Endocrinology and Metabolism

From articles published in Endocrinology and Metabolism during the past two years (2022 ~ ).

Review Article

Calcium & bone metabolism
Cardiovascular Impact of Calcium and Vitamin D Supplements: A Narrative Review: Fatima Zarzour, Ahmad Didi, Mohammed Almohaya, David Kendler; Endocrinol Metab. 2023;38(1):56-68. Published online February 16, 2023; DOI: https://doi.org/10.3803/EnM.2022.1644

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Calcium and vitamin D play an important role in mineral homeostasis and the maintenance of skeletal health. Calcium and vitamin D supplements have been widely used for fracture prevention in elderly populations. Many trials have studied the effectiveness and cardiovascular safety of calcium and vitamin D supplementation, with disparate results. In this review, we summarize the most important trials and systematic reviews. There is significant heterogeneity in clinical trial design, differences in the nature of trial outcomes (self-reported vs. verified), prior calcium intake, and trial size. Inconsistent results have been reported concerning the effects of calcium and vitamin D supplementation on cardiovascular outcomes. Most current guidelines recommend calcium intake of up to 1,200 mg daily, preferably from the diet, without concern for cardiovascular risk. Recommendations regarding vitamin D supplementation vary widely. There is compelling evidence from well-conducted randomized trials that modest vitamin D supplementation is safe but does not confer cardiovascular benefit or cardiovascular harm.

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Evaluating adherence, tolerability and safety of oral calcium citrate in elderly osteopenic subjects: a real-life non-interventional, prospective, multicenter study
Mariangela Rondanelli, Salvatore Minisola, Marco Barale, Daniele Barbaro, Francesca Mansueto, Santina Battaglia, Gloria Bonaccorsi, Santina Caliri, Alessandro Cavioni, Luciano Colangelo, Sabrina Corbetta, Federica Coretti, Giorgia Dito, Valentina Gavioli,
Aging Clinical and Experimental Research.2024;[Epub] CrossRef
Association between Daily Dietary Calcium Intake and the Risk of Cardiovascular Disease (CVD) in Postmenopausal Korean Women
Jae Kyung Lee, Thi Minh Chau Tran, Euna Choi, Jinkyung Baek, Hae-Rim Kim, Heeyon Kim, Bo Hyon Yun, Seok Kyo Seo
Nutrients.2024; 16(7): 1043. CrossRef
Effect of Denosumab on Bone Density in Postmenopausal Osteoporosis: A Comparison with and without Calcium Supplementation in Patients on Standard Diets in Korea
Chaiho Jeong, Jinyoung Kim, Jeongmin Lee, Yejee Lim, Dong-Jun Lim, Ki-Hyun Baek, Jeonghoon Ha
Journal of Clinical Medicine.2023; 12(21): 6904. CrossRef

Original Articles

Diabetes, Obesity and Metabolism
Impact of Post-Transplant Diabetes Mellitus on Survival and Cardiovascular Events in Kidney Transplant Recipients: Ja Young Jeon, Shin Han-Bit, Bum Hee Park, Nami Lee, Hae Jin Kim, Dae Jung Kim, Kwan-Woo Lee, Seung Jin Han; Endocrinol Metab. 2023;38(1):139-145. Published online February 6, 2023; DOI: https://doi.org/10.3803/EnM.2022.1594

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Background
Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients.
Methods
We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model.
Results
Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE.
Conclusion
Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.

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Effect of post-transplant diabetes mellitus on cardiovascular events and mortality: a single‐center retrospective cohort study
Uğur Ünlütürk, Tolga Yıldırım, Merve Savaş, Seda Hanife Oğuz, Büşra Fırlatan, Deniz Yüce, Nesrin Damla Karakaplan, Cemile Selimova, Rahmi Yılmaz, Yunus Erdem, Miyase Bayraktar
Endocrine.2024;[Epub] CrossRef
Prevalence of new-onset diabetes mellitus after kidney transplantation: a systematic review and meta-analysis
Qiufeng Du, Tao Li, Xiaodong Yi, Shuang Song, Jing Kang, Yunlan Jiang
Acta Diabetologica.2024;[Epub] CrossRef
Safety and efficacy of semaglutide in post kidney transplant patients with type 2 diabetes or Post-Transplant diabetes
Moeber Mohammed Mahzari, Omar Buraykan Alluhayyan, Mahdi Hamad Almutairi, Mohammed Abdullah Bayounis, Yazeed Hasan Alrayani, Amir A. Omair, Awad Saad Alshahrani
Journal of Clinical & Translational Endocrinology.2024; 36: 100343. CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Metformin and Cervical Cancer Risk in Patients with Newly Diagnosed Type 2 Diabetes: A Population-Based Study in Korea: Hyun Min Kim, Min Jin Kang, Sun Ok Song; Endocrinol Metab. 2022;37(6):929-937. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1613; Correction in: Endocrinol Metab 2023;38(1):174

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Background
Cervical cancer is a prevalent malignancy that is a major health problem for women worldwide. The cancer-preventive properties of metformin are well-known, but insufficient data have been reported regarding its relationship to cervical cancer. Therefore, in a nationwide population-based study, we investigated the association between metformin use and cervical cancer incidence in patients with newly diagnosed type 2 diabetes.
Methods
This retrospective cohort study used the Korean National Health Insurance claims database. Individuals newly diagnosed with type 2 diabetes between January 2005 and December 2009 were included. The occurrence of cervical cancer was explored by matching for age, economic status, region of residence, and use of anti-diabetic medication.
Results
In total, 66,013 metformin users and 64,756 non-users were analyzed. Cervical cancer occurred in 219 metformin users (0.33%) and 274 metformin non-users (0.42%) (hazard ratio [HR], 0.783; 95% confidence interval [CI], 0.655 to 0.036; P=0.007). Moreover, cervical cancer risk was considerably reduced in those treated with a high dose (>1,200,000 mg) or for an extended period (≥2,000 days) compared to non-users (HR, 0.151; 95% CI, 0.093 to 0.243; P<0.001; and HR, 0.141; 95% CI, 0.077 to 0.258; P<0.001). The incidence was also significantly lower in metformin users among those over 50 years old (HR, 0.791; 95% CI, 0.650 to 0.961; P<0.001).
Conclusion
Metformin use in patients with newly diagnosed diabetes was associated with a lower risk of cervical cancer in Korea. Furthermore, a significant association was found between the use of metformin and cervical cancer in a dose- and duration-dependent manner and among those over 50 years old.

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Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp
Mohamad Ali Hijazi, André Gessner, Nahed El-Najjar
Cancers.2023; 15(12): 3199. CrossRef
Network-based drug repurposing for HPV-associated cervical cancer
Faheem Ahmed, Young Jin Yang, Anupama Samantasinghar, Young Woo Kim, Jeong Beom Ko, Kyung Hyun Choi
Computational and Structural Biotechnology Journal.2023; 21: 5186. CrossRef
The Use of Metformin and Postoperative Insulin Pump Were Predictive Factors for Outcomes of Diabetic Colorectal Cancer Patients after Surgery
Xu-Rui Liu, Fei Liu, Zi-Wei Li, Quan Lv, Xin-Peng Shu, Lian-Shuo Li, Yue Tong, Wei Zhang, Dong Peng
Nutrition and Cancer.2023; 75(10): 1926. CrossRef

Review Article

Thyroid
Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Maternal Thyroid Dysfunction, and Child Autism Spectrum Disorder: Hyeong-Moo Shin, Jiwon Oh, Rebecca J. Schmidt, Elizabeth N. Pearce; Endocrinol Metab. 2022;37(6):819-829. Published online November 23, 2022; DOI: https://doi.org/10.3803/EnM.2022.1598

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Autism spectrum disorder (ASD), with its high economic and societal costs, is a growing public health concern whose prevalence has risen steadily over the last two decades. Although actual increased incidence versus improved diagnosis remains controversial, the increased prevalence of ASD suggests non-inherited factors as likely contributors. There is increasing epidemiologic evidence that abnormal maternal thyroid function during pregnancy is associated with increased risk of child ASD and other neurodevelopmental disorders. Prenatal exposure to endocrine-disrupting chemicals such as per- and polyfluoroalkyl substances (PFAS) is known to disrupt thyroid function and can affect early brain development; thus, thyroid dysfunction is hypothesized to mediate this relationship. The concept of a potential pathway from prenatal PFAS exposure through thyroid dysfunction to ASD etiology is not new; however, the extant literature on this topic is scant. The aim of this review is to evaluate and summarize reports with regard to potential mechanisms in this pathway.

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Endocrine Disruptors and Thyroid Health
Elizabeth N. Pearce
Endocrine Practice.2024; 30(2): 172. CrossRef
Maternal Thyroid Dysfunction During Pregnancy as an Etiologic Factor in Autism Spectrum Disorder: Challenges and Opportunities for Research
Zoe B. Kaplan, Elizabeth N. Pearce, Sun Y. Lee, Hyeong-Moo Shin, Rebecca J. Schmidt
Thyroid®.2024; 34(2): 144. CrossRef
Effects of Endocrine-Disrupting Chemicals on Human Health
Jun Hyung Lee, Sung-Eun Cho
Laboratory Medicine Online.2023; 13(3): 129. CrossRef

Original Articles

Diabetes, Obesity and Metabolism
Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction: Giang Nguyen, So Young Park, Dinh Vinh Do, Dae-Hee Choi, Eun-Hee Cho; Endocrinol Metab. 2022;37(6):918-928. Published online November 15, 2022; DOI: https://doi.org/10.3803/EnM.2022.1530

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Background
Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis.
Methods
To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of α-smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol–induced mouse model of nonalcoholic steatohepatitis (NASH).
Results
Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction.
Conclusion
Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease.

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Improvement effect of gemigliptin on salivary gland dysfunction in exogenous methylglyoxal-injected rats
Woo Kwon Jung, Su-Bin Park, Hwa Young Yu, Junghyun Kim
Heliyon.2024; 10(8): e29362. CrossRef
Gemigliptin, a DPP4 inhibitor, ameliorates nonalcoholic steatohepatitis through AMP-activated protein kinase-independent and ULK1-mediated autophagy
Youngmi Song, Hyekyung Yang, Juhee Kim, Yoonjin Lee, Sung-Ho Kim, In-Gu Do, Cheol-Young Park
Molecular Metabolism.2023; 78: 101806. CrossRef
DPP-4 Inhibitor in Type 2 Diabetes Mellitus Patient with Non-Alcoholic Fatty Liver Disease: Achieving Two Goals at Once?
Ji Cheol Bae
Endocrinology and Metabolism.2022; 37(6): 858. CrossRef

Diabetes, Obesity and Metabolism
Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults: Chul Woo Ahn, Sungjae Shin, Seunghyun Lee, Hye-Sun Park, Namki Hong, Yumie Rhee; Endocrinol Metab. 2022;37(5):781-790. Published online October 25, 2022; DOI: https://doi.org/10.3803/EnM.2022.1532

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Background
Shift work is associated with obesity and metabolic syndrome. However, this association in the normal-weight population remains unclear. This study aimed to investigate whether shift work is associated with normal-weight obesity (NWO).
Methods
From the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset (2008 to 2011), 3,800 full-time workers aged ≥19 years with a body mass index (BMI) ≤25 kg/m² were analysed. We defined NWO as BMI ≤25 kg/m² and body fat percentage ≥25% in men and ≥37% in women. Working patterns were classified into “daytime,” “other than daytime,” and “shift.” Multivariable logistic regression analysis was performed to evaluate the relationship between shift work and NWO.
Results
Shift work was associated with higher odds of NWO than daytime work (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.04 to 2.09) and night/evening work (aOR, 1.87; 95% CI, 1.11 to 3.14) after adjustment for type of work, working hours, age, sex, BMI, 25-hydroxyvitamin D levels, homeostatic model assessment for insulin resistance, and other sociodemographic factors. In subgroup analyses, the association between shift work and NWO was more robust in those aged ≥60 years and those working ≥56 hours/week.
Conclusion
Shift work was associated with NWO in community-dwelling Korean adults, independent of age, sex, BMI, and other covariates.

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Impaired Melatonin Secretion, Oxidative Stress and Metabolic Syndrome in Night Shift Work
Sorina Hohor, Cristina Mandanach, Andreea Maftei, Corina Aurelia Zugravu, Marina Ruxandra Oțelea
Antioxidants.2023; 12(4): 959. CrossRef
Normal-Weight Obesity and Metabolic Syndrome in Korean Adults: A Population-Based Cross-Sectional Study
Jeonghyeon Kim, Seamon Kang, Hyunsik Kang
Healthcare.2023; 11(16): 2303. CrossRef
You Can’t Avoid Shift Work? Then Focus on Body Fat Rather than Weight
Eun Kyung Lee
Endocrinology and Metabolism.2022; 37(5): 756. CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Association among Current Smoking, Alcohol Consumption, Regular Exercise, and Lower Extremity Amputation in Patients with Diabetic Foot: Nationwide Population-Based Study: Yoon Jae Lee, Kyung-Do Han, Jun Hyeok Kim; Endocrinol Metab. 2022;37(5):770-780. Published online October 12, 2022; DOI: https://doi.org/10.3803/EnM.2022.1519

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Background
The present study investigates whether modifiable behavioral factors of current cigarette smoking, heavy alcohol consumption, and regular exercise are associated with risk of lower extremity amputation (LEA) in diabetic patients.
Methods
A total of 2,644,440 diabetic patients (aged ≥20 years) was analyzed using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios (HRs) for the behavioral factors with risk of LEA under adjustment for potential confounders.
Results
The risk of LEA was significantly increased by current cigarette smoking and heavy alcohol consumption (HR, 1.436; 95% confidence interval [CI], 1.367 to 1.508 and HR, 1.082; 95% CI, 1.011 to 1.158) but significantly decreased with regular exercise (HR, 0.745; 95% CI, 0.706 to 0.786) after adjusting for age, sex, smoking, alcohol consumption, exercise, low income, hypertension, dyslipidemia, body mass index, using insulin or oral antidiabetic drugs, and diabetic duration. A synergistically increased risk of LEA was observed with larger number of risky behaviors.
Conclusion
Modification of behaviors of current smoking, heavy alcohol intake, and exercise prevents LEA and can improve physical, emotional, and social quality of life in diabetic patients.

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Adjuvant effect of antimicrobial photodynamic therapy (aPDT) in the treatment of diabetic foot ulcers: A case series
Rita de Cassia Ferreira, Rebeca Boltes Cecatto, Silvana Torres Perez, Raquel Agnelli Mesquita‐Ferrari, Sandra Kalil Bussadori, Cinthya Cosme Duran, Anna Carolina Tempestini Horliana, Kristianne Porta Santos Fernandes
Journal of Biophotonics.2024;[Epub] CrossRef
Factors associated with diabetic foot ulcers and lower limb amputations in type 1 and type 2 diabetes supported by real‐world data from the German/Austrian DPV registry
Alexander J. Eckert, Stefan Zimny, Marcus Altmeier, Ana Dugic, Anton Gillessen, Latife Bozkurt, Gabriele Götz, Wolfram Karges, Frank J. Wosch, Stephan Kress, Reinhard W. Holl
Journal of Diabetes.2024;[Epub] CrossRef
Investigating Diabetic Foot Pathophysiology and Amputation Prevention Strategies through Behavioral Modification
Jun Hyeok Kim
Journal of Wound Management and Research.2023; 19(3): 167. CrossRef

Thyroid
Quality of Life of Survivors of Thyroid Cancer Is Not Inferior to That in Subjects without Cancer: Long-Term after Over 5 Years: Jeongmin Lee, Youn-Ju Lee, Dong-Jun Lim, Jung-Min Lee, Sang-Ah Chang, Min-Hee Kim; Endocrinol Metab. 2022;37(4):664-673. Published online August 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1499

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Background
Patients with thyroid cancer undergo less extensive surgery and additional therapies compared to those with other cancers. We aimed to compare the quality of life (QoL) between patients with thyroid cancer and healthy subjects using representative data from Korea. Differences in QoL of thyroid cancer survivors according to the duration after cancer diagnosis was also evaluated.
Methods
This population-based cohort study included 50,278 subjects who participated in the Korea National Health and Nutrition Examination Survey between 2007 and 2017. QoL was compared between patients with thyroid cancer and healthy subjects using self-reported data from the EuroQoL (EQ)-5 dimension (5D) and EQ-visual analog scale (VAS). Propensity score matching was used to match thyroid cancer survivors to healthy subjects (1:5 matching).
Results
Linear regression with univariate analysis showed that the presence of thyroid cancer was positively correlated with better EQ-5D index scores (β-coefficient=0.010, p=0.046). After adjusting for multiple covariables, statistical significance was maintained. EQ-VAS fails to demonstrate any significant correlation. Among the EQ-5D categories, patients with thyroid cancer showed better self-care than healthy subjects. Thyroid cancer duration did not correlate with the EQ-5D index score. In subgroup analyses, compared to patients with thyroid cancer duration of <5 years, no significant difference was observed in the correlation between the EQ-5D index score and survival duration in those with thyroid cancer duration of 5 to 9 years and ≥10 years.
Conclusion
Using a large-scale nationwide population-based database, our study demonstrated better QoL, especially in terms of self-care, among thyroid cancer survivors than among healthy subjects without cancer.

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Quality of Life Considerations in Patients Treated for Differentiated Thyroid Cancer
Jie Liu
Clinical Thyroidology.2023; 35(4): 160. CrossRef
The psychosocial impact of thyroid cancer
Parker Haymart, Nina Jackson Levin, Megan R. Haymart
Current Opinion in Endocrinology, Diabetes & Obesity.2023; 30(5): 252. CrossRef
Longitudinal Changes in Quality of Life Before and After Thyroidectomy in Patients With Differentiated Thyroid Cancer
Byung Hun Kim, Soo Rack Ryu, Jin Won Lee, Chang Myeon Song, Yong Bae Ji, Seok Hyun Cho, Seung Hwan Lee, Kyung Tae
The Journal of Clinical Endocrinology & Metabolism.2023;[Epub] CrossRef

Review Articles

Hypothalamus and Pituitary Gland
Advances in Pituitary Surgery: Yoon Hwan Byun, Ho Kang, Yong Hwy Kim; Endocrinol Metab. 2022;37(4):608-616. Published online August 19, 2022; DOI: https://doi.org/10.3803/EnM.2022.1546

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Pituitary surgery has advanced considerably in recent years with the exploration and development of various endoscopic approaches and techniques. Different endoscopic skull base approaches are being applied to access sellar tumors in different locations. Moreover, extracapsular dissection and cavernous sinus exploration have enabled gross total resection of sellar tumors where it could not have been achieved in the past. Techniques for skull base reconstruction have also progressed, allowing surgeons to remove larger and more complicated tumors than before. This review article discusses different endoscopic skull base approaches, surgical techniques for removing pituitary adenomas, and reconstruction methods for repairing postoperative low-flow and high-flow cerebrospinal fluid leakage.

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Serum and hair steroid profiles in patients with nonfunctioning pituitary adenoma undergoing surgery: A prospective observational study
Seung Shin Park, Yong Hwy Kim, Ho Kang, Chang Ho Ahn, Dong Jun Byun, Man Ho Choi, Jung Hee Kim
The Journal of Steroid Biochemistry and Molecular Biology.2023; 230: 106276. CrossRef
Pituitary disease and anaesthesia
Kim Rhodes, Robert John, Astri Luoma
Anaesthesia & Intensive Care Medicine.2023; 24(6): 348. CrossRef
Орфанні ендокринні захворювання: сучасні тенденції хірургічного лікування в Україні
M.D. Tronko, B.B. Guda
Endokrynologia.2022; 27(4): 287. CrossRef

Calcium & Bone Metabolism
A Key Metabolic Regulator of Bone and Cartilage Health: Elizabeth Pérez-Hernández, Jesús Javier Pastrana-Carballo, Fernando Gómez-Chávez, Ramesh C. Gupta, Nury Pérez-Hernández; Endocrinol Metab. 2022;37(4):559-574. Published online August 8, 2022; DOI: https://doi.org/10.3803/EnM.2022.1443

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Taurine, a cysteine-derived zwitterionic sulfonic acid, is a common ingredient in energy drinks and is naturally found in fish and other seafood. In humans, taurine is produced mainly in the liver, and it can also be obtained from food. In target tissues, such as the retina, heart, and skeletal muscle, it functions as an essential antioxidant, osmolyte, and antiapoptotic agent. Taurine is also involved in energy metabolism and calcium homeostasis. Taurine plays a considerable role in bone growth and development, and high-profile reports have demonstrated the importance of its metabolism for bone health. However, these reports have not been collated for more than 10 years. Therefore, this review focuses on taurine–bone interactions and covers recently discovered aspects of taurine’s effects on osteoblastogenesis, osteoclastogenesis, bone structure, and bone pathologies (e.g., osteoporosis and fracture healing), with due attention to the taurine–cartilage relationship.

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Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
Mengxing Yin, Dezhi Zhou, Fu Jia, Xiaosan Su, Xiufang Li, Ruifen Sun, Junmin Li
Journal of Orthopaedic Surgery and Research.2023;[Epub] CrossRef
An in-silico approach to the potential modulatory effect of taurine on sclerostin (SOST) and its probable role during osteoporosis
Mazumder Adhish, I. Manjubala
Journal of Biomolecular Structure and Dynamics.2023; : 1. CrossRef
Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that’ s the question
Kwok M. Ho, Anna Lee, William Wu, Matthew T.V. Chan, Lowell Ling, Jeffrey Lipman, Jason Roberts, Edward Litton, Gavin M. Joynt, Martin Wong
Journal of Geriatric Cardiology.2023; 20(11): 813. CrossRef

Original Articles

Diabetes, Obesity and Metabolism
High Cardiorespiratory Fitness Protects against Molecular Impairments of Metabolism, Heart, and Brain with Higher Efficacy in Obesity-Induced Premature Aging: Patcharapong Pantiya, Chanisa Thonusin, Natticha Sumneang, Benjamin Ongnok, Titikorn Chunchai, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Busarin Arunsak, Natthaphat Siri-Angkul, Sirawit Sriwichaiin, Nipon Chattipakorn, Siriporn C. Chattipakorn; Endocrinol Metab. 2022;37(4):630-640. Published online August 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1430

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Background
High cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats.
Methods
Seven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a highfat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies.
Results
The obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer’s disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats.
Conclusion
The protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.

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Associations that Cardiorespiratory Fitness and Body Mass Index Loss Have with Deficit Accumulation Frailty
KAYLONI OLSON, DENISE K. HOUSTON, JOHNATHAN ROSS, RENA R. WING, FELICIA R. SIMPSON, AMBARISH PANDEY, MICHAEL P. WALKUP, MIA YANG, MARK A. ESPELAND
Medicine & Science in Sports & Exercise.2024; 56(4): 717. CrossRef
Interplay between obesity and aging on myocardial geometry and function: Role of leptin-STAT3-stress signaling
Wei Jin, Fei Tu, Feng Dong, Qinqin Deng, Miyesaier Abudureyimu, Wei Yu, Guo-jun Cai, Jian-ming Pei, Zhaohui Pei, Jun Ren
Biochimica et Biophysica Acta (BBA) - General Subjects.2023; 1867(2): 130281. CrossRef
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

Diabetes, Obesity and Metabolism
The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis: Dinh Vinh Do, So Young Park, Giang Thi Nguyen, Dae Hee Choi, Eun-Hee Cho; Endocrinol Metab. 2022;37(4):620-629. Published online July 22, 2022; DOI: https://doi.org/10.3803/EnM.2022.1412

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Background
Hepatic stellate cells (HSCs) are the central players interacting with multiple cell types in liver fibrosis. The crosstalk between HSCs and macrophages has recently become clearer. Irisin, an exercise-responsive myokine, was known to have a potentially protective role in liver and renal fibrosis, especially in connection with stellate cells. This study investigated the effects of irisin on the interaction between HSCs and macrophages.
Methods
Tamm-Horsfall protein-1 (THP-1) human monocytes were differentiated into macrophages, polarized into the inflammatory M1 phenotype with lipopolysaccharide. Lieming Xu-2 (LX-2) cells, human HSCs, were treated with conditioned media (CM) from M1 macrophages, with or without recombinant irisin. HSCs responses to CM from M1 macrophages were evaluated regarding activation, proliferation, wound healing, trans-well migration, contractility, and related signaling pathway.
Results
CM from M1 macrophages significantly promoted HSC proliferation, wound healing, transwell migration, and contractility, but not activation of HSCs. Irisin co-treatment attenuated these responses of HSCs to CM. However, CM and irisin treatment did not induce any changes in HSC activation. Further, irisin co-treatment alleviated CM-induced increase of phopho-protein kinase B (pAKT), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1).
Conclusion
These findings suggested that irisin may play a protective role in the pathogenesis of liver fibrosis, especially when working in the crosstalk between HSCs and macrophages.

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Matrix metalloproteinases induce extracellular matrix degradation through various pathways to alleviate hepatic fibrosis
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Review Article

Diabetes, Obesity and Metabolism
Extra-Glycemic Effects of Anti-Diabetic Medications: Two Birds with One Stone?: Eun-Jung Rhee; Endocrinol Metab. 2022;37(3):415-429. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.304

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The world is suffering from a rapid increase in the number of people with diabetes due to the increased prevalence of obesity and lengthened life span. Since the development of insulin thanks to the efforts of Prof. Banting and Dr. Best in 1922, for which they won the Nobel Prize, remarkable developments in anti-diabetic medications have dramatically lengthened the lifespan of patients with diabetes. However, the control rate of hyperglycemia in patients with diabetes remains unsatisfactory, since glycemic control requires both medication and lifestyle modifications to slow the deterioration of pancreatic beta-cell function and prevent diabetic complications. From the initial “triumvirate” to the “ominous octet,” and now the “egregious eleven,” the number of organs recognized as being involved in hyperglycemia and diabetes has increased with the development of anti-diabetic medications. Recent unexpected results from outcome trials of anti-diabetic medications have enabled anti-diabetic medications to be indicated for the prevention of chronic kidney disease and heart failure, even in patients without diabetes. In this review, I would like to summarize the extra-glycemic effects of anti-diabetic medications.

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Original Articles

Diabetes, Obesity and Metabolism
Effect of the Concomitant Use of Subcutaneous Basal Insulin and Intravenous Insulin Infusion in the Treatment of Severe Hyperglycemic Patients: Yejee Lim, Jung Hun Ohn, Joo Jeong, Jiwon Ryu, Sun-wook Kim, Jae Ho Cho, Hee-Sun Park, Hye Won Kim, Jongchan Lee, Eun Sun Kim, Nak-Hyun Kim, You Hwan Jo, Hak Chul Jang; Endocrinol Metab. 2022;37(3):444-454. Published online June 3, 2022; DOI: https://doi.org/10.3803/EnM.2021.1341

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Background
No consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia.
Methods
Patients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108).
Results
The rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups.
Conclusion
Early co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

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Hypothalamus and Pituitary Gland
Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency: Yun Jeong Lee, Yunha Choi, Han-Wook Yoo, Young Ah Lee, Choong Ho Shin, Han Saem Choi, Ho-Seong Kim, Jae Hyun Kim, Jung Eun Moon, Cheol Woo Ko, Moon Bae Ahn, Byung-Kyu Suh, Jin-Ho Choi; Endocrinol Metab. 2022;37(2):359-368. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1384

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Background
Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.
Methods
This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.
Results
Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.
Conclusion
GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

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