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대한내분비학회> Endocrinology and Metabolism(구 대한내분비학회지)> Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults

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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
  • : 대한내분비학회
  • : Endocrinology and Metabolism(구 대한내분비학회지) 37권5호
  • : 연속간행물
  • : 2022년 10월
  • : 781-790(10pages)
Endocrinology and Metabolism(구 대한내분비학회지)

DOI


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INTRODUCTION
METHODS
RESULTS
DISCUSSION
CONFLICTS OF INTEREST
AUTHOR CONTRIBUTIONS
ORCID
REFERENCES

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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.

UCI(KEPA)

간행물정보

  • : 의약학분야  > 내과학
  • : KCI등재
  • : SCOPUS
  • : 격월
  • : 2093-596X
  • : 2093-5978
  • : 학술지
  • : 연속간행물
  • : 1986-2022
  • : 2677


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1Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Maternal Thyroid Dysfunction, and Child Autism Spectrum Disorder

저자 : Hyeong-moo Shin , Jiwon Oh , Rebecca J. Schmidt , Elizabeth N. Pearce

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 819-829 (11 pages)

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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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2Preclinical Models of Follicular Cell-Derived Thyroid Cancer: An Overview from Cancer Cell Lines to Mouse Models

저자 : Min Ji Jeon , Bryan R. Haugen

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 830-838 (9 pages)

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The overall prognosis of thyroid cancer is excellent, but some patients have grossly invasive disease and distant metastases with limited responses to systemic therapies. Thus, relevant preclinical models are needed to investigate thyroid cancer biology and novel treatments. Different preclinical models have recently emerged with advances in thyroid cancer genetics, mouse modeling and new cell lines. Choosing the appropriate model according to the research question is crucial to studying thyroid cancer. This review will discuss the current preclinical models frequently used in thyroid cancer research, from cell lines to mouse models, and future perspectives on patient-derived and humanized preclinical models in this field.

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3Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society

저자 : Hyemi Kwon , Eun Roh , Chang Ho Ahn , Hee Kyung Kim , Cheol Ryong Ku , Kyong Yeun Jung , Ju Hee Lee , Eun Heui Kim , Sunghwan Suh , Sangmo Hong , Jeonghoon Ha , Jun Sung Moon , Jin Hwa Kim , Mi-kyung Ki

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 839-850 (12 pages)

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Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

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4Forty Years Together, New Leap Forward! The 40th Anniversary of the Korean Endocrine Society

저자 : Jong Chul Won , Ki-hyun Baek

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 851-857 (7 pages)

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5DPP-4 Inhibitor in Type 2 Diabetes Mellitus Patient with Non-Alcoholic Fatty Liver Disease: Achieving Two Goals at Once?

저자 : Ji Cheol Bae

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 858-860 (3 pages)

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6Efficacy and Safety of Long-Term Methimazole versus Radioactive Iodine in the Treatment of Toxic Multinodular Goiter

저자 : Fereidoun Azizi , Navid Saadat , Mir Alireza Takyar , Hengameh Abdi , Ladan Mehran , Atieh Amouzegar

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 861-869 (9 pages)

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Background: This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI).
Methods: In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter.
Results: After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3±15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group.
Conclusion: In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

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7Identification of Mutations in the Thyroxine-Binding Globulin (TBG) Gene in Patients with TBG Deficiency in Korea

저자 : Jung Heo , Sang-mi Kim , Hyun Jin Ryu , Hyunju Park , Tae Hyuk Kim , Jae Hoon Chung , Hyung-doo Park , Sun Wook Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 870-878 (9 pages)

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Background: Thyroxine-binding globulin (TBG) is a major transporter protein for thyroid hormones. The serpin family A member 7 (SERPINA7) gene codes for TBG, and mutations of the SERPINA7 gene result in TBG deficiency. Although more than 40 mutations have been reported in several countries, only a few studies of TBG deficiency and SERPINA7 gene mutation have been performed in Korea. The aim of this study is to review the clinical presentations and laboratory findings of patients with TBG deficiency and to investigate the types of SERPINA7 gene mutation.
Methods: Five unrelated Korean adults with TBG deficiency attending endocrinology clinic underwent SERPINA7 gene sequencing. Four patients harbored a SERPINA7 gene mutation. Serum thyroid hormones, anti-microsomal antibodies, and TBG were measured. Genomic DNA was extracted from whole blood. All exons and intron-exon boundaries of the TBG gene were amplified and sequencing was performed.
Results: Two patients were heterozygous females, and the other two were hemizygous males. One heterozygous female had coexisting hypothyroidism. The other heterozygous female was erroneously prescribed levothyroxine at a local clinic. One hemizygous male harbored a novel mutation, p.Phe269Cysfs*18, which caused TBG partial deficiency. Three patients had the p.Leu372Phefs*23 mutation, which is known as TBG-complete deficiency Japan (TBG-CDJ) and was also presented in previous mutation analyses in Korea.
Conclusion: This study presents four patients diagnosed with TBG deficiency and provides the results of SERPINA7 gene sequencing. One novel mutation, p.Phe269Cysfs*18, causing TBD-partial deficiency and three cases of TBG-CDJ were demonstrated. It is necessary to identify TBG deficiency to prevent improper treatment. Also, sequencing of the SERPINA7 gene would provide valuable information about the TBG variants in Korea.

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8BRAFV600E Mutation Enhances Estrogen-Induced Metastatic Potential of Thyroid Cancer by Regulating the Expression of Estrogen Receptors

저자 : Minjun Kim , Su-jin Kim , Seong Yun Ha , Zhen Xu , Youngjin Han , Hyeon-gun Jee , Sun Wook Cho , Young Joo Park , Kyu Eun Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 879-890 (12 pages)

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Background: Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer.
Methods: Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data.
Results: Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis.
Conclusion: Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

KCI등재 SCOPUS

9Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves' Disease

저자 : Ho Yeop Lee , Byeong Chang Sim , Ha Thi Nga , Ji Sun Moon , Jingwen Tian , Nguyen Thi Linh , Sang Hyeon Ju , Dong Wook Choi , Daiki Setoyama , Hyon-seung Yi

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 891-900 (10 pages)

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Background: An excess of thyroid hormones in Graves' disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed to provide a comprehensive understanding of the metabolite changes that occur when patients with GD transition from hyperthyroidism to euthyroidism with methimazole treatment.
Methods: Eighteen patients (mean age, 38.6±14.7 years; 66.7% female) with newly diagnosed or relapsed GD attending the endocrinology outpatient clinics in a single institution were recruited between January 2019 and July 2020. All subjects were treated with methimazole to achieve euthyroidism. We explored metabolomics by performing liquid chromatography-mass spectrometry analysis of plasma samples of these patients and then performed multivariate statistical analysis of the metabolomics data.
Results: Two hundred metabolites were measured before and after 12 weeks of methimazole treatment in patients with GD. The levels of 61 metabolites, including palmitic acid (C16:0) and oleic acid (C18:1), were elevated in methimazole-naïve patients with GD, and these levels were decreased by methimazole treatment. The levels of another 15 metabolites, including glycine and creatinine, were increased after recovery of euthyroidism upon methimazole treatment in patients with GD. Pathway analysis of metabolomics data showed that hyperthyroidism was closely related to aminoacyl-transfer ribonucleic acid biosynthesis and branched-chain amino acid biosynthesis pathways.
Conclusion: In this study, significant variations of plasma metabolomic patterns that occur during the transition from hyperthyroidism to euthyroidism were detected in patients with GD via untargeted metabolomics analysis.

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10Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa

저자 : Shenghan Su , Qingrui Zhao , Lingfeng Dan , Yuqing Lin , Xuebei Li , Yunjin Zhang , Chunxiao Yang , Yimeng Dong , Xiaohan Li , Romano Regazzi , Changhao Sun , Xia Chu , Huimin Lu

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 6호 발행 연도 : 2022 페이지 : pp. 901-917 (17 pages)

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Background: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process.
Methods: β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs.
Results: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR-8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5p- and miR-8114-transfected β-cells.
Conclusion: These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a-5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

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1Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach

저자 : Chan Kwon Jung , Andrey Bychkov , Kennichi Kakudo

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 703-718 (16 pages)

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The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms “follicular nodular disease” and “differentiated high-grade thyroid carcinoma” are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term “Hürthle cells” is replaced with “oncocytic cells.” Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term “variant” to describe a subclass of tumor has been replaced with the term “subtype.” Instead, the term “variant” is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: “salivary gland-type carcinomas of the thyroid” and “thyroid tumors of uncertain histogenesis.” This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.

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2Independent Skeletal Actions of Pituitary Hormones

저자 : Se-min Kim , Farhath Sultana , Funda Korkmaz , Daria Lizneva , Tony Yuen , Mone Zaidi

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 719-731 (13 pages)

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Over the past years, pituitary hormones and their receptors have been shown to have non-traditional actions that allow them to bypass the hypothalamus-pituitary-effector glands axis. Bone cells―osteoblasts and osteoclasts―express receptors for growth hormone, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin, and vasopressin. Independent skeletal actions of pituitary hormones on bone have been studied using genetically modified mice with haploinsufficiency and by activating or inactivating the receptors pharmacologically, without altering systemic effector hormone levels. On another front, the discovery of a TSH variant (TSH-βv) in immune cells in the bone marrow and skeletal action of FSHβ through tumor necrosis factor α provides new insights underscoring the integrated physiology of bone-immune-endocrine axis. Here we discuss the interaction of each pituitary hormone with bone and the potential it holds in understanding bone physiology and as a therapeutic target.

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3Updates on Paget's Disease of Bone

저자 : Yong Jun Choi , Young Bae Sohn , Yoon-sok Chung

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 732-743 (12 pages)

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Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.

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4Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism

저자 : Hye-sun Park , Namki Hong , Jong Ju Jeong , Mijin Yun , Yumie Rhee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 744-755 (12 pages)

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Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi-single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient's clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

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5You Can't Avoid Shift Work? Then Focus on Body Fat Rather than Weight

저자 : Eun Kyung Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 756-758 (3 pages)

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6Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis

저자 : Seung Min Chung , Ji-in Lee , Eugene Han , Hyun-ae Seo , Eonju Jeon , Hye Soon Kim , Ji Sung Yoon

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 759-769 (11 pages)

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Background: This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death.
Methods: This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]-4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed.
Results: A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321).
Conclusion: Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

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7Association among Current Smoking, Alcohol Consumption, Regular Exercise, and Lower Extremity Amputation in Patients with Diabetic Foot: Nationwide Population-Based Study

저자 : Yoon Jae Lee , Kyung-do Han , Jun Hyeok Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 770-780 (11 pages)

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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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8Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults

저자 : Chul Woo Ahn , Sungjae Shin , Seunghyun Lee , Hye-sun Park , Namki Hong , Yumie Rhee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 781-790 (10 pages)

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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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9Recent Changes in the Incidence of Thyroid Cancer in Korea between 2005 and 2018: Analysis of Korean National Data

저자 : Yun Mi Choi , Jiwoo Lee , Mi Kyung Kwak , Min Ji Jeon , Tae Yong Kim , Eun-gyoung Hong , Won Bae Kim , Won Gu Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 791-799 (9 pages)

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Background: In this study, we evaluated the recent changes in the standardized, age-specific, stage-specific incidence rates (IRs) of thyroid cancer in Korea and compared them with the incidence data reported by the Surveillance, Epidemiology, and End Results Program.
Methods: The analysis was conducted using the incidence data (2005 to 2018) from the Statistics Korea and Korea Central Cancer Registry.
Results: The age-standardized IR (SIR) of thyroid cancer increased from 24.09 per 100,000 in 2005 to 74.83 in 2012 (annual percent change [APC], 14.5). From 2012 to 2015, the SIR decreased to 42.52 (APC, -17.9) and then remained stable until 2018 (APC, 2.1). This trend was similar in both men and women. Regarding age-specific IRs, the IRs for ages of 30 years and older showed a trend similar to that of the SIR; however, for ages below 30 years, no significant reduction was observed from the vertex of IR in 2015. Regarding stage-specific IRs, the increase was more prominent in those with regional disease (APC, 17.4) than in those with localized disease until 2012; then, the IR decreased until 2015 (APC, -16.1). The average APC from 2005 to 2018 increased in men, those under the age of 30 years, and those with regional disease.
Conclusion: The SIR in Korea peaked in 2012 and decreased until 2015 and then remained stable until 2018. However, in young individuals under the age of 30 years, the IR did not significantly decrease but tended to increase again. In terms of stage-specific IRs, the sharpest increase was seen among those with regional disease.

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10DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation

저자 : Sudeep Kumar , Jonghwa Jin , Hyeon Young Park , Mi-jin Kim , Jungwook Chin , Sungwoo Lee , Jina Kim , Jung-guk Kim , Yeon-kyung Choi , Keun-gyu Park

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 800-809 (10 pages)

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Background: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation.
Methods: VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice.
Results: DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice.
Conclusion: Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis.

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