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대한내분비학회> Endocrinology and Metabolism(구 대한내분비학회지)> Cumulative Exposure to High γ-Glutamyl Transferase Level and Risk of Diabetes: A Nationwide Population-Based Study

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

Ji-yeon Park , Kyungdo Han , Hun-sung Kim , Jae-hyoung Cho , Kun-ho Yoon , Mee Kyoung Kim , Seung-hwan Lee
  • : 대한내분비학회
  • : Endocrinology and Metabolism(구 대한내분비학회지) 37권2호
  • : 연속간행물
  • : 2022년 04월
  • : 272-286(15pages)
Endocrinology and Metabolism(구 대한내분비학회지)

DOI


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INTRODUCTION
METHODS
RESULTS
DISCUSSION
CONFLICTS OF INTEREST
ACKNOWLEDGMENTS
AUTHOR CONTRIBUTIONS
ORCID
REFERENCES

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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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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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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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