Endocrinology and Metabolism

Volume 35(3); September 2020

Review Articles

Obesity and Metabolism
Metabolically Healthy and Unhealthy Normal Weight and Obesity: Norbert Stefan; Endocrinol Metab. 2020;35(3):487-493. Published online August 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.301

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Increased fat mass is an established risk factor for the cardiometabolic diseases type 2 diabetes and cardiovascular disease (CVD) and is associated with increased risk of all-cause and CVD mortality. However, also very low fat mass associates with such an increased risk. Whether impaired metabolic health, characterized by hypertension, dyslipidemia, hyperglycemia, insulin resistance, and subclinical inflammation, may explain part of the elevated risk of cardiometabolic diseases that is found in many subjects with very low fat mass, as it does in many obese subjects, is unknown. An important pathomechanism of impaired metabolic health is disproportionate fat distribution. In this article the risk of cardiometabolic diseases and mortality in subjects with metabolically healthy and unhealthy normal weight and obesity is summarized. Furthermore, the change of metabolic health during a longer period of follow-up and its impact on cardiometabolic diseases is being discussed. Finally, the implementation of the concept of metabolic health in daily clinical practice is being highlighted.

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Precision medicine in complex diseases—Molecular subgrouping for improved prediction and treatment stratification
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Miscellaneous
WD40-Repeat Proteins in Ciliopathies and Congenital Disorders of Endocrine System: Yeonjoo Kim, Soo-Hyun Kim; Endocrinol Metab. 2020;35(3):494-506. Published online September 8, 2020; DOI: https://doi.org/10.3803/EnM.2020.302

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WD40-repeat (WDR)-containing proteins constitute an evolutionarily conserved large protein family with a broad range of biological functions. In human proteome, WDR makes up one of the most abundant protein-protein interaction domains. Members of the WDR protein family play important roles in nearly all major cellular signalling pathways. Mutations of WDR proteins have been associated with various human pathologies including neurological disorders, cancer, obesity, ciliopathies and endocrine disorders. This review provides an updated overview of the biological functions of WDR proteins and their mutations found in congenital disorders. We also highlight the significant role of WDR proteins in ciliopathies and endocrine disorders. The new insights may help develop therapeutic approaches targeting WDR motifs.

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Miscellaneous
Systems Biology: A Multi-Omics Integration Approach to Metabolism and the Microbiome: Jang Won Son, Saeed Shoaie, Sunjae Lee; Endocrinol Metab. 2020;35(3):507-514. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.303

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The complex and dynamic nature of human physiology, as exemplified by metabolism, has often been overlooked due to the lack of quantitative and systems approaches. Recently, systems biology approaches have pushed the boundaries of our current understanding of complex biochemical, physiological, and environmental interactions, enabling proactive medicine in the near future. From this perspective, we review how state-of-the-art computational modelling of human metabolism, i.e., genome-scale metabolic modelling, could be used to identify the metabolic footprints of diseases, to guide the design of personalized treatments, and to estimate the microbiome contributions to host metabolism. These state-of-the-art models can serve as a scaffold for integrating multi-omics data, thereby enabling the identification of signatures of dysregulated metabolism by systems approaches. For example, increased plasma mannose levels due to decreased uptake in the liver have been identified as a potential biomarker of early insulin resistance by multi-omics approaches. In addition, we also review the emerging axis of human physiology and the human microbiome, discussing its contribution to host metabolism and quantitative approaches to study its variations in individuals.

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Thyroid
Mechanisms of TERT Reactivation and Its Interaction with BRAF^V600E: Young Shin Song, Young Joo Park; Endocrinol Metab. 2020;35(3):515-525. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.304

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The telomerase reverse transcriptase (TERT) gene, which is repressed in most differentiated human cells, can be reactivated by somatic TERT alterations and epigenetic modulations. Moreover, the recruitment, accessibility, and binding of transcription factors also affect the regulation of TERT expression. Reactivated TERT contributes to the development and progression of cancer through telomere lengthening-dependent and independent ways. In particular, because of recent advances in high-throughput sequencing technologies, studies on genomic alterations in various cancers that cause increased TERT transcriptional activity have been actively conducted. TERT reactivation has been reported to be associated with poor prognosis in several cancers, and TERT promoter mutations are among the most potent prognostic markers in thyroid cancer. In particular, when a TERT promoter mutation coexists with the BRAF^V600E mutation, these mutations exert synergistic effects on a poor prognosis. Efforts have been made to uncover the mechanisms of these synergistic interactions. In this review, we discuss the role of TERT reactivation in tumorigenesis, the mechanisms of TERT reactivation across all human cancers and in thyroid cancer, and the mechanisms of interactions between BRAF^V600E and TERT promoter mutations.

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Hypothalamus and Pituitary gland
Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations: Ahmed Al-Sharefi, Richard Quinton; Endocrinol Metab. 2020;35(3):526-540. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.760

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Male hypogonadism—rebadged by some as testosterone deficiency syndrome—is a clinical and biochemical diagnosis of increasing worldwide interest. Organic male hypogonadism—usually permanent—is well-established, but aging men may also exhibit lower serum testosterone levels; principally due to burden of extra-gonadal comorbidities such as obesity, diabetes and metabolic syndrome, but with an underlying intact hypothalamo-pituitary-testicular (HPT) axis capable of springing back into operation once comorbidities are addressed. Despite encouraging observational data and plausible theoretical underpinning, evidence for efficacy and safety of testosterone in this “aging” group of men is lacking; addressing comorbid illnesses remains the key priority instead. Nevertheless, in recent years, accumulation of misleading information online has triggered a global tsunami of testosterone prescriptions. Despite this, many men with organic hypogonadism remain undiagnosed or untreated; many more face a diagnostic odyssey before achieving care by the appropriate specialist. As testosterone therapy is not without risk several clinical practice guidelines have been published specialist societies to guide physicians on best practice. However, these are heterogeneous in key areas, reflecting divergent approaches to the same evidence basis. Herein, we navigate the major clinical practice guidelines on male hypogonadism and test their respective recommendations against current best evidence.

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Diabetes
Lessons from Use of Continuous Glucose Monitoring Systems in Digital Healthcare: Hun-Sung Kim, Kun-Ho Yoon; Endocrinol Metab. 2020;35(3):541-548. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.675

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We live in a digital world where a variety of wearable medical devices are available. These technologies enable us to measure our health in our daily lives. It is increasingly possible to manage our own health directly through data gathered from these wearable devices. Likewise, healthcare professionals have also been able to indirectly monitor patients’ health. Healthcare professionals have accepted that digital technologies will play an increasingly important role in healthcare. Wearable technologies allow better collection of personal medical data, which healthcare professionals can use to improve the quality of healthcare provided to the public. The use of continuous glucose monitoring systems (CGMS) is the most representative and desirable case in the adoption of digital technology in healthcare. Using the case of CGMS and examining its use from the perspective of healthcare professionals, this paper discusses the necessary adjustments required in clinical practices. There is a need for various stakeholders, such as medical staff, patients, industry partners, and policy-makers, to utilize and harness the potential of digital technology.

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Editorial

Bone Metabolism
Why Do We Need Proactive Management for Fracture Prevention in Long-Term Glucocorticoid Users?: Han Seok Choi; Endocrinol Metab. 2020;35(3):549-551. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.308

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Original Articles

Clinical Study
The Prevalence and Risk of Type 2 Diabetes in Adults with Disabilities in Korea: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2020;35(3):552-561. Published online July 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.653

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Background
People with disabilities are at risk of secondary conditions such as diabetes. The aim of this study was to evaluate the prevalence and risk of type 2 diabetes in South Korea, especially among people with all types of disabilities.
Methods
We conducted a cross-sectional study using data from the Korean National Health Insurance Service, with two disabilityfree controls matched for each participant with disabilities by age and sex. Information regarding the type, severity and grade of disabilities was obtained based on the National Disability Registry. Diagnosis of type 2 diabetes was defined according to the following criteria: presence of International Classification of Diseases, Tenth Revision, Clinical Modification codes E11, E12, E13, or E14 and claims for at least one oral anti-diabetic agent or insulin at baseline, or fasting glucose level ≥126 mg/dL.
Results
We included 1,297,806 participants with disabilities and 2,943,719 control. Out of 4,241,525 participants, 841,990 (19.9%) were diagnosed with diabetes. The prevalence of diabetes was higher in the disability group compared with individuals without disabilities (23.1% vs. 18.4%). The odds of having diabetes was higher in the disability group compared with the control group (adjusted odds ratio, 1.34; 95% confidence interval, 1.33 to 1.34). The results showed higher prevalence of diabetes in the mildly disabled group (23.2%) than in the severely disabled group (22.7%).
Conclusion
The prevalence and risk of diabetes were higher in people with disabilities compared with the general population. Physicians and public health authorities should focus on people with disabilities for proper diabetes management.

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Widening disparities in the national prevalence of diabetes mellitus for people with disabilities in South Korea
I. Hwang, S.Y. Kim, Y.Y. Kim, J.H. Park
Public Health.2024; 226: 173. CrossRef
Bipolar disorder and the risk of cardiometabolic diseases, heart failure, and all-cause mortality: a population-based matched cohort study in South Korea
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Psychotic Disorders and the Risk of Type 2 Diabetes Mellitus, Atherosclerotic Cardiovascular Diseases, and All-Cause Mortality: A Population-Based Matched Cohort Study
You-Bin Lee, Hyewon Kim, Jungkuk Lee, Dongwoo Kang, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim, Hong Jin Jeon, Kyu Yeon Hur
Diabetes & Metabolism Journal.2024; 48(1): 122. CrossRef
Pathways linking health literacy to self-care in diabetic patients with physical disabilities: A moderated mediation model
Hye Jin Nam, Ju Young Yoon, Wen-Jun Tu
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Dysphagia Requiring Medical Attention in Parkinson’s Disease: A Korean Population-Based Study
Seungwoo Cha, Won Kee Chang, Hee-Mun Cho, Kyungdo Han, Nam-Jong Paik, Sohyun Kwon, Won-Seok Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef
Disparities in diabetes-related avoidable hospitalization among diabetes patients with disability using a nationwide cohort study
Hin Moi Youn, Dong-Woo Choi, Sung-In Jang, Eun-Cheol Park
Scientific Reports.2022;[Epub] CrossRef
Disability type–specific mortality patterns and life expectancy among disabled people in South Korea using 10-year combined data between 2008 and 2017
Jinwook Bahk, Hee-Yeon Kang, Young-Ho Khang
Preventive Medicine Reports.2022; 29: 101958. CrossRef
Cholecystectomy reduces the risk of myocardial and cerebral infarction in patients with gallstone-related infection
Seon Mee Park, Hyun Jung Kim, Tae Uk Kang, Heather Swan, Hyeong Sik Ahn
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Nationwide trends in the incidence of tuberculosis among people with disabilities in Korea: a nationwide serial cross-sectional study
Jinsoo Min, So Young Kim, Jong Eun Park, Yeon Yong Kim, Jong Hyock Park
Epidemiology and Health.2022; 44: e2022098. CrossRef
Prevalence of Type 2 Diabetes among Persons with Disabilities in the South-East Asian Region
Rajeswaran Thiagesan, Vijayaprasad Gopichandran, Sudharshini Subramaniam, Hilaria Soundari, Kalpana Kosalram
Current Medical Issues.2022; 20(3): 161. CrossRef
Cumulative exposure to impaired fasting glucose and future risk of type 2 diabetes mellitus
Mee Kyoung Kim, Kyungdo Han, Eun Sil Koh, Oak-Kee Hong, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
Diabetes Research and Clinical Practice.2021; 175: 108799. CrossRef
Diabetes in People with Disabilities: a Call for Action
Inha Jung, Eun-Jung Rhee, Won-Young Lee
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Clinical Study
Effects of Systemic Glucocorticoid Use on Fracture Risk: A Population-Based Study: Ji Weon Koh, Junkang Kim, Hyemin Cho, Yong-Chan Ha, Tae-Young Kim, Young-Kyun Lee, Ha Young Kim, Sunmee Jang; Endocrinol Metab. 2020;35(3):562-570. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.659

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Background
Long-term glucocorticoid use increases fracture risk by reducing bone mass. This study evaluated the relationship between hip and vertebral fractures and the total amount of systematic glucocorticoid use.
Methods
We randomly selected 1,896,159 people aged 20 to 100 years who participated in the National Health Checkup program in 2006. The amount of glucocorticoids prescribed was calculated based on the defined daily dose (DDD). The total DDD was obtained by adding oral and parenteral glucocorticoids for 6 months from the index date. Subjects were categorized into four groups according to total glucocorticoid DDDs: non-users (DDDs=0), low users (0< DDDs ≤45), intermediate users (45< DDDs ≤90), and high users (90< DDDs). We followed them for 2 years. A multivariate Cox proportional hazard model was used to evaluate the effects of the total amount of glucocorticoid use on hip and vertebral fractures.
Results
Higher glucocorticoid use was associated with a higher risk of vertebral fracture. Relative to non-users, the vertebral fracture risk was 1.39 times higher in the low-user group, 1.94 times higher in the intermediate-user group, and 2.43 times higher in the highuser group. The risk of hip fracture was 1.72 times higher in intermediate users and 3.28 times higher in high users than in non-users.
Conclusion
As the amount of glucocorticoid use for 6 months increased, the risk of hip and vertebral fractures became higher. In order to prevent fractures, it is necessary for doctors to evaluate the total amount of glucocorticoid prescribed to the patient and to provide appropriate treatment.

Citations

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Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90 days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide h
Masayuki Iki, Kenji Fujimori, Shinichi Nakatoh, Junko Tamaki, Shigeyuki Ishii, Nobukazu Okimoto, Hironori Imano, Sumito Ogawa
Osteoporosis International.2024; 35(5): 805. CrossRef
Low-dose glucocorticoid increase the risk of fracture in postmenopausal women with low bone mass: a retrospective cohort study
So Young Park, Seong Hee Ahn, Gi Hwan Bae, Sunmee Jang, Mi Kyung Kwak, Ha Young Kim, Se Hwa Kim
Osteoporosis International.2024;[Epub] CrossRef
Chronic airway disease as a major risk factor for fractures in osteopenic women: Nationwide cohort study
Sung Hye Kong, Ae Jeong Jo, Chan Mi Park, Kyun Ik Park, Ji Eun Yun, Jung Hee Kim
Frontiers in Endocrinology.2023;[Epub] CrossRef
Bad to the bones: prescribing of drugs for the prevention and treatment of osteoporosis in patients on chronic glucocorticoids
Sarah J. Billups, Vinh K Thai, Jacob Denkins, Ian C. Dettman, Micol S. Rothman
Archives of Osteoporosis.2023;[Epub] CrossRef
High Risk of Fractures Within 7 Years of Diagnosis in Asian Patients With Inflammatory Bowel Diseases
Hyung Jin Ahn, Ye-Jee Kim, Ho-Su Lee, Jin Hwa Park, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Beom-Jun Kim, Sang Hyoung Park
Clinical Gastroenterology and Hepatology.2022; 20(5): e1022. CrossRef
Challenges in the diagnosis and management of glucocorticoid‐induced osteoporosis in younger and older adults
Madhuni Herath, Bente Langdahl, Peter R. Ebeling, Frances Milat
Clinical Endocrinology.2022; 96(4): 460. CrossRef
Comparative effectiveness of bisphosphonate treatments for the prevention of re-fracture in glucocorticoid-induced osteoporosis: protocol for a systematic review and meta-analysis
Hongmin Chu, Bo-Hyoung Jang, GaYoon Kim, Seowoo Bae, Hyeju Lee, Seonghee Nam, Jeonghoon Ahn
BMJ Open.2022; 12(9): e062537. CrossRef
Why Do We Need Proactive Management for Fracture Prevention in Long-Term Glucocorticoid Users?
Han Seok Choi
Endocrinology and Metabolism.2020; 35(3): 549. CrossRef

Clinical Study
A Phase II Multi-Center, Non-Randomized, Parallel Group, Non-Inferiority Study to Compare the Efficacy of No Radioactive Iodine Remnant Ablation to Remnant Ablation Treatment in Low- to Intermediate-Risk of Papillary Thyroid Cancer: The MOREthyroid Trial Protocol: Eun Kyung Lee, You Jin Lee, Young Joo Park, Jae Hoon Moon, Ka Hee Yi, Koon Soon Kim, Joo Hee Lee, Sun Wook Cho, Jungnam Joo, Yul Hwangbo, Sujeong Go, Do Joon Park; Endocrinol Metab. 2020;35(3):571-577. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.681

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Background
Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades.
Methods
This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio <0.4). Patients choose to undergo RAI ablation (¹³¹I, dose 1.1 GBq) or diagnostic whole-body scan (DxWBS) (¹³¹I or ¹²³I, dose 0.074 to 0.222 GBq), followed by subsequent measurement of stimulated thyroglobulin (sTg) within 1 year. Survey for quality of life (QOL) will be performed at baseline and at 1 year after follow-up. The total enrollment period is 5 years, and patients will be followed up for 1 year. The primary endpoint is the non-inferiority of surgery alone to surgery with ablation in terms of biochemical remission (BCR) rate (sTg ≤2 ng/mL) without evidence of structural recurrence. The secondary endpoint was the difference of QOL.
Conclusion
This study will evaluate whether surgery alone achieves similar BCR and improved QOL compared to RAI ablation in patients with low- to intermediate-risk PTC within 1 year.

Citations

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Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 6. Radioactive Iodine Treatment after Thyroidectomy 2024
Sohyun Park, Ari Chong, Ho-Cheol Kang, Keunyoung Kim, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Ji-In Bang, Youngduk Seo, Young Shin Song, So Won Oh, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Chae Moon Hong, Sang-Woo Lee
International Journal of Thyroidology.2024; 17(1): 97. CrossRef

Clinical Study
Relationship of Sarcopenia with Microcirculation Measured by Skin Perfusion Pressure in Patients with Type 2 Diabetes: Chan-Hee Jung, Yoon Young Cho, Dughyun Choi, Bo-Yeon Kim, Chul-Hee Kim, Ji-Oh Mok; Endocrinol Metab. 2020;35(3):578-586. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.679

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Background
Few studies have examined the relationship of sarcopenia with the microcirculation. The current study investigated the relationship of sarcopenia with microcirculatory function, as assessed by skin perfusion pressure (SPP), in type 2 diabetes mellitus (T2DM) patients.
Methods
In total, 102 T2DM patients who underwent SPP measurements and bioelectrical impedance analysis (BIA) were enrolled in this cross-sectional study. SPP was assessed using the laser Doppler technique. Sarcopenia was defined as low height-adjusted appendicular muscle mass (men, <7 kg/m²; women, <5.7 kg/m²) using BIA. We divided the participants into two groups based on SPP (≤50 and >50 mm Hg), and an SPP below 50 mm Hg was considered to reflect impaired microcirculation.
Results
Fourteen patients (13.7%) were diagnosed with impaired microcirculatory function of the lower limb based on SPP. The prevalence of sarcopenia in all subjects was 11.8%, but the percentage of patients with an SPP ≤50 mm Hg who had sarcopenia was more than triple that of patients with an SPP >50 mm Hg (28.6% vs. 9.1%, P=0.036). A significant positive correlation was found between SPP and appendicular muscle mass adjusted for height (P=0.041 for right-sided SPP). Multiple logistic regression analysis showed that patients with sarcopenia had an odds ratio of 4.1 (95% confidence interval, 1.01 to 24.9) for having an SPP ≤50 mm Hg even after adjustment for confounding factors.
Conclusion
These results suggest that sarcopenia may be significantly associated with impaired microcirculation in patients with T2DM. Nonetheless, the small number of patients and wide CI require cautious interpretation of the results.

Citations

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Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation
Yuqing Du, Jie Wang, Weijing Fan, Renyan Huang, Hongfei Wang, Guobin Liu
International Wound Journal.2023; 20(10): 4394. CrossRef
Bioelectrical Impedance Analysis for the Assessment of Body Composition in Sarcopenia and Type 2 Diabetes
Stefano Sbrignadello, Christian Göbl, Andrea Tura
Nutrients.2022; 14(9): 1864. CrossRef
Discrimination between possible sarcopenia and metabolic syndrome using the arterial pulse spectrum and machine-learning analysis
Li-Wei Wu, Te OuYoung, Yu-Chih Chiu, Ho-Feng Hsieh, Hsin Hsiu
Scientific Reports.2022;[Epub] CrossRef
The prevalence and risk factors of sarcopenia in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
Yaqin Ai, Ruoxin Xu, Lingping Liu
Diabetology & Metabolic Syndrome.2021;[Epub] CrossRef

Clinical Study
Vandetanib for the Management of Advanced Medullary Thyroid Cancer: A Real-World Multicenter Experience: Mijin Kim, Jee Hee Yoon, Jonghwa Ahn, Min Ji Jeon, Hee Kyung Kim, Dong Jun Lim, Ho-Cheol Kang, In Joo Kim, Young Kee Shong, Tae Yong Kim, Bo Hyun Kim; Endocrinol Metab. 2020;35(3):587-594. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.687

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Background
Vandetanib is the most widely used tyrosine kinase inhibitor for the treatment of patients with advanced medullary thyroid cancer (MTC). However, only limited data regarding its use outside clinical trials are available. We aimed to evaluate the efficacy and safety of vandetanib in patients with advanced MTC in routine clinical practice.
Methods
In this multicenter retrospective study, 12 patients with locally advanced or metastatic MTC treated with vandetanib at four tertiary hospitals were included. The primary outcome was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors. The progression-free survival (PFS), overall survival (OS), and toxicities were also evaluated.
Results
Eleven patients (92%) had distant metastasis and 10 (83%) had disease progression at enrollment. Partial response was observed in five patients (ORR, 42%) and stable disease lasting ≥24 weeks was reported in an additional five patients (83%). During the median 31.7 months of follow-up, disease progression was seen in five patients (42%); of these, two died due to disease progression. The median PFS was 25.9 months, while the median OS was not reached. All patients experienced adverse events (AEs) which were generally consistent with the known safety profile of vandetanib. Vandetanib was discontinued in two patients due to skin toxicity.
Conclusion
Consistent with the phase III trial, this study confirmed the efficacy of vandetanib for advanced MTC in terms of both ORR and PFS in the real-world setting. Vandetanib was well tolerated in the majority of patients, and there were no fatal AEs.

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Alternative and efficient one-pot three-component synthesis of substituted 2-aryl-4-styrylquinazolines/4-styrylquinazolines from synthetically available 1-(2-aminophenyl)-3-arylprop-2-en-1-ones: characterization and evaluation of their antiproliferative a
Diego Fernando Rodríguez, Kelly Johanna Lipez, Elena Stashenko, Iván Díaz, Justo Cobo, Alirio Palma
RSC Advances.2024; 14(29): 20951. CrossRef
Metastatic medullary thyroid carcinoma (MTC): disease course, treatment modalities and factors predisposing for drug resistance
Katerina Saltiki, George Simeakis, Olga Karapanou, Stavroula A. Paschou, Maria Alevizaki
Endocrine.2023; 80(3): 570. CrossRef
Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea
Han-Sang Baek, Jeonghoon Ha, Seunggyun Ha, Ja Seong Bae, Chan Kwon Jung, Dong-Jun Lim
Current Oncology.2023; 30(3): 3020. CrossRef
Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in the RET
Nicolas Sahakian, Frédéric Castinetti, Pauline Romanet
Cancers.2023; 15(19): 4865. CrossRef
Sporadic Medullary Thyroid Carcinoma: Towards a Precision Medicine
Antonio Matrone, Carla Gambale, Alessandro Prete, Rossella Elisei
Frontiers in Endocrinology.2022;[Epub] CrossRef
Targeted therapy and drug resistance in thyroid cancer
Yujie Zhang, Zhichao Xing, Tianyou Liu, Minghai Tang, Li Mi, Jingqiang Zhu, Wenshuang Wu, Tao Wei
European Journal of Medicinal Chemistry.2022; 238: 114500. CrossRef
Daily Management of Patients on Multikinase Inhibitors’ Treatment
Carla Colombo, Simone De Leo, Matteo Trevisan, Noemi Giancola, Anna Scaltrito, Laura Fugazzola
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Cătălina Ionescu, Bogdan Oprea, Georgeta Ciobanu, Milena Georgescu, Ramona Bică, Garofiţa-Olivia Mateescu, Fidan Huseynova, Veronique Barragan-Montero
Medicina.2022; 58(7): 903. CrossRef
Reassessing vascular endothelial growth factor (VEGF) in anti-angiogenic cancer therapy
Tobiloba C. Elebiyo, Damilare Rotimi, Ikponmwosa O. Evbuomwan, Rotdelmwa Filibus Maimako, Matthew Iyobhebhe, Oluwafemi Adeleke Ojo, Olarewaju M. Oluba, Oluyomi S. Adeyemi
Cancer Treatment and Research Communications.2022; 32: 100620. CrossRef
Current Guidelines for Management of Medullary Thyroid Carcinoma
Mijin Kim, Bo Hyun Kim
Endocrinology and Metabolism.2021; 36(3): 514. CrossRef
Recent advances in precision medicine for the treatment of medullary thyroid cancer
Jolanta Krajewska, Aleksandra Kukulska, Malgorzata Oczko-Wojciechowska, Barbara Jarzab
Expert Review of Precision Medicine and Drug Development.2021; 6(5): 307. CrossRef
Functional evaluation of vandetanib metabolism by CYP3A4 variants and potential drug interactions in vitro
Mingming Han, Xiaodan Zhang, Zhize Ye, Jing Wang, Jianchang Qian, Guoxin Hu, Jianping Cai
Chemico-Biological Interactions.2021; 350: 109700. CrossRef
Nephrotoxicity in advanced thyroid cancer treated with tyrosine kinase inhibitors: An update
Alice Nervo, Francesca Retta, Alberto Ragni, Alessandro Piovesan, Alberto Mella, Luigi Biancone, Marco Manganaro, Marco Gallo, Emanuela Arvat
Critical Reviews in Oncology/Hematology.2021; 168: 103533. CrossRef

Clinical Study
Fasting Plasma Glucose Level Independently Predicts the Mortality of Patients with Coronavirus Disease 2019 Infection: A Multicenter, Retrospective Cohort Study: Min Cheol Chang, Jong-Moon Hwang, Jae-Han Jeon, Sang Gyu Kwak, Donghwi Park, Jun Sung Moon; Endocrinol Metab. 2020;35(3):595-601. Published online August 26, 2020; DOI: https://doi.org/10.3803/EnM.2020.719

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Background
Coronavirus disease 2019 (COVID-19) has become a global pandemic, which prompts a consensus for the necessity to seek risk factors for this critical disease. Risk factors affecting mortality of the disease remain elusive. Diabetes and hyperglycemia are known to negatively affect a host’s antiviral immunity. We evaluated the relationship between a history of diabetes, fasting plasma glucose (FPG) levels and mortality among severely ill patients with COVID-19.
Methods
This was a retrospective cohort study that assessed 106 adult inpatients (aged ≥18 years) from two tertiary hospitals in Daegu, South Korea. The participants were transferred to tertiary hospitals because their medical condition required immediate intensive care. The demographic and laboratory data were compared between COVID-19 patients who survived and those who did not.
Results
Compared with the survivor group, age, and the proportions of diabetes, chronic lung disease and FPG were significantly higher in the deceased group. In the Cox proportional hazards regression model for survival analysis, FPG level and age were identified as significant predictors of mortality (P<0.05). The threshold values for predicting high mortality were age >68 years and FPG of 168 mg/dL, respectively. Among those without diabetes, high FPG remained a significant predictor of mortality (P<0.04).
Conclusion
High FPG levels significantly predicted mortality in COVID-19, regardless of a known history of diabetes. These results suggest intensive monitoring should be provided to COVID-19 patients who have a high FPG level.

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Pathogens.2022; 11(5): 563. CrossRef
Global, Regional and National Burden of Cancers Attributable to High Fasting Plasma Glucose in 204 Countries and Territories, 1990-2019
Saeid Safiri, Seyed Aria Nejadghaderi, Nahid Karamzad, Jay S. Kaufman, Kristin Carson-Chahhoud, Nicola Luigi Bragazzi, Mark J. M. Sullman, Mohammad Reza Beyranvand, Mohammad Ali Mansournia, Amir Almasi-Hashiani, Gary S. Collins, Ali-Asghar Kolahi
Frontiers in Endocrinology.2022;[Epub] CrossRef
COVID-19 and diabetes—Two giants colliding: From pathophysiology to management
Maria Chiara Pelle, Isabella Zaffina, Michele Provenzano, Giovenale Moirano, Franco Arturi
Frontiers in Endocrinology.2022;[Epub] CrossRef
SARS-CoV-2 omicron variant clearance delayed in breakthrough cases with elevated fasting blood glucose
Xiujun Zhang, Guocan Si, Huifen Lu, Wei Zhang, Shuqin Zheng, Zeyu Huang, Longgen Liu, Yuan Xue, Guojun Zheng
Virology Journal.2022;[Epub] CrossRef
Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19
Alon Y. Mazori, Ilana Ramer Bass, Lili Chan, Kusum S. Mathews, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily Leven, Jing Gennie Wang, Gohar Mosoyan, Pattharawin Pattharanitima, Giampaolo Greco, Emily J. Gallagher
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Clinical Study
Clinical Outcomes of N1b Papillary Thyroid Cancer Patients Treated with Two Different Doses of Radioiodine Ablation Therapy: Meihua Jin, Jonghwa Ahn, Yu-Mi Lee, Tae-Yon Sung, Won Gu Kim, Tae Yong Kim, Jin-Sook Ryu, Won Bae Kim, Young Kee Shong, Min Ji Jeon; Endocrinol Metab. 2020;35(3):602-609. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.741

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Background
The optimal dose of radioactive iodine (RAI) therapy for N1b papillary thyroid carcinoma (PTC) is controversial. We evaluated the clinical outcome of N1b PTC patients treated with either 100 or 150 mCi of RAI.
Methods
We retrospectively analyzed N1b PTC patients who underwent total thyroidectomy and postoperative RAI therapy at a tertiary referral center between 2012 and 2017. As the baseline characteristics differed between treatment groups, we performed exact matching for various pathological factors according to RAI dose. We evaluated the response to therapy and recurrence-free survival (RFS) in the matched patients. Structural recurrent/persistent disease was defined as new structural disease detected after initial therapy, which was confirmed by cytology or pathology.
Results
Of the total 436 patients, 37 (8.5%) received 100 mCi of RAI and 399 (91.5%) received 150 mCi of RAI. After an exact 1:3 matching, 34 patients in the 100 mCi group and 100 patients in the 150 mCi group remained. There was no significant difference in response to therapy between the groups in the matched population (P=0.63). An excellent response was achieved in 70.6% (n=24) of patients in the 100 mCi group and 76.0% (n=76) in the 150 mCi group. Two (5.9%) patients in the 100 mCi group and four (4.0%) in the 150 mCi group had recurrence and there was no significant difference in RFS between the groups in the matched population (P=0.351).
Conclusion
There were no differences in response to therapy and RFS in N1b PTC patients according to RAI dose.

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Controversies in the Management of Intermediate-Risk Differentiated Thyroid Cancer
David Toro-Tobon, Juan P. Brito
Endocrine Practice.2024; 30(9): 879. CrossRef

Clinical Study
Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study: Jong Dai Kim, Dong-Mee Lim, Keun-Young Park, Se Eun Park, Eun Jung Rhee, Cheol-Young Park, Won-Young Lee, Ki Won Oh; Endocrinol Metab. 2020;35(3):610-617. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.721

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Background
It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes.
Methods
Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis.
Results
The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, P<0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, P<0.001 and r=0.077, P<0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, P<0.001 and r=–0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006).
Conclusion
Transferrin is positively associated with incident type 2 diabetes in Koreans.

Citations

Citations to this article as recorded by

Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes
Xingyue Wang, You Wang, Junjie Hou, Hongyang Liu, Rong Zeng, Xiangyu Li, Mei Han, Qingrun Li, Linong Ji, Desi Pan, Weiping Jia, Wen Zhong, Tao Xu
Scientific Reports.2024;[Epub] CrossRef
Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes
Muhammad Mujammami, Mohamed Rafiullah, Khalid Akkour, Assim A. Alfadda, Afshan Masood, Salini Scaria Joy, Hani Alhalal, Maria Arafah, Eman Alshehri, Ibrahim O. Alanazi, Hicham Benabdelkamel
ACS Omega.2024; 9(4): 4721. CrossRef
Association between systemic iron status and β-cell function and insulin sensitivity in patients with newly diagnosed type 2 diabetes
Yao Qin, Yiting Huang, Yuxiao Li, Lu Qin, Qianying Wei, Xin Chen, Chuanhui Yang, Mei Zhang
Frontiers in Endocrinology.2023;[Epub] CrossRef
Association of Body Iron Metabolism with Type 2 Diabetes Mellitus in Chinese Women of Childbearing Age: Results from the China Adult Chronic Disease and Nutrition Surveillance (2015)
Jie Feng, Xiaoyun Shan, Lijuan Wang, Jiaxi Lu, Yang Cao, Lichen Yang
Nutrients.2023; 15(8): 1935. CrossRef
Serum Level of Ceruloplasmin, Angiotensin-Converting Enzyme and Transferrin as Markers of Severity in SARS-CoV-2 Infection in Patients with Type 2 Diabetes
Patricia-Andrada Reștea, Ștefan Țigan, Laura Grațiela Vicaș, Luminița Fritea, Eleonora Marian, Tunde Jurca, Annamaria Pallag, Iulius Liviu Mureșan, Corina Moisa, Otilia Micle, Mariana Eugenia Mureșan
Microbiology Research.2023; 14(4): 1670. CrossRef

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