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대한내분비학회> Endocrinology and Metabolism(구 대한내분비학회지)> Applications of Machine Learning in Bone and Mineral Research

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Applications of Machine Learning in Bone and Mineral Research

Sung Hye Kong , Chan Soo Shin
  • : 대한내분비학회
  • : Endocrinology and Metabolism(구 대한내분비학회지) 36권5호
  • : 연속간행물
  • : 2021년 10월
  • : 928-937(10pages)
Endocrinology and Metabolism(구 대한내분비학회지)

DOI


목차

INTRODUCTION
A SHORT GUIDE FOR INTERPRETATION
APPLICATIONS IN DIAGNOSIS
APPLICATIONS IN RISK PREDICTION
FUTURE DIRECTIONS
CONCLUSIONS
CONFLICTS OF INTEREST
ACKNOWLEDGMENTS
ORCID
REFERENCES

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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.

UCI(KEPA)

I410-ECN-0102-2022-500-000903158

간행물정보

  • : 의약학분야  > 내과학
  • : KCI등재
  • : SCOPUS
  • : 격월
  • : 2093-596X
  • : 2093-5978
  • : 학술지
  • : 연속간행물
  • : 1986-2022
  • : 2631


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1Euthyroid Thyroperoxidase Antibody Positivity during Pregnancy, to Treat or Not to Treat?

저자 : Tim I. M. Korevaar

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 387-391 (5 pages)

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Thyroperoxidase antibody (TPOAb) positivity is a well-known risk factor for thyroid dysfunction during pregnancy and is associated with a suboptimal response to thyroidal stimulation by human chorionic gonadotropin. About 75% of TPOAb positive women are euthyroid and there seems to be a higher risk of predominantly miscarriage and preterm birth in this subgroup. Nonetheless, clinical decision making with regards to gestational levothyroxine treatment remains difficult due to a lack of large randomized trials. Future studies assessing dose-dependent associations and additional biomarkers that can distinguish low-risk from high-risk individuals will be key in disentangling the crude clinical data.

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2Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer

저자 : Siva Swapna Kasarla , Vannuruswamy Garikapati , Yashwant Kumar , Sujatha Dodoala

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 392-407 (16 pages)

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Vitamin D has received considerable optimistic attention as a potentially important factor in many pathological states over the past few decades. However, the proportion of the active form of vitamin D metabolites responsible for biological activity is highly questionable in disease states due to flexible alterations in the enzymes responsible for their metabolism. For instance, CYP3A4 plays a crucial role in the biotransformation of vitamin D and other drug substances. Food-drug and/or drug-drug interactions, the disease state, genetic polymorphism, age, sex, diet, and environmental factors all influence CYP3A4 activity. Genetic polymorphisms in CYP450-encoding genes have received considerable attention in the past few decades due to their extensive impact on the pharmacokinetic and dynamic properties of drugs and endogenous substances. In this review, we focused on CYP3A4 polymorphisms and their interplay with vitamin D metabolism and summarized the role of vitamin D in calcium homeostasis, bone diseases, diabetes, cancer, other diseases, and drug substances. We also reviewed clinical observations pertaining to CYP3A4 polymorphisms among the aforementioned disease conditions. In addition, we highlighted the future perspectives of studying the pharmacogenetics of CYP3A4, which may have potential clinical significance for developing novel diagnostic genetic markers that will ascertain disease risk and progression.

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3Human Tissue-Engineered Skeletal Muscle: A Tool for Metabolic Research

저자 : Ji-hoon Kim , Seung-min Yu , Jang Won Son

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 408-414 (7 pages)

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Skeletal muscle is now regarded as an endocrine organ based on its secretion of myokines and exerkines, which, in response to metabolic stimuli, regulate the crosstalk between the skeletal muscle and other metabolic organs in terms of systemic energy homeostasis. This conceptual basis of skeletal muscle as a metabolically active organ has provided insights into the potential role of physical inactivity and conditions altering muscle quality and quantity in the development of multiple metabolic disorders, including insulin resistance, obesity, and diabetes. Therefore, it is important to understand human muscle physiology more deeply in relation to the pathophysiology of metabolic diseases. Since monolayer cell lines or animal models used in conventional research differ from the pathophysiological features of the human body, there is increasing need for more physiologically relevant in vitro models of human skeletal muscle. Here, we introduce recent studies on in vitro models of human skeletal muscle generated from adult myogenic progenitors or pluripotent stem cells and summarize recent progress in the development of three-dimensional (3D) bioartificial muscle, which mimics the physiological complexity of native skeletal muscle tissue in terms of maturation and functionality. We then discuss the future of skeletal muscle 3D-organoid culture technology in the field of metabolic research for studying pathological mechanisms and developing personalized therapeutic strategies.

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4Extra-Glycemic Effects of Anti-Diabetic Medications: Two Birds with One Stone?

저자 : Eun-jung Rhee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 415-429 (15 pages)

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

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5Sclerostin as a Putative Myokine in Sarcopenia

저자 : Hyon-seung Yi

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 430-431 (2 pages)

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6Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis

저자 : Xiaoying Ma , Qiong Wang

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 432-443 (12 pages)

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Background: This study investigated the effect of short-chain fatty acids (SCFAs) on diabetes in a mouse model.
Methods: Autophagy in Akita mice and streptozocin (STZ)-induced diabetic C57BL/6 mice was determined by Western blots and immunohistochemistry (IHC). Western blots, IHC, hematoxylin and eosin staining, Masson staining, periodic acid-Schiff staining, and picrosirius red staining were conducted to detect whether autophagy and renal function improved in Akita mice and STZ-induced diabetic C57BL/6 mice after treatment of SCFAs. Western blots, IHC, and chromatin immunoprecipitation were performed to determine whether SCFAs affected diabetic mice via the histone deacetylase (HDAC2)/unc-51 like autophagy activating kinase 1 (ULK1) axis. Diabetic mice with kidney-specific knockout of HDAC2 were constructed, and IHC, Masson staining, and Western blots were carried out to detect whether the deletion of endogenous HDAC2 contributed to the improvement of autophagy and renal fibrosis in diabetic mice.
Results: Reduced autophagy and severe fibrosis were observed in Akita mice and STZ-induced diabetic C57BL/6 mice. Increased autophagy and reduced renal cell fibrosis were found in SCFA-treated Akita diabetic mice and STZ-induced diabetic C57BL/6 mice. Diabetic mice treated with SCFAs had lower HDAC2 expression and more enriched binding of ULK1 promoter sequences to H3K27Ac. Endogenous knockout of HDAC2 caused enhanced autophagy and decreased renal fibrosis in diabetic mice treated with SCFAs.
Conclusion: SCFAs enhanced autophagy of renal tubular cells and attenuated renal fibrosis in diabetic mice through the HDAC2/ULK1 axis.

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7Effect of the Concomitant Use of Subcutaneous Basal Insulin and Intravenous Insulin Infusion in the Treatment of Severe Hyperglycemic Patients

저자 : Yejee Lim , Jung Hun Ohn , Joo Jeong , Jiwon Ryu , Sun-wook Kim , Jae Ho Cho , Hee-sun Park , Hye Won Kim , Jongchan Lee , Eun Sun Kim , Nak-hyun Kim , You Hwan Jo , Hak Chul Jang

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 444-454 (11 pages)

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

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8The Impact of Insulin Resistance on Hepatic Fibrosis among United States Adults with Non-Alcoholic Fatty Liver Disease: NHANES 2017 to 2018

저자 : Ji Cheol Bae , Lauren A. Beste , Kristina M. Utzschneider

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 455-465 (11 pages)

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Background: We aimed to investigate the association of hepatic steatosis with liver fibrosis and to assess the interactive effects of hepatic steatosis and insulin resistance on liver fibrosis in a nationally representative sample of United States adults.
Methods: We conducted a cross-sectional analysis using data from National Health and Nutrition Examination Survey 2017 to 2018, which for the first time included transient elastography to assess liver stiffness and hepatic steatosis. We evaluated the association between hepatic steatosis (using controlled attenuation parameter [CAP]) and clinically significant liver fibrosis (defined as liver stiffness ≥7.5 kPa) using logistic regression with an interaction term for hepatic steatosis and insulin resistance (defined as homeostatic model assessment of insulin resistance ≥3.0).
Results: Among adults undergoing transient elastography (n=2,023), 45.9% had moderate or greater hepatic steatosis and 11.3% had clinically significant liver fibrosis. After adjustment for demographic and metabolic factors, the odds of significant liver fibrosis increased as CAP score rose (odds ratio, 1.35 per standard deviation increment; 95% confidence interval, 1.11 to 1.64). We detected a significant interaction effect between CAP score and insulin resistance on the probability of significant liver fibrosis (P=0.016 for interaction). The probability of significant liver fibrosis increased in the presence of insulin resistance with increasing CAP score, while those without insulin resistance had low probability of significant liver fibrosis, even with high CAP scores.
Conclusion: Individuals with hepatic steatosis had higher odds of fibrosis when insulin resistance was present. Our findings emphasize the importance of the metabolic aspects of the disease on fibrosis risk and suggest a need to better identify patients with metabolic associated fatty liver disease.

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9Improvement in Age at Mortality and Changes in Causes of Death in the Population with Diabetes: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018

저자 : Eugene Han , Sun Ok Song , Hye Soon Kim , Kang Ju Son , Sun Ha Jee , Bong-soo Cha , Byung-wan Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 466-474 (9 pages)

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Background: Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate.
Methods: The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed.
Results: In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (P<0.001). In a subgroup analysis according to the presence of comorbid diseases, the number and proportion of deaths remained steady in the group with diabetes only, but steadily increased in the groups with diabetes combined with dyslipidemia and/or hypertension. Compared to the control population, the increase in the mean death age was higher in the population with diabetes. This trend was more prominent in the groups with dyslipidemia and/or hypertension than in the diabetes only group. Deaths from vascular disease and diabetes decreased, whereas deaths from cancer and pneumonia increased. The decline in the proportion of deaths from vascular disease was greater in the diabetes groups with hypertension and/or dyslipidemia than in the control population.
Conclusion: The age at death in the population with diabetes increased more steeply and reached a comparable level to those without diabetes.

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10Association between the Blautia/Bacteroides Ratio and Altered Body Mass Index after Bariatric Surgery

저자 : Yoonhong Kim , Dooheon Son , Bu Kyung Kim , Ki Hyun Kim , Kyung Won Seo , Kyoungwon Jung , Seun Ja Park , Sanghyun Lim , Jae Hyun Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 3호 발행 연도 : 2022 페이지 : pp. 475-486 (12 pages)

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Background: Current evidence support that the gut microbiota plays a potential role in obesity. Bariatric surgery can reduce excess weight and decrease the risk of life-threatening weight-related health problems and may also influence gut microbiota. In this study, we aimed to investigate the changes in gut microbiota before and after bariatric surgery and evaluate the association of the gut microbial shift and altered body mass index (BMI) after bariatric surgery.
Methods: Between January 2019 and July 2020, stools from 58 patients scheduled for bariatric surgery were collected. Six months after bariatric surgery, stools from 22 of these patients were re-collected, and the changes in gut microbiota before and after bariatric surgery were evaluated. In addition, the differences in gut microbiota between patients with severe obesity (BMI >35 kg/m2, n=42) and healthy volunteers with normal BMI (18.8 to 22.8 kg/m2, n=41) were investigated.
Results: The gut microbiota of patients who underwent bariatric surgery showed increased α-diversity and differed β-diversity compared with those before surgery. Interestingly, Blautia was decreased and Bacteriodes was increased at the genus level after bariatric surgery. Further, the Blautia/Bacteroides ratio showed a positive correlation with BMI. To validate these results, we compared the gut microbiota from severely obese patients with high BMI with those from healthy volunteers and demonstrated that the Blautia/Bacteroides ratio correlated positively with BMI.
Conclusion: In the gut microbial analysis of patients who underwent bariatric surgery, we presented that the Blautia/Bacteroides ratio had changed after bariatric surgery and showed a positive correlation with BMI.

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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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