Yuvraj Gulati, Madhuri Priyadarshi, S. K. Sinha
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Original Articles

Thyroid
Prognostic Indicators and Comparative Treatment Outcomes in High-Risk Thyroid Cancer with Laryngotracheal Invasion: Eman A. Toraih, Jessan A. Jishu, Mohammad H. Hussein, Aly A. M. Shaalan, Manal S. Fawzy, Emad Kandil; Endocrinol Metab. 2025;40(2):201-215. Published online January 22, 2025; DOI: https://doi.org/10.3803/EnM.2024.2033

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Background
Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation.
Methods
This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients. Temporal trends and geographic variation in invasion rates were assessed. Logistic regression and propensity score matching were employed to identify predictors of secondary malignancy, mortality, and treatment impact on overall and thyroid cancer (TC)-specific survival.
Results
Of 131,721 WDTC patients, 1,662 (1.3%) had tracheal invasion and 976 (0.7%) had laryngeal invasion at diagnosis. Tracheal and laryngeal invasion rates declined from 3.7%–0.7% and 1.5%–0.6%, respectively, from 2000 to 2015. Compared to 98,835 noninvasive cases, patients with laryngotracheal invasion were older and more often male, Asian, and Hispanic (all P<0.001). This group had larger tumors with higher rates of nodal (N1: 61.8% vs. 15.1%) and distant metastases (M1: 9.3% vs. 0.4%). Age ≥55 years (hazard ratio [HR], 1.19; P=0.004) and metastases (HR, 1.75; P<0.001) increased TC-specific mortality, whereas the converse pattern was found for Asian race (HR, 0.63; P=0.002) and surgery (HR, 0.35; P<0.001). In rigorously matched groups to control confounding, adding radioactive iodine to surgery reduced mortality by 30% (P<0.001). However, external beam radiation and systemic therapy did not improve survival over surgery alone.
Conclusion
Laryngotracheal invasion is present in 0.7% to 1.3% of cases, conferring over double the mortality risk. Radioactive iodine with surgery improves outcomes in this aggressive WDTC subset.

Citations

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Thyroid cancer in Chinese military flight personnel: Characteristics and management advances
Yan Wang, Jing Liu, Chun-Xia Zhang, Guo-Li Gu
World Journal of Clinical Oncology.2026;[Epub] CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea: Jung A Kim, Kyeong Jin Kim, Jimi Choi, Kyoung Jin Kim, Eyun Song, Ji Hee Yu, Nam Hoon Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim; Endocrinol Metab. 2025;40(1):125-134. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2093

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Background
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Citations

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Treatment of Graves’ Disease: Faster Remission or Longer but Safe, That Is the Question
Chan-Hee Jung
Endocrinology and Metabolism.2025; 40(1): 70. CrossRef
Process to radioactive iodine treatment for Graves’ hyperthyroidism: condemned or absolved?
Luigi Bartalena, Daniela Gallo, George J. Kahaly, Eliana Piantanida, Maria Laura Tanda
Journal of Endocrinological Investigation.2025; 48(9): 1927. CrossRef

Thyroid
Prevalence of Subclinical Hypothyroidism in a Non-Diabetic Young Female Population and Its Impact on Diabetes and Cardiometabolic Risk: Nawoda Hewage, Udaya Wijesekara, Rasika Perera; Endocrinol Metab. 2024;39(6):864-876. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2015

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Background
We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes.
Methods
This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese).
Results
The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk.
Conclusion
SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.

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Increased Serum Lipopolysaccharide Levels are Related to a Higher Prevalent Risk of Subclinical Hypothyroidism
Xuan An, Xiaoyi Wang, Jin Zhang, Mingtong Xu, Muchao Wu, Suraiya Saleem
International Journal of Endocrinology.2025;[Epub] CrossRef
Incidence of Subclinical Hypothyroidism in Obese Adults and Its Metabolic Implications: A Prospective Cohort Study
Umer Jameel, Obaidullah Durrani, Ahmad Munib, Amanullah Khan
Cureus.2025;[Epub] CrossRef

Thyroid
Small Multi-Gene DNA Panel Can Aid in Reducing the Surgical Resection Rate and Predicting the Malignancy Risk of Thyroid Nodules: Moon Young Oh, Hye-Mi Choi, Jinsun Jang, Heejun Son, Seung Shin Park, Minchul Song, Yoo Hyung Kim, Sun Wook Cho, Young Jun Chai, Woosung Chung, Young Joo Park; Endocrinol Metab. 2024;39(5):777-792. Published online October 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.2034

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Background
We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules.
Methods
Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group).
Results
In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P<0.001), and indeterminate nodules (23.5% vs. 68.2%, P<0.001). Malignancy risk was significantly different between the panel and control groups (81.5% vs. 63.9%, P=0.008) for all nodules.
Conclusion
Our panel aids in managing thyroid nodules by providing information on malignancy risk based on mutations, potentially reducing unnecessary surgery in benign nodules or patients with less aggressive malignancies.

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Integrative multi-omics refines the molecular subtypes of thyroid cancers and enhances cancer-progression prediction: a retrospective cohort study
Yoo Hyung Kim, Joseph Wang, Jae-Kyung Won, Youngsoo Kim, Sun Wook Cho, Dohyun Han, Young Joo Park
International Journal of Surgery.2026;[Epub] CrossRef
Great Debate: Molecular Testing and Extent of Surgery in Well-Differentiated Thyroid Cancer
Cord Sturgeon, Ashok R. Shaha, Linwah Yip
Annals of Surgical Oncology.2025; 32(7): 4597. CrossRef
Prediction of malignancy risk in Bethesda III nodules: development and validation of multiple machine learning models
Wentian Li, Jiayu Zhu, Ying Wang, Jingxiu Li, Zhonghui Li, Cuicui Wang, Jingli Xue, Peng Zhou, Qingqing He
Frontiers in Endocrinology.2025;[Epub] CrossRef
Inside the Matrix: Integrated Cytology and Molecular Testing of Thyroid FNAC Samples Using a Commercial Synthetic 3D Scaffold
Diana Raluca Streinu, Dana Liana Stoian, Octavian Constantin Neagoe, Mihnea Derban, Paula Diana Ciordas, Catalin Marian
International Journal of Molecular Sciences.2025; 26(22): 11100. CrossRef

Thyroid
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration: Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim; Endocrinol Metab. 2024;39(4):579-589. Published online May 23, 2024; DOI: https://doi.org/10.3803/EnM.2024.1918

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Background
Changes in thyrotropin receptor antibody (TRAb) levels are associated with the clinical outcomes of Graves’ hyperthyroidism. However, the effects of the patterns of TRAb changes on patient prognosis according to the treatment duration of antithyroid drugs (ATDs) are not well established.
Methods
In this retrospective cohort study, 1,235 patients with Graves’ hyperthyroidism who were treated with ATDs for more than 12 months were included. Patients were divided into two groups according to treatment duration: group 1 (12–24 months) and group 2 (>24 months). Risk prediction models comprising age, sex, and either TRAb levels at ATD withdrawal (model A) or patterns of TRAb changes (model B) were compared.
Results
The median treatment duration in groups 1 (n=667, 54%) and 2 (n=568, 46%) was 17.3 and 37.1 months, respectively. The recurrence rate was significantly higher in group 2 (47.9%) than in group 1 (41.4%, P=0.025). Group 2 had significantly more goiter, thyroid eye disease, and fluctuating and smoldering type of TRAb pattern compared with group 1 (all P<0.001). The patterns of TRAb changes were an independent risk factor for recurrence after adjusting for other confounding factors in all patients, except in group 1. Integrated discrimination improvement and net reclassification improvement analyses showed that model B performed better than model A in all patients, except in group 1.
Conclusion
The dynamic risk model, including the patterns of TRAb changes, was more suitable for predicting prognosis in patients with Graves’ hyperthyroidism who underwent longer ATD treatment duration.

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Integrating shear wave elastography into clinical prediction of Graves’ disease recurrence: a novel risk scoring system
Xiao-Yun Zha, Ze-Hong Xu, Jia-Jia Dong, Liang-Xiao Xie, Peng-Bin Lai, Chang-Shun Wei, Hua-Qiang Zheng, Duo-Bin Huang, Jin-Zhi Wu
Frontiers in Endocrinology.2025;[Epub] CrossRef
Risk factors and outcomes of Graves’ orbitopathy after radioactive iodine therapy
Hwa Young Ahn, Jooyoung Lee, Mina Kim, Jeong Kyu Lee
Endocrine.2025; 90(1): 248. CrossRef
High TRAb Titer at Diagnosis Predicts Persistent Positivity and Relapse in Graves’ Disease after Prolonged Antithyroid Therapy
Zimiao Chen, Jinglu Xu, Wenrui Kang, Yang Zhang, Rujun Chen, Xiaohua Gong
Endocrinology and Metabolism.2025; 40(6): 950. CrossRef

Thyroid
Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review: Jee Hee Yoon, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2024;39(1):152-163. Published online January 22, 2024; DOI: https://doi.org/10.3803/EnM.2023.1794

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Background
Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).
Methods
Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.
Results
In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%–10.8% and 16.0%–25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%–1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.
Conclusion
AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

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Shared Decision-Making for Determining Treatment Strategies in Low-Risk Thyroid Cancer: Protocol of a Multicenter Cluster-Randomized Trial (MAeSTro-SDM)
Eun Kyung Lee, Min Joo Kim, Yul Hwangbo, Jae Hoon Moon, Sun Wook Cho, Young Jun Chai, June Young Choi, Yuh-Seog Jung, Kyu Eun Lee, Eun-Jae Chung, Kyungsik Kim, Su-jin Kim, Woochul Kim, Yoo Hyung Kim, Young Ki Lee, Jinsun Jang, Young Shin Song, Ka Hee Yi,
Journal of Korean Medical Science.2026;[Epub] CrossRef
Thyroid Nodules: Past, Present, and Future
Alan A. Parsa, Hossein Gharib
Endocrine Practice.2025; 31(1): 114. CrossRef
Approach to the Patient With Thyroid Cancer: Selection and Management of Candidates for Lobectomy
Eyal Robenshtok, Gideon Bachar, Amit Ritter
The Journal of Clinical Endocrinology & Metabolism.2025; 110(7): e2327. CrossRef
Navigating Active Surveillance for Low-Risk PTMC by Standardizing Ultrasound Evaluation: Key Takeaways from the Latest Korean Society of Thyroid Radiology Consensus Statements
Young Joo Park
Clinical Thyroidology®.2025; 37(1): 27. CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shin Je Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyo
International Journal of Thyroidology.2025; 18(1): 30. CrossRef
Global research landscape on active surveillance for papillary thyroid microcarcinoma: a bibliometric analysis
Dong-Shu Kang, Yu-Hao Lin, Jian-Qing Tian
Discover Oncology.2025;[Epub] CrossRef
Novel Technologies and Treatment Strategies in Thyroid Cancer Surgery
David Z. Allen, Mark Zafereo
Endocrinology and Metabolism Clinics of North America.2025; 54(3): 377. CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shinje Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyon
Endocrinology and Metabolism.2025; 40(3): 307. CrossRef
Risk factors for lateral neck lymph node metastasis in papillary thyroid ultra micro carcinoma with implications for active surveillance
Hyeung Kyoo Kim, Ho Jung Jeong, Jin Seok Lee, Soo Young Kim, Yong Sang Lee, Hang-Seok Chang
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From screening to follow-up: a review of quality of life and psychological status across the clinical care continuum in patients with differentiated thyroid cancer
Zifeng Kuang, Hao Zhao, Chenjia Zhang, Xiaoyi Li
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It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Kyeong Jin Kim
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Diabetes, obesity and metabolism
Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study: Joon Ho Moon, Yongkang Kim, Tae Jung Oh, Jae Hoon Moon, Soo Heon Kwak, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi, Nam H. Cho; Endocrinol Metab. 2023;38(4):406-417. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1703

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Background
While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.
Methods
Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD.
Results
Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs.
Conclusion
The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

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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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Journal of Clinical Medicine.2023; 12(22): 7169. CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Association among Current Smoking, Alcohol Consumption, Regular Exercise, and Lower Extremity Amputation in Patients with Diabetic Foot: Nationwide Population-Based Study: Yoon Jae Lee, Kyung-Do Han, Jun Hyeok Kim; Endocrinol Metab. 2022;37(5):770-780. Published online October 12, 2022; DOI: https://doi.org/10.3803/EnM.2022.1519

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Background
The present study investigates whether modifiable behavioral factors of current cigarette smoking, heavy alcohol consumption, and regular exercise are associated with risk of lower extremity amputation (LEA) in diabetic patients.
Methods
A total of 2,644,440 diabetic patients (aged ≥20 years) was analyzed using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios (HRs) for the behavioral factors with risk of LEA under adjustment for potential confounders.
Results
The risk of LEA was significantly increased by current cigarette smoking and heavy alcohol consumption (HR, 1.436; 95% confidence interval [CI], 1.367 to 1.508 and HR, 1.082; 95% CI, 1.011 to 1.158) but significantly decreased with regular exercise (HR, 0.745; 95% CI, 0.706 to 0.786) after adjusting for age, sex, smoking, alcohol consumption, exercise, low income, hypertension, dyslipidemia, body mass index, using insulin or oral antidiabetic drugs, and diabetic duration. A synergistically increased risk of LEA was observed with larger number of risky behaviors.
Conclusion
Modification of behaviors of current smoking, heavy alcohol intake, and exercise prevents LEA and can improve physical, emotional, and social quality of life in diabetic patients.

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Fatores associados à amputação de membros inferiores em pacientes diabéticos: uma abordagem epidemiológica
Edimar Chaves Junior, Ana Clara Paulino Queiroz, Arthur Felipe Vieira Bastos, Isadora Borges Toledo, Jessica Coelho Costa, Julien Barbosa, Lilian Nunes de Assis Lacerda, Marcos Bruno Couto Garcia, Maria Eduarda Avelina Bontempo, Maria Eduarda Mendes Reis,
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Are There Sex Differences in the Association of Alcohol Consumption With the Risk of Soft Tissue Sarcoma? A Nationwide Population-based Study in Korea
Min Wook Joo, Kyungdo Han, Yoon Joo Cho, Nicholas Matthew Bernthal, Ye Bin Park
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Knowledge, attitudes, and practices among patients with diabetic foot ulcers towards disease management
Liangxiao Xie, Changshun Wei, Liqun Chen, Huaqiang Zheng, Jiajia Dong, Jinzhi Wu
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Diabetes‐Associated Major Limb Amputation in Solomon Islands: A National, 5‐Year Retrospective Study
Dylan M. Bush, Adrian Garcia Hernandez, Anita Pickard, Thomas H. Fitzpatrick, Rooney Jagilly, Micky Olangi, Michael Buin, Johanna Roth, Hendrick Kaniki, Jones Ghabu, Tony Quity, Alexandra L. Martiniuk
World Journal of Surgery.2025; 49(8): 2266. CrossRef
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
Endocrinology and Metabolism.2025; 40(4): 574. CrossRef
Nationwide study of income-based disparities in diabetic limb preservation in South Korea
Yoon Jae Lee, Kyung-Do Han, Jun Hyeok Kim
Scientific Reports.2025;[Epub] CrossRef
Adjuvant effect of antimicrobial photodynamic therapy (aPDT) in the treatment of diabetic foot ulcers: A case series
Rita de Cassia Ferreira, Rebeca Boltes Cecatto, Silvana Torres Perez, Raquel Agnelli Mesquita‐Ferrari, Sandra Kalil Bussadori, Cinthya Cosme Duran, Anna Carolina Tempestini Horliana, Kristianne Porta Santos Fernandes
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Factors associated with diabetic foot ulcers and lower limb amputations in type 1 and type 2 diabetes supported by real‐world data from the German/Austrian DPV registry
Alexander J. Eckert, Stefan Zimny, Marcus Altmeier, Ana Dugic, Anton Gillessen, Latife Bozkurt, Gabriele Götz, Wolfram Karges, Frank J. Wosch, Stephan Kress, Reinhard W. Holl
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Patients with diabetic foot ulcers: A qualitative study of patient knowledge, experience, and encountered obstacles
Vahide Semerci Çakmak, Serap Çetinkaya Özdemir
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A randomized controlled trial of an app-based intervention on physical activity and glycemic control in people with type 2 diabetes
Gyuri Kim, Seohyun Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
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Magdalena Walicka, Arkadiusz Krysiński, Giusy Rita Maria La Rosa, Ang Sun, Davide Campagna, Agostino Di Ciaula, Tabinda Dugal, Andre Kengne, Phuong Le Dinh, Anoop Misra, Riccardo Polosa, Syed Abbas Raza, Cristina Russo, Roberta Sammut, Noel Somasundaram
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Visceral Adiposity as an Independent Risk Factor for Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus: A Retrospective Study
Rui-Ling Wu, Niyao Chen, Yanni Chen, Xiaohong Wu, Chih-Yuan Ko, Xiao-Yu Chen, Takayuki Masaki
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Age Characteristics of Patients With Type 2 Diabetic Foot Ulcers and Predictive Risk Factors for Lower Limb Amputation: A Population‐Based Retrospective Study
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Mineral, Bone & Muscle
Development of a Spine X-Ray-Based Fracture Prediction Model Using a Deep Learning Algorithm: Sung Hye Kong, Jae-Won Lee, Byeong Uk Bae, Jin Kyeong Sung, Kyu Hwan Jung, Jung Hee Kim, Chan Soo Shin; Endocrinol Metab. 2022;37(4):674-683. Published online August 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1461

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Background
Since image-based fracture prediction models using deep learning are lacking, we aimed to develop an X-ray-based fracture prediction model using deep learning with longitudinal data.
Methods
This study included 1,595 participants aged 50 to 75 years with at least two lumbosacral radiographs without baseline fractures from 2010 to 2015 at Seoul National University Hospital. Positive and negative cases were defined according to whether vertebral fractures developed during follow-up. The cases were divided into training (n=1,416) and test (n=179) sets. A convolutional neural network (CNN)-based prediction algorithm, DeepSurv, was trained with images and baseline clinical information (age, sex, body mass index, glucocorticoid use, and secondary osteoporosis). The concordance index (C-index) was used to compare performance between DeepSurv and the Fracture Risk Assessment Tool (FRAX) and Cox proportional hazard (CoxPH) models.
Results
Of the total participants, 1,188 (74.4%) were women, and the mean age was 60.5 years. During a mean follow-up period of 40.7 months, vertebral fractures occurred in 7.5% (120/1,595) of participants. In the test set, when DeepSurv learned with images and clinical features, it showed higher performance than FRAX and CoxPH in terms of C-index values (DeepSurv, 0.612; 95% confidence interval [CI], 0.571 to 0.653; FRAX, 0.547; CoxPH, 0.594; 95% CI, 0.552 to 0.555). Notably, the DeepSurv method without clinical features had a higher C-index (0.614; 95% CI, 0.572 to 0.656) than that of FRAX in women.
Conclusion
DeepSurv, a CNN-based prediction algorithm using baseline image and clinical information, outperformed the FRAX and CoxPH models in predicting osteoporotic fracture from spine radiographs in a longitudinal cohort.

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Mir Sadat-Ali, Bandar A Alzahrani, Turki S Alqahtani, Musaad A Alotaibi, Abdallah M Alhalafi, Ahmed A Alsousi, Abdullah M Alasiri
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Namki Hong, Sang Wouk Cho, Young Han Lee, Chang Oh Kim, Hyeon Chang Kim, Yumie Rhee, William D Leslie, Steven R Cummings, Kyoung Min Kim
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Diabetes, Obesity and Metabolism
The Presence of Clonal Hematopoiesis Is Negatively Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes: Tae Jung Oh, Han Song, Youngil Koh, Sung Hee Choi; Endocrinol Metab. 2022;37(2):243-248. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1337

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Background
Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to be associated with increased cardiovascular disease, aging and insulin resistance. Despite the debate of causal contribution of CHIP on metabolic diseases, we want to explore whether CHIP is related to diabetic peripheral neuropathy (DPN).
Methods
This study analyzed the prevalence of CHIP in patients with type 2 diabetes classified according to DPN status. Logistic regression analysis was used to evaluate the association between CHIP and DPN.
Results
CHIP was more prevalent in subjects without DPN than those with DPN (19.9% vs. 8.8%, respectively; P=0.013). Individuals having any CHIP, or DNA methyltransferase 3A (DNMT3A) CHIP were less likely to have any abnormality shown in DPN test; the adjusted odds ratio were 0.85 (95% confidence interval [CI], 0.73 to 1.00) and 0.70 (95% CI, 0.56 to 0.89), respectively. Interestingly, DNMT3A CHIP showed the negative association, but Tet methylcytosine dioxygenase 2 (TET2) CHIP showed the positive association with abnormal feet electrochemical skin conductance level.
Conclusion
On the contrary to expectations, CHIP was negatively associated with DPN. Functional linking between the mutation in hematopoietic cells and DPN, and the opposite role of DNMT3A and TET2 should be investigated.

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Clonal Hematopoiesis of Indeterminate Potential and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Cohort Study
Jiahe Wei, Yuefeng Yu, Hanzhang Wu, Yingjun Li, Ningjian Wang, Xiao Tan
Diabetes.2025; 74(4): 585. CrossRef
Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases
Jing-Lei Zhang, Shuo-Lan Tong, Qi-Qi Zhuang, Sheng-Jie Jin, Jia-Qiu Li, Jie Sun
Military Medical Research.2025;[Epub] CrossRef
Clonal Hematopoiesis of Indeterminate Potential and Cardiometabolic Disease: Challenges, Controversies and Future Perspectives
Ioanna A. Anastasiou, Dimitris Kounatidis, Natalia G. Vallianou, Eleni Rebelos, Irene Karampela, Maria Dalamaga
International Journal of Molecular Sciences.2025; 27(1): 233. CrossRef
TET2 mutation as prototypic clonal hematopoiesis lesion
Luca Guarnera, Babal K. Jha
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Clonal hematopoiesis with DNMT3A mutation is associated with lower white matter hyperintensity volume
Woo‐Jin Lee, Keun‐Hwa Jung, Han Song, Heesun Lee, Hyo Eun Park, Youngil Koh, Su‐Yeon Choi, Kyung‐Il Park
CNS Neuroscience & Therapeutics.2023; 29(5): 1243. 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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Yanyan Xuan, Fangfang He, Qing Liu, Dandan Dai, Dingting Wu, Yanmei Shi, Qi Yao
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Frontiers in Endocrinology.2025;[Epub] CrossRef
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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.2024; 31(6): 931. CrossRef
Risk Factors for Colorectal Adenoma and Cancer in Comprehensive Health Checkups: Usefulness of Gamma-Glutamyltransferase
Yoko Yamanouchi, Maiko Osawa, Takaaki Senbonmatsu, Yuki Shiko, Yohei Kawasaki, Toshihiro Muramatsu
Journal of Personalized Medicine.2024; 14(11): 1082. 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
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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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Review Articles

Mineral, Bone & Muscle
Review and Update of the Risk Factors and Prevention of Antiresorptive-Related Osteonecrosis of the Jaw: Ha Young Kim; Endocrinol Metab. 2021;36(5):917-927. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1170

13,801 View
380 Download
23 Web of Science
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Abstract PDF PubReader ePub

Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but serious adverse event of bisphosphonate or denosumab administration; it is associated with severe pain and a deteriorated quality of life. Since its first report in 2003, there have been many studies on its definition, epidemiology, pathophysiology, diagnosis, and treatment. Nevertheless, the epidemiology and mechanisms underlying this condition have not yet been fully delineated and several risk factors are known. Moreover, as there is no effective treatment currently available for osteonecrosis of the jaw, prevention is essential. Furthermore, close cooperation between prescribing physicians and dentists is important. The aim of this review was to provide up-to-date information regarding the risk factors and prevention of ARONJ from a physician’s perspective.

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Obesity and Metabolism
An Update on Contraception in Polycystic Ovary Syndrome: Seda Hanife Oguz, Bulent Okan Yildiz; Endocrinol Metab. 2021;36(2):296-311. Published online April 15, 2021; DOI: https://doi.org/10.3803/EnM.2021.958

35,241 View
1,170 Download
46 Web of Science
52 Crossref

Abstract PDF PubReader ePub

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology. Combined oral contraceptives (COCs), along with lifestyle modifications, represent the first-line medical treatment for the long-term management of PCOS. Containing low doses of estrogen and different types of progestin, COCs restore menstrual cyclicity, improve hyperandrogenism, and provide additional benefits such as reducing the risk of endometrial cancer. However, potential cardiometabolic risk associated with these agents has been a concern. COCs increase the risk of venous thromboembolism (VTE), related both to the dose of estrogen and the type of progestin involved. Arterial thrombotic events related to COC use occur much less frequently, and usually not a concern for young patients. All patients diagnosed with PCOS should be carefully evaluated for cardiometabolic risk factors at baseline, before initiating a COC. Age, smoking, obesity, glucose intolerance or diabetes, hypertension, dyslipidemia, thrombophilia, and family history of VTE should be recorded. Patients should be re-assessed at consecutive visits, more closely if any baseline cardiometabolic risk factor is present. Individual risk assessment is the key in order to avoid unfavorable outcomes related to COC use in women with PCOS.

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Original Articles

Clinical Study
Development of a Non-Invasive Liver Fibrosis Score Based on Transient Elastography for Risk Stratification in Patients with Type 2 Diabetes: Chi-Ho Lee, Wai-Kay Seto, Kelly Ieong, David T.W. Lui, Carol H.Y. Fong, Helen Y. Wan, Wing-Sun Chow, Yu-Cho Woo, Man-Fung Yuen, Karen S.L. Lam; Endocrinol Metab. 2021;36(1):134-145. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.887

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Background
In non-alcoholic fatty liver disease (NAFLD), transient elastography (TE) is an accurate non-invasive method to identify patients at risk of advanced fibrosis (AF). We developed a diabetes-specific, non-invasive liver fibrosis score based on TE to facilitate AF risk stratification, especially for use in diabetes clinics where TE is not readily available.
Methods
Seven hundred sixty-six adults with type 2 diabetes and NAFLD were recruited and randomly divided into a training set (n=534) for the development of diabetes fibrosis score (DFS), and a testing set (n=232) for internal validation. DFS identified patients with AF on TE, defined as liver stiffness (LS) ≥9.6 kPa, based on a clinical model comprising significant determinants of LS with the lowest Akaike information criteria. The performance of DFS was compared with conventional liver fibrosis scores (NFS, FIB-4, and APRI), using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values (NPV).
Results
DFS comprised body mass index, platelet, aspartate aminotransferase, high-density lipoprotein cholesterol, and albuminuria, five routine measurements in standard diabetes care. Derived low and high DFS cut-offs were 0.1 and 0.3, with 90% sensitivity and 90% specificity, respectively. Both cut-offs provided better NPVs of >90% than conventional fibrosis scores. The AUROC of DFS for AF on TE was also higher (P<0.01) than the conventional fibrosis scores, being 0.85 and 0.81 in the training and testing sets, respectively.
Conclusion
Compared to conventional fibrosis scores, DFS, with a high NPV, more accurately identified diabetes patients at-risk of AF, who need further evaluation by hepatologists.

Citations

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Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes—A real‐world study
Chi‐Ho Lee, David Tak‐Wai Lui, Lung‐Yi Mak, Carol Ho‐Yi Fong, Kylie Sze‐Wing Chan, Jimmy Ho‐Cheung Mak, Chloe Yu‐Yan Cheung, Wing‐Sun Chow, Yu‐Cho Woo, Man‐Fung Yuen, Wai‐Kay Seto, Karen Siu‐Ling Lam
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Moving diagnosis of liver fibrosis into the community
Elisa Pose, Salvatore Piano, Maja Thiele, Núria Fabrellas, Emmanuel A. Tsochatzis, Pere Ginès
Journal of Hepatology.2025; 83(1): 258. CrossRef
Implementation of a liver health check in people with type 2 diabetes
Kushala W M Abeysekera, Luca Valenti, Zobair Younossi, John F Dillon, Alina M Allen, Mazen Noureddin, Mary E Rinella, Frank Tacke, Sven Francque, Pere Ginès, Maja Thiele, Philip N Newsome, Indra Neil Guha, Mohammed Eslam, Jörn M Schattenberg, Saleh A Alqa
The Lancet Gastroenterology & Hepatology.2024; 9(1): 83. CrossRef
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease
Chi-Ho Lee, David Tak-Wai Lui, Raymond Hang-Wun Li, Michele Mae-Ann Yuen, Carol Ho-Yi Fong, Ambrose Pak-Wah Leung, Justin Chiu-Man Chu, Loey Lung-Yi Mak, Tai-Hing Lam, Jean Woo, Yu-Cho Woo, Aimin Xu, Hung-Fat Tse, Kathryn Choon-Beng Tan, Bernard Man-Yung
Frontiers in Endocrinology.2023;[Epub] CrossRef
Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review
Luca Rinaldi, Chiara Giorgione, Andrea Mormone, Francesca Esposito, Michele Rinaldi, Massimiliano Berretta, Raffaele Marfella, Ciro Romano
Viruses.2023; 15(8): 1730. CrossRef
Metabolic dysfunction-associated fatty liver disease — How relevant is this to primary care physicians and diabetologists?
Chi-Ho Lee
Primary Care Diabetes.2022; 16(2): 245. CrossRef
Non‐alcoholic fatty liver disease and type 2 diabetes: An update
Chi‐H Lee, David TW Lui, Karen SL Lam
Journal of Diabetes Investigation.2022; 13(6): 930. CrossRef
Ultrasound-Based Hepatic Elastography in Non-Alcoholic Fatty Liver Disease: Focus on Patients with Type 2 Diabetes
Georgiana-Diana Cazac, Cristina-Mihaela Lăcătușu, Cătălina Mihai, Elena-Daniela Grigorescu, Alina Onofriescu, Bogdan-Mircea Mihai
Biomedicines.2022; 10(10): 2375. 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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Overcoming Missing Data: Accurately Predicting Cardiovascular Risk in Type 2 Diabetes, A Systematic Review
Wenhui Ren, Keyu Fan, Zheng Liu, Yanqiu Wu, Haiyan An, Huixin Liu
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Development and validation of prediction models for stroke and myocardial infarction in type 2 diabetes based on health insurance claims: does machine learning outperform traditional regression approaches?
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Diabetes Research and Clinical Practice.2024; 209: 111574. CrossRef
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Archives of Public Health.2024;[Epub] 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
Serum/plasma biomarkers and the progression of cardiometabolic multimorbidity: a systematic review and meta-analysis
Yichen Jin, Ziyuan Xu, Yuting Zhang, Yue Zhang, Danyang Wang, Yangyang Cheng, Yaguan Zhou, Muhammad Fawad, Xiaolin Xu
Frontiers in Public Health.2023;[Epub] CrossRef
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
Journal of Lipid and Atherosclerosis.2022; 11(1): 73. CrossRef
Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality
Kyung-Soo Kim, Sangmo Hong, You-Cheol Hwang, Hong-Yup Ahn, Cheol-Young Park
Journal of General Internal Medicine.2022; 37(16): 4153. CrossRef
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
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Nonalcoholic fatty liver disease and the risk of insulin-requiring gestational diabetes
Sang Youn You, Kyungdo Han, Seung-Hawn Lee, Mee Kyoung Kim
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Clinical Study
Achievement of LDL-C Targets Defined by ESC/EAS (2011) Guidelines in Risk-Stratified Korean Patients with Dyslipidemia Receiving Lipid-Modifying Treatments: Ye Seul Yang, Seo Young Lee, Jung-Sun Kim, Kyung Mook Choi, Kang Wook Lee, Sang-Chol Lee, Jung Rae Cho, Seung-Jin Oh, Ji-Hyun Kim, Sung Hee Choi; Endocrinol Metab. 2020;35(2):367-376. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.367

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Background
This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs).
Methods
In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed.
Results
Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators’ assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients’ LDL-C levels was the primary reason for non-intensification of statin therapy.
Conclusion
Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.

Citations

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Effects of statin use on serum creatinine phosphokinase levels in normal thyroid function
Jeonghoon Ha, Joonyub Lee, Jin Yu, Hakyoung Park, Jiwon Shinn, Seung-Hwan Lee, Jae-Hyoung Cho, Hun-Sung Kim
The Korean Journal of Internal Medicine.2024; 39(4): 650. CrossRef
Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
Journal of Lipid and Atherosclerosis.2023; 12(1): 12. CrossRef
Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
Diabetes & Metabolism Journal.2023; 47(1): 1. CrossRef
Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion
Jagdish Hiremath, J C Mohan, Prakash Hazra, JP S Sawhney, Ashwani Mehta, Sadanand Shetty, Abraham Oomman, Mahesh K Shah, Ganapathi Bantwal, Rajeev Agarwal, Rajiv Karnik, Peeyush Jain, Saumitra Ray, Sambit Das, Vibhuti Jadhao, Sachin Suryawanshi, Hanmant B
Cureus.2023;[Epub] CrossRef
Optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines in patients with and without atherosclerotic cardiovascular disease across Europe: a simulation based on the DA VINCI study
Julia Brandts, Sarah Bray, Guillermo Villa, Alberico L. Catapano, Neil R. Poulter, Antonio J. Vallejo-Vaz, Kausik K. Ray
The Lancet Regional Health - Europe.2023; 31: 100665. CrossRef
Management of Dyslipidemia in Patients with Diabetes Mellitus
Kyung Ae Lee
The Journal of Korean Diabetes.2023; 24(3): 111. CrossRef
Target Low-Density Lipoprotein-Cholesterol and Secondary Prevention for Patients with Acute Myocardial Infarction: A Korean Nationwide Cohort Study
Ju Hyeon Kim, Jung-Joon Cha, Subin Lim, Jungseok An, Mi-Na Kim, Soon Jun Hong, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Do-Sun Lim, Kyeongmin Byeon, Sang-Wook Kim, Eun-Seok Shin, Kwang Soo Cha, Jei Keon Chae, Youngkeun Ahn, Myung Ho Jeong, Tae Hoo
Journal of Clinical Medicine.2022; 11(9): 2650. CrossRef
Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin Yun, In-Kyung Jeong, Jin-Hye Cha, Juneyoung Lee, Ho Chan Cho, Sung Hee Choi, SungWan Chun, Hyun Jeong Jeon, Ho-Cheol Kang, Sang Soo Kim, Seung-Hyun Ko, Gwanpyo Koh, Su Kyoung Kwon, Jae Hyuk Lee, Min Kyong Moon, Junghyun Noh, Cheol-Young Park, Sung
Diabetes & Metabolism Journal.2022; 46(3): 464. CrossRef
There is urgent need to treat atherosclerotic cardiovascular disease risk earlier, more intensively, and with greater precision: A review of current practice and recommendations for improved effectiveness
Michael E. Makover, Michael D. Shapiro, Peter P. Toth
American Journal of Preventive Cardiology.2022; 12: 100371. CrossRef
Non-achievement of the Low-Density Lipoprotein Cholesterol Goal in Older Patients with Type 2 Diabetes Mellitus and a Very High Cardiovascular Disease Risk: A Multicenter Study in Vietnam
Huan Thanh Nguyen, Khang Pham Trong Ha, An Huu Nguyen, Thu Thanh Nguyen, Hang My Lam
Annals of Geriatric Medicine and Research.2021; 25(4): 278. CrossRef

Clinical Study
Low Predictive Value of FRAX Adjusted by Trabecular Bone Score for Osteoporotic Fractures in Korean Women: A Community-Based Cohort Study: Hana Kim, Jung Hee Kim, Min Joo Kim, A Ram Hong, HyungJin Choi, EuJeong Ku, Ji Hyun Lee, Chan Soo Shin, Nam H. Cho; Endocrinol Metab. 2020;35(2):359-366. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.359

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Background
The value of the Fracture Risk Assessment Tool (FRAX) and the trabecular bone score (TBS) for assessing osteoporotic fracture risk has not been fully elucidated in Koreans. We conducted this study to clarify the predictive value of FRAX adjusted by TBS for osteoporotic fractures in Korean women.
Methods
After screening 7,192 eligible subjects from the Ansung cohort, 1,165 women aged 45 to 76 years with available bone mineral density (BMD) and TBS data were enrolled in this study. We assessed their clinical risk factors for osteoporotic fractures and evaluated the predictive value of FRAX with or without BMD and TBS.
Results
During the mean follow-up period of 7.5 years, 99 (8.5%) women suffered major osteoporotic fractures (MOFs) and 28 (2.4%) experienced hip fractures. FRAX without BMD, BMD-adjusted FRAX, and TBS-adjusted FRAX were significantly associated with the risk of MOFs (hazard ratio [HR] per percent increase, 1.08; 95% confidence interval [CI], 1.03 to 1.14; HR, 1.09; 95% CI, 1.03 to 1.15; and HR, 1.07; 95% CI, 1.02 to 1.13, respectively). However, BMD-adjusted FRAX and TBS-adjusted FRAX did not predict MOFs better than FRAX without BMD based on the Harrell’s C statistic. FRAX probabilities showed limited value for predicting hip fractures. The cut-off values of FRAX without BMD, FRAX with BMD, and FRAX with BMD adjusted by TBS for predicting MOFs were 7.2%, 5.0%, and 6.7%, respectively.
Conclusion
FRAX with BMD and TBS adjustment did not show better predictive value for osteoporotic fractures in this study than FRAX without adjustment. Moreover, the cut-off values of FRAX probabilities for treatment might be lower in Korean women than in other countries.

Citations

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Update on the utility of trabecular bone score (TBS) in clinical practice for the management of osteoporosis: a systematic review by the Egyptian Academy of Bone and Muscle Health
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Egyptian Rheumatology and Rehabilitation.2024;[Epub] CrossRef
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Michelle Gates, Jennifer Pillay, Megan Nuspl, Aireen Wingert, Ben Vandermeer, Lisa Hartling
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Sung Hye Kong, Ae Jeong Jo, Chan Mi Park, Kyun Ik Park, Ji Eun Yun, Jung Hee Kim
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Review Articles

Diabetes
Recent Updates on Vascular Complications in Patients with Type 2 Diabetes Mellitus: Chan-Hee Jung, Ji-Oh Mok; Endocrinol Metab. 2020;35(2):260-271. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.260

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It is well known that patients with type 2 diabetes mellitus (T2DM) are at an increased risk of morbidity and mortality from atherosclerotic cardiovascular (CV) complications. Previously, the concept that diabetes mellitus (DM) is a “coronary artery disease (CAD) risk equivalent” was widely accepted, implying that all DM patients should receive intensive management. However, considerable evidence exist for wide heterogeneity in the risk of CV events among T2DM patients and the concept of a “CAD risk equivalent” has changed. Recent guidelines recommend further CV risk stratification in T2DM patients, with treatment tailored to the risk level. Although imaging modalities for atherosclerotic cardiovascular disease (ASCVD) have been used to improve risk prediction, there is currently no evidence that imaging-oriented therapy improves clinical outcomes. Therefore, controversy remains whether we should screen for CVD in asymptomatic T2DM. The coexistence of T2DM and heart failure (HF) is common. Based on recent CV outcome trials, sodium glucose cotransporter-2 inhibitors and glucagon like peptide-1 receptor agonists are recommended who have established ASCVD, indicators of high risk, or HF because of their demonstrated benefits for CVD. These circumstances have led to an increasing emphasis on ASCVD and HF in T2DM patients. In this review, we examine the literature published within the last 5 years on the risk assessment of CVD in asymptomatic T2DM patients. In particular, we review recent guidelines regarding screening for CVD and research focusing on the role of coronary artery calcium, coronary computed tomography angiography, and carotid intima-media thickness in asymptomatic T2DM patients.

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Diabetes
Prevalence and Current Management of Cardiovascular Risk Factors in Korean Adults Based on Fact Sheets: Eun-Jung Rhee; Endocrinol Metab. 2020;35(1):85-94. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.85

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Korea is currently an aged society and is on the cusp of becoming a superaged society in a few years. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. In 2018, the prevalence of obesity in Korea was 35.7% (men, 45.4%; women, 26.5%) according to the Obesity Fact Sheet 2019, based on National Health Insurance Corporation medical checkup data. In 2016, the prevalence of diabetes was 14.4% in Koreans older than 30 years according to the Diabetes Fact Sheet published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2018 was 28.3% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2018 was 40.5% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations.

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Mineral, Bone & Muscle
Potential Biomarkers to Improve the Prediction of Osteoporotic Fractures: Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh; Endocrinol Metab. 2020;35(1):55-63. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.55

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Osteoporotic fracture (OF) is associated with high disability and morbidity rates. The burden of OF may be reduced by early identification of subjects who are vulnerable to fracture. Although the current fracture risk assessment model includes clinical risk factors (CRFs) and bone mineral density (BMD), its overall ability to identify individuals at high risk for fracture remains suboptimal. Efforts have therefore been made to identify potential biomarkers that can predict the risk of OF, independent of or combined with CRFs and BMD. This review highlights the emerging biomarkers of bone metabolism, including sphongosine-1-phosphate, leucine-rich repeat-containing 17, macrophage migration inhibitory factor, sclerostin, receptor activator of nuclear factor-κB ligand, and periostin, and the importance of biomarker risk score, generated by combining these markers, in enhancing the accuracy of fracture prediction.

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Thyroid
Management of Low-Risk Papillary Thyroid Cancer: Nicole M. Iñiguez-Ariza, Juan P. Brito; Endocrinol Metab. 2018;33(2):185-194. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.185

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The incidence of thyroid cancer has increased, mainly due to the incidental finding of low-risk papillary thyroid cancers (PTC). These malignancies grow slowly, and are unlikely to cause morbidity and mortality. New understanding about the prognosis of tumor features has led to reclassification of many tumors within the low-risk thyroid category, and to the development of a new one “very low-risk tumors.” Alternative less aggressive approaches to therapy are now available including active surveillance and minimally invasive interventions. In this narrative review, we have summarized the available evidence for the management of low-risk PTC.

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Original Article

Clinical Study
Disease-Specific Mortality of Differentiated Thyroid Cancer Patients in Korea: A Multicenter Cohort Study: Min Ji Jeon, Won Gu Kim, Tae Hyuk Kim, Hee Kyung Kim, Bo Hyun Kim, Hyon-Seung Yi, Eun Sook Kim, Hosu Kim, Young Nam Kim, Eun Heui Kim, Tae Yong Kim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2017;32(4):434-441. Published online November 22, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.4.434

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Background

Little is known regarding disease-specific mortality of differentiated thyroid cancer (DTC) patients and its risk factors in Korea.

Methods

We retrospectively reviewed a large multi-center cohort of thyroid cancer from six Korean hospitals and included 8,058 DTC patients who underwent initial surgery between 1996 and 2005.

Results

Mean age of patients at diagnosis was 46.2±12.3 years; 87% were females. Most patients had papillary thyroid cancer (PTC; 97%) and underwent total thyroidectomy (85%). Mean size of the primary tumor was 1.6±1.0 cm. Approximately 40% of patients had cervical lymph node (LN) metastases and 1.3% had synchronous distant metastases. During 11.3 years of follow-up, 150 disease-specific mortalities (1.9%) occurred; the 10-year disease-specific survival (DSS) rate was 98%. According to the year of diagnosis, the number of disease-specific mortality was not different. However, the rate of disease-specific mortality decreased during the study period (from 7.7% to 0.7%). Older age (≥45 years) at diagnosis, male, follicular thyroid cancer (FTC) versus PTC, larger tumor size (>2 cm), presence of extrathyroidal extension (ETE), lateral cervical LN metastasis, distant metastasis and tumor node metastasis (TNM) stage were independent risk factors of disease-specific mortality of DTC patients.

Conclusion

The rate of disease-specific mortality of Korean DTC patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN metastasis, distant metastasis, and TNM stages were significant risk factors of disease-specific mortality of Korean DTC patients.

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Review Article

Calcium and Cardiovascular Disease: Ian R. Reid, Sarah M. Birstow, Mark J. Bolland; Endocrinol Metab. 2017;32(3):339-349. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.339

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Circulating calcium is a risk factor for vascular disease, a conclusion arising from prospective studies involving hundreds of thousands of participants and extending over periods of up to 30 years. These associations may be partially mediated by other cardiovascular risk factors such as circulating lipid levels, blood pressure, and body mass index, but there appears to be a residual independent effect of serum calcium. Polymorphisms of the calcium-sensing receptor associated with small elevations of serum calcium are also associated with cardiovascular disease, suggesting that calcium plays a causative role. Trials of calcium supplements in patients on dialysis and those with less severe renal failure demonstrate increased mortality and/or acceleration of vascular disease, and meta-analyses of trials in those without overt renal disease suggest a similar adverse effect. Interpretation of the latter trials is complicated by a significant interaction between baseline use of calcium supplements and the effect of randomisation to calcium in the largest trial. Restriction of analysis to those who are calcium-naive demonstrates a consistent adverse effect. Observational studies of dietary calcium do not demonstrate a consistent adverse effect on cardiovascular health, though very high or very low intakes may be deleterious. Thus, obtaining calcium from the diet rather than supplements is to be encouraged.

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Original Articles

Utility of the Visceral Adiposity Index and Hypertriglyceridemic Waist Phenotype for Predicting Incident Hypertension: Mohsen Janghorbani, Mohammad Reza Salamat, Ashraf Aminorroaya, Masoud Amini; Endocrinol Metab. 2017;32(2):221-229. Published online May 19, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.221

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Abstract PDF PubReader

Background

The aim of this study was to assess the utility of the visceral adiposity index (VAI) and the hypertriglyceridemic waist (HTGW) phenotype as possible hypertension (HTN) predictors in a high-risk population without diabetes and HTN.

Methods

Incident HTN over a 7-year follow-up was assessed among 1,375 first-degree non-diabetic and non-hypertensive relatives of consecutive patients with type 2 diabetes who were 30 to 70 years of age. HTN was defined as a blood pressure reading ≥140/90 mm Hg or the use of antihypertensive medications. We examined the incidence of HTN across VAI quintiles and four groups defined according to baseline fasting serum triglyceride (TG) levels and waist circumference (WC).

Results

The VAI and the HTGW phenotype at baseline were related to an increased risk for HTN. In comparison with the lowest VAI quintile, the highest VAI quintile showed a significant associated with HTN in an age- and gender-adjusted model (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.07 to 2.55). Those with HTGW were 2.3 times (OR, 2.27; 95% CI, 1.54 to 3.35) more likely to develop HTN than those with a normal WC and normal TG levels.

Conclusion

Greater VAI values weakly predicted HTN, whereas the HTGW phenotype was a stronger predictor of incident HTN in an Iranian high-risk population.

Citations

Citations to this article as recorded by

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World Journal of Diabetes.2020; 11(5): 202. CrossRef
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Letter: Utility of the Visceral Adiposity Index and Hypertriglyceridemic Waist Phenotype for Predicting Incident Hypertension (Endocrinol Metab 2017;32:221-9, Mohsen Janghorbani et al.)
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Clinical Study
Urinary Albumin Excretion Reflects Cardiovascular Risk in Postmenopausal Women without Diabetes: The 2011 to 2013 Korean National Health and Nutrition Examination Survey: Hee Jung Ahn, Do Sik Moon, Da Yeong Kang, Jung In Lee, Da Young Kim, Jin Hwa Kim, Sang Yong Kim, Hak Yeon Bae; Endocrinol Metab. 2016;31(4):537-546. Published online November 3, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.537

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Background

The objective of the current study was to determine whether there was an association between urinary albumin excretion and cardiovascular disease (CVD) risk by estimating the Framingham Risk Score (FRS) in postmenopausal women without diabetes.

Methods

This study was based on data from the Korea National Health and Nutrition Examination Survey, which was conducted by the Korean Ministry of Health and Welfare in 2011 to 2013. Data on 2,316 postmenopausal women from a total of 24,594 participants was included in the analysis.

Results

The mean FRS was significantly different in each of the urinary albumin to creatinine ratio (UACR) subgroups, and it increased with UACR. The FRS was 12.69±0.12 in the optimal group, 14.30±0.19 in the intermediate normal group, 14.62±0.26 in the high normal group, and 15.86±0.36 in the microalbuminuria group. After fully adjusting for potential confounding factors, high normal levels and microalbuminuria were significantly associated with the highest tertile of FRS ([odds ratio (OR), 1.642; 95% confidence interval (CI), 1.124 to 2.400] and [OR, 3.385; 95% CI, 2.088 to 5.488], respectively) compared with the optimal subgroup. High normal levels and microalbuminuria were also significantly associated with a ≥10% 10-year risk of CVD ([OR, 1.853; 95% CI, 1.122 to 3.060] and [OR, 2.831; 95% CI, 1.327 to 6.037], respectively) after adjusting for potential confounding covariates.

Conclusion

Urinary albumin excretion reflects CVD risk in postmenopausal women without diabetes, and high normal levels and microalbuminuria were independently associated with a higher risk of CVD.

Citations

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Review Article

Endocrine Risk Factors for Cognitive Impairment: Jae Hoon Moon; Endocrinol Metab. 2016;31(2):185-192. Published online April 25, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.185

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Cognitive impairment, including Alzheimer's disease and other kinds of dementia, is a major health problem in older adults worldwide. Although numerous investigators have attempted to develop effective treatment modalities or drugs, there is no reasonably efficacious strategy for preventing or recovering from cognitive impairment. Therefore, modifiable risk factors for cognitive impairment have received attention, and the growing literature of metabolic risk factors for cognitive impairment has expanded from epidemiology to molecular pathogenesis and therapeutic management. This review focuses on the epidemiological evidence for the association between cognitive impairment and several endocrine risk factors, including insulin resistance, dyslipidemia, thyroid dysfunction, vitamin D deficiency, and subclinical atherosclerosis. Researches suggesting possible mechanisms for this association are reviewed. The research investigating modifiable endocrine risk factors for cognitive impairment provides clues for understanding the pathogenesis of cognitive impairment and developing novel treatment modalities. However, so far, interventional studies investigating the beneficial effect of the "modification" of these "modifiable risk factors" on cognitive impairment have reported variable results. Therefore, well-designed, randomized prospective interventional studies are needed.

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Original Articles

Clinical Study
The Relationship between 10-Year Cardiovascular Risk Calculated Using the Pooled Cohort Equation and the Severity of Non-Alcoholic Fatty Liver Disease: Jeong In Lee, Min Chul Kim, Byung Sub Moon, Young Seok Song, Eun Na Han, Hyo Sun Lee, Yoonjeong Son, Jihyun Kim, Eun Jin Han, Hye-Jeong Park, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(1):86-92. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.86

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Background

We investigated the association between the severity of non-alcoholic fatty liver disease (NAFLD) and the estimated 10-year risk of cardiovascular disease (CVD) calculated by Pooled Cohort Equation (PCE) and Framingham risk score (FRS).

Methods

A total of 15,913 participants (mean age, 46.3 years) in a health screening program were selected for analysis. The presence and severity of fatty liver was assessed by abdominal ultrasonogram. Subjects who drank alcohol more than three times a week were excluded from the study.

Results

Among the participants, 57.6% had no NAFLD, 35.4% had grade I, 6.5% had grade II, and 0.5% had grade III NAFLD. Mean estimated 10-year CVD risk was 2.59%, 3.93%, 4.68%, and 5.23% calculated using the PCE (P for trend <0.01) and 4.55%, 6.39%, 7.33%, and 7.13% calculated using FRS, according to NAFLD severity from none to severe (P for trend <0.01). The odds ratio for ≥7.5% estimated CVD risk calculated using the PCE showed a higher correlation with increasing severity of NAFLD even after adjustment for conventional CVD risk factors (1.52, 2.56, 3.35 vs. the no NAFLD group as a reference, P<0.01) compared with calculated risk using FRS (1.65, 1.62, 1.72 vs. no NAFLD group as a reference, P<0.01).

Conclusion

In our study of apparently healthy Korean adults, increasing severity of NAFLD showed a higher correlation with estimated 10-year CVD risk when calculated using the PCE than when calculated using FRS.

Citations

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Obesity and Metabolism
Factors Associated with Glycemic Variability in Patients with Type 2 Diabetes: Focus on Oral Hypoglycemic Agents and Cardiovascular Risk Factors: Soyeon Yoo, Sang-Ouk Chin, Sang-Ah Lee, Gwanpyo Koh; Endocrinol Metab. 2015;30(3):352-360. Published online August 4, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.352

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Background

The role of glycemic variability (GV) in development of cardiovascular diseases remains controversial, and factors that determine glucose fluctuation in patients with diabetes are unknown. We investigated relationships between GV indices, kinds of oral hypoglycemic agents (OHAs), and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM).

Methods

We analyzed 209 patients with T2DM. The GV index (standard deviation [SD] and mean absolute glucose change [MAG]) were calculated from 7-point self-monitoring of blood glucose profiles. The patients were classified into four groups according to whether they take OHAs known as GV-lowering (A) and GV-increasing (B): 1 (A only), 2 (neither), 3 (both A and B), and 4 (B only). The 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Equations.

Results

GV indices were significantly higher in patients taking sulfonylureas (SUs), but lower in those taking dipeptidyl peptidase-4 inhibitors. In hierarchical regression analysis, the use of SUs remained independent correlates of the SD (β=0.209, P=0.009) and MAG (β=0.214, P=0.011). In four OHA groups, GV indices increased progressively from group 1 to group 4. However, these did not differ according to quartiles of 10-year ASCVD risk.

Conclusion

GV indices correlated significantly with the use of OHAs, particularly SU, and differed significantly according to combination of OHAs. However, cardiovascular risk factors and 10-year ASCVD risk were not related to GV indices. These findings suggest that GV is largely determined by properties of OHAs and not to cardiovascular complications in patients with T2DM.

Citations

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Obesity and Metabolism
Associations between Dietary Acid-Base Load and Cardiometabolic Risk Factors in Adults: The Tehran Lipid and Glucose Study: Zahra Bahadoran, Parvin Mirmiran, Hadise Khosravi, Fereidoun Azizi; Endocrinol Metab. 2015;30(2):201-207. Published online June 30, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.2.201

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Background

In this study we investigated the associations of dietary acid-base load, identified by potential renal acid load (PRAL) and protein to potassium (Pro:K) ratio, with cardiometabolic risk factors in Tehranian adults.

Methods

A cross-sectional study was conducted within the framework of the fourth phase of the Tehran Lipid and Glucose Study (2009 to 2011) on 5,620 men and women aged 19 to 70 years. Dietary data were collected by a trained dietitian using a validated, 147-food item, semi-quantitative food frequency questionnaire, and dietary PRAL and Pro:K ratio were calculated. Multiple linear regression models with adjustment for potential confounding variables were used to evaluate the associations of dietary acid-base load with anthropometric measures, blood pressure, serum triglycerides, high density lipoprotein cholesterol (HDL-C), serum creatinine, and fasting blood glucose.

Results

The mean±SD age of the participants was 39.8±12.8 years and 54% of participants were women. Mean±SD PRAL was -22.0±29.1; mean PRAL was -15.6 in men and -26.8 in women. Dietary PRAL was associated with weight (β=0.098, P<0.001), waist circumference (β=0.062, P<0.01), serum triglycerides (β=0.143, P<0.01), HDL-C (β=-0.11, P<0.01), diastolic blood pressure (β=0.062, P<0.01), and serum creatinine (β=0.142, P<0.001). Pro:K ratio was associated with weight (β=0.055, P<0.001), waist circumference (β=0.04, P<0.01), serum HDL-C (β=-0.06, P<0.01), serum triglycerides (β=0.03, P<0.05), diastolic blood pressure (β=0.026, P<0.05), and serum creatinine (β=0.07, P<0.01).

Conclusion

A more acidic dietary acid-base load may be a risk factor for the development of metabolic disorders.

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Obesity and Metabolism
Helicobacter pylori Stool Antigen Levels and Serological Biomarkers of Gastric Inflammation are Associated with Cardio-Metabolic Risk Factors in Type 2 Diabetic Patients: Zahra Bahadoran, Parvin Mirmiran, Maryam Zarif-yeaganeh, Homayoun Zojaji, Fereidoun Azizi; Endocrinol Metab. 2015;30(3):280-287. Published online May 18, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.280

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Background

Helicobacter pylori infection and subsequent gastric inflammation have been proposed as risk factors for the development of insulin resistance and cardiovascular disease. In this study we assessed the possible association of H. pylori bacterial load, and serum biomarker of gastric inflammation with cardiometabolic risk factors in diabetic patients.

Methods

In this cross-sectional study, 84 H. pylori-infected type 2 diabetic patients were assessed for anthropometrics, biochemical and clinical measurements. Pearson correlation test, linear, and logarithmic regression curve estimation models were used to assess the association of H. pylori stool antigen (HpSAg) levels, and pepsinogen I (PGI) to pepsinogen II (PGII) ratio with fasting serum glucose, insulin, serum lipid and lipoprotein parameters, malondialdehyde, high-sensitive C-reactive protein (hs-CRP), systolic and diastolic blood pressure, body weight, waist circumference and lipid accumulation product (LAP) index.

Results

The mean age of participants was 54±10 years, and 44% were men. Mean HpSAg levels and PGI/PGII ratio were 0.24±0.23 µg/mL and 9.9±9.0, respectively. Higher HpSAg as well as lower PGI/PGII was correlated with higher anthropometric measures and LAP. A significant negative correlation between PGI/PGII ratio and blood pressure (r=-0.21 and r=-0.22, systolic and diastolic, respectively, P<0.05), serum insulin (r=-0.17, P=0.05), and hs-CRP (r=-0.17, P=0.05) was observed. A significant linear association between PGI/PGII ratio with serum triglycerides (β=-0.24, P<0.05), serum high density lipoprotein cholesterol (HDL-C; β=0.43, P<0.01), and triglycerides/HDL-C ratio (β=-0.28, P<0.05) were observed.

Conclusion

Higher H. pylori bacterial load and lower PGI/PGII ratio was associated with higher levels of cardiometabolic risk factors in H. pylori infected type 2 diabetic patients.

Citations

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Review Article

Thyroid
Prevalence and Risk Factors of Subclinical Thyroid Disease: Ye An Kim, Young Joo Park; Endocrinol Metab. 2014;29(1):20-29. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.20

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Abstract PDF PubReader

Subclinical thyroid disease is defined biochemically by an abnormal thyrotropin (TSH) level and normal serum-free thyroxine level. The prevalence of this condition varies according to the reference range for TSH and geographic or demographic factors. Recently, several studies, including our community-based cohort studies, have reported on the incidence of subclinical thyroid disease in Korea. Using these studies, we reviewed the prevalence and risk factors of subclinical thyroid disease, focusing on subclinical hypothyroidism.

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Namgok Lecture 2013

Obesity and Metabolism
Ectopic Fat Assessment Focusing on Cardiometabolic and Renal Risk: Soo Lim; Endocrinol Metab. 2014;29(1):1-4. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.1

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Abstract PDF PubReader

It is well known that people with high levels of body fat are at higher risk for developing diabetes mellitus, kidney disease, and cardiovascular disorders. Since individuals who are slightly overweight, or even individuals of normal weight, can vary in body fat distribution, their metabolic profiles and the degree of association of these profiles with cardiometabolic risk factors may differ. Fat distribution might be more of a predictive factor for cardiorenometabolic risk than obesity itself, which has led researchers to investigate whether ectopic fat accumulation may partially account for the development of cardiorenometabolic disorders. In addition to visceral obesity, fat can accumulate in the liver and muscle, and these intrahepatic and intramuscular lipid stores are associated with insulin resistance and adverse metabolic phenotypes. More recently, pericardial fat, perivascular fat, and perirenal fat were found to be associated with coronary atherosclerosis, cardiovascular diseases, and kidney damage, respectively. Thus, regional fat distribution may play a key role in understanding the development of cardiorenometabolic diseases in nonobese people.

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Jong-Hee Ko, Woo-Jin Jeon, Hyuk-Sang Kwon, Seung-Woo Yeon, Jae-Hoon Kang
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Original Articles

Obesity and Metabolism
Variation in Serum Creatinine Level Is Correlated to Risk of Type 2 Diabetes: Jun Sung Moon, Ji Eun Lee, Ji Sung Yoon; Endocrinol Metab. 2013;28(3):207-213. Published online September 13, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.3.207

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Background

Skeletal muscle is well established as a major target organ of insulin action, and is associated with the pathogenesis of type 2 diabetes. Therefore, we attempted to determine whether a variation in serum creatinine is related to the development of type 2 diabetes and other risk factors for diabetes.

Methods

A total of 2,676 nondiabetic subjects with stable and normal renal function (estimated glomerular filtration rate >60 mL/min/1.73 m²) were followed up for approximately 4.5 years. New onset diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated hemoglobin (HbA1c) ≥6.5%, or subjects taking antidiabetic agents. Variation of serum creatinine (ΔCre) was defined as a difference between follow-up and baseline creatinine. In subgroup analysis, body composition was examined by bioelectric impedance analysis method.

Results

A total of 106 subjects were diagnosed with new-onset diabetes during the follow-up period. Baseline serum creatinine was not different between the new-onset diabetes and no diabetes groups. Negative ΔCre (ΔCre <0) showed an association with increased risk of type 2 diabetes after adjusting for age, sex, body mass index, systolic blood pressure, FPG, HbA1c, triglyceride, high density lipoprotein cholesterol, and γ-glutamyl transpeptidase (odds ratio, 1.885; 95% confidence interval, 1.127 to 3.153). Serum creatinine level demonstrated positive correlation with muscle mass and negative correlation with percentage of body fat in body composition analysis.

Conclusion

Serum creatinine reflected body muscle mass and the decrease of serum creatinine might be regarded as a risk factor for type 2 diabetes.

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Obesity and Metabolism
Hemoglobin A1c Is Positively Correlated with Framingham Risk Score in Older, Apparently Healthy Nondiabetic Korean Adults: Ji Hye Shin, Ji In Kang, Yun Jung, Young Min Choi, Hyun Jung Park, Jung Hae So, Jin Hwa Kim, Sang Yong Kim, Hak Yeon Bae; Endocrinol Metab. 2013;28(2):103-109. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.103

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Background

Several studies have suggested that elevated levels of hemoglobin A1c (HbA1c) are associated with cardiovascular disease (CVD) in nondiabetic individuals. However, it is unclear whether HbA1c levels can serve as a simple screening marker for increased CVD risk in nondiabetic individuals. Our objective was to evaluate the relationship between HbA1c levels and CVD risk using the Framingham risk score (FRS) in older, apparently healthy nondiabetic Korean adults.

Methods

We retrospectively studied 2,879 Korean adults between the ages of 40 and 79 who underwent voluntary health check-ups at the Health Promotion Center of our hospital from July 2009 to June 2011. Subjects were subdivided based on their HbA1c levels into four groups: tertiles within the HbA1c normal tolerance range and a group for subjects with an increased risk for diabetes (IRD).

Results

The mean FRS for the upper tertile (9.6±3.8) group was significantly higher than that of the middle tertile (8.4±4.0) and lower tertile (7.6±3.8) groups. In addition, FRS was highest in the IRD group (10.5±3.7). Multiple linear regression analysis demonstrated that HbA1c levels exhibited a significant positive correlation with FRS when adjusted for confounding variables in all subjects (β±standard error [SE], 0.018±0.002; R², 0.131), women (β±SE, 0.023±0.003; R², 0.170), and men (β±SE, 0.016±0.004; R², 0.109).

Conclusion

HbA1c levels were positively correlated with FRS in older, apparently healthy nondiabetic Korean adults. We propose that HbA1c levels may reflect CVD risk in nondiabetic individuals.

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The Changes in Atherosclerotic Markers and Adiopocytokines after Treatment with Growth Hormone for the Patients with Hypopituitarism and Growth Hormone Deficiency.: Hyun Won Shin, In Kyung Jeong, Goo Yeong Cho, Cheul Young Choi, Jong Yeop Kim, Yeong Je Chae, Min Ho Cho, Byung Wan Lee, Seong Jin Lee, Chul Young Park, Eun Gyoung Hong, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yu, Sung Hee Ihm, Moon Ki Choi, Hyung Joon Yoo, Sung Woo Park; J Korean Endocr Soc. 2006;21(6):515-525. Published online December 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.6.515

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BACKGROUND
It is known that patients with hypopituitarism have a high mortality rate due to the presence of atherosclerosis, cardiovascular diseases and stroke. The aim of this study was the effect of growth hormone (GH) on the atherosclerotic markers and the adipocytokine levels. METHOD: The study was conducted on 13 adult patients with hypopituitarism and growth hormone deficiency (GHD), and they had been stabilized after receiving hormone replacement therapy for other insufficient pituitary hormones, other than GH, for more than one year. Before treatment with GH, we compared the lipid metabolism, glucose metabolism, cardiovascular risk factors and adipocytokine levels, including adiponectin, leptin, TNF-alpha and IL-6, between the GHD patients and 13 healthy adults who were of a similar age and gender distribution. Patients with GHD were treated with 1 U/day of GH for 6 months. We measured insulin-like growth factor-I (IGF-I), blood pressure, body composition, lipid metabolism, glucose metabolism and hs-CRP, cardiac function, adiponectin, leptin, TNF-alpha and IL-6 levels, flow mediated vasodilation (FMD) and nitroglycerin mediated vasodilation (NMD) before and after GH treatment. RESULTS: The patients with hypopituitarism and GHD showed significantly higher levels of total cholesterol (P = 0.002), low-density lipoprotein cholesterol (LDL-C) (P = 0.036), hs-CRP (P = 0.0087) and leptin (P < 0.001) than did the normal healthy adults. However, there was no difference between the normal adults and the patients with GHD for the systolic and diastolic BP, the levels of apoA, apoB, fasting blood glucose(FBG) and HOMA-IR. In the subjects with GHD after treatment with GH, the level of fat mass (P = 0.0017), total cholesterol (P = 0.004), LDL-C (P = 0.001), leptin (P = 0.013), TNF-alpha (P < 0.001) and hs-CRP (P = 0.0001) were significantly reduced, while lean body mass (P = 0.0161), FFA (P = 0.049) and FMD (P = 0.0051) showed a significant increase. However, there was no significant difference in the level of the systolic and diastolic BP, LDL-C, apoA, apoB, LP (a), HOMA-IR, ejection fraction, left ventricular posterior wall, E/A ratio, intraventricular septum, NMD, intima-media thickness, adiponectin, IL-6, FBG and fasting insulin before and after GH treatment. CONCLUSION: The subjects with GHD were vulnerable to cardiovascular disease. GH therapy for 6 months had a positive effect on their various cardiovascular risk factors.

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Molecular Biology of Atherosclerosis
In-Kyung Jeong
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Contributing Factors to Different Natural Courses of Posttansplantation Diabetes Mellitus in Renal Allograft Recipients.: Kyu Yeon Hur, Myoung Soo Kim, Jae Hyun Nam, Eun Seok Kang, Hyun Joo Lee, So Hun Kim, Bong Soo Cha, Chul Woo Ahn, Soon Il Kim, Yu Seun Kim, Hyun Chul Lee; J Korean Endocr Soc. 2006;21(5):373-381. Published online October 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.5.373

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Abstract PDF

BACKGROUND
New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. METHODS: A total of 77 renal allograft recipients without previously known diabetes were enrolled and performed a serial 75 g oral glucose tolerance test at 0, 1, and 7 years after kidney transplantation. Patients were classified according to the onset and persistency of PTDM: early PTMD (E-PTDM), late PTDM (L-PTDM), persistent PTDM (P-PTDM), transient PTMD (T-PTDM), and non-PTDN (N-PTDM). RESULTS: The incidence of each group was as follows: E-PTDM, 39%; L-PTDM, 11.7%; P-PTDM, 23.4% T-PTDM, 15.6%; N-PTDM, 49.3%. Tacrolimus and female gender were associated with the development of E-PTDM. Among E-PTDM, age at transplantation was a high risk factor for the development of P-PTDM. Higher BMI at year1 was associated with the development of L-PTDM. CONCLUSION: Different risk factors were associated with various natural courses of PTDM. Since old age and female gender are not modifiable risk factors, it may be important to modify immunosuppressive therapy regimens for the prevention of E-PTDM and control of body weight for L-PTDM.

Citations

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Efficacy and Safety of Gemigliptin in Post-Transplant Patients With Type 2 Diabetes Mellitus
Jaehyun Bae, Youjin Kim, Yongin Cho, Minyoung Lee, Ji-Yeon Lee, Yong-ho Lee, Byung-Wan Lee, Bong-Soo Cha, Dong Jin Joo, Kyu Ha Huh, Myoung Soo Kim, Yu Seun Kim, Eun Seok Kang
Transplantation Proceedings.2019; 51(10): 3444. CrossRef
Post-transplantation Diabetes Mellitus
Kun-Ho Yoon
Journal of Korean Endocrine Society.2006; 21(5): 370. CrossRef

Multi-country Study on the Prevalence and Clinical Features of Peripheral Arterial Disease in Type 2 Diabetic Patients Who are at High Risk for Atherosclerosis.: Sang Youl Rhee, Seungjoon Oh, Young Kil Choi, Doo Man Kim, Bong Yun Cha, Hyun Chul Lee, Seung Woo Ha, In Kyu Lee, Tae Sun Park, Min Young Chung, In Joo Kim, Moon Kyu Lee, Sung Soo Koong, Kyung Soo Park, Kyung Wan Min, Young Seol Kim; J Korean Endocr Soc. 2006;21(4):290-301. Published online August 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.4.290

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Abstract PDF: BACKGROUND
PAD-SEARCH (Peripheral Arterial Disease-Screening and Evaluation of diabetic patients in Asian Regions Characterized by High risk factors) is the first international study to investigate the prevalence of peripheral arterial disease (PAD) in Asian type 2 diabetic patients and to demonstrate the relationships between the putative risk factors and PAD in this population. METHODS: A total of 6,625 type 2 diabetic patients (2,873 males and 3,752 females aged 50 and older) were enrolled in PAD-SEARCH in Korea, China, Taiwan, Hong Kong, Indonesia, Thailand and Philippines from October 2003 to March 2004. The Fukuda vascular profile VS-1000(TM) was used to determine the ankle-brachial index (ABI) and the brachial-ankle pulse wave velocity (baPWV). RESULTS: The mean patient age was 63.7 +/- 8.2 years and the mean duration of diabetes was 10.3 +/- 8.0 years. 1,172 (17.7%) subjects were diagnosed as PAD by the ABI (< or = 0.9). Subjects with PAD had a significantly longer duration of diabetes or hypertension, a higher HbA1c level and a significantly lower mean BMI than did the non-PAD subjects. In terms of the lipid profiles, triglyceride was the only significant variable. Notably, the mean ABI and baPWV in the females were significantly poorer than the age matched males for the in subjects with a normal ABI. However, the mean ABI and baPWV in males were significantly poorer than those of the age matched females for the subjects with PAD. On the multivariate analysis, gender, age, BMI, smoking status, duration of diabetes and a previous history of cerebrovascular disease were identified as the independent risk factors of PAD. CONCLUSION: These findings suggest that PAD is a common complication in Asian type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for Asian diabetic patients with high risk factors.

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