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대한내분비학회> Endocrinology and Metabolism(구 대한내분비학회지)> Review and Update of the Risk Factors and Prevention of Antiresorptive-Related Osteonecrosis of the Jaw

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Review and Update of the Risk Factors and Prevention of Antiresorptive-Related Osteonecrosis of the Jaw

Ha Young Kim
  • : 대한내분비학회
  • : Endocrinology and Metabolism(구 대한내분비학회지) 36권5호
  • : 연속간행물
  • : 2021년 10월
  • : 917-927(11pages)
Endocrinology and Metabolism(구 대한내분비학회지)

DOI


목차

INTRODUCTION
ANTIRESORPTIVE-RELATED FACTORS
TRIGGERING LOCAL FACTORS
SYSTEMIC RISK FACTORS
INDIVIDUAL RISK CATEGORIZATION
PROPHYLACTIC DENTAL CARE
TEMPORARY DISCONTINUATION OF THE DRUG
CONCLUSIONS
CONFLICTS OF INTEREST
ORCID
REFERENCES

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Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but serious adverse event of bisphosphonate or denosumab administration; it is associated with severe pain and a deteriorated quality of life. Since its first report in 2003, there have been many studies on its definition, epidemiology, pathophysiology, diagnosis, and treatment. Nevertheless, the epidemiology and mechanisms underlying this condition have not yet been fully delineated and several risk factors are known. Moreover, as there is no effective treatment currently available for osteonecrosis of the jaw, prevention is essential. Furthermore, close cooperation between prescribing physicians and dentists is important. The aim of this review was to provide up-to-date information regarding the risk factors and prevention of ARONJ from a physician’s perspective.

UCI(KEPA)

I410-ECN-0102-2022-500-000903143

간행물정보

  • : 의약학분야  > 내과학
  • : KCI등재
  • : SCOPUS
  • : 격월
  • : 2093-596X
  • : 2093-5978
  • : 학술지
  • : 연속간행물
  • : 1986-2022
  • : 2613


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1Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature

저자 : Wei Lin Tay , Donovan Tay

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 183-194 (12 pages)

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Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of nuclear factor kappa B ligand (RANKL), involved in bone resorption. Continued use of denosumab results in a potent and sustained decrease in bone turnover, an increase in bone mineral density (BMD), and a reduction in vertebral and hip fractures. The anti-resorptive effects of denosumab are reversible upon cessation, and this reversal is accompanied by a transient marked increase in bone turnover that is associated with bone loss, and of concern, an increased risk of multiple vertebral fractures. In this review, we outline the effects of denosumab withdrawal on bone turnover markers, BMD, histomorphometry, and fracture risk. We provide an update on recent clinical trials that sought to answer how clinicians can transition away from denosumab safely with follow-on therapy to mitigate bone loss and summarise the recommendations of various international guidelines.

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2A Study on Methodologies of Drug Repositioning Using Biomedical Big Data: A Focus on Diabetes Mellitus

저자 : Suehyun Lee , Seongwoo Jeon , Hun-sung Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 195-208 (14 pages)

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Drug repositioning is a strategy for identifying new applications of an existing drug that has been previously proven to be safe. Based on several examples of drug repositioning, we aimed to determine the methodologies and relevant steps associated with drug repositioning that should be pursued in the future. Reports on drug repositioning, retrieved from PubMed from January 2011 to December 2020, were classified based on an analysis of the methodology and reviewed by experts. Among various drug repositioning methods, the network-based approach was the most common (38.0%, 186/490 cases), followed by machine learning/deep learning-based (34.3%, 168/490 cases), text mining-based (7.1%, 35/490 cases), semantic-based (5.3%, 26/490 cases), and others (15.3%, 75/490 cases). Although drug repositioning offers several advantages, its implementation is curtailed by the need for prior, conclusive clinical proof. This approach requires the construction of various databases, and a deep understanding of the process underlying repositioning is quintessential. An in-depth understanding of drug repositioning could reduce the time, cost, and risks inherent to early drug development, providing reliable scientific evidence. Furthermore, regarding patient safety, drug repurposing might allow the discovery of new relationships between drugs and diseases.

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3Thyroid Function across the Lifespan: Do Age-Related Changes Matter?

저자 : John P. Walsh

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 208-219 (12 pages)

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Circulating concentrations of thyrotropin (TSH) and thyroxine (T4) are tightly regulated. Each individual has setpoints for TSH and free T4 which are genetically determined, and subject to environmental and epigenetic influence. Pituitary-thyroid axis setpoints are probably established in utero, with maturation of thyroid function continuing until late gestation. From neonatal life (characterized by a surge of TSH and T4 secretion) through childhood and adolescence (when free triiodothyronine levels are higher than in adults), thyroid function tests display complex, dynamic patterns which are sexually dimorphic. In later life, TSH increases with age in healthy older adults without an accompanying fall in free T4, indicating alteration in TSH setpoint. In view of this, and evidence that mild subclinical hypothyroidism in older people has no health impact, a strong case can be made for implementation of age-related TSH reference ranges in adults, as is routine in children.

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4Effect of Hyperthyroidism on Preventing Renal Insufficiency

저자 : Tae Yong Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 220-220 (1 pages)

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5Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors

저자 : Yong-jik Lee , Yoo-na Jang , Hyun-min Kim , Yoon-mi Han , Hong Seog Seo , Youngsub Eom , Jong-suk Song , Ji Hoon Jeong , Tae Woo Jung

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 221-232 (12 pages)

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Background: Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts.
Methods: To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity.
Results: Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5'-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptor-delta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase.
Conclusion: The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

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6Comparative Study of Ex Vivo Antiplatelet Activity of Aspirin and Cilostazol in Patients with Diabetes and High Risk of Cardiovascular Disease

저자 : Sangmo Hong , Woo Je Lee , Cheol-young Park

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 233-245 (13 pages)

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Background: The role of aspirin in primary cardiovascular disease prevention in patients with diabetes remains controversial. However, some studies have suggested beneficial effects of cilostazol on cardiovascular disease in patients with diabetes. We prospectively investigated the antiplatelet effects of cilostazol compared with aspirin in patients with diabetes and cardiovascular risk factors.
Methods: We randomly assigned 116 patients with type 2 diabetes and cardiovascular risk factors but no evident cardiovascular disease to receive aspirin at a dose of 100 mg or cilostazol at a dose of 200 mg daily for 14 days. The primary efficacy outcome was antiplatelet effects of aspirin and cilostazol assessed with the VerifyNow system (aspirin response units [ARU]) and PFA-100 (closure time [CT]). Secondary outcomes were changes of clinical laboratory data (ClinicalTrials.gov Identifier: NCT02933788).
Results: After 14 days, there was greater decrease in ARU in aspirin (-28.9%±9.9%) compared cilostazol (-0.4%±7.1%, P<0.001) and was greater increase in CT in aspirin (99.6%±63.5%) compared cilostazol (25.7%±54.1%, P<0.001). The prevalence of aspirin resistance was 7.5% according to VerifyNow (defined by ARU ≥550) and 18.9% according to PFA-100 (CT <192 seconds). Compared with aspirin, cilostazol treatment was associated with increased high density lipoprotein cholesterol (7.1%±12.7% vs. 4.2%±18.0%, P=0.006) and decreased triglycerides (-9.4%±33.7% vs. 4.4%±17.57%, P=0.016). However, there were no significant changes in total and low density lipoprotein cholesterol, C-reactive protein level, and cluster of differentiation 40 ligand between cilostazol and aspirin groups.
Conclusion: Aspirin showed better antiplatelet effects assessed with VerifyNow and PFA-100 compared with cilostazol. However, there were favorable changes in atherogenic dyslipidemia only in the cilostazol.

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7The Presence of Clonal Hematopoiesis Is Negatively Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes

저자 : Tae Jung Oh , Han Song , Youngil Koh , Sung Hee Choi

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 243-248 (6 pages)

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Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to be associated with increased cardiovascular disease, aging and insulin resistance. Despite the debate of causal contribution of CHIP on metabolic diseases, we want to explore whether CHIP is related to diabetic peripheral neuropathy (DPN).
Methods: This study analyzed the prevalence of CHIP in patients with type 2 diabetes classified according to DPN status. Logistic regression analysis was used to evaluate the association between CHIP and DPN.
Results: CHIP was more prevalent in subjects without DPN than those with DPN (19.9% vs. 8.8%, respectively; P=0.013). Individuals having any CHIP, or DNA methyltransferase 3A (DNMT3A) CHIP were less likely to have any abnormality shown in DPN test; the adjusted odds ratio were 0.85 (95% confidence interval [CI], 0.73 to 1.00) and 0.70 (95% CI, 0.56 to 0.89), respectively. Interestingly, DNMT3A CHIP showed the negative association, but Tet methylcytosine dioxygenase 2 (TET2) CHIP showed the positive association with abnormal feet electrochemical skin conductance level.
Conclusion: On the contrary to expectations, CHIP was negatively associated with DPN. Functional linking between the mutation in hematopoietic cells and DPN, and the opposite role of DNMT3A and TET2 should be investigated.

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8Associations of Phthalate Metabolites and Bisphenol A Levels with Obesity in Children: The Korean National Environmental Health Survey (KoNEHS) 2015 to 2017

저자 : Moon Young Seo , Shinje Moon , Shin-hye Kim , Mi Jung Park

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 249-261 (13 pages)

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Background: Phthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity.
Methods: A total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte.
Results: The urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity.
Conclusion: The concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

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9Association of High-Density Lipoprotein Cholesterol Phenotypes with the Risk of Cardiovascular Diseases and Mortality: A Cohort Study in Korea

저자 : Ga Eun Nam , Youn Huh , Jin-hyung Jung , Kyungdo Han , Seon Mee Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 261-279 (19 pages)

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Background: We investigated whether low high-density lipoprotein cholesterol (HDL-C) and isolated and non-isolated low HDL-C levels are associated with the risk of cardiovascular diseases and all-cause mortality among Korean adults.
Methods: We included 8,665,841 individuals aged ≥20 years who had undergone a health examination provided by the Korean National Health Insurance Service (NHIS) in 2009 and were followed up until the end of 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for study outcomes were calculated using multivariable Cox proportional hazard regression analysis.
Results: During the 8.2 years of mean follow-up, myocardial infarction (MI), stroke, and all-cause mortality occurred in 81,431, 110,996, and 244,309 individuals, respectively. After adjusting for confounding variables (model 3), individuals with low HDL-C and lower HDL quartiles were associated with significantly increased risks of all three outcomes, compared to those with normal HDL-C and highest HDL-C quartile (all P<0.001), respectively. HRs for incident MI (1.28; 95% CI, 1.26 to 1.30), stroke (1.13; 95% CI, 1.11 to 1.15), and all-cause mortality (1.07; 95% CI, 1.05 to 1.08) increased in the non-isolated low HDL-C group compared to the normal HDL-C group. Isolated low HDL-C also showed an increase in the HRs of incident stroke (1.06; 95% CI, 1.04 to 1.08) and all-cause mortality (1.30; 95% CI, 1.28 to 1.32).
Conclusion: Low HDL-C and non-isolated low HDL-C were associated with increased risk of MI, stroke, and all-cause mortality, and isolated low HDL-C was associated with incident stroke and all-cause mortality risk.

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10Cumulative Exposure to High γ-Glutamyl Transferase Level and Risk of Diabetes: A Nationwide Population-Based Study

저자 : Ji-yeon Park , Kyungdo Han , Hun-sung Kim , Jae-hyoung Cho , Kun-ho Yoon , Mee Kyoung Kim , Seung-hwan Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 2호 발행 연도 : 2022 페이지 : pp. 272-286 (15 pages)

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Background: Elevated γ-glutamyl transferase (γ-GTP) level is associated with metabolic syndrome, impaired glucose tolerance, and insulin resistance, which are risk factors for type 2 diabetes. We aimed to investigate the association of cumulative exposure to high γ-GTP level with risk of diabetes.
Methods: Using nationally representative data from the Korean National Health Insurance system, 346,206 people who were free of diabetes and who underwent 5 consecutive health examinations from 2005 to 2009 were followed to the end of 2018. High γ-GTP level was defined as those in the highest quartile, and the number of exposures to high γ-GTP level ranged from 0 to 5. Hazard ratio (HR) and 95% confidence interval (CI) for diabetes were analyzed using the multivariable Cox proportional-hazards model.
Results: The mean follow-up duration was 9.2±1.0 years, during which 15,183 (4.4%) patients developed diabetes. There was a linear increase in the incidence rate and the risk of diabetes with cumulative exposure to high γ-GTP level. After adjusting for possible confounders, the HR of diabetes in subjects with five consecutive high γ-GTP levels were 2.60 (95% CI, 2.47 to 2.73) in men and 3.05 (95% CI, 2.73 to 3.41) in women compared with those who never had a high γ-GTP level. Similar results were observed in various subgroup and sensitivity analyses.
Conclusion: There was a linear relationship between cumulative exposure to high γ-GTP level and risk of diabetes. Monitoring and lowering γ-GTP level should be considered for prevention of diabetes in the general population.

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1Review and Update of the Risk Factors and Prevention of Antiresorptive-Related Osteonecrosis of the Jaw

저자 : Ha Young Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 917-927 (11 pages)

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Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but serious adverse event of bisphosphonate or denosumab administration; it is associated with severe pain and a deteriorated quality of life. Since its first report in 2003, there have been many studies on its definition, epidemiology, pathophysiology, diagnosis, and treatment. Nevertheless, the epidemiology and mechanisms underlying this condition have not yet been fully delineated and several risk factors are known. Moreover, as there is no effective treatment currently available for osteonecrosis of the jaw, prevention is essential. Furthermore, close cooperation between prescribing physicians and dentists is important. The aim of this review was to provide up-to-date information regarding the risk factors and prevention of ARONJ from a physician's perspective.

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2Applications of Machine Learning in Bone and Mineral Research

저자 : Sung Hye Kong , Chan Soo Shin

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 928-937 (10 pages)

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In this unprecedented era of the overwhelming volume of medical data, machine learning can be a promising tool that may shed light on an individualized approach and a better understanding of the disease in the field of osteoporosis research, similar to that in other research fields. This review aimed to provide an overview of the latest studies using machine learning to address issues, mainly focusing on osteoporosis and fractures. Machine learning models for diagnosing and classifying osteoporosis and detecting fractures from images have shown promising performance. Fracture risk prediction is another promising field of research, and studies are being conducted using various data sources. However, these approaches may be biased due to the nature of the techniques or the quality of the data. Therefore, more studies based on the proposed guidelines are needed to improve the technical feasibility and generalizability of artificial intelligence algorithms.

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3T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity

저자 : Wilmar M. Wiersinga

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 938-951 (14 pages)

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Thyroxine (T4)+triiodothyronine (T3) combination therapy can be considered in case of persistent symptoms despite normal serum thyroid stimulating hormone in levothyroxine (LT4)-treated hypothyroid patients. Combination therapy has gained popularity in the last two decades, especially in countries with a relatively high gross domestic product. The prevalence of persistent symptoms has also increased; most frequent are complaints about energy levels and fatigue (80% to 90%), weight management (70% to 75%), memory (60% to 80%), and mood (40% to 50%). Pathophysiological explanations for persistent problems are unrealistic patient expectations, comorbidities, somatic symptoms, related disorders (Diagnostic and Statistical Manual of Mental Disorders [DSM-5]), autoimmune neuroinflammation, and low tissue T3. There is fair circumstantial evidence for the latter cause (tissue and specifically brain T3 content is normalized by T4+T3, not by T4 alone), but the other causes are viewed as more relevant in current practice. This might be related to the 'hype' that has emerged surrounding T4+T3 therapy. Although more and better-designed trials are needed to validate the efficacy of T4+T3 combination, the management of persistent symptoms should also be directed towards alternative causes. Improving the doctor-patient relationship and including more and better information is crucial. For example, dissatisfaction with the outcomes of T4 treatment for subclinical hypothyroidism can be anticipated as recent trials have demonstrated that LT4 is hardly effective in improving symptoms associated with subclinical hypothyroidism.

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4Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions

저자 : Laura Sabatino , Cristina Vassalle , Cristina Del Seppia , Giorgio Iervasi

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 952-964 (13 pages)

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Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of the biologically active triiodothyronine (T3) and regulates TH homeostasis at the local level, in a cell- and time-dependent manner. Three deiodinases have been identified―namely iodothyronine deiodinase 1 (DIO1), DIO2, and DIO3―that differ in their catalytic properties and tissue distribution. The deiodinases represent a dynamic system that changes in the different stages of life according to their functions and roles in various cell types and tissues. Deiodinase activity at the tissue level permits cell-targeted fine regulation of TH homeostasis, mediating the activation (DIO1 and DIO2) and inactivation (DIO3) of THs. Deiodinase homeostasis is the driving force that leads T3-target cells towards customized TH signaling, which takes into account both the hormonal circulating levels and the tissue-specific response. This review analyzes the complex role of deiodinases in physiological and pathological contexts, exploring new challenges and opportunities deriving from a deeper knowledge of the dynamics underlying their roles and functions.

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5Adrenal Venous Sampling for Subtype Diagnosis of Primary Hyperaldosteronism

저자 : Mitsuhide Naruse , Akiyo Tanabe , Koichi Yamamoto , Hiromi Rakugi , Mitsuhiro Kometani , Takashi Yoneda , Hiroki Kobayashi , Masanori Abe , Youichi Ohno , Nobuya Inagaki , Shoichiro Izawa , Masakatsu Sone

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 965-973 (9 pages)

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Adrenal venous sampling (AVS) is the key procedure for lateralization of primary hyperaldosteronism (PA) before surgery. Identification of the adrenal veins using computed tomography (CT) and intraoperative cortisol assay facilitates the success of catheterization. Although administration of adrenocorticotropic hormone (ACTH) has benefits such as improving the success rate, some unilateral cases could be falsely diagnosed as bilateral. Selectivity index of 5 with ACTH stimulation to assess the selectivity of catheterization and lateralization index (LI) >4 with ACTH stimulation for unilateral diagnosis is used in many centers. Co-secretion of cortisol from the tumor potentially affects the lateralization by the LI. Patients aged <35 years with hypokalemia, marked aldosterone excess, and unilateral adrenal nodule on CT have a higher probability of unilateral disease. Patients with normokalemia, mild aldosterone excess, and no adrenal tumor on CT have a higher probability of bilateral disease. Although no methods have 100% specificity for subtype diagnosis that would allow bypassing AVS, prediction of the subtype should be considered when recommending AVS to patients. Methodological standardization and strict indication improve diagnostic quality of AVS. Development of non-invasive imaging and biochemical markers will drive a paradigm shift in the clinical practice of PA.

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7The Effects of Glucose Lowering Agents on the Secondary Prevention of Coronary Artery Disease in Patients with Type 2 Diabetes

저자 : Inha Jung , Hyemi Kwon , Se Eun Park , Kyung-do Han , Yong-gyu Park , Eun-jung Rhee , Won-Young Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 977-987 (11 pages)

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Background: Patients with diabetes have a higher risk of requiring repeated percutaneous coronary intervention (PCI) than non-diabetic patients. We aimed to evaluate and compare the effects of anti-diabetic drugs on the secondary prevention of myocardial infarction among type 2 diabetes mellitus patients.
Methods: We analyzed the general health check-up dataset and claims data of the Korean National Health Insurance Service of 199,714 participants (age ≥30 years) who underwent PCIs between 2010 and 2013. Those who underwent additional PCI within 1 year of their first PCI (n=3,325) and those who died within 1 year (n=1,312) were excluded. Patients were classified according to their prescription records for glucose-lowering agents. The primary endpoint was the incidence rate of coronary revascularization.
Results: A total of 35,348 patients were included in the study. Metformin significantly decreased the risk of requiring repeat PCI in all patients (adjusted hazard ratio [aHR], 0.77). In obese patients with body mass index (BMI) ≥25 kg/m2, patients treated with thiazolidinedione (TZD) exhibited a decreased risk of requiring repeat revascularization than those who were not treated with TZD (aHR, 0.77; 95% confidence interval, 0.63 to 0.95). Patients treated with metformin showed a decreased risk of requiring revascularization regardless of their BMI. Insulin, meglitinide, and alpha-glucosidase inhibitor were associated with increased risk of repeated PCI.
Conclusion: The risk of requiring repeat revascularization was lower in diabetic patients treated with metformin and in obese patients treated with TZD. These results suggest that physicians should choose appropriate glucose-lowering agents for the secondary prevention of coronary artery disease.

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8How Can We Adopt the Glucose Tolerance Test to Facilitate Predicting Pregnancy Outcome in Gestational Diabetes Mellitus?

저자 : Kyeong Jin Kim , Nam Hoon Kim , Jimi Choi , Sin Gon Kim , Kyung Ju Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 988-996 (9 pages)

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Background: We investigated how 100-g oral glucose tolerance test (OGTT) results can be used to predict adverse pregnancy out-comes in gestational diabetes mellitus (GDM) patients.
Methods: We analyzed 1,059 pregnant women who completed the 100-g OGTT between 24 and 28 weeks of gestation. We com-pared the risk of adverse pregnancy outcomes according to OGTT patterns by latent profile analysis (LPA), numbers to meet the OGTT criteria, and area under the curve (AUC) of the OGTT graph. Adverse pregnancy outcomes were defined as a composite of preterm birth, macrosomia, large for gestational age, low APGAR score at 1 minute, and pregnancy-induced hypertension.
Results: Overall, 257 participants were diagnosed with GDM, with a median age of 34 years. An LPA led to three different clusters of OGTT patterns; however, there were no significant associations between the clusters and adverse pregnancy outcomes after adjusting for confounders. Notwithstanding, the risk of adverse pregnancy outcome increased with an increase in number to meet the OGTT criteria (P for trend=0.011); odds ratios in a full adjustment model were 1.27 (95% confidence interval [CI], 0.72 to 2.23), 2.16 (95% CI, 1.21 to 3.85), and 2.32 (95% CI, 0.66 to 8.15) in those meeting the 2, 3, and 4 criteria, respectively. The AUCs of the OGTT curves also distinguished the patients at risk of adverse pregnancy outcomes; the larger the AUC, the higher the risk (P for trend=0.007).
Conclusion: The total number of abnormal values and calculated AUCs for the 100-g OGTT may facilitate tailored management of patients with GDM by predicting adverse pregnancy outcomes.

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9Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity

저자 : Julio C. Sánchez , Aníbal Valencia-vásquez , Andrés M. García

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 997-1006 (10 pages)

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Background: Intracellular calcium (Ca2+) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca2+ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes.
Methods: Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated.
Results: Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect.
Conclusion: Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

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10Frequency of Exposure to Impaired Fasting Glucose and Risk of Mortality and Cardiovascular Outcomes

저자 : Seung-hwan Lee , Kyungdo Han , Hyuk-sang Kwon , Mee Kyoung Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 1007-1015 (9 pages)

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Background: Metabolic abnormalities, such as impaired fasting glucose (IFG), are dynamic phenomena; however, it is unclear whether the timing of IFG exposure and cumulative exposure to IFG are related to cardiovascular disease (CVD) and mortality risk.
Methods: Data were extracted from a nationwide population-based cohort in South Korea for adults (n=2,206,679) who were free of diabetes and had 4 years of consecutive health examination data. Fasting blood glucose levels of 100 to 125 mg/dL were defined as IFG, and the number of IFG diagnoses for each adult in the 4-year period was tabulated as the IFG exposure score (range, 0 to 4). Adults with persistent IFG for the 4-year period received a score of 4.
Results: The median follow-up was 8.2 years. There were 24,820 deaths, 13,502 cases of stroke, and 13,057 cases of myocardial infarction (MI). IFG exposure scores of 1, 2, 3, and 4 were associated with all-cause mortality (multivariable-adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.08 to 1.15; aHR, 1.16; 95% CI, 1.12 to 1.20; aHR, 1.20; 95% CI, 1.15 to 1.25; aHR, 1.18; 95% CI, 1.11 to 1.25, respectively) compared with an IFG exposure score of 0. Adjusting for hypertension and dyslipidemia attenuated the slightly increased risk of MI or stroke associated with high IFG exposure scores, but significant associations for all-cause mortality remained.
Conclusion: The intensity of IFG exposure was associated with an elevated risk of all-cause mortality, independent of cardiovascular risk factors. The association between IFG exposure and CVD risk was largely mediated by the coexistence of dyslipidemia and hypertension.

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