Endocrinology and Metabolism

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Diabetes, obesity and metabolism
Characteristics of Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Risk for Hepatic Fibrosis in 476,124 Korean Adults: A Cross-Sectional Study: Da Yeon Lee, Ji-Hee Ko, Han-Na Jang, Sun Joon Moon, Hye-Mi Kwon, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Eun-Jung Rhee; Endocrinol Metab. 2025;40(4):648-652. Published online March 27, 2025; DOI: https://doi.org/10.3803/EnM.2024.2281

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As the new terminology of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD) has emerged, the clinical significance of MASLD is increasing. This cross-sectional study analyzed 476,124 health checkup participants (2002–2022) to compare hepatic fibrosis risks across MASLD, MetALD, non-alcoholic fatty liver disease (NAFLD), and metabolic dysfunction-associated fatty liver disease (MAFLD). Steatotic liver was identified via ultrasonography, and fibrosis risk was assessed using aspartate aminotransferase to platelet ratio index and NAFLD fibrosis score. The prevalence of NAFLD, MAFLD, MASLD, and MetALD was 30.1%, 32.3%, 29.8%, and 3.0%, respectively, with a 27.9% overlap among three conditions. Participants with steatotic liver were predominantly male, with higher glucose, lipids, liver enzymes, and homeostasis model assessment of insulin resistance levels. Three disease definitions largely overlapped, with MASLD and NAFLD being very similar, while participants with MAFLD and MetALD showed increased fibrosis risk (clinical trial registration number: 2024-11-050).

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Associations between steatotic liver disease subtypes and incident diabetes in young Korean adults: A nationwide cohort study
Goh Eun Chung, Su Jong Yu, Jeayeon Park, Yoon Jun Kim, Jung‐Hwan Yoon, Kyungdo Han, Eun Ju Cho
Diabetes, Obesity and Metabolism.2026; 28(3): 1947. CrossRef
Epidemiology and characteristics of obesity in Koreans based on the 2024 Obesity Fact Sheet
Eun-Jung Rhee
Journal of the Korean Medical Association.2026; 69(1): 4. CrossRef

Original Articles

Diabetes, obesity and metabolism
Docosahexanoic Acid Attenuates Palmitate-Induced Apoptosis by Autophagy Upregulation via GPR120/mTOR Axis in Insulin-Secreting Cells: Seok-Woo Hong, Jinmi Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2024;39(2):353-363. Published online January 23, 2024; DOI: https://doi.org/10.3803/EnM.2023.1809

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Background
Polyunsaturated fatty acids (PUFAs) reportedly have protective effects on pancreatic β-cells; however, the underlying mechanisms are unknown.
Methods
To investigate the cellular mechanism of PUFA-induced cell protection, mouse insulinoma 6 (MIN6) cells were cultured with palmitic acid (PA) and/or docosahexaenoic acid (DHA), and alterations in cellular signaling and apoptosis were examined.
Results
DHA treatment remarkably repressed caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positive red dot signals in PA-treated MIN6 cells, with upregulation of autophagy, an increase in microtubule- associated protein 1-light chain 3 (LC3)-II, autophagy-related 5 (Atg5), and decreased p62. Upstream factors involved in autophagy regulation (Beclin-1, unc51 like autophagy activating kinase 1 [ULK1], phosphorylated mammalian target of rapamycin [mTOR], and protein kinase B) were also altered by DHA treatment. DHA specifically induced phosphorylation on S2448 in mTOR; however, phosphorylation on S2481 decreased. The role of G protein-coupled receptor 120 (GPR120) in the effect of DHA was demonstrated using a GPR120 agonist and antagonist. Additional treatment with AH7614, a GPR120 antagonist, significantly attenuated DHA-induced autophagy and protection. Taken together, DHA-induced autophagy activation with protection against PA-induced apoptosis mediated by the GPR120/mTOR axis.
Conclusion
These findings indicate that DHA has therapeutic effects on PA-induced pancreatic β-cells, and that the cellular mechanism of β-cell protection by DHA may be a new research target with potential pharmacotherapeutic implications in β-cell protection.

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Maternal fish oil supplementation enhances nutrient transport in the placenta and milk biosynthesis in the mammary gland via the GPR120 signaling pathway
Qihui Li, Qianzi Zhang, Senlin Su, Siwang Yang, Jiayuan Shao, Wutai Guan, Shihai Zhang
Journal of Advanced Research.2025; 76: 73. CrossRef
Innovative applications of medium‐ and long‐chain triacylglycerol in nutritional support: Current perspectives and future directions
Yandan Wang, Wei Wei, Yongjin Wang, Le Yu, Zhiqiang Xing, Jianwen Zhang, Zong Meng, Xingguo Wang
Comprehensive Reviews in Food Science and Food Safety.2025;[Epub] CrossRef
Cordycepin Ameliorates Kainic Acid‐Induced HT22 Cell Neurotoxicity by Activating GPR120‐Mediated Mitophagy
Yongzhi San, Minghua Wang
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Potential Therapeutic Exploitation of G Protein-Coupled Receptor 120 (GPR120/FFAR4) Signaling in Obesity-Related Metabolic Disorders
Dariusz Szukiewicz
International Journal of Molecular Sciences.2025; 26(6): 2501. CrossRef
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Lenny Yi Tong Cheong, Eka Norfaishanty Saipuljumri, Gavin Wen Zhao Loi, Jialiu Zeng, Chih Hung Lo
Current Obesity Reports.2025;[Epub] CrossRef
Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies
Youngwoo Jang, Eun-Jung Rhee, Sung Hee Choi
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Activating protein kinases to treat diseases: Current understanding and future challenges
Peng Jin, Minru Liao, Huidi Liu, Kun Huang, Leilei Fu, Xin Jin
Acta Pharmaceutica Sinica B.2025;[Epub] CrossRef
Fatty Acids of Erythrocyte Membranes and Blood Serum as Possible Predictors of Exacerbation in Patients with Inflammatory Bowel Diseases
M. V. Kruchinina, M. F. Osipenko, A. I. Valuyskikh, E. Yu. Valuiskikh, I. O. Svetlova
Russian Journal of Gastroenterology, Hepatology, Coloproctology.2024; 34(6): 28. CrossRef

Diabetes, obesity and metabolism
Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway: Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Yu-Mi Lim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2024;39(1):98-108. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1786

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Background
Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states.
Methods
Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco’s modified Eagle’s medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours.
Results
SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation.
Conclusion
These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

Citations

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Development of Cellular Energy Metabolism During Differentiation of Human iPSCs into Cortical Neurons
Šárka Danačíková, Petr Pecina, Alena Pecinová, Jan Svoboda, David Vondrášek, Davide Alessandro Basello, Tomáš Čajka, Daniel Hadraba, Tomáš Mráček, Vladimír Kořínek, Jakub Otáhal
Molecular Neurobiology.2026;[Epub] CrossRef
Differential expression and correlation analysis of whole transcriptome for type 2 diabetes mellitus
Fang Liu, Aihong Peng, Xiaoli Zhu, Guangming Wang
Frontiers in Endocrinology.2025;[Epub] CrossRef
Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Transcription Regulation of AgRP and POMC Genes
Dong Hee Kim, Min Jin Lee, Dasol Kang, Ah Reum Khang, Ji Hyun Bae, Joo Yeon Kim, Su Hyun Kim, Yang Ho Kang, Dongwon Yi
Current Issues in Molecular Biology.2024; 46(7): 7505. CrossRef
Sodium-glucose cotransporter 2 inhibitors ameliorate ER stress-induced pro-inflammatory cytokine expression by inhibiting CD36 in NAFLD progression in vitro
Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Yu-Mi Lim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Biochemical and Biophysical Research Communications.2024; 735: 150620. CrossRef

Diabetes, obesity and metabolism
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; Endocrinol Metab. 2023;38(5):568-577. Published online October 10, 2023; DOI: https://doi.org/10.3803/EnM.2023.1770

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Background
Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden.
Methods
We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease.
Results
The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100.
Conclusion
CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

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Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies
Youngwoo Jang, Eun-Jung Rhee, Sung Hee Choi
Endocrinology and Metabolism.2025; 40(5): 668. CrossRef

Diabetes, Obesity and Metabolism
Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway: Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2022;37(1):74-83. Published online February 9, 2022; DOI: https://doi.org/10.3803/EnM.2021.1293

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Background
Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has been shown to reduce body weight and liver fat content in patients with type 2 diabetes. Family with sequence similarity 3 member A (FAM3A) plays a vital role in regulating glucose and lipid metabolism. The aim of this study was to determine the mechanisms by which dulaglutide protects against hepatic steatosis in HepG2 cells treated with palmitic acid (PA).
Methods
HepG2 cells were pretreated with 400 μM PA for 24 hours, followed by treatment with or without 100 nM dulaglutide for 24 hours. Hepatic lipid accumulation was determined using Oil red O staining and triglyceride (TG) assay, and the expression of lipid metabolism-associated factor was analyzed using quantitative real time polymerase chain reaction and Western blotting.
Results
Dulaglutide significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells. However, exendin-(9-39), a GLP-1R antagonist, reversed the expression of FAM3A, and fatty acid oxidation-associated factors increased due to dulaglutide. In addition, inhibition of FAM3A by siRNA attenuated the reducing effect of dulaglutide on TG content and its increasing effect on regulation of fatty acid oxidation.
Conclusion
These results suggest that dulaglutide could be used therapeutically for improving nonalcoholic fatty liver disease, and its effect could be mediated in part via upregulation of FAM3A expression through a GLP-1R-dependent pathway.

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Effect of Submaximal-Dose Semaglutide on MASLD Biopsy-Free Scoring Systems in Patients with Obesity
Boris Focko, Martin Jozef Péč, Zuzana Miertová, Jakub Jurica, Andrej Miert, Lucia Kubíková, Peter Tudík, Norbert Nagy, Patrik Lecký, Ivana Ságová, Tomáš Bolek, Daniel Ján Havaj, Ľubomír Skladaný, Marián Mokáň, Matej Samoš
Livers.2026; 6(1): 3. CrossRef
Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes
Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-DeMarzio
Scientific Reports.2025;[Epub] CrossRef
Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling
Weidong Pu, Yang Pan, Kang Yang, Jian Gao, Fen Tian, Jingrui Song, Yubing Huang, Yanmei Li
Frontiers in Pharmacology.2025;[Epub] CrossRef
Glucagon-like peptide-1 receptor agonists improve cholesterol metabolism by inhibiting SREBP-2 via SIRT6-AMPK pathway in HepG2 cells treated with palmitic acid
Jinmi Lee, Eun-Jung Rhee, Yu-Mi Lim, Seok-Woo Hong, Won-Young Lee
Cardiovascular Prevention and Pharmacotherapy.2025; 7(3): 61. CrossRef
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Arya Singh, Rahnuma Ahmad, Kona Chowdhury, Mahendra Narwaria, Mainul Haque
Advances in Human Biology.2025;[Epub] CrossRef
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Haoran Jiang, Linquan Zang
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Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan
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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
Tirzepatide against obesity and insulin-resistance: pathophysiological aspects and clinical evidence
Salvatore Corrao, Chiara Pollicino, Dalila Maggio, Alessandra Torres, Christiano Argano
Frontiers in Endocrinology.2024;[Epub] CrossRef
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Toshitaka Sawamura, Ren Mizoguchi, Ai Ohmori, Mitsuhiro Kometani, Takashi Yoneda, Shigehiro Karashima
Journal of Diabetes & Metabolic Disorders.2024; 23(2): 2105. CrossRef
FABP1 induces lipogenesis by regulating the processing of SREBP1 in hepatocytes of large yellow croaker (Larimichthys crocea)
Fan Chen, Tingting Hao, Qiang Chen, Yuning Sun, Yanan Shen, Zengqi Zhao, Jianlong Du, Yueru Li, Kangsen Mai, Qinghui Ai
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Riccardo Nevola, Raffaella Epifani, Simona Imbriani, Giovanni Tortorella, Concetta Aprea, Raffaele Galiero, Luca Rinaldi, Raffaele Marfella, Ferdinando Carlo Sasso
International Journal of Molecular Sciences.2023; 24(2): 1703. CrossRef
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Lei Yang, Baoshun Du, Shitao Zhang, Maode Wang
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Diabetes, Obesity and Metabolism
Changes in Insulin Resistance Index and the Risk of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease without Diabetes: Kangbuk Samsung Health Study: Dae-Jeong Koo, Mi Yeon Lee, Inha Jung, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(5):1016-1028. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1110

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Background
Fibrosis is the most important prognostic factor for nonalcoholic fatty liver disease (NAFLD). Insulin resistance plays a key role of fibrosis progression. We evaluated the association between changes in homeostasis model assessment of insulin resistance (HOMA-IR) values and changes in fibrosis status in NAFLD.
Methods
We analyzed the data of 15,728 participants with NAFLD (86% men, mean age 40.5 years) who had no diabetes at baseline and visited our centers for health check-ups both in 2012 and 2016. The participants were classified into four groups according to the degree of change in HOMA-IR values from baseline to the end of follow-up: G1 (<0), G2 (0–0.50), G3 (0.51–1.00), and G4 (>1.00). NAFLD was assessed by ultrasonography, and fibrosis status was evaluated by the NAFLD fibrosis score (NFS) and the aspartate aminotransferase to platelet ratio index (APRI).
Results
After the 4-year follow-up, the multivariable-adjusted odds ratio (OR) for progression of fibrosis probability increased with increasing HOMA-IR values (OR, 2.25; 95% confidence interval [CI], 1.87 to 2.71 for NFS; and OR, 2.55; 95% CI, 2.05 to 3.18 for APRI, G4). This tendency remained consistent throughout the subgroup analyses, except in those for female sex and a body mass index <25 kg/m². The OR for regression of fibrosis probability decreased with increasing HOMA-IR values (OR, 0.33; 95% CI, 0.25 to 0.43 for NFS, G4).
Conclusion
Changes in HOMA-IR values were associated with changes in fibrosis status in patients with NAFLD without diabetes, which underscores the role of insulin resistance in liver fibrosis.

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Metabolic Dysfunction-Associated Steatotic Liver Disease: The Role of Hepatic Steatosis in Insulin Resistance and Metabolic Health
Ji Cheol Bae
Endocrinology and Metabolism.2025; 40(2): 304. CrossRef
Associations between non-insulin-based insulin resistance surrogate markers and liver-related outcomes in metabolic dysfunction-associated steatotic liver disease: a nationwide cohort study in South Korea
Sang Yi Moon, Minkook Son, Yeo Wool Kang, Myeongseok Koh, Jong Yoon Lee, Yang Hyun Baek
BMC Gastroenterology.2025;[Epub] CrossRef
Application of insulin resistance score in type 2 diabetes mellitus complicated with fatty liver and liver fibrosis
Shaojie Duan, Mengdie Chen, Jie Chen, Yaojian Shao, Xiaolong Jin, Chaohui Wang, Ping Feng, Xiaosheng Teng, Zhenjun Yu
European Journal of Gastroenterology & Hepatology.2025; 37(10): 1155. CrossRef
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Minjeong Sung, Dae-Hwan Kim, Eun-Gene Sun, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung, Hyun-Jeong Shim, Woo Kyun Bae
Endocrinology and Metabolism.2025;[Epub] CrossRef
Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis
Mohammad E. Khamseh, Mojtaba Malek, Soodeh Jahangiri, Sohrab Nobarani, Azita Hekmatdoost, Marieh Salavatizadeh, Samira Soltanieh, Haleh Chehrehgosha, Hoda Taheri, Zeinab Montazeri, Fereshteh Attaran, Faramarz Ismail-Beigi, Fariba Alaei-Shahmiri
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Gyuri Kim, Tae Yang Yu, Jae Hwan Jee, Ji Cheol Bae, Mira Kang, Jae Hyeon Kim
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Takumi Kawaguchi, Kenta Murotani, Hiromitsu Kajiyama, Hitoshi Obara, Hironori Yamaguchi, Yuko Toyofuku, Fumi Kaneko, Yutaka Seino, Saeko Uchida
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Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
The Effects of Glucose Lowering Agents on the Secondary Prevention of Coronary Artery Disease in Patients with Type 2 Diabetes: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(5):977-987. Published online October 14, 2021; DOI: https://doi.org/10.3803/EnM.2021.1046

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Background
Patients with diabetes have a higher risk of requiring repeated percutaneous coronary intervention (PCI) than non-diabetic patients. We aimed to evaluate and compare the effects of anti-diabetic drugs on the secondary prevention of myocardial infarction among type 2 diabetes mellitus patients.
Methods
We analyzed the general health check-up dataset and claims data of the Korean National Health Insurance Service of 199,714 participants (age ≥30 years) who underwent PCIs between 2010 and 2013. Those who underwent additional PCI within 1 year of their first PCI (n=3,325) and those who died within 1 year (n=1,312) were excluded. Patients were classified according to their prescription records for glucose-lowering agents. The primary endpoint was the incidence rate of coronary revascularization.
Results
A total of 35,348 patients were included in the study. Metformin significantly decreased the risk of requiring repeat PCI in all patients (adjusted hazard ratio [aHR], 0.77). In obese patients with body mass index (BMI) ≥25 kg/m², patients treated with thiazolidinedione (TZD) exhibited a decreased risk of requiring repeat revascularization than those who were not treated with TZD (aHR, 0.77; 95% confidence interval, 0.63 to 0.95). Patients treated with metformin showed a decreased risk of requiring revascularization regardless of their BMI. Insulin, meglitinide, and alpha-glucosidase inhibitor were associated with increased risk of repeated PCI.
Conclusion
The risk of requiring repeat revascularization was lower in diabetic patients treated with metformin and in obese patients treated with TZD. These results suggest that physicians should choose appropriate glucose-lowering agents for the secondary prevention of coronary artery disease.

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Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies
Youngwoo Jang, Eun-Jung Rhee, Sung Hee Choi
Endocrinology and Metabolism.2025; 40(5): 668. CrossRef
Preadmission metformin use increased the incidence of hyperlactatemia at admission and 30-day in-hospital mortality among T2D patients with heart disease at high risk of hypoxia
Le Zhang, Xia Zhao, Zhongsu Wang, Hao Deng, Xue Zhang, Xuan Wang, Jiahui Lao, Mei Gao, Yinglong Hou, Yi Han
International Journal of Cardiology.2024; 412: 132338. CrossRef
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Zhuoyan Zhao, Huan Lian, Yixiang Liu, Lixian Sun, Ying Zhang
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Zhicheng Xu, Haidong Zhang, Chenghui Wu, Yuxiang Zheng, Jingzhou Jiang
Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
Establishment of a Predictive Model for Poor Prognosis of Incomplete Revascularization in Patients with Coronary Heart Disease and Multivessel Disease
Huan Lian, Zhuoyan Zhao, Kelin Ma, Zhenjiang Ding, Lixian Sun, Ying Zhang
Clinical and Applied Thrombosis/Hemostasis.2022;[Epub] 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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Impact of Change, Fluctuation, or Variability in Weight on the Risk of Nonalcoholic Fatty Liver Disease in General Population: A Systematic Review and Meta‐Analysis
Dorsa Alijanzadeh, Masoud Noroozi, Negin Rostami, Narges Norouzkhani, Mahdie ShojaeiBaghini, Saeed Zivari Lashkajani, Ali Mirzaei, Maryam Dianati, Maryam Salimi, Hamidreza Sadeghsalehi, Faezeh Jadidian, Sajjad Ghane Ezabadi, Mohammad Sadegh Fallahi, Mobin
Health Science Reports.2025;[Epub] CrossRef
Changes in Macronutrients during Dieting Lead to Weight Cycling and Metabolic Complications in Mouse Model
Anouk Charlot, Anthony Bringolf, Léa Debrut, Joris Mallard, Anne-Laure Charles, Emilie Crouchet, Delphine Duteil, Bernard Geny, Joffrey Zoll
Nutrients.2024; 16(5): 646. CrossRef
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
Obesity.2024; 32(6): 1210. 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
A machine-learned model for predicting weight loss success using weight change features early in treatment
Farzad Shahabi, Samuel L. Battalio, Angela Fidler Pfammatter, Donald Hedeker, Bonnie Spring, Nabil Alshurafa
npj Digital Medicine.2024;[Epub] CrossRef
Long-Term Yo-Yo Dieting Exaggerates Liver Steatosis and Lesions but Preserves Muscle Performance in Male Zebrafish
Tzu-Chieh Hsu, Chun-Hsien Chiang, I-Hsuan Liu, Chih-Yun Wang, Ching-Yi Chen
International Journal of Molecular Sciences.2024; 25(23): 13225. CrossRef
Weight variability, physical functioning and incident disability in older adults
Katie J. McMenamin, Tamara B. Harris, Joshua F. Baker
Journal of Cachexia, Sarcopenia and Muscle.2023; 14(4): 1648. CrossRef
Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway
Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
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
Obesity.2022; 30(6): 1279. CrossRef
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
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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
Non-Laboratory-Based Simple Screening Model for Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Developed Using Multi-Center Cohorts: Jiwon Kim, Minyoung Lee, Soo Yeon Kim, Ji-Hye Kim, Ji Sun Nam, Sung Wan Chun, Se Eun Park, Kwang Joon Kim, Yong-ho Lee, Joo Young Nam, Eun Seok Kang; Endocrinol Metab. 2021;36(4):823-834. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1074

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Background
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM.
Methods
A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD.
Results
Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters.
Conclusion
The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinical practice.

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An interpretable machine learning model for predicting metabolic dysfunction‐associated steatotic liver disease in patients with type 2 diabetes
Zhuolin Zhou, Nan Gao, Jiaojiao Liu, Xuerong Ma, Zhijuan Ge, Cheng Ji
Diabetes, Obesity and Metabolism.2026; 28(1): 122. CrossRef
Prevalence, Sonographic Characteristics, and Metabolic Predictors of Nonalcoholic Fatty Liver Disease in Adults With Type 2 Diabetes in Tanzania
Zubeir Zubeir, Zuhura Nkrumbih, Salama Ally, Yasser H. Hadi
Dr. Sulaiman Al Habib Medical Journal.2025; 7(3): 180. 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
Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus—The Chicken or the Egg Dilemma
Marcin Kosmalski, Agnieszka Śliwińska, Józef Drzewoski
Biomedicines.2023; 11(4): 1097. CrossRef

Endocrine Research
Clusterin Protects Lipotoxicity-Induced Apoptosis via Upregulation of Autophagy in Insulin-Secreting Cells: Seok-Woo Hong, Jinmi Lee, Min Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2020;35(4):943-953. Published online December 2, 2020; DOI: https://doi.org/10.3803/EnM.2020.768

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Background
There is a great need to discover factors that could protect pancreatic β-cells from apoptosis and thus prevent diabetes mellitus. Clusterin (CLU), a chaperone protein, plays an important role in cell protection in numerous cells and is involved in various cellular mechanisms, including autophagy. In the present study, we investigated the protective role of CLU through autophagy regulation in pancreatic β-cells.
Methods
To identify the protective role of CLU, mouse insulinoma 6 (MIN6) cells were incubated with CLU and/or free fatty acid (FFA) palmitate, and cellular apoptosis and autophagy were examined.
Results
Treatment with CLU remarkably upregulated microtubule-associated protein 1-light chain 3 (LC3)-II conversion in a doseand time-dependent manner with a significant increase in the autophagy-related 3 (Atg3) gene expression level, which is a mediator of LC3-II conversion. Moreover, co-immunoprecipitation and fluorescence microscopy experiments showed that the molecular interaction of LC3 with Atg3 and p62 was markedly increased by CLU. Stimulation of LC3-II conversion by CLU persisted in lipotoxic conditions, and FFA-induced apoptosis and dysfunction were simultaneously improved by CLU treatment. Finally, inhibition of LC3-II conversion by Atg3 gene knockdown markedly attenuated the cytoprotective effect of CLU.
Conclusion
Taken together, these findings suggest that CLU protects pancreatic β-cells against lipotoxicity-induced apoptosis via autophagy stimulation mediated by facilitating LC3-II conversion. Thus, CLU has therapeutic effects on FFA-induced pancreatic β-cell dysfunction.

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Pooja Shivshankar, Stacey L. Mueller-Ortiz, Aleksey Y. Domozhirov, Weizhen Bi, Scott D. Collum, Marie-Francoise Doursout, Manish Patel, Isabella N. LeFebvre, Bindu Akkanti, Simon Yau, Howard J. Huang, Rahat Hussain, Harry Karmouty-Quintana
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Elucidating the function of clusterin in the progression of diabetic kidney disease
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Docosahexanoic Acid Attenuates Palmitate-Induced Apoptosis by Autophagy Upregulation via GPR120/mTOR Axis in Insulin-Secreting Cells
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Dysregulation of pancreatic β-cell autophagy and the risk of type 2 diabetes
Hayder M. Al-kuraishy, Majid S. Jabir, Ali I. Al-Gareeb, Daniel J. Klionsky, Ali K. Albuhadily
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Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells
Sara M. Ahmed, Hoda A. Elkhenany, Toka A. Ahmed, Nehal I. Ghoneim, Mohamed Abd Elkodous, Rania Hassan Mohamed, Sameh Magdeldin, Aya Osama, Ali Mostafa Anwar, Mahmoud M. Gabr, Nagwa El-Badri
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Role of Autophagy in Type 2 Diabetes Mellitus: The Metabolic Clash
Yousef Abud Alanazi, Haydar M. Al‐kuraishy, Ali I. Al‐Gareeb, Athanasios Alexiou, Marios Papadakis, Mostafa M. Bahaa, Walaa A. Negm, Faisal Holil AlAnazi, Mohammed Alrouji, Gaber El‐Saber Batiha
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Alexandra Coomans de Brachène, Corentin Scoubeau, Anyïshai E. Musuaya, Jose Maria Costa-Junior, Angela Castela, Julie Carpentier, Vitalie Faoro, Malgorzata Klass, Miriam Cnop, Decio L. Eizirik
Diabetologia.2023; 66(3): 450. CrossRef
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Ning Yang, Bo Dong, Yanqiu Song, Yang Li, Lu Kou, Qin Qin
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Targets for rescue from fatty acid-induced lipotoxicity in pancreatic beta cells
Seok-Woo Hong, Won-Young Lee
Cardiovascular Prevention and Pharmacotherapy.2022; 4(2): 57. CrossRef
Co-regulators of autophagy and the cell cycle in HFD − As treated mice
Marzieh Zeinvand-Lorestani, Mohammad Javad Khodayar, Ali Teimoori, Najmaldin Saki, Akram Ahangarpour, Ali Ranjbar, Hamed Zeinvand-Lorestani
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Safia Costes, Gyslaine Bertrand, Magalie A. Ravier
International Journal of Molecular Sciences.2021; 22(10): 5303. CrossRef

Clinical Study
Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study: Jong Dai Kim, Dong-Mee Lim, Keun-Young Park, Se Eun Park, Eun Jung Rhee, Cheol-Young Park, Won-Young Lee, Ki Won Oh; Endocrinol Metab. 2020;35(3):610-617. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.721

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Background
It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes.
Methods
Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis.
Results
The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, P<0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, P<0.001 and r=0.077, P<0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, P<0.001 and r=–0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006).
Conclusion
Transferrin is positively associated with incident type 2 diabetes in Koreans.

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SERS profiling of blood serum filtrate components from patients with type II diabetes using 100 kDa filtration devices
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Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes
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Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes
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Lifestyle, biological, and genetic factors related to brain iron accumulation across adulthood
Jonatan Gustavsson, Zuzana Ištvánfyová, Goran Papenberg, Farshad Falahati, Erika J. Laukka, Jenni Lehtisalo, Francesca Mangialasche, Grégoria Kalpouzos
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Iron homeostasis and insulin sensitivity: unraveling the complex interactions
Katarzyna Sobieska, Angelika Buczyńska, Adam Jacek Krętowski, Anna Popławska-Kita
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Association between systemic iron status and β-cell function and insulin sensitivity in patients with newly diagnosed type 2 diabetes
Yao Qin, Yiting Huang, Yuxiao Li, Lu Qin, Qianying Wei, Xin Chen, Chuanhui Yang, Mei Zhang
Frontiers in Endocrinology.2023;[Epub] CrossRef
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Jie Feng, Xiaoyun Shan, Lijuan Wang, Jiaxi Lu, Yang Cao, Lichen Yang
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Clinical Study
The Prevalence and Risk of Type 2 Diabetes in Adults with Disabilities in Korea: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2020;35(3):552-561. Published online July 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.653

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Background
People with disabilities are at risk of secondary conditions such as diabetes. The aim of this study was to evaluate the prevalence and risk of type 2 diabetes in South Korea, especially among people with all types of disabilities.
Methods
We conducted a cross-sectional study using data from the Korean National Health Insurance Service, with two disabilityfree controls matched for each participant with disabilities by age and sex. Information regarding the type, severity and grade of disabilities was obtained based on the National Disability Registry. Diagnosis of type 2 diabetes was defined according to the following criteria: presence of International Classification of Diseases, Tenth Revision, Clinical Modification codes E11, E12, E13, or E14 and claims for at least one oral anti-diabetic agent or insulin at baseline, or fasting glucose level ≥126 mg/dL.
Results
We included 1,297,806 participants with disabilities and 2,943,719 control. Out of 4,241,525 participants, 841,990 (19.9%) were diagnosed with diabetes. The prevalence of diabetes was higher in the disability group compared with individuals without disabilities (23.1% vs. 18.4%). The odds of having diabetes was higher in the disability group compared with the control group (adjusted odds ratio, 1.34; 95% confidence interval, 1.33 to 1.34). The results showed higher prevalence of diabetes in the mildly disabled group (23.2%) than in the severely disabled group (22.7%).
Conclusion
The prevalence and risk of diabetes were higher in people with disabilities compared with the general population. Physicians and public health authorities should focus on people with disabilities for proper diabetes management.

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Clinical Study
Serum Adiponectin and Progranulin Level in Patients with Benign Thyroid Nodule or Papillary Thyroid Cancer: Hyemi Kwon, Se Eun Park, Ji-Sup Yun, Cheol-Young Park; Endocrinol Metab. 2020;35(2):396-406. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.396

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Background
Obesity is associated with thyroid cancer risk. Adiponectin has insulin-sensitizing and anti-inflammatory effects, while progranulin is associated with inflammation and tumorigenesis. We investigated serum adiponectin and progranulin levels in patients with benign thyroid nodule (benign group) and papillary thyroid cancer (PTC; PTC group). The associations between these levels and the clinicopathological features of PTC were evaluated.
Methods
We included 157 patients who underwent thyroid surgery (17% of benign and 83% of PTC group). Clinicopathological features including size, lymph node metastasis, extrathyroidal extension (ETE), multifocality, American Thyroid Association risk stratification were evaluated.
Results
The age was 42.0 years, and 69% were female. Serum adiponectin and progranulin levels were 6.3 μg/mL and 101.5 ng/mL in the benign group and 5.4 μg/mL and 106.1 ng/mL in the PTC group, respectively (P=0.6 and P=0.4, respectively). Serum adiponectin levels showed no significant differences according to clinicopathological features of PTC. The proportions of patients with primary tumor size >1 cm were 3%, 5%, 8%, and 8% according to serum progranulin level quartiles, respectively (P=0.03). The proportions of patients with microscopic/gross ETE were 8%/0%, 9%/1%, 11%/1%, and 11%/2% according to serum progranulin level quartiles, respectively. Median serum progranulin level was significantly higher in patients with PTC >1 cm than in patients with papillary thyroid microcarcinoma (P=0.04, 115.3 ng/mL and 104.7 ng/mL, respectively).
Conclusion
Serum adiponectin and progranulin levels showed no significant difference between benign and PTC groups. Increased serum progranulin levels were significantly associated with PTC >1 cm and microscopic and gross ETE.

Citations

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Progranulin promoted the proliferation, metastasis, and suppressed apoptosis via JAK2-STAT3/4 signaling pathway in papillary thyroid carcinoma
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Obesity and Thyroid Cancer Risk: An Update
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Endocrine Research
Deficiency of Sphingosine-1-Phosphate Reduces the Expression of Prohibitin and Causes β-Cell Impairment via Mitochondrial Dysregulation: Seok-Woo Hong, Jinmi Lee, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2018;33(3):403-412. Published online September 18, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.403

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Background

Emerging evidence suggests that sphingolipids may be involved in type 2 diabetes. However, the exact signaling defect through which disordered sphingolipid metabolism induces β-cell dysfunction remains unknown. The current study demonstrated that sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SphK), is an essential factor for maintaining β-cell function and survival via regulation of mitochondrial action, as mediated by prohibitin (PHB).

Methods

We examined β-cell function and viability, as measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in response to manipulation of cellular S1P and PHB levels.

Results

Lack of S1P induced by sphingosine kinase inhibitor (SphKi) treatment caused β-cell dysfunction and apoptosis, with repression of mitochondrial function shown by decreases in cellular adenosine triphosphate content, the oxygen consumption rate, the expression of oxidative phosphorylation complexes, the mitochondrial membrane potential, and the expression of key regulators of mitochondrial dynamics (mitochondrial dynamin-like GTPase [OPA1] and mitofusin 1 [MFN1]). Supplementation of S1P led to the recovery of mitochondrial function and greatly improved β-cell function and viability. Knockdown of SphK2 using small interfering RNA induced mitochondrial dysfunction, decreased glucose-stimulated insulin secretion (GSIS), and reduced the expression of PHB, an essential regulator of mitochondrial metabolism. PHB deficiency significantly reduced GSIS and induced mitochondrial dysfunction, and co-treatment with S1P did not reverse these trends.

Conclusion

Altogether, these data suggest that S1P is an essential factor in the maintenance of β-cell function and survival through its regulation of mitochondrial action and PHB expression.

Citations

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Thyroid
Prevalence and Annual Incidence of Thyroid Disease in Korea from 2006 to 2015: A Nationwide Population-Based Cohort Study: Hyemi Kwon, Jin-hyung Jung, Kyung-Do Han, Yong-Gyu Park, Jung-Hwan Cho, Da Young Lee, Ji Min Han, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2018;33(2):260-267. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.260

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Background

The incidence of thyroid nodules has increased worldwide in recent years. Thyroid dysfunction is a potential risk factor for hypercholesterolemia, cardiovascular disease, osteoporosis, arrhythmia, and neuropsychiatric disease. This study investigated the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism in Koreans.

Methods

In this nationwide population-based cohort study, 51,834,660 subjects were included using the National Health Information database from 2006 to 2015, after the exclusion of subjects with thyroid cancer.

Results

The prevalence in Korea in 2015 of thyroid nodules, hypothyroidism in patients taking thyroid hormone, and hyperthyroidism in patients undergoing treatment was 15.82/1,000 population, 15.94/1,000 population, and 2.76/1,000 population, respectively. All these diseases were more prevalent among women than among men. The number of incident cases of these three thyroid diseases steadily increased from 2006 to 2012, and then decreased through 2015. The incidence of thyroid nodules, hypothyroidism treated with thyroid hormone, and treated hyperthyroidism was 6.79/1,000 population, 1.76/1,000 population, and 0.55/1,000 population, respectively, in Korea in 2015. The use of methimazole continuously increased, from 33% of total antithyroid drug prescriptions in 2006 to 74.4% in 2015, and it became the most frequently prescribed antithyroid drug in Korea. In contrast, the use of propylthiouracil continuously decreased.

Conclusion

This was the first nationwide study of the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism to take into account recent changes and to include the current status of patients receiving treatment.

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Diabetes
Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum Stress in Pancreatic β-Cells: Seok-Woo Hong, Jinmi Lee, Jung Hwan Cho, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2018;33(1):105-113. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.105

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Background

The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear.

Methods

To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation.

Results

Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels.

Conclusion

Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus

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Diabetes
The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study: Yu Hyun Kwon, Seul-Ki Kim, Jung Hwan Cho, Hyemi Kwon, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2018;33(1):55-61. Published online January 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.55

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Background

Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time.

Methods

A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal (<150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014.

Results

Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80).

Conclusion

In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI.

Citations

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Response: The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study (Endocrinol Metab 2018;33:55–61, Yu Hyun Kwon et al.)
Eun-Jung Rhee, Yu Hyun Kwon
Endocrinology and Metabolism.2018; 33(3): 425. CrossRef
The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study (Endocrinol Metab 2018;33:55–61, Yu Hyun Kwon et al.)
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Endocrinology and Metabolism.2018; 33(2): 305. CrossRef

Clinical Study
Changes in Body Composition According to Age and Sex among Young Non-Diabetic Korean Adults: The Kangbuk Samsung Health Study: Seul-Ki Kim, Yu-Hyun Kwon, Jung Hwan Cho, Da Young Lee, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2017;32(4):442-450. Published online November 21, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.4.442

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Background

Age-related decreases in lean mass represent a serious health problem. We aimed to analyze the risks of rapid decreases in lean mass by age and sex in relatively young Korean adults during a 4-year follow-up study.

Methods

A total of 65,856 non-diabetic participants (59.5% men, mean age 39.1 years) in a health screening program were subjected to bioimpedance body composition analyses and metabolic parameter analyses at baseline and after 4 years. The participants were sub-divided according to age, and additionally to six groups by age and the degree of body weight change over the 4-year period. The actual changes in body weight, lean mass, and fat mass and the percent changes over the 4-year period were assessed.

Results

The percent change in lean mass decreased and the percent change of fat mass increased with increasing age in every age and sex group. However, the annual percent decrease in lean mass and percent increase in fat mass were significantly higher among women than among men (−0.26% vs. −0.15% and 0.34% vs. 0.42%, respectively; P<0.01). Participants who were older than 50 years and had a weight loss <−5% during the 4 years had significantly greater decreases in lean mass and smaller decreases in fat mass, compared to those who were younger than 50 years. An odds ratio analysis to determine the lowest quartile of the percent change in lean mass according to age group revealed that participants older than 60 years had a significantly increased risk of a rapid decrease in the lean mass percentage (2.081; 95% confidence interval, 1.678 to 2.581).

Conclusion

Even in this relatively young study population, the lean mass decreased significantly with age, and the risk of a rapid decrease in lean mass was higher among women than among men. Furthermore, the elderly exhibited a significantly more rapid decrease in lean mass, compared with younger participants.

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Clinical Study
Waist Circumference as a Marker of Obesity Is More Predictive of Coronary Artery Calcification than Body Mass Index in Apparently Healthy Korean Adults: The Kangbuk Samsung Health Study: Jongsin Park, Eun Seo Lee, Da Young Lee, Jihyun Kim, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(4):559-566. Published online December 20, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.559

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Background

We aimed to assess the risk for coronary artery calcification (CAC) according to groups subdivided by body mass index (BMI) and waist circumference (WC) in apparently healthy Korean adults.

Methods

Thirty-three thousand four hundred and thirty-two participants (mean age, 42 years) in a health screening program were divided into three groups according to BMI: <23 kg/m² (normal), 23 to 25 kg/m² (overweight), and >25 kg/m² (obese). In addition, the participants were divided into two groups according to WC. Coronary artery calcium score (CACS) was measured with multi-detector computed tomography in all participants. Presence of CAC was defined as CACS >0.

Results

When logistic regression analysis was performed with the presence of CAC as the dependent variable, the risk for CAC increased as BMI increased after adjusting for confounding variables (1.102 [95% confidence interval (CI), 1.000 to 1.216]; 1.284 [95% CI, 1.169 to 1.410]; in the overweight and obese groups vs. the normal weight group). When the participants were divided into six groups according to BMI and WC, the subjects with BMI and WC in the obese range showed the highest risk for CAC (1.321 [95% CI, 1.194 to 1.461]) and those with BMI in the overweight range and WC in the obese range showed the second highest risk for CAC (1.235 [95% CI, 1.194 to 1.461]).

Conclusion

Participants with obesity defined by both BMI and WC showed the highest risk for CAC. Those with BMIs in the overweight range but with WC in the obese range showed the second highest risk for CAC, suggesting that WC as a marker of obesity is more predictive of CAC than BMI.

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Clinical Study
Eligibility for Statin Treatment in Korean Subjects with Reduced Renal Function: An Observational Study: Byung Sub Moon, Jongho Kim, Ji Hyun Kim, Young Youl Hyun, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Kyu-Beck Lee, Hyang Kim, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(3):402-409. Published online August 26, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.402

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Abstract PDF PubReader

Background

The purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults.

Methods

Renal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m²; stage 2, eGFR 60 to 89 mL/min/1.73 m²; and stages 3 to 5, eGFR <60 mL/min/1.73 m². Statin eligibility in these groups was determined using the ATP III and ACC/AHA guidelines, and the risk for 10-year atherosclerotic cardiovascular disease (ASCVD) was calculated using the Framingham Risk Score (FRS) and Pooled Cohort Equation (PCE).

Results

There were 3,546 (18.9%) and 4,048 (21.5%) statin-eligible subjects according to ATP III and ACC/AHA guidelines, respectively. The proportion of statin-eligible subjects increased as renal function deteriorated. Statin eligibility by the ACC/AHA guidelines showed better agreement with the Kidney Disease Improving Global Outcomes (KDIGO) recommendations compared to the ATP III guidelines in subjects with stage 3 to 5 chronic kidney disease (CKD) (κ value, 0.689 vs. 0.531). When the 10-year ASCVD risk was assessed using the FRS and PCE, the mean risk calculated by both equations significantly increased as renal function declined.

Conclusions

The proportion of statin-eligible subjects significantly increased according to worsening renal function in this Korean cohort. ACC/AHA guideline showed better agreement for statin eligibility with that recommended by KDIGO guideline compared to ATP III in subjects with CKD.

Citations

Citations to this article as recorded by

Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus
Honghong Ren, Lijun Zhao, Yutong Zou, Yiting Wang, Junlin Zhang, Yucheng Wu, Rui Zhang, Tingli Wang, Jiali Wang, Yitao Zhu, Ruikun Guo, Huan Xu, Lin Li, Mark E. Cooper, Fang Liu
Renal Failure.2021; 43(1): 477. CrossRef
Long-term effects of various types of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on changes in glomerular filtration rate in Korea
Seo Yeon Baik, Hyunah Kim, So Jung Yang, Tong Min Kim, Seung-Hwan Lee, Jae Hyoung Cho, Hyunyong Lee, Hyeon Woo Yim, Kun-Ho Yoon, Hun-Sung Kim
Frontiers of Medicine.2019; 13(6): 713. CrossRef
Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea
Y. J. Jeong, H. Kim, S. J. Baik, T. M. Kim, S. J. Yang, S.-H. Lee, J.-H. Cho, H. Lee, H. W. Yim, I. Y. Choi, K.-H. Yoon, H.-S. Kim
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Comparison between Atorvastatin and Rosuvastatin in Renal Function Decline among Patients with Diabetes
Eugene Han, Gyuri Kim, Ji-Yeon Lee, Yong-ho Lee, Beom Seok Kim, Byung-Wan Lee, Bong-Soo Cha, Eun Seok Kang
Endocrinology and Metabolism.2017; 32(2): 274. CrossRef

Clinical Study
C-Peptide-Based Index Is More Related to Incident Type 2 Diabetes in Non-Diabetic Subjects than Insulin-Based Index: Jong-Dai Kim, Sung Ju Kang, Min Kyung Lee, Se Eun Park, Eun Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2016;31(2):320-327. Published online June 21, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.320

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Background

Diabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans.

Methods

This is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline.

Results

Thirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014).

Conclusion

C-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index.

Citations

Citations to this article as recorded by

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Won-Young Lee
Endocrinology and Metabolism.2017; 32(1): 62. CrossRef
Obesity Influence on Insulin Activity and Resting Metabolic Rate in Type 2 Diabetes
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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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Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Nonalcoholic Fatty Liver Disease Increases Cardiovascular Risk in Inflammatory Bowel Diseases
Dana Kablawi, Faisal Aljohani, Chiara Saroli Palumbo, Sophie Restellini, Alain Bitton, Gary Wild, Waqqas Afif, Peter L Lakatos, Talat Bessissow, Giada Sebastiani
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Low Relative Handgrip Strength Is Associated with a High Risk of Non-Alcoholic Fatty Liver Disease in Italian Adults: A Retrospective Cohort Study
Samantha Maurotti, Roberta Pujia, Elisa Mazza, Maria Francesca Pileggi, Franco Arturi, Maria Grazia Tarsitano, Tiziana Montalcini, Arturo Pujia, Yvelise Ferro
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Fatty Liver Disease: Diagnosis and Stratification
Yedidya Saiman, Andres Duarte-Rojo, Mary E. Rinella
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Adriana Cervo, Giada Sebastiani, Jovana Milic, Thomas Krahn, Sergio Mazzola, Salvatore Petta, Antonio Cascio, Giovanni Guaraldi, Giovanni Mazzola
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Julia Karády, Maros Ferencik, Thomas Mayrhofer, Nandini M. Meyersohn, Daniel O. Bittner, Pedro V. Staziaki, Balint Szilveszter, Travis R. Hallett, Michael T. Lu, Stefan B. Puchner, Tracey G. Simon, Borek Foldyna, Geoffrey S. Ginsburg, Robert W. McGarrah,
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Mohammad E. Khamseh, Mojtaba Malek, Rowshanak Abbasi, Hoda Taheri, Maryam Lahouti, Fariba Alaei-Shahmiri
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Grazia Pennisi, Vito Di Marco, Carola Buscemi, Giovanni Mazzola, Cristiana Randazzo, Federica Spatola, Antonio Craxì, Silvio Buscemi, Salvatore Petta
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Pegah Golabi, Natsu Fukui, James Paik, Mehmet Sayiner, Alita Mishra, Zobair M. Younossi
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Gyuri Kim, Suk‐Yong Jang, Eugene Han, Yong‐ho Lee, Se‐young Park, Chung Mo Nam, Eun Seok Kang
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The Journal of Korean Diabetes.2017; 18(2): 81. CrossRef
Increased risk for development of coronary artery calcification in subjects with non-alcoholic fatty liver disease and systemic inflammation
Jihyun Kim, Da Young Lee, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee, Susanne Kaser
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Eugene Han, Yong-ho Lee
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Clinical Study
Association of Waist-Height Ratio with Diabetes Risk: A 4-Year Longitudinal Retrospective Study: Yoon Jeong Son, Jihyun Kim, 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):127-133. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.127

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Background

Waist-to-height ratio (WHtR) is an easy and inexpensive adiposity index that reflects central obesity. In this study, we examined the association of various baseline adiposity indices, including WHtR, with the development of diabetes over 4 years of follow-up in apparently healthy Korean individuals.

Methods

A total of 2,900 nondiabetic participants (mean age, 44.3 years; 2,078 men) in a health screening program, who repeated the medical check-up in 2005 and 2009, were recruited. Subjects were divided into two groups according to development of diabetes after 4 years. The cut-off values of baseline body mass index (BMI), waist circumference (WC), and WHtR for the development of diabetes over 4 years were calculated. The sensitivity, specificity, and mean area under the receiver operator characteristic curve (AUROC) of each index were assessed. The odds ratio (OR) for diabetes development was analyzed for each of the three baseline adiposity indices.

Results

During the follow-up period, 101 new cases (3.5%) of diabetes were diagnosed. The cut-off WHtR value for diabetes development was 0.51. Moreover, WHtR had the highest AUROC value for diabetes development among the three adiposity indices (0.716, 95% confidence interval [CI], 0.669 to 0.763; 0.702, 95% CI, 0.655 to 0.750 for WC; 0.700, 95% CI, 0.651 to 0.750 for BMI). After adjusting for confounding variables, the ORs of WHtR and WC for diabetes development were 1.95 (95% CI, 1.14 to 3.34) and 1.96 (95% CI, 1.10 to 3.49), respectively. No significant differences were observed between the two groups regarding BMI.

Conclusion

Increased baseline WHtR and WC correlated with the development of diabetes after 4 years. WHtR might be a useful screening measurement to identify individuals at high risk for diabetes.

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Erfan Sadeghi, Alireza Khodadadiyan, Seyed Ali Hosseini, Sayed Mohsen Hosseini, Ashraf Aminorroaya, Massoud Amini, Sara Javadi
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Clinical Study
Metabolic Health Is More Important than Obesity in the Development of Nonalcoholic Fatty Liver Disease: A 4-Year Retrospective Study: Min-Kyung Lee, Eun-Jung Rhee, Min Chul Kim, Byung Sub Moon, Jeong In Lee, Young Seok Song, Eun Na Han, Hyo Sun Lee, Yoonjeong Son, Se Eun Park, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2015;30(4):522-530. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.522

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Background

The aim of this study is to compare the risk for future development of nonalcoholic fatty liver disease (NAFLD) according to different status of metabolic health and obesity.

Methods

A total of 3,045 subjects without NAFLD and diabetes at baseline were followed for 4 years. Subjects were categorized into four groups according to the following baseline metabolic health and obesity statuses: metabolically healthy, non-obese (MHNO); metabolically healthy, obese (MHO); metabolically unhealthy, non-obese (MUHNO); and metabolically unhealthy, obese (MUHO). Being metabolically healthy was defined as having fewer than two of the following five components: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostasis model assessment-insulin resistance index. Obesity was defined as a body mass index >25 kg/m². The presence of NAFLD was assessed by ultrasonography.

Results

The proportions of subjects included in the MHNO, MHO, MUHNO, and MUHO groups were 71.4%, 9.8%, 13.0%, and 5.8%, respectively. The proportions of subjects who developed NAFLD were 10.5%, 31.4%, 23.2%, and 42% in the MHNO, MHO, MUHNO, and MUHO groups, respectively. The risk for developing NAFLD was highest in subjects who were metabolically unhealthy both at baseline and after 4 years compared with subjects who were consistently metabolically healthy during the follow-up period (odds ratio, 2.862). Using the MHNO group as reference, the odds ratios for the MHO, MUHNO, and MUHO groups were 1.731, 1.877, and 2.501, respectively.

Conclusion

The risk for NAFLD was lower in MHO subjects than in MUNO subjects.

Citations

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Obesity and Metabolism
Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status: Tae Hoon Lee, Won Seon Jeon, Ki Joong Han, Shin Yeoung Lee, Nam Hee Kim, Hyun Beom Chae, Choel Min Jang, Kyung Mo Yoo, Hae Jung Park, Min Kyung Lee, Se Eun Park, Hyung Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2015;30(2):185-194. Published online June 30, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.2.185

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Background

Metabolic health is an emerging concept that is highly correlated with various metabolic complications, and adipocytokines have been causally linked to a wide range of metabolic diseases. Thus, this study compared serum adipocytokine levels according to metabolic health and obesity status.

Methods

Four hundred and fifty-six nondiabetic subjects (mean age, 40.5 years) were categorized into four groups according to metabolic health and obesity status: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined as the presence of fewer than two of the following five metabolic abnormalities: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostatic model assessment of insulin resistance index. Obesity status was assessed using body mass index (BMI), with obesity defined as a BMI higher than 25 kg/m². Levels of serum interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF-α), and adipocyte fatty acid binding protein (A-FABP) were also evaluated.

Results

Of the 456 subjects, 247 (54.2%) were in the MHNO group, 66 (14.5%) were in the MHO group, 66 (14.5%) were in the MUHNO group, and 77 (16.9%) were in the MUHO group. There were no significant differences in IL-6 or MCP-1 levels among the groups, but levels of TNF-α and A-FABP were significantly higher in the MUHNO group compared to the MHNO group.

Conclusion

High TNF-α and A-FABP levels are significantly associated with metabolically unhealthiness in nonobese Korean individuals.

Citations

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Relationship between the thrombospondin-1/Toll-like receptor 4 (TSP1/TLR4) pathway and vitamin D levels in obese and normal weight subjects with different metabolic phenotypes
Eman Y. Khairy, Azza Saad
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Pattern of Adiponectin, Osteocalcin, Irisin, FGF-21, and MCP-1 According to the Body Size Phenotype: Could They Be Markers of Metabolic Health in Mexican-Mestizo Middle-Aged Women?
Lourdes Balcázar-Hernandez, Lourdes Basurto, Leticia Manuel-Apolinar, Sara Vega-García, Norma Basurto-Acevedo, Carlos Martínez-Murillo, Rosalinda Sánchez-Arenas
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Poor Vitamin D Status in Active Pulmonary Tuberculosis Patients and Its Correlation with Leptin and TNF-α
Qiuzhen WANG, Aiguo MA, Tianlin GAO, Yufeng LIU, Lisheng REN, Lei HAN, Boyang WEI, Qian LIU, Chunjiang DONG, Yuze MU, Duo LI, Frans J KOK, Evert G SCHOUTEN
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Christine Graf, Nina Ferrari
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Ligiane Marques Loureiro, Suzane Lessa, Rodrigo Mendes, Sílvia Pereira, Carlos José Saboya, Andrea Ramalho
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Finja Jockenhöfer, Knut Kröger, Joachim Klode, Regina Renner, Cornelia Erfurt‐Berge, Joachim Dissemond
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Hye-Jeong Park, Se Eun Park, Cheol-Young Park, Seong Yong Lim, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee
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Finja Jockenhöfer, Knut Kröger, Joachim Klode, Regina Renner, Cornelia Erfurt‐Berge, Joachim Dissemond
JDDG: Journal der Deutschen Dermatologischen Gesellschaft.2016; 14(3): 277. CrossRef
Response: Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status (Endocrinol Metab2015;30:185-94, Tae Hoon Lee et al.)
Eun-Jung Rhee
Endocrinology and Metabolism.2015; 30(3): 416. CrossRef
Letter: Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status (Endocrinol Metab2015;30:185-94, Tae Hoon Lee et al.)
Mikyung Kim
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Obesity and Metabolism
Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK: Jinmi Lee, Seok-Woo Hong, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2015;30(2):177-184. Published online June 30, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.2.177

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Background

Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown.

Methods

The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression.

Results

Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositol-requiring kinase 1α, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA.

Conclusion

These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.

Citations

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Gabriel Reichert Blume, Luiz Fernando Freire Royes
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Inha Jung, Dae-Jeong Koo, Won-Young Lee
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Maternal Organic Selenium Supplementation Relieves Intestinal Endoplasmic Reticulum Stress in Piglets by Enhancing the Expression of Glutathione Peroxidase 4 and Selenoprotein S
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Alliin, capsaicin, and gingerol attenuate endoplasmic reticulum stress-induced hepatic steatosis in HepG2 cells and C57BL/6N mice
Ye-Rang Yun, Ji-Eun Lee
Journal of Functional Foods.2022; 95: 105186. CrossRef
PNPLA3 I148M is involved in the variability in anti-NAFLD response to exenatide
Yunzhi Chen, Xuemei Yan, Xiao Xu, Shuhua Yuan, Fen Xu, Hua Liang
Endocrine.2020; 70(3): 517. CrossRef
Green tea extracts reduce leukocyte cell–Derived chemotaxin 2 and selenoprotein P levels in the livers of C57BL/6J mice fed a high-fat diet
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Palmitic acid induces ceramide accumulation, mitochondrial protein hyperacetylation, and mitochondrial dysfunction in porcine oocytes†
Nobuhiko Itami, Koumei Shirasuna, Takehito Kuwayama, Hisataka Iwata
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Bing Zhou, Dan-li Zhou, Xiao-hong Wei, Rong-yu Zhong, Jie Xu, Liao Sun
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Obesity and Metabolism
Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-α-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes: Seok-Woo Hong, Jinmi Lee, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2014;29(4):553-560. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.553

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Background

Tumor necrosis factor (TNF)-α and AMP-activated protein kinase (AMPK) are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated.

Methods

The key factors and mechanism of action of TNF-α and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 α (eIF2α) by Western blot and an immunofluorescence assay in 24-hour TNF-α-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation.

Results

Enhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR) suppressed TNF-α-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-α and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2α, a component of the unfolded protein response signaling pathway, was observed in TNF-α or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-α-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2α.

Conclusion

These data indicated that AICAR-induced AMPK activation attenuates TNF-α-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2α activity is a novel mechanism of the anti-lipolytic effect of AICAR.

Citations

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Obesity and Metabolism
Increased Risk of Diabetes Development in Subjects with the Hypertriglyceridemic Waist Phenotype: A 4-Year Longitudinal Study: Ki Joong Han, Shin Yeoung Lee, Nam Hee Kim, Hyun Beom Chae, Tae Hoon Lee, Choel Min Jang, Kyung Mo Yoo, Hae Jung Park, Min Kyung Lee, Won Seon Jeon, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2014;29(4):514-521. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.514

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Background

The hypertriglyceridemic waist (HTGW) phenotype is a simple and inexpensive screening parameter to identify people at increased risk of cardiovascular disease. We evaluated whether the HTGW phenotype predicts diabetes in urban Korean adults.

Methods

A total of 2,900 nondiabetic subjects (mean age 44.3 years), comprising 2,078 males (71.7%) and 822 females (28.3%) who underwent annual medical check-ups at our center between January 2005 and December 2009, were recruited. The subjects were divided into four groups according to baseline serum triglyceride (TG) level and waist circumference (WC): normal WC-normal TG (NWNT) level, normal WC-high TG level, enlarged WC-normal TG level, and enlarged WC-high TG (EWHT) level. High serum TG level was defined as ≥150 mg/dL and enlarged WC was defined as ≥90 cm for men and ≥85 cm for women. New cases of diabetes were determined according to questionnaires filled in by participants and the diagnostic criteria of the American Diabetes Association. Cox proportional hazards model analysis was used to assess the association of HTGW phenotype with the incidence of diabetes.

Results

A total of 101 (3.5%) new diabetes cases were diagnosed during the study period. The EWHT group had a higher incidence of diabetes (8.3%) compared with the NWNT group (2.2%). The adjusted hazard ratio for diabetes for subjects with the EWHT phenotype at baseline was 4.113 (95% confidence interval [CI], 2.397 to 7.059) after adjustment for age, and 2.429 (95% CI, 1.370 to 4.307) after adjustment for age, sex, total cholesterol, systolic blood pressure, and alcohol drinking history. It was attenuated by inclusion of baseline fasting glucose level in the model.

Conclusion

Subjects with the HTGW phenotype showed the highest risk of incident diabetes. This tool could be useful for identifying individuals at high risk of diabetes.

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Age Is the Strongest Effector for the Relationship between Estimated Glomerular Filtration Rate and Coronary Artery Calcification in Apparently Healthy Korean Adults: Hyun Beom Chae, Shin Yeoung Lee, Nam Hee Kim, Ki Joong Han, Tae Hoon Lee, Choel Min Jang, Kyung Mo Yoo, Hae Jung Park, Min Kyung Lee, Won Seon Jeon, Se Eun Park, Heui-Soo Moon, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2014;29(3):312-319. Published online September 25, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.3.312

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Background

Chronic kidney disease (CKD) is considered one of the most common risk factors for cardiovascular disease. Coronary artery calcification (CAC) is a potential mechanism that explains the association between renal function and cardiovascular mortality. We aimed to evaluate the association between renal function and CAC in apparently healthy Korean subjects.

Methods

A total of 23,617 participants in a health-screening program at Kangbuk Samsung Hospital were included in the study. Estimated glomerular filtration rate (eGFR) was assessed using the Cockcroft-Gault equation. Coronary artery calcium score (CACS) was measured via multidetector computed tomography. Subjects were divided into three groups according to the CKD Staging system with eGFR grade: stage 1, eGFR ≥90 mL/min/1.73 m²; stage 2, eGFR 60 to 89 mL/min/1.73 m²; and stage 3, eGFR 30 to 59 mL/min/1.73 m².

Results

The mean age of the participants was 41.4 years and the mean eGFR was 103.6±21.7 mL/min/1.73 m². Hypertension and diabetes were noted in 43.7% and 5.5% of the participants, respectively. eGFR showed a weakly negative but significant association with CACS in bivariate correlation analysis (r=-0.076, P<0.01). Mean CACS significantly increased from CKD stage 1 to 3. The proportion of subjects who had CAC significantly increased from CKD stage 1 to 3. Although the odds ratio for CAC significantly increased from stage 1 to 3 after adjustment for confounding factors, this significance was reversed when age was included in the model.

Conclusion

In early CKD, renal function negatively correlated with the degree of CAC in Korean subjects. Age was the strongest effector for this association.

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Obesity and Metabolism
Association of Serum Adipocyte-Specific Fatty Acid Binding Protein with Fatty Liver Index as a Predictive Indicator of Nonalcoholic Fatty Liver Disease: Won Seon Jeon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2013;28(4):283-287. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.283

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Background

Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein expressed in macrophages and adipocytes and it plays a role in insulin resistance and metabolic syndrome. Recently, the fatty liver index (FLI) was introduced as an indicator of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the relationship between baseline serum A-FABP levels and FLI after 4 years in apparently healthy subjects.

Methods

A total of 238 subjects without a past history of alcoholism or hepatitis were recruited from a medical check-up program. The NAFLD state was evaluated 4 years later in the same subjects using FLI. Fatty liver disease was diagnosed as diffusely increased echogenicity of the hepatic parenchyma compared to the kidneys, vascular blurring, and deep-echo attenuation. NAFLD was defined as subjects with fatty liver and no history of alcohol consumption (>20 g/day).

Results

Baseline serum A-FABP levels were significantly associated with FLI after adjustment for age and sex (P<0.001). The subjects with higher A-FABP levels had a higher mean FLI (P for trend=0.006). After adjusting for age and sex, serum A-FABP levels at baseline were shown to be significantly associated with FLI as a marker of development of NAFLD after 4 years (odds ratio, 2.68; 95% confidence interval, 1.24 to 5.80 for highest tertile vs. lowest tertile; P=0.012).

Conclusion

This study demonstrated that higher baseline serum A-FABP levels were associated with FLI as a predictive indicator of NAFLD after 4 years of follow-up in healthy Korean adults.

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Background

Tumor necrosis factor (TNF)-α is associated with insulin resistance and systemic inflammatory responses. The aim of this study was to investigate the relationship between TNF-α and the development of nonalcoholic fatty liver disease (NAFLD) in a longitudinal study.

Methods

Three hundred and sixty-three apparently healthy subjects (mean age, 40.5±6.1 years; male, 57.6%) without NAFLD were enrolled in 2003. Anthropometric and laboratory measurements were performed. The participants were grouped into tertiles according to their serum TNF-α levels from samples taken in 2003. At a 4-year follow-up, we compared the odds ratios (ORs) of the development of NAFLD according to the tertiles of TNF-α levels measured in 2003.

Results

At the 4-year follow-up, the cumulative incidence of NAFLD was 29.2% (106/363). The group that developed NAFLD had higher levels of TNF-α than those in the group without NAFLD (3.65±1.79 pg/mL vs. 3.15±1.78 pg/mL; P=0.016). When the 2003 serum TNF-α levels were categorized into tertiles: incidence of NAFLD observed in 2007 was significantly higher with increasing tertiles (22.6%, 35.8%, and 41.5%, respectively; P<0.05). The risk of developing NAFLD was significantly greater in the highest tertile of TNF-α than in the lowest tertile after adjusting for age, smoking, and BMI (OR, 2.20; 95% confidence interval, 1.12 to 4.01; P<0.05).

Conclusion

Higher serum TNF-α levels in subjects without NAFLD were associated with the development of NAFLD. The results of study might suggest a pathologic role of inflammation in NAFLD.

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Isolation of Density Enrichment Fraction of Adipose-Derived Stem Cells from Stromal Vascular Fraction by Gradient Centrifugation Method.: Min Kyung Kim, Yong Soon Park, Hee Soon Park, Jung Mook Choi, Won Jun Kim, Se Eun Park, Eun Jung Rhee, Cheol Young Park, Won Young Lee, Ki Won Oh, Sung Woo Park, Sun Woo Kim, Kwang Sik Suh, Jeong Taek Woo; Endocrinol Metab. 2010;25(2):103-109. Published online June 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.2.103

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Abstract PDF

BACKGROUND
Adipose tissues include multipotent cells, the same as bone marrow-derived mesenchymal stem cells. The stromal vascular fractions (SVFs) from adipose tissues represent a heterogeneous cell population. The purpose of this study was to isolate and purify adipose-derived stem cells (ASCs) in SVFs by the density gradient method. METHODS: SVFs were extracted from the subcutaneous, epididymal, mesenteric and retroperitoneal adipose tissue of 8 weeks old male Sprague-Dawley rats (n = 15) and these were separated into 4 layers according to a Nycodenz gradient (Fx-1: < 11%, Fx-2: 11-13%, Fx-3: 13-19% and Fx-4: 19-30%). The post-confluent SVFs were cultured in adipogenic medium for 2 days, in insulin medium for 2 days and in 10% fetal bovine serum medium for 5 days. To observe lipid droplets in SVFs, we performed Oil Red O staining. RESLTS: The SVFs' cellular fractions (Fx-1, Fx-2, Fx-3 and Fx-4) were isolated by density gradient centrifugation from the adipose tissues of rats. The SVFs extracted to fraction 3 (Fx-3) had the most abundant cells compared to that of the other fractions. However fraction 1 (Fx-1) or 2 (Fx-2) had a superior ability to make lipid droplets. The adipogenic differentiation of Fx-1 or 2 was higher than that of the unfractionated cells. The SVFs extracted from retroperitoneal adipose tissue had the highest efficiency for adipogenic differentiation, whereas the SVFs from mesenteric adipose tissue did not differentiate. CONCLUSION: This density gradient fractionated method leads to efficient isolation and purification of cells with the characteristics of ASCs.

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Embolic Infarction Presented after Intravenous Injection of Stromal Vascular Fraction
Jin Young Seo, Ju-Hun Lee, Hong-Ki Song, Jong Seok Bae, Yerim Kim
Journal of Neurosonology and Neuroimaging.2018; 10(2): 181. CrossRef

Case Reports

Non-functional Pituitary Adenoma Detected on (18)F-fluorodeoxyglucose Positron Emission Tomography ((18)F-FDG-PET) in a Patient with Mucosa-associated Lymphoid Tissue Lymphoma.: Jin Ha Lee, Seung Jin Han, Se Eun Park, Mi Ae Cho, June Won Cheong, Mijin Yun, Yumie Rhee, Eun Jig Lee, Sung Kil Lim; J Korean Endocr Soc. 2008;23(2):137-141. Published online April 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.2.137

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Abstract PDF

Magnetic resonance imaging (MRI) is the modality of choice for the detection and characterization of a pituitary adenoma. Uptake of (18)F-fluorodeoxyglucose (FDG) by intrasellar tumors, including pituitary adenomas, has been reported in several previous studies. We report a case where a pituitary adenoma was detected on FDG-positron emission tomography (PET), but the tumor was not detected with the use of sellar MRI. A 31-year-old woman was referred to the clinic due to a focal increase of FDG uptake at the pituitary fossa seen on whole body FDG-PET. The patient was receiving chemotherapy due to a recurred B-cell lymphoma of the mucosa-associated lymphoid tissue type. Subsequently, sellar MRI was performed, and images showed a small non-enhancing heterogenous cystic lesion in the midline of the pituitary gland, radiologically suggestive of a Rathke's cleft cyst. However, sellar MRI failed to identify a lesion consistent with a pituitary tumor that corresponded to the site of increased FDG uptake detected by the use of PET, despite the inclusion of a dynamic contrast enhanced sequence. Despite the negative findings of the MRI examination, basal and stimulated levels of the GnRH free alpha-subunit were profoundly increased. Therefore, we suspected the presence of a non-functional pituitary tumor in addition to a Rathke's cleft cyst, rather than pituitary involvement of a lymphoma, based on the hormone levels and PET scan findings.

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Clinical Characteristics of 16 Patients with Pituitary Tumor Incidentally Detected by18F-Fluorodeoxyglucose PET-CT (18F-FDG PET-CT)
Hyung Jin Kim, Gi Jeong Cheon, A Ra Cho, Chang Hoon Lee, Sang Min Youn, Se jin Ahn, Sang Eon Jang, Jung Min Kim, Yun Yong Lee, Ka Hee Yi
Endocrinology and Metabolism.2010; 25(4): 321. CrossRef

A Case of Multiple Endocrine Neoplasia Type 1 with Mutation in MENIN Gene.: Se Eun Park, Eun Seok Kang, Hyun Joo Lee, So Hun Kim, Mi Young Do, Shin Ae Kang, Seung Jin Han, Hyeong Jin Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Il Jin Kim, Hyun Chul Lee; J Korean Endocr Soc. 2005;20(1):71-77. Published online February 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.1.71

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Abstract PDF

Multiple endocrine neoplasia type 1(MEN 1) is an autosomal dominantly inherited syndrome, characterized by the combined occurrence of tumors of the parathyroid glands, endocrine pancreas, and anterior pituitary gland. The MENIN gene, which is a kind of tumor suppressor gene, is located at the chromosomal locus 11q13. It consists of one untranslated exon and nine exons encoding the menin protein. We report a case of a 22-yearss-old woman with MEN type 1, who was proven to have a mutation in the MENIN gene. The patient was admitted because of repeated hypoglycemia. The fasting plasma glucose level was 32mg/dL. Seventy two hours fasting test showed an the insulin/glucose ratio as 0.33. Endoscopic ultrasonography detected multiple masses on the pancreas. The arterial -stimulated venous sampling(ASVS) with calcium showed sudden step up of insulin at the head and tail portions of the pancreas. The sellar MRI showed a pituitary mass that produced prolactin. Instead of a pathologic diagnosis from operational specimen, the genetic analysis revealed a mutation in the MENIN 1 gene(exon 2, 200~201insAGCCC).

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Genetic and Epigenetic Analysis in Korean Patients with Multiple Endocrine Neoplasia Type 1
Yoon Jung Chung, Sena Hwang, Jong Ju Jeong, Sun Yong Song, Se Hoon Kim, Yumie Rhee
Endocrinology and Metabolism.2014; 29(3): 270. CrossRef
A Case of Familial Multiple Endocrine Neoplasia Type 1 with a Novel Mutation in theMEN1Gene
Min Jung Kim, Eun Hee Kim, Mi-Seon Shin, Joo Hui Kim, Hee Kyung Na, Seong Joon Park, Sang Ah Lee, Eun Hee Koh, Woo Je Lee, Ki Ho Song, Joong-Yeol Park, Ki-Up Lee, Gu-Hwan Kim, Han-Wook Yoo, Min-Seon Kim
Endocrinology and Metabolism.2011; 26(2): 171. CrossRef
Somatic Mutational Analysis of MEN1 and Phenotypic Correlation in Sporadic Parathyroid Tumors
Young Su Chae, Hee Jin Kim, Sun Wook Kim, Myung-Chul Chang
Journal of the Korean Surgical Society.2009; 76(1): 15. CrossRef
Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene
Heekyoung Choi, Sehyun Kim, Jae-Hoon Moon, Yoon Hee Lee, Yumie Rhee, Eun Seok Kang, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Kyung Rae Kim, Hyun Chul Lee, Seon Yong Jeong, Hyun Ju Kim, Sung-Kil Lim
Yonsei Medical Journal.2008; 49(4): 655. CrossRef
A Case of Familial Multiple Endocrine Neoplasia Type 1 with MEN1 Gene Mutation
Young Eun Jo, Yong-Jun Choi, Yun Kyung Kim, Sang Mi Ahn, Sun Hye Jung, Hae Jin Kim, Dae Jung Kim, Kwan Woo Lee, Ji-Hee Hong, Seon-Yong Jeong, Hyon J Kim, Yoon-Sok Chung
Journal of Korean Endocrine Society.2007; 22(1): 68. CrossRef
A Case of Familial Multiple Endocrine Neoplasia with MEN1 Gene Mutation
Hye-Young Sung, Yeon-Joo Chun, Hyeug Lee, Bum Jun Kwon, Kun Woo Park, Jung Min Lee, Sung Dae Moon, Sang Ah Chang, Je-Ho Han
Journal of Korean Endocrine Society.2006; 21(6): 560. CrossRef

Original Article

Adiponectin Gene Polymorphism and Carotid Artery Intima-Media thickness in Type 2 Diabetes.: Eun Seok Kang, So Young Park, So Hun Kim, Hyun Joo Lee, Kyu Yeon Hur, Seung Jin Han, Se Eun Park, Hyeong Jin Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; J Korean Endocr Soc. 2005;20(1):29-39. Published online February 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.1.29

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Abstract PDF: BACKGROUND
The aim of this study was to examine the association between the common polymorphisms of the adiponectin gene(ACDC) and the intima-media thickness(IMT) of the common carotid arteries in type 2 diabetic patients. METHODS: The B mode ultrasound examination of carotid artery was performed on 133 type 2 diabetic patients. The carotid IMT was calculated using the Intimascope computer program. The SNP45 and SNP276 of the ACDC were examined. RESULTS: There was no significant difference in the carotid IMT among the SNP45 genotypes(0.66+/-0.18mm for TT, 0.71+/-0.12mm for TG and 0.64+/-0.15mm for GG, P=NS). Subjects carrying the SNP276 GG genotype had a markedly lower serum adiponectin concentration than those carrying the TT genotype(3.35+/-2.00microgram/mL vs. 4.98+/-2.24microgram/mL, P=0.029) The carotid IMT was significantly higher in patients with the SNP276 GG genotype than those with the TT genotype (0.70+/-0.17mm vs. 0.59+/-0.13mm, P=0.032). Patients with the +45GG/+276GG genotype combination showed significantly higher mean carotid IMT than the other genotype combinations(0.78+/-0.09mm vs. 0.71+/-0.15mm, P=0.013) CONCLUSIONS: These results suggest that the adiponectin gene, SNP276 is associated with the carotid IMT in type 2 diabetic patients. Further studies are will be needed to confirm these genotypephenotype associations.

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