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Review Article
Diabetes, Obesity and Metabolism
Effects of Intermittent Fasting on the Circulating Levels and Circadian Rhythms of Hormones
Bo Hye Kim, Yena Joo, Min-Seon Kim, Han Kyoung Choe, Qingchun Tong, Obin Kwon
Endocrinol Metab. 2021;36(4):745-756.   Published online August 27, 2021
DOI: https://doi.org/10.3803/EnM.2021.405
  • 21,201 View
  • 895 Download
  • 24 Web of Science
  • 25 Crossref
AbstractAbstract PDFPubReader   ePub   
Intermittent fasting has become an increasingly popular strategy in losing weight and associated reduction in obesity-related medical complications. Overwhelming studies support metabolic improvements from intermittent fasting in blood glucose levels, cardiac and brain function, and other health benefits, in addition to weight loss. However, concerns have also been raised on side effects including muscle loss, ketosis, and electrolyte imbalance. Of particular concern, the effect of intermittent fasting on hormonal circadian rhythms has received little attention. Given the known importance of circadian hormonal changes to normal physiology, potential detrimental effects by dysregulation of hormonal changes deserve careful discussions. In this review, we describe the changes in circadian rhythms of hormones caused by intermittent fasting. We covered major hormones commonly pathophysiologically involved in clinical endocrinology, including insulin, thyroid hormones, and glucocorticoids. Given that intermittent fasting could alter both the level and frequency of hormone secretion, decisions on practicing intermittent fasting should take more considerations on potential detrimental consequences versus beneficial effects pertaining to individual health conditions.

Citations

Citations to this article as recorded by  
  • Common and divergent molecular mechanisms of fasting and ketogenic diets
    Antonio Paoli, Grant M. Tinsley, Mark P. Mattson, Immaculata De Vivo, Ravi Dhawan, Tatiana Moro
    Trends in Endocrinology & Metabolism.2024; 35(2): 125.     CrossRef
  • Identifying Acss1, Mtfp1 and Oxct1 as key regulators and promising biomarkers of sarcopenia in various models
    Hailong Cui, Die Hu, Yanling Liu, Jiejie Zhao
    Gene.2024; 896: 148053.     CrossRef
  • Circadian Rhythms, Chrononutrition, Physical Training, and Redox Homeostasis—Molecular Mechanisms in Human Health
    Cristina Manuela Drăgoi, Alina Crenguţa Nicolae, Anca Ungurianu, Denisa Marilena Margină, Daniela Grădinaru, Ion-Bogdan Dumitrescu
    Cells.2024; 13(2): 138.     CrossRef
  • Various types of fasting diet and possible benefits in nonalcoholic fatty liver: Mechanism of actions and literature update
    Zahra Sadat Mirrazavi, Vahideh Behrouz
    Clinical Nutrition.2024; 43(2): 519.     CrossRef
  • Attention to Innate Circadian Rhythm and the Impact of Its Disruption on Diabetes
    Da Young Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Nan Hee Kim
    Diabetes & Metabolism Journal.2024; 48(1): 37.     CrossRef
  • Fasting intervention and its clinical effects on the human host and microbiome
    Sofia K. Forslund
    Journal of Internal Medicine.2023; 293(2): 166.     CrossRef
  • Umbrella review of time-restricted eating on weight loss, fasting blood glucose, and lipid profile
    Han Shi Jocelyn Chew, Wei How Darryl Ang, Zhen Yang Abel Tan, Wen Wei Ang, Kin Sun Chan, Ying Lau
    Nutrition Reviews.2023; 81(9): 1180.     CrossRef
  • Thermodynamic Assessment of the Effects of Intermittent Fasting and Fatty Liver Disease Diets on Longevity
    Melek Ece Öngel, Cennet Yildiz, Özge Başer, Bayram Yilmaz, Mustafa Özilgen
    Entropy.2023; 25(2): 227.     CrossRef
  • Effects of Intermittent Fasting on Hypothalamus–Pituitary–Thyroid Axis, Palatable Food Intake, and Body Weight in Stressed Rats
    Cinthia García-Luna, Ixchel Prieto, Paulina Soberanes-Chávez, Elena Alvarez-Salas, Iván Torre-Villalvazo, Gilberto Matamoros-Trejo, Patricia de Gortari
    Nutrients.2023; 15(5): 1164.     CrossRef
  • Possible homeostatic, glucose uptake mechanisms and hepato-pancreatic histological effects of intermittent fasting, exercise, starvation, and honey in streptozotocin-induced diabetes in rats
    Ejime A. Chijiokwu, Eze K. Nwangwa, Mega O. Oyovwi, Benneth Ben-Azu, Alexander O. Naiho, Emuesiri Goodies Moke, Victor Emojevwe, Prosper A. Ehiwarior, Udoka S. Nwabuoku
    Nutrire.2023;[Epub]     CrossRef
  • Mid-Point of the Active Phase Is Better to Achieve the Natriuretic Effect of Acute Salt Load in Mice
    Momoko Imamura, Hiroyuki Sasaki, Katsuki Hayashi, Shigenobu Shibata
    Nutrients.2023; 15(7): 1679.     CrossRef
  • All That Glitters Is Not Gold: The Same Sleep Time, but Different Diabetogenic Outcomes
    Bohye Kim, Obin Kwon
    Endocrinology and Metabolism.2023; 38(1): 78.     CrossRef
  • The emerging role of circadian rhythms in the development and function of thermogenic fat
    Xuemin Peng, Yong Chen
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Time-restricted Feeding Changes as Inspiration for Drug Design
    Zhangyuting He, Huayu Yang, Yilei Mao
    Current Pharmaceutical Design.2023; 29(8): 559.     CrossRef
  • Brain Dopamine–Clock Interactions Regulate Cardiometabolic Physiology: Mechanisms of the Observed Cardioprotective Effects of Circadian-Timed Bromocriptine-QR Therapy in Type 2 Diabetes Subjects
    Anthony H. Cincotta
    International Journal of Molecular Sciences.2023; 24(17): 13255.     CrossRef
  • Adaptive Circadian Rhythms for Autonomous and Biologically Inspired Robot Behavior
    Marcos Maroto-Gómez, María Malfaz, Álvaro Castro-González, Sara Carrasco-Martínez, Miguel Ángel Salichs
    Biomimetics.2023; 8(5): 413.     CrossRef
  • Intermittent Fasting on Human Health and Disease
    Denisa Marilena Margină, Cristina Manuela Drăgoi
    Nutrients.2023; 15(21): 4491.     CrossRef
  • Synthetic augmentation of bilirubin metabolism in human pluripotent stem cell-derived liver organoids
    Hasan Al Reza, Zishaan Farooqui, Abid Al Reza, Callen Conroy, Kentaro Iwasawa, Yasuhiro Ogura, Keisuke Okita, Kenji Osafune, Takanori Takebe
    Stem Cell Reports.2023; 18(11): 2071.     CrossRef
  • Average phenotype but not plasticity in two metabolic hormones covary in wild female bonobos (Pan paniscus)
    Ruth Sonnweber, Gottfried Hohmann, Jeroen M. G. Stevens, Tobias Deschner, Barbara Fruth, Anna-Lena Fiedler, Niina O. Nurmi, Verena Behringer
    Frontiers in Ecology and Evolution.2023;[Epub]     CrossRef
  • Intermittent fasting, high-intensity interval training, or a combination of both have beneficial effects in obese mice with nonalcoholic fatty liver disease
    Patrícia de Castro-de-Paiva, Thatiany de Souza Marinho, Carlos Alberto Mandarim-de-Lacerda, Marcia Barbosa Aguila
    The Journal of Nutritional Biochemistry.2022; 104: 108997.     CrossRef
  • Optimal Timing of Thyroid Hormone Replacement During Ramadan Fasting: A Randomized Controlled Trial in Patients with Prior Total Thyroidectomy
    Khalid M. Al-Qahtani, Ibraheem Ahmed Aldeeri, Amal M. Alshaibi, Norah Salman Alshabib, Rakan M. Barghouthi, Ebtihal Y. Alyusuf, Anwar Ali Jammah
    Thyroid.2022; 32(9): 1029.     CrossRef
  • Exploring the Effects of Energy Constraints on Performance, Body Composition, Endocrinological/Hematological Biomarkers, and Immune System among Athletes: An Overview of the Fasting State
    Hadi Nobari, Saber Saedmocheshi, Eugenia Murawska-Ciałowicz, Filipe Manuel Clemente, Katsuhiko Suzuki, Ana Filipa Silva
    Nutrients.2022; 14(15): 3197.     CrossRef
  • Alternate day fasting and time-restricted feeding may confer similar neuroprotective effects during aging in male rats
    Sukanya Bhoumik, Rashmi Kesherwani, Raushan Kumar, Syed Ibrahim Rizvi
    Biogerontology.2022; 23(6): 757.     CrossRef
  • Intermittent Fasting—A Healthy Dietary Pattern for Diabetic Nephropathy
    Ming Yang, Wei Chen, Liyu He, Di Liu, Li Zhao, Xi Wang
    Nutrients.2022; 14(19): 3995.     CrossRef
  • β-hydroxybutyrate as an Anti-Aging Metabolite
    Lian Wang, Peijie Chen, Weihua Xiao
    Nutrients.2021; 13(10): 3420.     CrossRef
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Brief Report
Diabetes, Obesity and Metabolism
Dipeptidyl Peptidase-4 Inhibitors and COVID-19-Related Deaths among Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies
Dimitrios Patoulias, Michael Doumas
Endocrinol Metab. 2021;36(4):904-908.   Published online July 27, 2021
DOI: https://doi.org/10.3803/EnM.2021.1048
  • 10,657 View
  • 214 Download
  • 17 Web of Science
  • 19 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.

Citations

Citations to this article as recorded by  
  • Noninsulin‐based antihyperglycemic medications in patients with diabetes and COVID‐19: A systematic review and meta‐analysis
    Mahmoud Nassar, Hazem Abosheaishaa, Awadhesh Kumar Singh, Anoop Misra, Zachary Bloomgarden
    Journal of Diabetes.2023; 15(2): 86.     CrossRef
  • Effects of novel glucose-lowering drugs on the COVID-19 patients with diabetes: A network meta-analysis of clinical outcomes
    Yang Yang, Ling Zhao, Yeying Wang, Chengjiang Liu, Tingyu Ke
    International Journal of Diabetes in Developing Countries.2023;[Epub]     CrossRef
  • COVID-19 and metabolic syndrome
    Harsha Dissanayake
    Best Practice & Research Clinical Endocrinology & Metabolism.2023; 37(4): 101753.     CrossRef
  • Current management of diabetes patients with COVID-19
    Arup Kumar Misra, Gaurav Rangari, Madhavrao C, Sushil Sharma
    Expert Review of Endocrinology & Metabolism.2023; 18(2): 199.     CrossRef
  • Current management of diabetes patients with COVID-19
    Arup Kumar Misra, Gaurav Rangari, Madhavrao C, Sushil Sharma
    Expert Review of Endocrinology & Metabolism.2023; : 1.     CrossRef
  • Dipeptidyl Peptidase-4 Inhibitors, Glucagon-like Peptide-1 Receptor Agonists, and Sodium-Glucose Cotransporter-2 Inhibitors and COVID-19 Outcomes
    Andreana Foresta, Luisa Ojeda-Fernandez, Giulia Macaluso, Maria Carla Roncaglioni, Mauro Tettamanti, Ida Fortino, Olivia Leoni, Stefano Genovese, Marta Baviera
    Clinical Therapeutics.2023; 45(4): e115.     CrossRef
  • DPP-4 Inhibitors as a savior for COVID-19 patients with diabetes
    Snehasish Nag, Samanwita Mandal, Oindrila Mukherjee, Suprabhat Mukherjee, Rakesh Kundu
    Future Virology.2023; 18(5): 321.     CrossRef
  • DrugRep-HeSiaGraph: when heterogenous siamese neural network meets knowledge graphs for drug repurposing
    Zahra Ghorbanali, Fatemeh Zare-Mirakabad, Najmeh Salehi, Mohammad Akbari, Ali Masoudi-Nejad
    BMC Bioinformatics.2023;[Epub]     CrossRef
  • Immunomodulatory activity of dipeptidyl peptidase‐4 inhibitors in immune‐related diseases
    Marija Drakul, Miodrag Čolić
    European Journal of Immunology.2023;[Epub]     CrossRef
  • Dipeptidyl peptidase-4 (DPP-IV) inhibitor was associated with mortality reduction in COVID-19 — A systematic review and meta-analysis
    Ahmad Fariz Malvi Zamzam Zein, Wilson Matthew Raffaello
    Primary Care Diabetes.2022; 16(1): 162.     CrossRef
  • Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis
    Nam Nhat Nguyen, Dung Si Ho, Hung Song Nguyen, Dang Khanh Ngan Ho, Hung-Yuan Li, Chia-Yuan Lin, Hsiao-Yean Chiu, Yang-Ching Chen
    Metabolism.2022; 131: 155196.     CrossRef
  • The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis
    Yidan Chen, Xingfei Lv, Sang Lin, Mohammad Arshad, Mengjun Dai
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Type 2 Diabetes Mellitus and COVID-19: A Narrative Review
    Cristina Rey-Reñones, Sara Martinez-Torres, Francisco M. Martín-Luján, Carles Pericas, Ana Redondo, Carles Vilaplana-Carnerero, Angela Dominguez, María Grau
    Biomedicines.2022; 10(9): 2089.     CrossRef
  • Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology
    Alba Sebastián-Martín, Belén G. Sánchez, José M. Mora-Rodríguez, Alicia Bort, Inés Díaz-Laviada
    Biomedicines.2022; 10(8): 2026.     CrossRef
  • Non-Insulin Novel Antidiabetic Drugs Mechanisms in the Pathogenesis of COVID-19
    Teodor Salmen, Valeria-Anca Pietroșel, Bianca-Margareta Mihai, Ioana Cristina Bica, Claudiu Teodorescu, Horia Păunescu, Oana Andreia Coman, Doina-Andrada Mihai, Anca Pantea Stoian
    Biomedicines.2022; 10(10): 2624.     CrossRef
  • Antidiabetic treatment and COVID-19 Outcomes: A population-based cohort study in primary health care in Catalonia during the first wave of the pandemic
    Dan Ouchi, Carles Vilaplana-Carnerero, Vanessa de Dios, Maria Giner-Soriano, Rosa Morros
    Primary Care Diabetes.2022; 16(6): 753.     CrossRef
  • Immunotropic effects of hypoglycemic agents on coronavirus infection: a view from the perspective of pharmacogenetics
    Konstantin G. Gurevich, Yulia A. Sorokina, Alexander L. Urakov, Snezhana D. Sinyushkina, Maria I. Pryazhnikova, Alyona V. Gorinova, Lyubov V. Lovtsova, Olga V. Zanozina
    Reviews on Clinical Pharmacology and Drug Therapy.2022; 20(3): 269.     CrossRef
  • Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control
    Niya Narayanan, Dukhabandhu Naik, Jayaprakash Sahoo, Sadishkumar Kamalanathan
    World Journal of Virology.2022; 11(6): 399.     CrossRef
  • Improvement of glycemic control and reduction of major cardiovascular events in 18 cardiovascular outcome trials: an updated meta-regression
    Maria Ida Maiorino, Miriam Longo, Lorenzo Scappaticcio, Giuseppe Bellastella, Paolo Chiodini, Katherine Esposito, Dario Giugliano
    Cardiovascular Diabetology.2021;[Epub]     CrossRef
Close layer
Review Article
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
  • 14,798 View
  • 1,080 Download
  • 15 Web of Science
  • 17 Crossref
AbstractAbstract PDFPubReader   ePub   
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

Citations to this article as recorded by  
  • Accuracy and Safety of the 15-Day CareSens Air Continuous Glucose Monitoring System
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    Diabetes Technology & Therapeutics.2024;[Epub]     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
  • 5,623 View
  • 279 Download
  • 11 Web of Science
  • 14 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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    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
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Original Articles
Diabetes, Obesity and Metabolism
Efficacy and Safety of the New Appetite Suppressant, Liraglutide: A Meta-Analysis of Randomized Controlled Trials
Shinje Moon, Jibeom Lee, Hye Soo Chung, Yoon Jung Kim, Jae Myung Yu, Sung Hoon Yu, Chang-Myung Oh
Endocrinol Metab. 2021;36(3):647-660.   Published online June 18, 2021
DOI: https://doi.org/10.3803/EnM.2020.934
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Obesity is a chronic disease associated with metabolic diseases such as diabetes and cardiovascular disease. Since the U.S. Food and Drug Administration approved liraglutide as an anti-obesity drug for nondiabetic patients in 2014, it has been widely used for weight control in overweight and obese people. This study aimed to systematically analyze the effects of liraglutide on body weight and other cardiometabolic parameters.
Methods
We investigated articles from PubMed, EMBASE, and the Cochrane Library to search randomized clinical trials that examined body weight changes with liraglutide treatment.
Results
We included 31 studies with 8,060 participants for this meta-analysis. The mean difference (MD) between the liraglutide group and the placebo group was −4.19 kg (95% confidence interval [CI], −4.84 to −3.55), with a −4.16% change from the baseline (95% CI, −4.90 to −3.43). Liraglutide treatment correlated with a significantly reduced body mass index (MD: −1.55; 95% CI, −1.76 to −1.34) and waist circumference (MD: −3.11 cm; 95% CI, −3.59 to −2.62) and significantly decreased blood pressure (systolic blood pressure, MD: −2.85 mm Hg; 95% CI, −3.36 to −2.35; diastolic blood pressure, MD: −0.66 mm Hg; 95% CI, −1.02 to −0.30), glycated hemoglobin (MD: −0.40%; 95% CI, −0.49 to −0.31), and low-density lipoprotein cholesterol (MD: –2.91 mg/dL; 95% CI, −5.28 to −0.53; MD: −0.87% change from baseline; 95% CI, −1.17 to −0.56).
Conclusion
Liraglutide is effective for weight control and can be a promising drug for cardiovascular protection in overweight and obese people.

Citations

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    Walmir Coutinho, Bruno Halpern
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Close layer
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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  • 13 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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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Review Article
Diabetes, Obesity and Metabolism
Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia
Joon Ho Moon, Kyuho Kim, Sung Hee Choi
Endocrinol Metab. 2022;37(4):575-586.   Published online August 29, 2022
DOI: https://doi.org/10.3803/EnM.2022.402
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AbstractAbstract PDFPubReader   ePub   
High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)–lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.

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Original Articles
Diabetes, Obesity and Metabolism
Reference Values for Skeletal Muscle Mass at the Third Lumbar Vertebral Level Measured by Computed Tomography in a Healthy Korean Population
Ja Kyung Yoon, Sunyoung Lee, Kyoung Won Kim, Ji Eun Lee, Jeong Ah Hwang, Taeyong Park, Jeongjin Lee
Endocrinol Metab. 2021;36(3):672-677.   Published online June 8, 2021
DOI: https://doi.org/10.3803/EnM.2021.1041
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AbstractAbstract PDFPubReader   ePub   
Background
Sarcopenia is defined as the loss of skeletal muscle mass and is associated with negative clinical outcomes. This study aimed to establish sex-specific cutoff values for the skeletal muscle area (SMA) and skeletal muscle index (SMI) at the third lumbar vertebral (L3) level using computed tomography (CT) imaging to identify sarcopenia in healthy Korean liver donors.
Methods
This retrospective study included 659 healthy liver donors (408 men and 251 women) aged 20 to 60 years who had undergone abdominal CT examinations between January 2017 and December 2018. Assessment of body composition was performed with an automated segmentation technique using a deep-learning system. Sex-specific SMA and SMI distributions were assessed, and cutoff values for determining sarcopenia were defined as values at either two standard deviations (SDs) below the mean reference value or below the fifth percentile.
Results
Using the SD definition, cutoff values for SMA and SMI were 117.04 cm2 and 39.33 cm2/m2, respectively, in men and 71.39 cm2 and 27.77 cm2/m2, respectively, in women. Using the fifth percentile definition, cutoff values for SMA and SMI were 126.88 cm2 and 40.96 cm2/m2, respectively, in men and 78.85 cm2 and 30.60 cm2/m2, respectively, in women.
Conclusion
Our data provide sex-specific cutoff values for the SMA and SMI at the L3 level measured by CT imaging in a healthy Korean population, which may be applicable for identifying sarcopenia in this population.

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Diabetes, Obesity and Metabolism
Big Data Articles (National Health Insurance Service Database)
Frequency of Exposure to Impaired Fasting Glucose and Risk of Mortality and Cardiovascular Outcomes
Seung-Hwan Lee, Kyungdo Han, Hyuk-Sang Kwon, Mee Kyoung Kim
Endocrinol Metab. 2021;36(5):1007-1015.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1218
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  • 10 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Metabolic abnormalities, such as impaired fasting glucose (IFG), are dynamic phenomena; however, it is unclear whether the timing of IFG exposure and cumulative exposure to IFG are related to cardiovascular disease (CVD) and mortality risk.
Methods
Data were extracted from a nationwide population-based cohort in South Korea for adults (n=2,206,679) who were free of diabetes and had 4 years of consecutive health examination data. Fasting blood glucose levels of 100 to 125 mg/dL were defined as IFG, and the number of IFG diagnoses for each adult in the 4-year period was tabulated as the IFG exposure score (range, 0 to 4). Adults with persistent IFG for the 4-year period received a score of 4.
Results
The median follow-up was 8.2 years. There were 24,820 deaths, 13,502 cases of stroke, and 13,057 cases of myocardial infarction (MI). IFG exposure scores of 1, 2, 3, and 4 were associated with all-cause mortality (multivariable-adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.08 to 1.15; aHR, 1.16; 95% CI, 1.12 to 1.20; aHR, 1.20; 95% CI, 1.15 to 1.25; aHR, 1.18; 95% CI, 1.11 to 1.25, respectively) compared with an IFG exposure score of 0. Adjusting for hypertension and dyslipidemia attenuated the slightly increased risk of MI or stroke associated with high IFG exposure scores, but significant associations for allcause mortality remained.
Conclusion
The intensity of IFG exposure was associated with an elevated risk of all-cause mortality, independent of cardiovascular risk factors. The association between IFG exposure and CVD risk was largely mediated by the coexistence of dyslipidemia and hypertension.

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    Mee Kyoung Kim, Kyungdo Han, Hun-Sung Kim, Kun-Ho Yoon, Seung-Hwan Lee
    European Journal of Preventive Cardiology.2022; 29(14): 1866.     CrossRef
  • Low-Density Lipoprotein Cholesterol Level, Statin Use and Myocardial Infarction Risk in Young Adults
    Heekyoung Jeong, Kyungdo Han, Soon Jib Yoo, Mee Kyoung Kim
    Journal of Lipid and Atherosclerosis.2022; 11(3): 288.     CrossRef
  • Additive interaction of diabetes mellitus and chronic kidney disease in cancer patient mortality risk
    Seohyun Kim, Gyuri Kim, Jae Hyeon Kim
    Scientific Reports.2022;[Epub]     CrossRef
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Diabetes, Obesity and Metabolism
Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis
Xiaoying Ma, Qiong Wang
Endocrinol Metab. 2022;37(3):432-443.   Published online May 16, 2022
DOI: https://doi.org/10.3803/EnM.2021.1336
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AbstractAbstract PDFPubReader   ePub   
Background
This study investigated the effect of short-chain fatty acids (SCFAs) on diabetes in a mouse model.
Methods
Autophagy in Akita mice and streptozocin (STZ)-induced diabetic C57BL/6 mice was determined by Western blots and immunohistochemistry (IHC). Western blots, IHC, hematoxylin and eosin staining, Masson staining, periodic acid-Schiff staining, and picrosirius red staining were conducted to detect whether autophagy and renal function improved in Akita mice and STZ-induced diabetic C57BL/6 mice after treatment of SCFAs. Western blots, IHC, and chromatin immunoprecipitation were performed to determine whether SCFAs affected diabetic mice via the histone deacetylase (HDAC2)/unc-51 like autophagy activating kinase 1 (ULK1) axis. Diabetic mice with kidney-specific knockout of HDAC2 were constructed, and IHC, Masson staining, and Western blots were carried out to detect whether the deletion of endogenous HDAC2 contributed to the improvement of autophagy and renal fibrosis in diabetic mice.
Results
Reduced autophagy and severe fibrosis were observed in Akita mice and STZ-induced diabetic C57BL/6 mice. Increased autophagy and reduced renal cell fibrosis were found in SCFA-treated Akita diabetic mice and STZ-induced diabetic C57BL/6 mice. Diabetic mice treated with SCFAs had lower HDAC2 expression and more enriched binding of ULK1 promoter sequences to H3K27Ac. Endogenous knockout of HDAC2 caused enhanced autophagy and decreased renal fibrosis in diabetic mice treated with SCFAs.
Conclusion
SCFAs enhanced autophagy of renal tubular cells and attenuated renal fibrosis in diabetic mice through the HDAC2/ULK1 axis.

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    Jia Liu, Weihui Yang
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Diabetes, Obesity and Metabolism
The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE−/−FXR−/− Mice
Yenna Lee, Bo-Rahm Kim, Geun-Hyung Kang, Gwan Jae Lee, Young Joo Park, Haeryoung Kim, Hak Chul Jang, Sung Hee Choi
Endocrinol Metab. 2021;36(6):1243-1253.   Published online December 28, 2021
DOI: https://doi.org/10.3803/EnM.2021.1100
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Farnesoid X receptor (FXR), a bile acid–activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.
Methods
En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)−/− and ApoE−/−FXR−/− mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.
Results
Compared with ApoE−/− mice, ApoE−/−FXR−/− mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE−/−FXR−/− mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).
Conclusion
Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

Citations

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    Joon Ho Moon, Kyuho Kim, Sung Hee Choi
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    Lu Wang, Shiqi Wang, Qing Zhang, Chengqi He, Chenying Fu, Quan Wei
    Molecular Biomedicine.2022;[Epub]     CrossRef
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Diabetes, Obesity and Metabolism
Big Data Articles (National Health Insurance Service Database)
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinol Metab. 2021;36(3):628-636.   Published online May 26, 2021
DOI: https://doi.org/10.3803/EnM.2020.948
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To investigate the clinical characteristics of gestational diabetes mellitus (GDM) in Korea, using a nationwide database.
Methods
We analyzed 417,139 women who gave birth between 2011 and 2015 using the Korean National Health Information Database. They underwent the Korean National Health Screening Program within one year before pregnancy and were not prescribed drugs for diabetes nor diagnosed with diabetes mellitus before 280 days antepartum. Patients with GDM were defined as those who visited the outpatient clinic more than twice with GDM codes.
Results
The prevalence of GDM was 12.70% and increased with increasing maternal age, prepregnancy body mass index (BMI), waist circumference (WC), and fasting plasma glucose (FPG) (P for trend <0.05). As compared with those aged <25 years, the odds ratio for women with GDM aged ≥40 years were 4.804 (95% confidence interval [CI], 4.436 to 5.203) after adjustment for covariates. Women with prepregnancy BMI ≥30 kg/m2 were at 1.898 times (95% CI, 1.736 to 2.075) greater risk for GDM than those with prepregnancy BMI <18.5 kg/m2. Women with WC of ≥95 cm were at 1.158 times (95% CI, 1.029 to 1.191) greater risk for GDM than women with WC of less than 65 cm. High FPG, high income, smoking, and drinking were associated with an elevated risk of GDM.
Conclusion
The prevalence of GDM in Korean women increased up to 12.70% during 2011 to 2015. These data suggest the importance of GDM screening and prevention in high-risk groups in Korea.

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Close layer
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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AbstractAbstract PDFPubReader   ePub   
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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Diabetes, Obesity and Metabolism
Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics
Jong Hyeon Yoon, Ki-Sun Kwon
Endocrinol Metab. 2021;36(3):478-490.   Published online June 28, 2021
DOI: https://doi.org/10.3803/EnM.2021.1081
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AbstractAbstract PDFPubReader   ePub   
Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.

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Original Article
Diabetes, Obesity and Metabolism
Associations of Phthalate Metabolites and Bisphenol A Levels with Obesity in Children: The Korean National Environmental Health Survey (KoNEHS) 2015 to 2017
Moon Young Seo, Shinje Moon, Shin-Hye Kim, Mi Jung Park
Endocrinol Metab. 2022;37(2):249-260.   Published online April 7, 2022
DOI: https://doi.org/10.3803/EnM.2021.1235
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Phthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity. Methods: A total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte. Results: The urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity. Conclusion: The concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

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  • Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long‐term dietary administration
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Endocrinol Metab : Endocrinology and Metabolism