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Brief Report
Diabetes, obesity and metabolism
Impact of Diabetes on COVID-19 Susceptibility: A Nationwide Propensity Score Matching Study
Han Na Jang, Sun Joon Moon, Jin Hyung Jung, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Endocrinol Metab. 2024;39(5):813-818.   Published online August 28, 2024
DOI: https://doi.org/10.3803/EnM.2024.2014
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  • 34 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.
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Letter
Diabetes, obesity and metabolism
Multiple Definitions of Fatty Liver Disease: Which One Most Accurately Predicts Diabetes?
Eun-Jung Rhee
Endocrinol Metab. 2024;39(2):397-398.   Published online April 25, 2024
DOI: https://doi.org/10.3803/EnM.2024.202
  • 1,384 View
  • 46 Download
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Original Articles
Diabetes, obesity and metabolism
Impact of Antidiabetic Drugs on Clinical Outcomes of COVID-19: A Nationwide Population-Based Study
Han Na Jang, Sun Joon Moon, Jin Hyung Jung, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Endocrinol Metab. 2024;39(3):479-488.   Published online January 29, 2024
DOI: https://doi.org/10.3803/EnM.2023.1857
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  • 125 Download
AbstractAbstract PDFPubReader   ePub   
Background
Inconsistent results have been reported regarding the association between the use of antidiabetic drugs and the clinical outcomes of coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of antidiabetic drugs on COVID-19 outcomes in patients with diabetes using data from the National Health Insurance Service (NHIS) in South Korea.
Methods
We analyzed the NHIS data of patients aged ≥20 years who tested positive for COVID-19 and were taking antidiabetic drugs between December 2019 and June 2020. Multiple logistic regression analysis was performed to analyze the clinical outcomes of COVID-19 based on the use of antidiabetic drugs.
Results
A total of 556 patients taking antidiabetic drugs tested positive for COVID-19, including 271 male (48.7%), most of whom were in their sixties. Of all patients, 433 (77.9%) were hospitalized, 119 (21.4%) received oxygen treatment, 87 (15.6%) were admitted to the intensive care unit, 31 (5.6%) required mechanical ventilation, and 61 (11.0%) died. Metformin was significantly associated with the lower risks of mechanical ventilation (odds ratio [OR], 0.281; 95% confidence interval [CI], 0.109 to 0.720; P=0.008), and death (OR, 0.395; 95% CI, 0.182 to 0.854; P=0.018). Dipeptidylpeptidase-4 inhibitor (DPP-4i) were significantly associated with the lower risks of oxygen treatment (OR, 0.565; 95% CI, 0.356 to 0.895; P=0.015) and death (OR, 0.454; 95% CI, 0.217 to 0.949; P=0.036). Sulfonylurea was significantly associated with the higher risk of mechanical ventilation (OR, 2.579; 95% CI, 1.004 to 6.626; P=0.049).
Conclusion
In patients with diabetes and COVID-19, metformin exhibited reduced risks of mechanical ventilation and death, DPP- 4i was linked with lower risks of oxygen treatment and death, while sulfonylurea was related to the increased risk of mechanical ventilation.
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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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  • 2 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • 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
  • 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.2024;[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
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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
  • 3,181 View
  • 147 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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

Citations to this article as recorded by  
  • 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
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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
  • 4,224 View
  • 173 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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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Review Article
Diabetes, Obesity and Metabolism
Extra-Glycemic Effects of Anti-Diabetic Medications: Two Birds with One Stone?
Eun-Jung Rhee
Endocrinol Metab. 2022;37(3):415-429.   Published online June 29, 2022
DOI: https://doi.org/10.3803/EnM.2022.304
  • 6,276 View
  • 306 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFPubReader   ePub   
The world is suffering from a rapid increase in the number of people with diabetes due to the increased prevalence of obesity and lengthened life span. Since the development of insulin thanks to the efforts of Prof. Banting and Dr. Best in 1922, for which they won the Nobel Prize, remarkable developments in anti-diabetic medications have dramatically lengthened the lifespan of patients with diabetes. However, the control rate of hyperglycemia in patients with diabetes remains unsatisfactory, since glycemic control requires both medication and lifestyle modifications to slow the deterioration of pancreatic beta-cell function and prevent diabetic complications. From the initial “triumvirate” to the “ominous octet,” and now the “egregious eleven,” the number of organs recognized as being involved in hyperglycemia and diabetes has increased with the development of anti-diabetic medications. Recent unexpected results from outcome trials of anti-diabetic medications have enabled anti-diabetic medications to be indicated for the prevention of chronic kidney disease and heart failure, even in patients without diabetes. In this review, I would like to summarize the extra-glycemic effects of anti-diabetic medications.

Citations

Citations to this article as recorded by  
  • Association between underweight and risk of heart failure in diabetes patients
    Tae Kyung Yoo, Kyung‐Do Han, Eun‐Jung Rhee, Won‐Young Lee
    Journal of Cachexia, Sarcopenia and Muscle.2024; 15(2): 671.     CrossRef
  • Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification
    Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
    Diabetes & Metabolism Journal.2024; 48(1): 83.     CrossRef
  • To do one and to get more: Part I. Diabetes and bone
    Wen-Ling Lee, Peng-Hui Wang, Szu-Ting Yang, Chia-Hao Liu, Wen-Hsun Chang, Fa-Kung Lee
    Journal of the Chinese Medical Association.2022; 85(10): 965.     CrossRef
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Namgok Lecture 2021
Diabetes, Obesity and Metabolism
The Influence of Obesity and Metabolic Health on Vascular Health
Eun-Jung Rhee
Endocrinol Metab. 2022;37(1):1-8.   Published online February 28, 2022
DOI: https://doi.org/10.3803/EnM.2022.101
  • 12,159 View
  • 374 Download
  • 32 Web of Science
  • 38 Crossref
AbstractAbstract PDFPubReader   ePub   
The prevalence of obesity is rapidly increasing worldwide. Obesity should not be understood only as the accumulation of fat in the body, but instead as a phenomenon that exerts different effects on our health according to the place of fat deposition and its stability. Obesity is the starting point of most metabolic diseases, such as diabetes, hypertension, metabolic syndrome, sleep apnea, and eventually cardiovascular disease. There are different kinds of obesity, ranging from simple obesity to sarcopenic obesity. The main purpose of intervening to address obesity is to decrease the ultimate consequence of obesity—namely, cardiovascular disease. The main mechanism through which obesity, especially abdominal obesity, increases cardiovascular risk is the obesity-induced derangement of metabolic health, leading to the development of metabolic diseases such as diabetes, non-alcoholic fatty liver disease, and metabolic syndrome, which are the main initiators of vascular damage. In this review, I discuss the influence of various types of obesity on the risk of metabolic diseases, and how these diseases increase cardiovascular disease risk.

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  • 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
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    Ying Zhang, Xiu-Bin Jia, Yun-Chao Liu, Wen-Qian Yu, Yan-Hong Si, Shou-Dong Guo
    Frontiers in Nutrition.2022;[Epub]     CrossRef
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    Lizheng Guan, Tiantian Li, Xuan Wang, Kang Yu, Rong Xiao, Yuandi Xi
    Nutrients.2022; 14(19): 3911.     CrossRef
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    Journal of Interdisciplinary Medicine.2022; 7(4): 88.     CrossRef
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Original Articles
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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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • GLP-1/GLP-1RAs: New Options for the Drug Treatment of NAFLD
    Haoran Jiang, Linquan Zang
    Current Pharmaceutical Design.2024; 30(2): 100.     CrossRef
  • Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism
    Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan
    Diabetes & Metabolism Journal.2024; 48(3): 354.     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
  • 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
  • Effects of the switch from dulaglutide to tirzepatide on glycemic control, body weight, and fatty liver: a retrospective study
    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
    The FASEB Journal.2024;[Epub]     CrossRef
  • GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives
    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
  • FAM3A mediates the phenotypic switch of human aortic smooth muscle cells stimulated with oxidised low-density lipoprotein by influencing the PI3K-AKT pathway
    Lei Yang, Baoshun Du, Shitao Zhang, Maode Wang
    In Vitro Cellular & Developmental Biology - Animal.2023; 59(6): 431.     CrossRef
  • ATP Secretion and Metabolism in Regulating Pancreatic Beta Cell Functions and Hepatic Glycolipid Metabolism
    Jing Li, Han Yan, Rui Xiang, Weili Yang, Jingjing Ye, Ruili Yin, Jichun Yang, Yujing Chi
    Frontiers in Physiology.2022;[Epub]     CrossRef
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    Xiaohan Xu, Kyle L. Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang
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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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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • 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
    Digestive Diseases and Sciences.2024; 69(4): 1430.     CrossRef
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    Gyuri Kim, Tae Yang Yu, Jae Hwan Jee, Ji Cheol Bae, Mira Kang, Jae Hyeon Kim
    Diabetes & Metabolism.2024; 50(3): 101534.     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
  • Effects of luseogliflozin on suspected MASLD in patients with diabetes: a pooled meta-analysis of phase III clinical trials
    Takumi Kawaguchi, Kenta Murotani, Hiromitsu Kajiyama, Hitoshi Obara, Hironori Yamaguchi, Yuko Toyofuku, Fumi Kaneko, Yutaka Seino, Saeko Uchida
    Journal of Gastroenterology.2024; 59(9): 836.     CrossRef
  • Factors Associated with Liver Fibrosis in Chinese Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease
    Yu Luo, Cuiyu Wang, Tian Zhang, Xiaoyu He, Jianan Hao, Andong Shen, Hang Zhao, Shuchun Chen, Luping Ren
    International Journal of General Medicine.2023; Volume 16: 293.     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
  • Metabolic Score for Insulin Resistance Is Inversely Related to Incident Advanced Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
    Jun-Hyuk Lee, Yu-Jin Kwon, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn
    Nutrients.2022; 14(15): 3039.     CrossRef
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    Kexing Han, Kexuan Tan, Jiapei Shen, Yuting Gu, Zilong Wang, Jiayu He, Luyang Kang, Weijie Sun, Long Gao, Yufeng Gao
    Frontiers in Public Health.2022;[Epub]     CrossRef
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    Dae-Jeong Koo, Won-Young Lee
    Cardiovascular Prevention and Pharmacotherapy.2022; 4(4): 132.     CrossRef
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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
  • 5,185 View
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

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  • 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
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    Huan Lian, Zhuoyan Zhao, Kelin Ma, Zhenjiang Ding, Lixian Sun, Ying Zhang
    Clinical and Applied Thrombosis/Hemostasis.2022;[Epub]     CrossRef
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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
  • 6,328 View
  • 147 Download
  • 11 Web of Science
  • 12 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

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  • 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
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    Nathalie C. Leite, Claudia R. L. Cardoso, Cristiane A. Villela‐Nogueira, Gil F. Salles
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    Inha Jung, Dae-Jeong Koo, Won-Young Lee
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    Tzu-Chieh Hsu, Chun-Hsien Chiang, I-Hsuan Liu, Chih-Yun Wang, Ching-Yi Chen
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    Katie J. McMenamin, Tamara B. Harris, Joshua F. Baker
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  • 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
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    Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
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    Mohammed Eslam, Hashem B. El-Serag, Sven Francque, Shiv K. Sarin, Lai Wei, Elisabetta Bugianesi, Jacob George
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  • 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
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    Yeoree Yang, Jae-Hyoung Cho
    Endocrinology and Metabolism.2021; 36(4): 766.     CrossRef
  • Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease
    Inha Jung, Da Young Lee, Mi Yeon Lee, Hyemi Kwon, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Won-Young Lee, Sung-Woo Park, Se Eun Park
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
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Review Article
Diabetes
Best Achievements in Clinical Medicine in Diabetes and Dyslipidemia in 2020
Eun-Jung Rhee, Mee-Kyung Kim, Won-Young Lee
Endocrinol Metab. 2021;36(1):41-50.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2021.106
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AbstractAbstract PDFPubReader   ePub   
Over the last two decades, our understanding of diabetes and treatment strategies have evolved tremendously, from scientific, mechanistic, and human perspectives. The categories of anti-diabetic medications expanded from a few to numerous, enabling clinicians to personalize diabetes care and treatment. Thanks to rapid growth in the field of science and medical engineering, newer treatment options are coming to the market with various advantages and disadvantages to be aware of. Therefore, clinicians should rapidly adopt new trends based on guidelines and data from many clinical trials in the field of diabetes. In the treatment of dyslipidemia, trends and guidelines are changing every year, and novel therapies are being developed. In this review, we would like to summarize the major achievements in clinical medicine in 2020 in the field of diabetes mellitus and dyslipidemia.

Citations

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  • Efficacy and safety of enavogliflozin versus dapagliflozin added to metformin plus gemigliptin treatment in patients with type 2 diabetes: A double-blind, randomized, comparator-active study: ENHANCE-D study
    Kyung-Soo Kim, Kyung Ah Han, Tae Nyun Kim, Cheol-Young Park, Jung Hwan Park, Sang Yong Kim, Yong Hyun Kim, Kee Ho Song, Eun Seok Kang, Chul Sik Kim, Gwanpyo Koh, Jun Goo Kang, Mi Kyung Kim, Ji Min Han, Nan Hee Kim, Ji Oh Mok, Jae Hyuk Lee, Soo Lim, Sang S
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    Simin Zhang, Donghan Sun, Xiaoyi Qian, Li Li, Wenwen Wu
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    Heekyoung Jeong, Kyungdo Han, Soon Jib Yoo, Mee Kyoung Kim
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Original Articles
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
  • 6,770 View
  • 142 Download
  • 8 Web of Science
  • 10 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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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  • 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
    Endocrinology and Metabolism.2024; 39(2): 353.     CrossRef
  • 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
    Autophagy.2024; 20(11): 2361.     CrossRef
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    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
    Diabetology & Metabolic Syndrome.2024;[Epub]     CrossRef
  • 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
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    Ning Yang, Bo Dong, Yanqiu Song, Yang Li, Lu Kou, Qin Qin
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    Seok-Woo Hong, Won-Young Lee
    Cardiovascular Prevention and Pharmacotherapy.2022; 4(2): 57.     CrossRef
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    Marzieh Zeinvand-Lorestani, Mohammad Javad Khodayar, Ali Teimoori, Najmaldin Saki, Akram Ahangarpour, Ali Ranjbar, Hamed Zeinvand-Lorestani
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    Chirag Jain, Ansarullah, Sara Bilekova, Heiko Lickert
    Nature Metabolism.2022; 4(9): 1097.     CrossRef
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    Safia Costes, Gyslaine Bertrand, Magalie A. Ravier
    International Journal of Molecular Sciences.2021; 22(10): 5303.     CrossRef
Close layer
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
  • 9,532 View
  • 207 Download
  • 14 Web of Science
  • 17 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

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