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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
  • 8,796 View
  • 193 Download
  • 16 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
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
  • COVID-19 and metabolic syndrome
    Harsha Dissanayake
    Best Practice & Research Clinical Endocrinology & Metabolism.2023; : 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;[Epub]     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;[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
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
  • 12,582 View
  • 640 Download
  • 14 Citations
AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
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

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  • Fasting intervention and its clinical effects on the human host and microbiome
    Sofia K. Forslund
    Journal of Internal Medicine.2023; 293(2): 166.     CrossRef
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    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
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    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
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    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
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    Xuemin Peng, Yong Chen
    Frontiers in Endocrinology.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
  • 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.2022;[Epub]     CrossRef
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    Lian Wang, Peijie Chen, Weihua Xiao
    Nutrients.2021; 13(10): 3420.     CrossRef
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
  • 4,192 View
  • 256 Download
  • 10 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
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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  • Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis
    Yilin Li, Rong Lei, Honglin Lei, Qin Xiong, Fengjiao Xie, Chengjiao Yao, Peimin Feng
    European Journal of Gastroenterology & Hepatology.2023; 35(1): 1.     CrossRef
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    Hussein Ali Nwayyir, Esraa Majid Mutasher, Osama Mohammed Alabid, Muthana Abdulrazzaq Jabbar, Wefak Hasan Abdulraheem Al-Kawaz, Haider Ayad Alidrisi, Majid Alabbood, Muhammed Chabek, Munib AlZubaidi, Lujain Anwar Al-khazrajy, Ibtihal Shukri Abd Alhaleem,
    Postgraduate Medicine.2023; : 1.     CrossRef
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    Fatma Haddad, Ghadeer Dokmak, Maryam Bader, Rafik Karaman
    Life.2023; 13(4): 1012.     CrossRef
  • Liraglutide, a glucagon-like peptide-1 analog, in individuals with obesity in clinical practice
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    Cardiovascular Prevention and Pharmacotherapy.2023; 5(2): 49.     CrossRef
  • Efficacy and safety of once-weekly semaglutide in adults with overweight or obesity: a meta-analysis
    Ping Zhong, Hai Zeng, Miaochun Huang, Wenbin Fu, Zhixia Chen
    Endocrine.2022; 75(3): 718.     CrossRef
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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
  • 3,595 View
  • 124 Download
  • 9 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
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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  • Mitochondrial carnitine palmitoyltransferase-II dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis
    Min Yao, Ping Zhou, Yan-Yan Qin, Li Wang, Deng-Fu Yao
    World Journal of Gastroenterology.2023; 29(12): 1765.     CrossRef
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    Tess Yntema, Debby P. Y. Koonen, Folkert Kuipers
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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
  • 3,229 View
  • 205 Download
  • 9 Citations
AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - 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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Original Article
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
  • 2,721 View
  • 115 Download
  • 8 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
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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    Ji Young Kang, Kyungdo Han, Seung-Hwan Lee, Mee Kyoung Kim
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    Cuicui Wang, Xu Zhang, Chenwei Li, Na Li, Xueni Jia, Hui Zhao
    International Journal of General Medicine.2023; Volume 16: 1415.     CrossRef
  • A Longitudinal Retrospective Observational Study on Obesity Indicators and the Risk of Impaired Fasting Glucose in Pre- and Postmenopausal Women
    Myung Ji Nam, Hyunjin Kim, Yeon Joo Choi, Kyung-Hwan Cho, Seon Mee Kim, Yong-Kyun Roh, Kyungdo Han, Jin-Hyung Jung, Yong-Gyu Park, Joo-Hyun Park, Do-Hoon Kim
    Journal of Clinical Medicine.2022; 11(10): 2795.     CrossRef
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    Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee
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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
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    Seohyun Kim, Gyuri Kim, Jae Hyeon Kim
    Scientific Reports.2022;[Epub]     CrossRef
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
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - 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.

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Original Articles
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   CrossRef-TDMCrossref - TDM
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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  • Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets
    Feng Shu, Han Xiao, Qiu-Nuo Li, Xiao-Shuai Ren, Zhi-Gang Liu, Bo-Wen Hu, Hong-Sheng Wang, Hao Wang, Guan-Min Jiang
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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
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  • 7 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
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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  • Weight variability, physical functioning and incident disability in older adults
    Katie J. McMenamin, Tamara B. Harris, Joshua F. Baker
    Journal of Cachexia, Sarcopenia and Muscle.2023;[Epub]     CrossRef
  • Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway
    Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
    Endocrinology and Metabolism.2022; 37(1): 74.     CrossRef
  • Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
    Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
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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
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    Yeoree Yang, Jae-Hyoung Cho
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  • Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease
    Inha Jung, Da Young Lee, Mi Yeon Lee, Hyemi Kwon, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Won-Young Lee, Sung-Woo Park, Se Eun Park
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Diabetes, Obesity and Metabolism
Big Data Articles (National Health Insurance Service Database)
Cardiovascular Outcomes of Obesity According to Menopausal Status: A Nationwide Population-Based Study
Bo Kyung Koo, Sang-Hyun Park, Kyungdo Han, Min Kyong Moon
Endocrinol Metab. 2021;36(5):1029-1041.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1197
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
We estimated the effect of obesity on the incidence of cardiovascular disease (CVD) and mortality in women according to menopausal status.
Methods
Women aged 40 to 69 years under routine health check-ups provided by the National Health Insurance Service in 2009 were followed up till 2018 (n=2,208,559).
Results
In premenopausal women, a significant increment of mortality rate was found in underweight and obesity class II (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.31 to 1.67; and HR, 1.25; 95% CI, 1.12 to 1.39) compared to normal body mass index (BMI); overweight and obesity class I did not affect mortality rate. In postmenopausal women, obesity as well as overweight status reduced the risk of mortality compared to normal BMI (HR, 0.86; 95% CI, 0.83 to 0.88; and HR, 0.84; 95% CI, 0.82 to 0.86). By contrast, there was a linear association between CVD and BMI above the normal range irrespective of menopausal status, which was attenuated in diabetic women.
Conclusion
The current study replicated the J-shaped relationship between BMI and mortality, being more prominent in the postmenopausal group. The risk of CVD was linearly increased as BMI was increased above the normal range irrespective of menopausal status.

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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
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    Min Kyong Moon, Junghyun Noh, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong
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    Do Kyeong Song, Young Sun Hong, Yeon-Ah Sung, Hyejin Lee, Aysha Almas
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    Ji Young Kang, Kyungdo Han, Seung-Hwan Lee, Mee Kyoung Kim
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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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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - 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
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    Natsuko Hara, Hirotsugu Suwanai, Fumiyoshi Yakou, Keitaro Ishii, Hajime Iwasaki, Hironori Abe, Jumpei Shikuma, Hiroyuki Sakai, Takashi Miwa, Ryo Suzuki
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    Adithya Chennamadhavuni, Laith Abushahin, Ning Jin, Carolyn J. Presley, Ashish Manne
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  • 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
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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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  • 6 Citations
AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
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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    Bo Kyung Koo
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Review Article
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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  • 5 Citations
AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
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 Articles
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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  • 5 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
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.

Citations

Citations to this article as recorded by  
  • Serum afamin levels in predicting gestational diabetes mellitus and preeclampsia: A systematic review and meta-analysis
    Ying Yuan, Wenyin He, Xuejiao Fan, Junyu Liang, Zhen Cao, Lei Li
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications
    Joon Ho Moon, Hak Chul Jang
    Diabetes & Metabolism Journal.2022; 46(1): 3.     CrossRef
  • Current Trends of Big Data Research Using the Korean National Health Information Database
    Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee
    Diabetes & Metabolism Journal.2022; 46(4): 552.     CrossRef
  • Maternal Gestational Diabetes Influences DNA Methylation in the Serotonin System in the Human Placenta
    Jae Yen Song, Kyung Eun Lee, Eun Jeong Byeon, Jieun Choi, Sa Jin Kim, Jae Eun Shin
    Life.2022; 12(11): 1869.     CrossRef
  • Fetal Abdominal Obesity Detected At 24 to 28 Weeks of Gestation Persists Until Delivery Despite Management of Gestational Diabetes Mellitus (Diabetes Metab J 2021;45:547-57)
    Kyung-Soo Kim
    Diabetes & Metabolism Journal.2021; 45(6): 966.     CrossRef
Diabetes, Obesity and Metabolism
Musclin Is Related to Insulin Resistance and Body Composition, but Not to Body Mass Index or Cardiorespiratory Capacity in Adults
Yeliana L. Sánchez, Manuela Yepes-Calderón, Luis Valbuena, Andrés F. Milán, María C. Trillos-Almanza, Sergio Granados, Miguel Peña, Mauricio Estrada-Castrillón, Juan C. Aristizábal, Raúl Narvez-Sanchez, Jaime Gallo-Villegas, Juan C. Calderón
Endocrinol Metab. 2021;36(5):1055-1068.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1104
  • 3,221 View
  • 117 Download
  • 5 Citations
AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
We studied whether musclin function in humans is related to glycemic control, body composition, and cardiorespiratory capacity.
Methods
A cross-sectional study was performed in sedentary adults with or without metabolic syndrome (MS). Serum musclin was measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was evaluated by the homeostatic model assessment (HOMA-IR). Body composition was determined by dual-energy X-ray absorptiometry and muscle composition by measuring carnosine in the thigh, a surrogate of fiber types, through proton magnetic resonance spectroscopy. Cardiorespiratory capacity was assessed through direct ergospirometry.
Results
The control (n=29) and MS (n=61) groups were comparable in age (51.5±6.5 years old vs. 50.7±6.1 years old), sex (72.4% vs. 70.5% women), total lean mass (58.5%±7.4% vs. 57.3%±6.8%), and peak oxygen consumption (VOpeak) (31.0±5.8 mL O2./kg.min vs. 29.2±6.3 mL O2/kg.min). Individuals with MS had higher body mass index (BMI) (30.6±4.0 kg/m2 vs. 27.4± 3.6 kg/m2), HOMA-IR (3.5 [95% confidence interval, CI, 2.9 to 4.6] vs. 1.7 [95% CI, 1.1 to 2.0]), and musclin (206.7 pg/mL [95% CI, 122.7 to 387.8] vs. 111.1 pg/mL [95% CI, 63.2 to 218.5]) values than controls (P˂0.05). Musclin showed a significant relationship with HOMA-IR (β=0.23; 95% CI, 0.12 to 0.33; P˂0.01), but not with VOpeak, in multiple linear regression models adjusted for age, sex, fat mass, lean mass, and physical activity. Musclin was significantly associated with insulin, glycemia, visceral fat, and regional muscle mass, but not with BMI, VCO2peak, maximum heart rate, maximum time of work, or carnosine.
Conclusion
In humans, musclin positively correlates with insulinemia, IR, and a body composition profile with high visceral adiposity and lean mass, but low body fat percentage. Musclin is not related to BMI or cardiorespiratory capacity.

Citations

Citations to this article as recorded by  
  • Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings
    Jaime A. Gallo-Villegas, Juan C. Calderón
    European Journal of Applied Physiology.2023; 123(5): 945.     CrossRef
  • Serum Levels of Myonectin Are Lower in Adults with Metabolic Syndrome and Are Negatively Correlated with Android Fat Mass
    Jorge L. Petro, María Carolina Fragozo-Ramos, Andrés F. Milán, Juan C. Aristizabal, Jaime A. Gallo-Villegas, Juan C. Calderón
    International Journal of Molecular Sciences.2023; 24(8): 6874.     CrossRef
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    Jie Zhang, Jing Shi, Zengguang Cheng, Wenchao Hu
    Cytokine.2023; 167: 156211.     CrossRef
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    Jaime Gallo-Villegas, Leonardo A. Castro-Valencia, Laura Pérez, Daniel Restrepo, Oscar Guerrero, Sergio Cardona, Yeliana L. Sánchez, Manuela Yepes-Calderón, Luis H. Valbuena, Miguel Peña, Andrés F. Milán, Maria C. Trillos-Almanza, Sergio Granados, Juan C.
    European Journal of Applied Physiology.2022; 122(2): 331.     CrossRef
  • Reactive Oxygen and Nitrogen Species (RONS) and Cytokines—Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle
    Paola Llanos, Jesus Palomero
    Cells.2022; 11(24): 4008.     CrossRef

Endocrinol Metab : Endocrinology and Metabolism