Endocrinology and Metabolism

Volume 37(1); February 2022

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

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Abstract PDF PubReader ePub Crossref - TDM

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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Mechanistic insights into dietary (poly)phenols and vascular dysfunction-related diseases using multi-omics and integrative approaches: Machine learning as a next challenge in nutrition research
Dragan Milenkovic, Tatjana Ruskovska
Molecular Aspects of Medicine.2023; 89: 101101. CrossRef
Pharmacological Support for the Treatment of Obesity—Present and Future
Marcin Kosmalski, Kacper Deska, Bartłomiej Bąk, Monika Różycka-Kosmalska, Tadeusz Pietras
Healthcare.2023; 11(3): 433. CrossRef
Prioritizing obesity treatment: expanding the role of cardiologists to improve cardiovascular health and outcomes
Donna H. Ryan, John E. Deanfield, Stephan Jacob
Cardiovascular Endocrinology & Metabolism.2023; 12(1): e0279. CrossRef
Adipopenia is associated with osteoporosis in community-dwelling non-underweight adults independent of sarcopenia
Seunghyun Lee, Kyoungmyoung Ko, Sungjae Shin, Hye Sun Park, Namki Hong, Yumie Rhee
Archives of Osteoporosis.2023;[Epub] 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
Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet
Ying Zhang, Xiu-Bin Jia, Yun-Chao Liu, Wen-Qian Yu, Yan-Hong Si, Shou-Dong Guo
Frontiers in Nutrition.2022;[Epub] CrossRef
Predictive Roles of Basal Metabolic Rate and Body Water Distribution in Sarcopenia and Sarcopenic Obesity: The link to Carbohydrates
Lizheng Guan, Tiantian Li, Xuan Wang, Kang Yu, Rong Xiao, Yuandi Xi
Nutrients.2022; 14(19): 3911. CrossRef
Metabolic risk factors in patients with comorbidity in Ufa primary health care
O.V. Molchanova, A.V. Mamaeva, A.R. Dunayeva, Z.A. Lust, E.M. Faskhetdinova, R.N. Shepel, D.O. Orlov, L.M. Zhamalov, G.F. Andreeva, O.M. Drapkina
Profilakticheskaya meditsina.2022; 25(9): 39. CrossRef
Assessment of Vitamin D Levels in Relation to Statin Therapy in Elderly Hypertensive Patients with Comorbidities
Kinga-Ilona Nyulas, Zsuzsánna Simon-Szabó, Zoltán Preg, Sándor Pál, Arundhati Sharma, Tünde Pál, Márta Germán-Salló, Enikő Nemes-Nagy
Journal of Interdisciplinary Medicine.2022; 7(4): 88. CrossRef

Review Articles

Diabetes, Obesity and Metabolism
Homeostatic Regulation of Glucose Metabolism by the Central Nervous System: Jong Han Choi, Min-Seon Kim; Endocrinol Metab. 2022;37(1):9-25. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1364

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Abstract PDF PubReader ePub Crossref - TDM

Evidence for involvement of the central nervous system (CNS) in the regulation of glucose metabolism dates back to the 19th century, although the majority of the research on glucose metabolism has focused on the peripheral metabolic organs. Due to recent advances in neuroscience, it has now become clear that the CNS is indeed vital for maintaining glucose homeostasis. To achieve normoglycemia, specific populations of neurons and glia in the hypothalamus sense changes in the blood concentrations of glucose and of glucoregulatory hormones such as insulin, leptin, glucagon-like peptide 1, and glucagon. This information is integrated and transmitted to other areas of the brain where it eventually modulates various processes in glucose metabolism (i.e., hepatic glucose production, glucose uptake in the brown adipose tissue and skeletal muscle, pancreatic insulin and glucagon secretion, renal glucose reabsorption, etc.). Errors in these processes lead to hyper- or hypoglycemia. We here review the current understanding of the brain regulation of glucose metabolism.

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Phenotypic screening using waveform analysis of synchronized calcium oscillations in primary cortical cultures
Richi Sakaguchi, Saki Nakamura, Hiroyuki Iha, Masaki Tanaka, Ming Tatt Lee
PLOS ONE.2023; 18(4): e0271782. CrossRef
Effects of Escitalopram on the Functional Neural Circuits in an Animal Model of Adolescent Depression
Se Jong Oh, Namhun Lee, Kyung Rok Nam, Kyung Jun Kang, Sang Jin Han, Jae Yong Choi
Molecular Imaging and Biology.2023;[Epub] CrossRef
Knockout of Nur77 Leads to Amino Acid, Lipid, and Glucose Metabolism Disorders in Zebrafish
Yang Xu, Juanjuan Tian, Qi Kang, Hang Yuan, Chengdong Liu, Zhehui Li, Jie Liu, Mingyu Li
Frontiers in Endocrinology.2022;[Epub] CrossRef
Effects of the POMC System on Glucose Homeostasis and Potential Therapeutic Targets for Obesity and Diabetes
Dan Yang, Xintong Hou, Guimei Yang, Mengnan Li, Jian Zhang, Minmin Han, Yi Zhang, Yunfeng Liu
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 2939. CrossRef

Diabetes, Obesity and Metabolism
Recent Updates to Clinical Practice Guidelines for Diabetes Mellitus: Jin Yu, Seung-Hwan Lee, Mee Kyoung Kim; Endocrinol Metab. 2022;37(1):26-37. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.105

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Abstract PDF PubReader ePub Crossref - TDM

Guidelines for the management of patients with diabetes have become an important part of clinical practice that improve the quality of care and help establish evidence-based medicine in this field. With rapidly accumulating evidence on various aspects of diabetes care, including landmark clinical trials of treatment agents and newer technologies, timely updates of the guidelines capture the most current state of the field and present a consensus. As a leading academic society, the Korean Diabetes Association publishes practice guidelines biennially and the American Diabetes Association does so annually. In this review, we summarize the key changes suggested in the most recent guidelines. Some of the important updates include treatment algorithms emphasizing comorbid conditions such as atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease in the selection of anti-diabetic agents; wider application of continuous glucose monitoring (CGM), insulin pump technologies and indices derived from CGM such as time in range; more active screening of subjects at high-risk of diabetes; and more detailed individualization in diabetes care. Although there are both similarities and differences among guidelines and some uncertainty remains, these updates provide a good approach for many clinical practitioners who are battling with diabetes.

Citations

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A nationwide cohort study on diabetes severity and risk of Parkinson disease
Kyungdo Han, Bongsung Kim, Seung Hwan Lee, Mee Kyoung Kim
npj Parkinson's Disease.2023;[Epub] CrossRef
Optimal Low-Density Lipoprotein Cholesterol Level for Primary Prevention in Koreans with Type 2 Diabetes Mellitus
Ji Yoon Kim, Nam Hoon Kim
Diabetes & Metabolism Journal.2023; 47(1): 42. CrossRef
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
Diabetes & Metabolism.2023; 49(4): 101440. CrossRef
Finerenone: Efficacy of a New Nonsteroidal Mineralocorticoid Receptor Antagonist in Treatment of Patients With Chronic Kidney Disease and Type 2 Diabetes
Subo Dey, Jasmine Garg, Andy Wang, Eva Holzner, William H. Frishman, Wilbert S. Aronow
Cardiology in Review.2023;[Epub] CrossRef
Impact of mental disorders on the risk of heart failure among Korean patients with diabetes: a cohort study
Tae Kyung Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Cardiovascular Diabetology.2023;[Epub] CrossRef
Chronic disease management program applied to type 2 diabetes patients and prevention of diabetic complications: a retrospective cohort study using nationwide data
Min Kyung Hyun, Jang Won Lee, Seung-Hyun Ko
BMC Public Health.2023;[Epub] CrossRef
Zinc Chloride Enhances the Antioxidant Status, Improving the Functional and Structural Organic Disturbances in Streptozotocin-Induced Diabetes in Rats
Irina Claudia Anton, Liliana Mititelu-Tartau, Eliza Gratiela Popa, Mihaela Poroch, Vladimir Poroch, Ana-Maria Pelin, Liliana Lacramioara Pavel, Ilie Cristian Drochioi, Gina Eosefina Botnariu
Medicina.2022; 58(11): 1620. CrossRef

Diabetes, Obesity and Metabolism
State-of-the-Art Overview of the Pharmacological Treatment of Non-Alcoholic Steatohepatitis: Yongin Cho, Yong-ho Lee; Endocrinol Metab. 2022;37(1):38-52. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.102

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Abstract PDF PubReader ePub Crossref - TDM

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH), a subtype of NAFLD, can progress to cirrhosis, hepatocellular carcinoma, and death. Nevertheless, the current treatment for NAFLD/NASH is limited to lifestyle modifications, and no drugs are currently officially approved as treatments for NASH. Many global pharmaceutical companies are pursuing the development of medications for the treatment of NASH, and results from phase 2 and 3 clinical trials have been published in recent years. Here, we review data from these recent clinical trials and reports on the efficacy of newly developed antidiabetic drugs in NASH treatment.

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Sodium-glucose cotransporter 2 inhibitors for non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus: A nationwide propensity-score matched cohort study
Jinyoung Kim, Kyungdo Han, Bongsung Kim, Ki-Hyun Baek, Ki-Ho Song, Mee Kyoung Kim, Hyuk-Sang Kwon
Diabetes Research and Clinical Practice.2022; 194: 110187. CrossRef

Thyroid
Development of Metabolic Synthetic Lethality and Its Implications for Thyroid Cancer: Sang-Hyeon Ju, Seong Eun Lee, Yea Eun Kang, Minho Shong; Endocrinol Metab. 2022;37(1):53-61. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.1402

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Abstract PDF PubReader ePub Crossref - TDM: Cancer therapies targeting genetic alterations are a topic of great interest in the field of thyroid cancer, which frequently harbors mutations in the RAS, RAF, and RET genes. Unfortunately, U.S. Food and Drug Administration-approved BRAF inhibitors have relatively low therapeutic efficacy against BRAF-mutant thyroid cancer; in addition, the cancer often acquires drug resistance, which prevents effective treatment. Recent advances in genomics and transcriptomics are leading to a more complete picture of the range of mutations, both driver and messenger, present in thyroid cancer. Furthermore, our understanding of cancer suggests that oncogenic mutations drive tumorigenesis and induce rewiring of cancer cell metabolism, which promotes survival of mutated cells. Synthetic lethality (SL) is a method of neutralizing mutated genes that were previously considered untargetable by traditional genotype-targeted treatments. Because these metabolic events are specific to cancer cells, we have the opportunity to develop new therapies that target tumor cells specifically without affecting healthy tissue. Here, we describe developments in metabolism-based cancer therapy, focusing on the concept of metabolic SL in thyroid cancer. Finally, we discuss the essential implications of metabolic reprogramming and its role in the future direction of SL for thyroid cancer.

Editorial

Diabetes, Obesity and Metabolism
Drug Repositioning: Exploring New Indications for Existing Drug-Disease Relationships: Hun-Sung Kim; Endocrinol Metab. 2022;37(1):62-64. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.1403

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PDF PubReader ePub Crossref - TDM

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Magic bullets, magic shields, and antimicrobials in between
Praveen Prathapan
Pharmaceutical Science Advances.2023; 1(1): 100002. CrossRef

Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Drug Repositioning Using Temporal Trajectories of Accompanying Comorbidities in Diabetes Mellitus: Namgi Park, Ja Young Jeon, Eugene Jeong, Soyeon Kim, Dukyong Yoon; Endocrinol Metab. 2022;37(1):65-73. Published online February 8, 2022; DOI: https://doi.org/10.3803/EnM.2021.1275

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
Most studies of systematic drug repositioning have used drug-oriented data such as chemical structures, gene expression patterns, and adverse effect profiles. As it is often difficult to prove repositioning candidates’ effectiveness in real-world clinical settings, we used patient-centered real-world data for screening repositioning candidate drugs for multiple diseases simultaneously, especially for diabetic complications.
Methods
Using the National Health Insurance Service-National Sample Cohort (2002 to 2013), we analyzed claims data of 43,048 patients with type 2 diabetes mellitus (age ≥40 years). To find repositioning candidate disease-drug pairs, a nested case-control study was used for 29 pairs of diabetic complications and the drugs that met our criteria. To validate this study design, we conducted an external validation for a selected candidate pair using electronic health records.
Results
We found 24 repositioning candidate disease-drug pairs. In the external validation study for the candidate pair cerebral infarction and glycopyrrolate, we found that glycopyrrolate was associated with decreased risk of cerebral infarction (hazard ratio, 0.10; 95% confidence interval, 0.02 to 0.44).
Conclusion
To reduce risks of diabetic complications, it would be possible to consider these candidate drugs instead of other drugs, given the same indications. Moreover, this methodology could be applied to diseases other than diabetes to discover their repositioning candidates, thereby offering a new approach to drug repositioning.

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Drug Repositioning: Exploring New Indications for Existing Drug-Disease Relationships
Hun-Sung Kim
Endocrinology and Metabolism.2022; 37(1): 62. 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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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

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

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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
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
Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)
Xiaohan Xu, Kyle L. Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang
Signal Transduction and Targeted Therapy.2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors: Hidefumi Inaba, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Takakazu Sugita, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, Takaaki Matsuoka; Endocrinol Metab. 2022;37(1):84-95. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1282

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7 Citations

Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear.
Methods
In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021.
Results
Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset.
Conclusion
Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

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Predictive Biomarkers for Immune-Related Endocrinopathies following Immune Checkpoint Inhibitors Treatment
Almog Shalit, Panagiotis Sarantis, Evangelos Koustas, Eleni-Myrto Trifylli, Dimitris Matthaios, Michalis V. Karamouzis
Cancers.2023; 15(2): 375. CrossRef
Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
Iñigo Les, Mireia Martínez, Inés Pérez-Francisco, María Cabero, Lucía Teijeira, Virginia Arrazubi, Nuria Torrego, Ana Campillo-Calatayud, Iñaki Elejalde, Grazyna Kochan, David Escors
Cancers.2023; 15(5): 1629. CrossRef
Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors
Hidefumi Inaba, Shuhei Morita, Daisuke Kosugi, Yuki Asai, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Masao Ota, Yuko Okudaira, Hiroyasu Nakatani, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, T
Frontiers in Immunology.2023;[Epub] CrossRef
Clinical characteristics and human leukocyte antigens in patients with immune checkpoint inhibitor-induced type 1 diabetes and pituitary dysfunction: a single center prospective study
Natsuko Hara, Hirotsugu Suwanai, Fumiyoshi Yakou, Keitaro Ishii, Hajime Iwasaki, Hironori Abe, Jumpei Shikuma, Hiroyuki Sakai, Takashi Miwa, Ryo Suzuki
Endocrine.2023;[Epub] CrossRef
Risk factors and predictors of immune-related adverse events: implications for patients with non-small cell lung cancer
Majd Issa, Joy Tang, Yizhen Guo, Chris Coss, Thomas A. Mace, Jason Bischof, Mitch Phelps, Carolyn J Presley, Dwight H Owen
Expert Review of Anticancer Therapy.2022; 22(8): 861. CrossRef
Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors
Adithya Chennamadhavuni, Laith Abushahin, Ning Jin, Carolyn J. Presley, Ashish Manne
Frontiers in Immunology.2022;[Epub] CrossRef
Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice
Pablo Rodríguez de Vera-Gómez, Ana Piñar-Gutiérrez, Raquel Guerrero-Vázquez, Virginia Bellido, Cristóbal Morales-Portillo, María Pilar Sancho-Márquez, Pablo Espejo-García, Noelia Gros-Herguido, Gema López-Gallardo, María Asunción Martínez-Brocca, Alfonso
Journal of Diabetes Research.2022; 2022: 1. CrossRef

Diabetes, Obesity and Metabolism
EW-7197 Attenuates the Progression of Diabetic Nephropathy in db/db Mice through Suppression of Fibrogenesis and Inflammation: Kyung Bong Ha, Weerapon Sangartit, Ah Reum Jeong, Eun Soo Lee, Hong Min Kim, Soyeon Shim, Upa Kukongviriyapan, Dae-Kee Kim, Eun Young Lee, Choon Hee Chung; Endocrinol Metab. 2022;37(1):96-111. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1305

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Abstract PDF PubReader ePub Crossref - TDM: Background
Diabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-β (TGF-β) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-β type 1 receptor kinase (ALK5), in retarding the progression of DN, both in vivo, using a diabetic mouse model (db/db mice), and in vitro, in podocytes and mesangial cells.
Methods
In vivo study: 8-week-old db/db mice were orally administered EW-7197 at a dose of 5 or 20 mg/kg/day for 10 weeks. Metabolic parameters and renal function were monitored. Glomerular histomorphology and renal protein expression were evaluated by histochemical staining and Western blot analyses, respectively. In vitro study: DN was induced by high glucose (30 mM) in podocytes and TGF-β (2 ng/mL) in mesangial cells. Cells were treated with EW-7197 (500 nM) for 24 hours and the mechanism associated with the attenuation of DN was investigated.
Results
Enhanced albuminuria and glomerular morphohistological changes were observed in db/db compared to that of the nondiabetic (db/m) mice. These alterations were associated with the activation of the TGF-β signaling pathway. Treatment with EW-7197 significantly inhibited TGF-β signaling, inflammation, apoptosis, reactive oxygen species, and endoplasmic reticulum stress in diabetic mice and renal cells.
Conclusion
EW-7197 exhibits renoprotective effect in DN. EW-7197 alleviates renal fibrosis and inflammation in diabetes by inhibiting downstream TGF-β signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN.

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Risk and Risk Factors for Postpartum Type 2 Diabetes Mellitus in Women with Gestational Diabetes: A Korean Nationwide Cohort Study: Mi Jin Choi, Jimi Choi, Chae Weon Chung; Endocrinol Metab. 2022;37(1):112-123. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1276

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Background
There are differences in risk and risk factor findings of postpartum type 2 diabetes mellitus (T2DM) after gestational diabetes depending on study design and subjects of previous studies. This study aimed to assess these risk and risk factors more accurately through a population-based study to provide basic data for prevention strategies.
Methods
This open retrospective cohort included data of 419,101 women with gestational diabetes and matched 1,228,802 control women who delivered between 2004 and 2016 from the South Korea National Health Information Database of the National Health Insurance Service. Following 14 (median 5.9) years of follow-up, the incidence and hazard ratio (HR) of postpartum T2DM were evaluated using Kaplan-Meier curves and Cox proportional regression models.
Results
The incidence and HR of postpartum T2DM in women with gestational diabetes (compared to women without gestational diabetes) after the 14-year follow-up was 21.3% and 2.78 (95% confidence interval [CI], 2.74 to 2.82), respectively. Comorbid obesity (body mass index [BMI] ≥25 kg/m²) increased postpartum T2DM risk 7.59 times (95% CI, 7.33 to 7.86). Significant risk factors for postpartum T2DM were fasting glucose level, BMI, age, family history of diabetes, hypertension, and insulin use during pregnancy.
Conclusion
This population-based study showed higher postpartum T2DM risk in women with gestational diabetes than in those without, which was further increased by comorbid obesity. BMI and fasting glucose level were important postpartum risk factors. The management of obesity and glycemic control may be important strategies to prevent the incidence of diabetes after delivery.

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Integration of nutrigenomics, melatonin, serotonin and inflammatory cytokines in the pathophysiology of pregnancy-specific urinary incontinence in women with gestational diabetes mellitus
Danielle Cristina Honorio França, Eduardo Luzía França, Luis Sobrevia, Angélica Mércia Pascon Barbosa, Adenilda Cristina Honorio-França, Marilza Vieira Cunha Rudge
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2023; 1869(6): 166737. CrossRef

Adrenal Gland
Adrenal Morphology as an Indicator of Long-Term Disease Control in Adults with Classic 21-Hydroxylase Deficiency: Taek Min Kim, Jung Hee Kim, Han Na Jang, Man Ho Choi, Jeong Yeon Cho, Sang Youn Kim; Endocrinol Metab. 2022;37(1):124-137. Published online February 8, 2022; DOI: https://doi.org/10.3803/EnM.2021.1278

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Abstract PDF PubReader ePub Crossref - TDM

Background
Monitoring adults with classical 21-hydroxylase deficiency (21OHD) is challenging due to variation in clinical and laboratory settings. Moreover, guidelines for adrenal imaging in 21OHD are not yet available. We evaluated the relationship between adrenal morphology and disease control status in classical 21OHD.
Methods
This retrospective, cross-sectional study included 90 adult 21OHD patients and 270 age- and sex-matched healthy controls. We assessed adrenal volume, width, and tumor presence using abdominal computed tomography and evaluated correlations of adrenal volume and width with hormonal status. We investigated the diagnostic performance of adrenal volume and width for identifying well-controlled status in 21OHD patients (17α-hydroxyprogesterone [17-OHP] <10 ng/mL).
Results
The adrenal morphology of 21OHD patients showed hypertrophy (45.6%), normal size (42.2%), and hypotrophy (12.2%). Adrenal tumors were detected in 12 patients (13.3%). The adrenal volume and width of 21OHD patients were significantly larger than those of controls (18.2±12.2 mL vs. 7.1±2.0 mL, 4.7±1.9 mm vs. 3.3±0.5 mm, P<0.001 for both). The 17-OHP and androstenedione levels were highest in patients with adrenal hypertrophy, followed by those with normal adrenal glands and adrenal hypotrophy (P<0.05 for both). Adrenal volume and width correlated positively with adrenocorticotropic hormone, 17-OHP, 11β-hydroxytestosterone, progesterone sulfate, and dehydroepiandrosterone sulfate in both sexes (r=0.33–0.95, P<0.05 for all). For identifying well-controlled patients, the optimal cut-off values of adrenal volume and width were 10.7 mL and 4 mm, respectively (area under the curve, 0.82–0.88; P<0.001 for both).
Conclusion
Adrenal volume and width may be reliable quantitative parameters for monitoring patients with classical 21OHD.

Citations

Citations to this article as recorded by

Long-Term Outcomes of Congenital Adrenal Hyperplasia
Anna Nordenström, Svetlana Lajic, Henrik Falhammar
Endocrinology and Metabolism.2022; 37(4): 587. CrossRef
Congenital adrenal hyperplasia in patients with adrenal tumors: a population-based case–control study
F. Sahlander, J. Patrova, B. Mannheimer, J. D. Lindh, H. Falhammar
Journal of Endocrinological Investigation.2022; 46(3): 559. CrossRef
Fully automatic volume measurement of the adrenal gland on CT using deep learning to classify adrenal hyperplasia
Taek Min Kim, Seung Jae Choi, Ji Yeon Ko, Sungwan Kim, Chang Wook Jeong, Jeong Yeon Cho, Sang Youn Kim, Young-Gon Kim
European Radiology.2022; 33(6): 4292. CrossRef

Adrenal Gland Big Data Articles (National Health Insurance Service Database)
Epidemiology and Long-Term Adverse Outcomes in Korean Patients with Congenital Adrenal Hyperplasia: A Nationwide Study: Jung Hee Kim, Sunkyu Choi, Young Ah Lee, Juneyoung Lee, Sin Gon Kim; Endocrinol Metab. 2022;37(1):138-147. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1328

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Background
Previous studies on the epidemiology and complications of congenital adrenal hyperplasia (CAH) were conducted in Western countries and in children/adolescents. We aimed to explore the epidemiology of CAH, as well as the risk of comorbidities and mortality, in a Korean nationwide case-control study.
Methods
CAH patients (n=2,840) were included between 2002 and 2017 from the National Health Insurance Service database and the Rare Intractable Disease program. CAH patients were compared, at a 1:10 ratio, with age-, sex-, and index year-matched controls (n=28,400).
Results
The point prevalence of CAH patients in Korea was 1 in 18,745 persons in 2017. The annual incidence rate declined between 2003 and 2017 from 3.25 to 0.41 per 100,000 persons. CAH patients were at elevated risk for cardiovascular disease (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.4 to 1.9), stroke (OR, 1.7; 95% CI, 1.3 to 2.0), diabetes mellitus (OR, 2.8; 95% CI, 2.6 to 3.1), dyslipidemia (OR, 2.4; 95% CI, 2.2 to 2.6), and psychiatric disorders (OR, 1.5; 95% CI, 1.3 to 1.6). Fracture risk increased in CAH patients aged over 40 years (OR, 1.4; 95% CI, 1.1 to 1.7). CAH patients were at higher risk of mortality than controls (hazard ratio, 1.6; 95% CI, 1.3 to 2.0).
Conclusion
Our nationwide study showed a recent decline in the incidence of CAH and an elevated risk for cardiovascular, metabolic, skeletal, and psychiatric disorders in CAH patients. Lifelong management for comorbidity risk is a crucial component of treating CAH patients.

Citations

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Анализ распространенности и заболеваемости надпочечниковой недостаточностью в мире
М. Ю. Юкина, Н. Ф. Нуралиева, Е. А. Трошина
Ateroscleroz.2023; 18(4): 426. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
Long-term cardiometabolic morbidity in young adults with classic 21-hydroxylase deficiency congenital adrenal hyperplasia
Beatrice Righi, Salma R. Ali, Jillian Bryce, Jeremy W. Tomlinson, Walter Bonfig, Federico Baronio, Eduardo C. Costa, Guilherme Guaragna-Filho, Guy T’Sjoen, Martine Cools, Renata Markosyan, Tania A. S. S. Bachega, Mirela C. Miranda, Violeta Iotova, Henrik
Endocrine.2023;[Epub] CrossRef
Long-Term Outcomes of Congenital Adrenal Hyperplasia
Anna Nordenström, Svetlana Lajic, Henrik Falhammar
Endocrinology and Metabolism.2022; 37(4): 587. CrossRef

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

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

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Fracture risks associated with sodium-glucose cotransporter-2 inhibitors in type 2 diabetes patients across eGFR and albuminuria categories: A population-based study in Hong Kong
David Tak Wai Lui, Tingting Wu, Eric Ho Man Tang, Ivan Chi Ho Au, Chi Ho Lee, Yu Cho Woo, Kathryn Choon Beng Tan, Carlos King Ho Wong
Diabetes Research and Clinical Practice.2023; 197: 110576. CrossRef
Diagnose und Management der Osteoporose bei Diabetes mellitus (Update 2023)
Christian Muschitz, Alexandra Kautzky-Willer, Yvonne Winhofer, Martina Rauner, Judith Haschka, Daniel Cejka, Robert Wakolbinger-Habel, Peter Pietschmann
Wiener klinische Wochenschrift.2023; 135(S1): 207. CrossRef
Association between exercise and risk of fractures in new-onset type 2 diabetes: a retrospective cohort study
Seung Eun Lee, Juhwan Yoo, Bong-Seong Kim, Kyoung-Ah Kim, Kyungdo Han, Han Seok Choi
Archives of Osteoporosis.2023;[Epub] CrossRef

Thyroid
Diagnostic Performance of Thyroid Core Needle Biopsy Using the Revised Reporting System: Comparison with Fine Needle Aspiration Cytology: Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, So Lyung Jung, Chan Kwon Jung; Endocrinol Metab. 2022;37(1):159-169. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1299

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
We aim to validate the diagnostic performance of thyroid core needle biopsy (CNB) for diagnosing malignancy in clinical settings to align with the changes made in recently updated thyroid CNB guidelines.
Methods
We retrospectively analyzed 1,381 thyroid CNB and 2,223 fine needle aspiration (FNA) samples. The FNA and CNB slides were interpreted according to the Bethesda System for Reporting Thyroid Cytopathology and updated practice guidelines for thyroid CNB, respectively.
Results
Compared to FNA, CNB showed lower rates of inconclusive results: categories I (2.8% vs. 11.2%) and III (1.2% vs. 6.2%), and higher rates of categories II (60.9% vs. 50.4%) and IV (17.5% vs. 2.0%). The upper and lower bounds of the risk of malignancy (ROM) for category IV of CNB were 43.2% and 26.6%, respectively. The CNB subcategory IVb with nuclear atypia had a higher ROM than the subcategory without nuclear atypia (40%–62% vs. 23%–36%). In histologically confirmed cases, there was no significant difference in the diagnostic performance between CNB and FNA for malignancy. However, neoplastic diseases were more frequently detected by CNB than by FNA (88.8% vs. 77.6%, P=0.046). In category IV, there was no difference in unnecessary surgery rate between CNB and FNA (4.7% vs. 6.9%, P=0.6361).
Conclusion
Thyroid CNB decreased the rate of inconclusive results and showed a higher category IV diagnostic rate than FNA. The revised guidelines for thyroid CNB proved to be an excellent reporting system for assessing thyroid nodules.

Citations

Citations to this article as recorded by

Preoperative Risk Stratification of Follicular-patterned Thyroid Lesions on Core Needle Biopsy by Histologic Subtyping and RAS Variant-specific Immunohistochemistry
Meejeong Kim, Sora Jeon, Chan Kwon Jung
Endocrine Pathology.2023;[Epub] CrossRef
A Matched-Pair Analysis of Nuclear Morphologic Features Between Core Needle Biopsy and Surgical Specimen in Thyroid Tumors Using a Deep Learning Model
Faridul Haq, Andrey Bychkov, Chan Kwon Jung
Endocrine Pathology.2022; 33(4): 472. CrossRef

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