Endocrinology and Metabolism

Original Articles

Diabetes, obesity and metabolism
Reference Standards for C-Peptide in Korean Population: A Korean Endocrine Hormone Reference Standard Data Center Study: Jooyoung Cho, Ho-Chan Cho, Ohk-Hyun Ryu, Hyo-Jeong Kim, Chang Geun Kim, Young Ran Yun, Choon Hee Chung, on Behalf of the Task Force Team for Korean Hormone Reference Standards; Endocrinol Metab. 2024;39(3):489-499. Published online May 9, 2024; DOI: https://doi.org/10.3803/EnM.2023.1888

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Abstract PDF Supplementary Material PubReader ePub: Background
The Korean Endocrine Hormone Reference Standard Data Center (KEHRS DC) has created reference standards (RSs) for endocrine hormones since 2020. This study is the first of its kind, wherein the KEHRS DC established RSs for serum Cpeptide levels in a healthy Korean population.
Methods
Healthy Korean adults were recruited from May 2021 to September 2023. After excluding participants according to our criteria, serum samples were collected; each participant could then choose between fasting glucose only or fasting glucose plus an oral glucose tolerance test (OGTT). If their sample showed high glucose (≥100 mg/dL) or hemoglobin A1c (HbA1c) (≥5.70%), their C-peptide levels were excluded from analyzing the RSs.
Results
A total of 1,532 participants were recruited; however, only the data of 1,050 participants were analyzed after excluding those whose samples showed hyperglycemia or high HbA1c. Post-30-minute OGTT data from 342 subjects and post-120-minute OGTT data from 351 subjects were used. The means±2 standard deviations and expanded uncertainties of fasting, post-30-minute and 120-minute OGTT C-peptide levels were 1.26±0.82 and 0.34–3.18, 4.74±3.57 and 1.14–8.33, and 4.85±3.58 and 1.25–8.34 ng/mL, respectively. Serum C-peptide levels correlated with obesity, serum glucose levels, and HbA1c levels.
Conclusion
The RSs for serum C-peptide levels established in this study are expected to be useful in both clinical and related fields.

Thyroid
Utilizing Immunoglobulin G4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis: Faridul Haq, Gyeongsin Park, Sora Jeon, Mitsuyoshi Hirokawa, Chan Kwon Jung; Endocrinol Metab. 2024;39(3):468-478. Published online May 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.1923

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Background
Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished.
Methods
This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm² were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery.
Results
Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm² was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT.
Conclusion
This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

Citations

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Advanced pathological subtype classification of thyroid cancer using efficientNetB0
Hongpeng Guo, Junjie Zhang, You Li, Xinghe Pan, Chenglin Sun
Diagnostic Pathology.2025;[Epub] 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.

Citations

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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;[Epub] 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
It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Kyeong Jin Kim
Endocrinology and Metabolism.2024; 39(1): 95. CrossRef

Miscellaneous
Association between N-Terminal Prohormone Brain Natriuretic Peptide and Decreased Skeletal Muscle Mass in a Healthy Adult Population: A Cross-Sectional Study: Tae Kyung Yoo, Marie Yung-Chen Wu, Moon Soo Kim, Mi-Yeon Lee, Yong-Taek Lee, Kyung Jae Yoon, Chul-Hyun Park; Endocrinol Metab. 2023;38(2):269-276. Published online March 13, 2023; DOI: https://doi.org/10.3803/EnM.2022.1588

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Background
Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted.
Methods
We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (−2 standard deviation [SD] < SMI ≤−1 [SD]), and severely LMM groups (SD ≤−2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors.
Results
This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89).
Conclusion
Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.

Citations

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N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP)—A Prognostic Biomarker in Older and/or Frail Adults with Advanced Gastroesophageal Cancer: A Post Hoc Analysis of the GO2 Clinical Trial
Yuewei Tao, Chim C. Lang, Russell D. Petty, Peter S. Hall, Mark A. Baxter
Cancers.2025; 17(4): 601. CrossRef
Differences in the Evaluation of Malnutrition and Body Composition Using Bioelectrical Impedance Analysis, Nutritional Ultrasound, and Dual-Energy X-ray Absorptiometry in Patients with Heart Failure
Ana Benitez-Velasco, Carlos Alzas-Teomiro, Carmen Zurera Gómez, Concepción Muñoz Jiménez, José López Aguilera, Manuel Crespin, Juan Antonio Vallejo-Casas, María Ángeles Gálvez-Moreno, María José Molina Puerta, Aura D. Herrera-Martínez
Nutrients.2024; 16(10): 1535. CrossRef

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

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

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Differential Exercise Requirements for Nonalcoholic Fatty Liver Disease Resolution Across Age Groups: A Longitudinal Study of Korean Military Officers
Jaejun Lee, Dong Yeup Lee, Jae Hyeop Jung, Eunkyoung Bae, Jeong A. Yu, Hyun Yang
Journal of Physical Activity and Health.2025; 22(3): 323. CrossRef
Increased risk of incident mental disorders in adults with new-onset type 1 diabetes diagnosed after the age of 19: A nationwide cohort study
Seohyun Kim, Gyuri Kim, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
Diabetes & Metabolism.2024; 50(1): 101505. CrossRef
Association between age at diagnosis of type 2 diabetes and cardiovascular morbidity and mortality risks: A nationwide population-based study
Da Hea Seo, Mina Kim, Young Ju Suh, Yongin Cho, Seong Hee Ahn, Seongbin Hong, So Hun Kim
Diabetes Research and Clinical Practice.2024; 208: 111098. CrossRef
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Hye-Sun Park, Yongin Cho, Da Hea Seo, Seong Hee Ahn, Seongbin Hong, Young Ju Suh, Suk Chon, Jeong-Taek Woo, Sei Hyun Baik, Kwan Woo Lee, So Hun Kim
Scientific Reports.2024;[Epub] CrossRef
Early onset type 2 diabetes mellitus: an update
Myrsini Strati, Melpomeni Moustaki, Theodora Psaltopoulou, Andromachi Vryonidou, Stavroula A. Paschou
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The Effect of Glycemic Control on Cardiovascular Disease Progression in Adults With Early-Onset Type 2 Diabetes: A Longitudinal Cohort Analysis
Amna Gilani, Khalid Umar, Fatima Gilani, Muhammad Ahmad, Mahnoor S Abbasi, Muhammad Yaseen, Muhammad Zeeshan, Naqeeb Ullah, Aiman Waseem, Fatima Batool, Sundas Safdar
Cureus.2024;[Epub] CrossRef
Complications and Treatment of Early-Onset Type 2 Diabetes
Fahimeh Soheilipour, Naghmeh Abbasi Kasbi, Mahshid Imankhan, Delaram Eskandari
International Journal of Endocrinology and Metabolism.2023;[Epub] CrossRef
Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes (Endocrinol Metab 2022;37:641-51, Han-sang Baek et al.)
Han-sang Baek, Ji-Yeon Park, Jin Yu, Joonyub Lee, Yeoree Yang, Jeonghoon Ha, Seung Hwan Lee, Jae Hyoung Cho, Dong-Jun Lim, Hun-Sung Kim
Endocrinology and Metabolism.2022; 37(6): 945. CrossRef
ISPAD Clinical Practice Consensus Guidelines 2022: Management of the child, adolescent, and young adult with diabetes in limited resource settings
Anju Virmani, Stuart J. Brink, Angela Middlehurst, Fauzia Mohsin, Franco Giraudo, Archana Sarda, Sana Ajmal, Julia E. von Oettingen, Kuben Pillay, Supawadee Likitmaskul, Luis Eduardo Calliari, Maria E. Craig
Pediatric Diabetes.2022; 23(8): 1529. CrossRef
Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes (Endocrinol Metab 2022;37:641-51, Han-sang Baek et al.)
May Thu Hla Aye, Sajid Adhi Raja, Vui Heng Chong
Endocrinology and Metabolism.2022; 37(6): 943. CrossRef

Diabetes, Obesity and Metabolism
Associations of Phthalate Metabolites and Bisphenol A Levels with Obesity in Children: The Korean National Environmental Health Survey (KoNEHS) 2015 to 2017: Moon Young Seo, Shinje Moon, Shin-Hye Kim, Mi Jung Park; Endocrinol Metab. 2022;37(2):249-260. Published online April 7, 2022; DOI: https://doi.org/10.3803/EnM.2021.1235

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Background
Phthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity. Methods: A total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte. Results: The urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity. Conclusion: The concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

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Viktoria V. Pupykina, Irina N. Zakharova
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Di(2-ethylhexyl)phthalate and type 2 diabetes
Sebolaishi Doris Makhubela, Ananias Hodi Kgopa, Matlou Phineas Mokgotho, Leshweni Jerry Shai
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Zhuo Li, Di Wu, Zhenyang Yu, Changzheng Cui, Daqiang Yin
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Thyroid Big Data Articles (National Health Insurance Service Database)
Risk of Diabetes in Patients with Long-Standing Graves’ Disease: A Longitudinal Study: Eyun Song, Min Ji Koo, Eunjin Noh, Soon Young Hwang, Min Jeong Park, Jung A Kim, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Geum Joon Cho, Hye Jin Yoo; Endocrinol Metab. 2021;36(6):1277-1286. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1251

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Background
The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies.
Methods
The risk of diabetes in patients with Graves’ disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group.
Results
A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019).
Conclusion
The risk of diabetes was significantly higher in patients with long-standing Graves’ disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

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Graves’ Disease and the Risk of Type 2 Diabetes: A Korean Population-Based Study
Yoon Young Cho, Bongseong Kim, Sang-Man Jin, Chan-Hee Jung, Ji Oh Mok, Sun Wook Kim, Jae Hoon Chung, Kyung-Do Han, Tae Hyuk Kim
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Safety of non-standard regimen of systemic steroid therapy in patients with Graves’ orbitopathy: a single-centre experience
Nadia Sawicka-Gutaj, Dawid Gruszczyński, Natalia Zawalna, Kacper Nijakowski, Agnieszka Skiba, Mateusz Pochylski, Jerzy Sowiński, Marek Ruchała
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Juan J. Díez, Pedro Iglesias
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Mihaela Simona Popoviciu, Lorena Paduraru, Raluca Marinela Nutas, Alexandra Maria Ujoc, Galal Yahya, Kamel Metwally, Simona Cavalu
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Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves’ Disease
Ho Yeop Lee, Byeong Chang Sim, Ha Thi Nga, Ji Sun Moon, Jingwen Tian, Nguyen Thi Linh, Sang Hyeon Ju, Dong Wook Choi, Daiki Setoyama, Hyon-Seung Yi
Endocrinology and Metabolism.2022; 37(6): 891. CrossRef
Diabetes and Hyperthyroidism: Is There a Causal Link?
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Thyroid
Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves’ Disease: A Retrospective Multicenter Study: Jee Hee Yoon, Meihua Jin, Mijin Kim, A Ram Hong, Hee Kyung Kim, Bo Hyun Kim, Won Bae Kim, Young Kee Shong, Min Ji Jeon, Ho-Cheol Kang; Endocrinol Metab. 2021;36(6):1268-1276. Published online November 26, 2021; DOI: https://doi.org/10.3803/EnM.2021.1227

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Background
The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.
Methods
Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).
Results
Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).
Conclusion
The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

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Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease
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Characterization of Immune Infiltrate Along the Leading Edge of Differentiated Thyroid Cancer
Anupam Kotwal, Krysten Vance, Kemal Hajric, Ana Yuil-Valdes, Benjamin Swanson, Ernesto Martinez Duarte, Oleg Shats, Michael Hollingsworth, Hamid Band, Whitney Goldner
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The Role of Risk Factors for the Progression of Patients with T1b-T2 Papillary Thyroid Carcinoma (PC) during Long-Term Follow-Up
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Antonio Mura, Sonia Vargiu, Angela Spanu, Giuseppe Madeddu
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Outcomes of Surgical Treatment for Graves’ Disease: A Single-Center Experience of 216 Cases
Hanxing Sun, Hui Tong, Xiaohui Shen, Haoji Gao, Jie Kuang, Xi Chen, Qinyu Li, Weihua Qiu, Zhuoran Liu, Jiqi Yan
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Cancer and Mortality Risks of Graves’ Disease in South Korea Based on National Data from 2010 to 2019
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Risk and Prognosis of Thyroid Cancer in Patients with Graves’ Disease: An Umbrella Review
Marco Palella, Francesca Maria Giustolisi, Adriana Modica Fiascaro, Martina Fichera, Antonella Palmieri, Rossella Cannarella, Aldo E. Calogero, Margherita Ferrante, Maria Fiore
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Endocrinology and Metabolism.2023; 38(4): 436. CrossRef
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Table of Contents

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Predisposition to and Prognosis of Thyroid Cancer May Not Be Affected by Graves’ Disease, But Some Questions Still Remain
Yanrui Huang, Haixia Guan
Clinical Thyroidology.2022; 34(2): 59. CrossRef
A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves’ Disease
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Maria Rondini, Angela Spanu, Giuseppe Madeddu
Diagnostics.2022; 12(11): 2801. CrossRef
An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
Pooja Tiwari, Uma Kaimal Saikia, Abhamoni Baro, Ashok Krishna Bhuyan
Thyroid Research and Practice.2022; 19(1): 47. CrossRef
An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
Pooja Tiwari, Uma Kaimal Saikia, Abhamoni Baro, Ashok Krishna Bhuyan
Thyroid Research and Practice.2021; 18(3): 129. CrossRef

Diabetes, Obesity and Metabolism
Prognostic Value of Triglyceride and Glucose Index for Incident Type 2 Diabetes beyond Metabolic Health and Obesity: Hwi Seung Kim, Jiwoo Lee, Yun Kyung Cho, Eun Hee Kim, Min Jung Lee, Hong-Kyu Kim, Joong-Yeol Park, Woo Je Lee, Chang Hee Jung; Endocrinol Metab. 2021;36(5):1042-1054. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1184

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Background
Metabolically healthy obese (MHO) phenotype is metabolically heterogeneous in terms of type 2 diabetes (T2D). Previously, the triglyceride and glucose (TyG) index has been considered for identifying metabolic health and future risk of T2D. This study aimed to evaluate the risk of incident T2D according to obesity status and metabolic health, categorized by four different criteria and the TyG index.
Methods
The study included 39,418 Koreans without T2D at baseline. The risk of T2D was evaluated based on four different definitions of metabolic health and obesity status and according to the baseline TyG index within each metabolic health and obesity group.
Results
During the median follow-up at 38.1 months, 726 individuals developed T2D. Compared with the metabolically healthy non-obese (MHNO) group with low TyG index, the MHO group with high TyG index showed increased risk of T2D in all four definitions of metabolic health with multivariate-adjusted hazard ratios of 2.57 (95% confidence interval [CI], 1.76 to 3.75), 3.72 (95% CI, 2.15 to 6.43), 4.13 (95% CI, 2.67 to 6.38), and 3.05 (95% CI, 2.24 to 4.15), when defined by Adult Treatment Panel III, Wildman, Karelis, and homeostasis model assessment (HOMA) criteria, respectively.
Conclusion
MHO subjects with high TyG index were at an increased risk of developing T2D compared with MHNO subjects, regardless of the definition of metabolic health. TyG index may serve as an additional factor for predicting the individual risk of incident T2D in MHO subjects.

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Ling-gui-zhu-gan promotes adipocytes browning via targeting the miR-27b/PRDM16 pathway in 3T3-L1 cells
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Bone Metabolism
Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: Jeonghoon Ha, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Seung Hyun Ko, Moo Il Kang, Sung Dae Moon, Ki-Hyun Baek; Endocrinol Metab. 2021;36(4):895-903. Published online August 9, 2021; DOI: https://doi.org/10.3803/EnM.2021.1026

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

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Dapagliflozin Improves High‐Fat Diet‐Induced Cognitive Impairment in Female Mice
Xiaolin Chen, Mingxia Fan, Zhuoni Xiao, Xiaoxing Xiong
Brain and Behavior.2025;[Epub] CrossRef
Meta-Analysis on the Association Between DPP-4 Inhibitors and Bone Mineral Density and Osteoporosis
Lili Huang, Wei Zhong, Xinghuan Liang, Huijuan Wang, Shi-en Fu, Zuojie Luo
Journal of Clinical Densitometry.2024; 27(1): 101455. CrossRef
A multicentre, double‐blind, placebo‐controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add‐on therapy in type 2 diabetic patients treated with metformin and dapagliflozin
Soo Lim, Seung‐Hwan Lee, Kyung‐Wan Min, Chang Beom Lee, Sang Yong Kim, Hye Jin Yoo, Nan Hee Kim, Jae Hyeon Kim, Seungjoon Oh, Jong Chul Won, Hyuk Sang Kwon, Mi Kyung Kim, Jung Hwan Park, In‐Kyung Jeong, Sungrae Kim
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Bone Loss in Diabetes Mellitus: Diaporosis
Krisztina Kupai, Hsu Lin Kang, Anikó Pósa, Ákos Csonka, Tamás Várkonyi, Zsuzsanna Valkusz
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Stavroula Psachna, Maria Eleni Chondrogianni, Konstantinos Stathopoulos, Antonis Polymeris, Antonios Chatzigeorgiou, Efstathios Chronopoulos, Symeon Tournis, Eva Kassi
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Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 1177. CrossRef
Complementary effects of dapagliflozin and lobeglitazone on metabolism in a diet-induced obese mouse model
Yun Kyung Lee, Tae Jung Oh, Ji In Lee, Bo Yoon Choi, Hyen Chung Cho, Hak Chul Jang, Sung Hee Choi
European Journal of Pharmacology.2023; 957: 175946. CrossRef

Diabetes, Obesity and Metabolism
Increased Risk of Nonalcoholic Fatty Liver Disease in Individuals with High Weight Variability: Inha Jung, Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(4):845-854. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1098

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Background
Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes.
Methods
We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years.
Results
On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53).
Conclusion
Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

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Anouk Charlot, Anthony Bringolf, Léa Debrut, Joris Mallard, Anne-Laure Charles, Emilie Crouchet, Delphine Duteil, Bernard Geny, Joffrey Zoll
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Body weight variability and the risk of liver‐related outcomes in type 2 diabetes and steatotic liver disease: a cohort study
Nathalie C. Leite, Claudia R. L. Cardoso, Cristiane A. Villela‐Nogueira, Gil F. Salles
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Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
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Katie J. McMenamin, Tamara B. Harris, Joshua F. Baker
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Endocrinology and Metabolism.2022; 37(1): 74. CrossRef
Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
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Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight
Mohammed Eslam, Hashem B. El-Serag, Sven Francque, Shiv K. Sarin, Lai Wei, Elisabetta Bugianesi, Jacob George
Nature Reviews Gastroenterology & Hepatology.2022; 19(10): 638. CrossRef
Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study
Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
Nutrients.2022; 14(14): 2795. CrossRef
Higher Weight Variability Could Bring You a Fatty Liver
Yeoree Yang, Jae-Hyoung Cho
Endocrinology and Metabolism.2021; 36(4): 766. CrossRef
Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease
Inha Jung, Da Young Lee, Mi Yeon Lee, Hyemi Kwon, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Won-Young Lee, Sung-Woo Park, Se Eun Park
Frontiers in Endocrinology.2021;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat: Sun Ok Song, You-Cheol Hwang, Han Uk Ryu, Steven E. Kahn, Donna L. Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko; Endocrinol Metab. 2021;36(4):835-844. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1130

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Background
Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.
Methods
All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.
Results
A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm² in men and 63.1±39.5 cm² in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.
Conclusion
These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

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Visceral Fat Area and Subcutaneous Fat Area Increase in Hyperthyroidism Patients After Treatment—A Single-Group Repeated-Measures Trial
Mengnan Li, Xifeng Yang, Ru Li, Baofeng Wu, Jinxuan Hao, Yijie Qi, Tao Bai, Luyang Yang, Yi Zhang, Yunfeng Liu
Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 2165. CrossRef
Subcutaneous Fat Thickness with HDL and LDL Levels in Overweight Female Student
Amilia Yuni Damayanti, Fatimah Fatimah, Lulu’ Luthfiya, Afina Deni Kusumadiastuti
Amerta Nutrition.2023; 7(2SP): 13. CrossRef
Fenofibrate add-on to statin treatment is associated with low all-cause death and cardiovascular disease in the general population with high triglyceride levels
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Diabetes, Obesity and Metabolism
High Fibrosis-4 Index Is Related with Worse Clinical Outcome in Patients with Coronavirus Disease 2019 and Diabetes Mellitus: A Multicenter Observational Study: Sung-Woo Kim, Jae-Han Jeon, Jun Sung Moon, Mi Kyung Kim; Endocrinol Metab. 2021;36(4):800-809. Published online August 20, 2021; DOI: https://doi.org/10.3803/EnM.2021.1040

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Background
Based on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality.
Methods
This multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.
Results
The patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index.
Conclusion
Both DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.

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Kai Liu, Shu Liu, Ting-ting Xu, Hong Qiao
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Raffaele Galiero, Giuseppe Loffredo, Vittorio Simeon, Alfredo Caturano, Erica Vetrano, Giulia Medicamento, Maria Alfano, Domenico Beccia, Chiara Brin, Sara Colantuoni, Jessica Di Salvo, Raffaella Epifani, Riccardo Nevola, Raffaele Marfella, Celestino Sard
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Clinical Study
Gender-Dependent Reference Range of Serum Calcitonin Levels in Healthy Korean Adults: Eyun Song, Min Ji Jeon, Hye Jin Yoo, Sung Jin Bae, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Hong-Kyu Kim, Won Gu Kim; Endocrinol Metab. 2021;36(2):365-373. Published online April 7, 2021; DOI: https://doi.org/10.3803/EnM.2020.939

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Background
Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults.
Methods
Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638).
Results
This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively.
Conclusion
Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.

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Pierpaolo Trimboli, Giuseppe Peloni, Dorotea Confalonieri, Elena Gamarra, Tommaso Piticchio, Francesco Frasca, Petra Makovac, Arnoldo Piccardo, Lorenzo Ruinelli
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Review Article

Obesity and Metabolism
Digital Therapeutics for Obesity and Eating-Related Problems: Meelim Kim, Hyung Jin Choi; Endocrinol Metab. 2021;36(2):220-228. Published online March 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.107

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In recent years, digital technologies have rapidly advanced and are being applied to remedy medical problems. These technologies allow us to monitor and manage our physical and mental health in our daily lives. Since lifestyle modification is the cornerstone of the management of obesity and eating behavior problems, digital therapeutics (DTx) represent a powerful and easily accessible treatment modality. This review discusses the critical issues to consider for enhancing the efficacy of DTx in future development initiatives. To competently adapt and expand public access to DTx, it is important for various stakeholders, including health professionals, patients, and guardians, to collaborate with other industry partners and policy-makers in the ecosystem.

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