Endocrinology and metabolism (Seoul, Korea)最新文献

{"title":"Identification of Healthy and Unhealthy Lifestyles by a Wearable Activity Tracker in Type 2 Diabetes: A Machine Learning-Based Analysis.","authors":"Kyoung Jin Kim,&nbsp;Jung-Been Lee,&nbsp;Jimi Choi,&nbsp;Ju Yeon Seo,&nbsp;Ji Won Yeom,&nbsp;Chul-Hyun Cho,&nbsp;Jae Hyun Bae,&nbsp;Sin Gon Kim,&nbsp;Heon-Jeong Lee,&nbsp;Nam Hoon Kim","doi":"10.3803/EnM.2022.1479","DOIUrl":"https://doi.org/10.3803/EnM.2022.1479","url":null,"abstract":"<p><p>Lifestyle is a critical aspect of diabetes management. We aimed to define a healthy lifestyle using objectively measured parameters obtained from a wearable activity tracker (Fitbit) in patients with type 2 diabetes. This prospective observational study included 24 patients (mean age, 46.8 years) with type 2 diabetes. Expectation-maximization clustering analysis produced two groups: A (n=9) and B (n=15). Group A had a higher daily step count, lower resting heart rate, longer sleep duration, and lower mean time differences in going to sleep and waking up than group B. A Shapley additive explanation summary analysis indicated that sleep-related factors were key elements for clustering. The mean hemoglobin A1c level was 0.3 percentage points lower at the end of follow-up in group A than in group B. Factors related to regular sleep patterns could be possible determinants of lifestyle clustering in patients with type 2 diabetes.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"547-551"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e1/e9/enm-2022-1479.PMC9262687.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40479116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Tissue-Engineered Skeletal Muscle: A Tool for Metabolic Research.","authors":"Ji-Hoon Kim,&nbsp;Seung-Min Yu,&nbsp;Jang Won Son","doi":"10.3803/EnM.2022.302","DOIUrl":"https://doi.org/10.3803/EnM.2022.302","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"408-414"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0b/ff/enm-2022-302.PMC9262682.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Insulin Resistance on Hepatic Fibrosis among United States Adults with Non-Alcoholic Fatty Liver Disease: NHANES 2017 to 2018.","authors":"Ji Cheol Bae,&nbsp;Lauren A Beste,&nbsp;Kristina M Utzschneider","doi":"10.3803/EnM.2022.1434","DOIUrl":"https://doi.org/10.3803/EnM.2022.1434","url":null,"abstract":"<p><strong>Backgruound: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"455-465"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/d8/enm-2022-1434.PMC9262684.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40105681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fancd2os Reduces Testosterone Production by Inhibiting Steroidogenic Enzymes and Promoting Cellular Apoptosis in Murine Testicular Leydig Cells.","authors":"Xiang Zhai,&nbsp;Xin-Yang Li,&nbsp;Yu-Jing Wang,&nbsp;Ke-Ru Qin,&nbsp;Jin-Rui Hu,&nbsp;Mei-Ning Li,&nbsp;Hai-Long Wang,&nbsp;Rui Guo","doi":"10.3803/EnM.2022.1431","DOIUrl":"https://doi.org/10.3803/EnM.2022.1431","url":null,"abstract":"<p><strong>Backgruound: </strong>It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive.</p><p><strong>Methods: </strong>The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells.</p><p><strong>Results: </strong>The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of Fancd2os elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while Fancd2os knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, Fancd2os knockdown restrained apoptosis in TM3 cells. In vivo assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells.</p><p><strong>Conclusion: </strong>Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"533-546"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/2a/enm-2022-1431.PMC9262688.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40479115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sestrin2 Regulates Beneficial β3-Adrenergic Receptor-Mediated Effects Observed in Inguinal White Adipose Tissue and Soleus Muscle.","authors":"Min Jeong Park,&nbsp;Joo Won Kim,&nbsp;Eun Roh,&nbsp;Kyung Mook Choi,&nbsp;Sei Hyun Baik,&nbsp;Hwan-Jin Hwang,&nbsp;Hye Jin Yoo","doi":"10.3803/EnM.2022.1421","DOIUrl":"https://doi.org/10.3803/EnM.2022.1421","url":null,"abstract":"<p><p>Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"552-557"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/16/enm-2022-1421.PMC9262693.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40479117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Euthyroid Thyroperoxidase Antibody Positivity during Pregnancy, to Treat or Not to Treat?","authors":"Tim I M Korevaar","doi":"10.3803/EnM.2022.301","DOIUrl":"https://doi.org/10.3803/EnM.2022.301","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"387-391"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b3/a5/enm-2022-301.PMC9262680.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sclerostin as a Putative Myokine in Sarcopenia.","authors":"Hyon-Seung Yi","doi":"10.3803/EnM.2022.303","DOIUrl":"https://doi.org/10.3803/EnM.2022.303","url":null,"abstract":"Sclerostin is an osteocyte-derived circulating protein that suppresses the Wnt/β-catenin signaling pathway and bone formation [1]. Sclerostin deficiency in humans and mice causes inherited high bone mass conditions characterized by exaggerated bone formation [1,2]. Many studies have demonstrated the role of sclerostin as a regulator of bone mass, and emerging studies have suggested that circulating sclerostin could serve as a biomarker for non-skeletal diseases [3,4]. However, relatively few studies have shown the effects of sclerostin on muscle physiology and pathology in humans. Sarcopenia, an age-associated multifactorial disease, includes a notable decline in muscle mass and strength, neuromuscular function, and performance [5-8]. Despite its effects on mortality and morbidity, sarcopenia biomarkers remain unknown. Based on the coexistence of sarcopenia and osteoporosis in the population with aging and frailty, as well as considerable overlap in the pathophysiology of these two diseases, in an article titled, “Decreased serum level of sclerostin in older adults with sarcopenia,” Ahn et al. [9] investigated whether circulating sclerostin is associated with sarcopenic indices in older adults. The authors showed that higher circulating levels of sclerostin were significantly associated with a lower risk of sarcopenia, low muscle mass, and muscle weakness in Korean older adults [9]. These data were statistically significant, even after considering the confounding effects of age, sex, and body mass index. These findings are consistent with previous investigations showing a negative correlation between serum sclerostin levels and skeletal muscle mass index in Korean subjects without diabetes [10]. Therefore, it is plausible to predict that sclerostin could serve as a potential novel biomarker for sarcopenia. However, this observational study could not determine the causal relationship between the variables. Thus, it would be interesting to determine how decreased serum sclerostin levels affect muscle mass and function, which may provide a new therapeutic target for sarcopenia. Moreover, further studies are needed to clarify the role of sclerostin in the muscle-bone relationship in a variety of racial and ethnic populations. Since it has been recognized that many hormones and growth factors regulate muscle mass and protein metabolism [7,11,12], it would be valuable to investigate the role of sclerostin in the myopathies of endocrine disorders.","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"430-431"},"PeriodicalIF":3.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/b3/enm-2022-303.PMC9262685.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway.","authors":"Jinmi Lee,&nbsp;Seok-Woo Hong,&nbsp;Min-Jeong Kim,&nbsp;Sun Joon Moon,&nbsp;Hyemi Kwon,&nbsp;Se Eun Park,&nbsp;Eun-Jung Rhee,&nbsp;Won-Young Lee","doi":"10.3803/EnM.2021.1293","DOIUrl":"https://doi.org/10.3803/EnM.2021.1293","url":null,"abstract":"<p><strong>Background: </strong>Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has been shown to reduce body weight and liver fat content in patients with type 2 diabetes. Family with sequence similarity 3 member A (FAM3A) plays a vital role in regulating glucose and lipid metabolism. The aim of this study was to determine the mechanisms by which dulaglutide protects against hepatic steatosis in HepG2 cells treated with palmitic acid (PA).</p><p><strong>Methods: </strong>HepG2 cells were pretreated with 400 μM PA for 24 hours, followed by treatment with or without 100 nM dulaglutide for 24 hours. Hepatic lipid accumulation was determined using Oil red O staining and triglyceride (TG) assay, and the expression of lipid metabolism-associated factor was analyzed using quantitative real time polymerase chain reaction and Western blotting.</p><p><strong>Results: </strong>Dulaglutide significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells. However, exendin-(9-39), a GLP-1R antagonist, reversed the expression of FAM3A, and fatty acid oxidation-associated factors increased due to dulaglutide. In addition, inhibition of FAM3A by siRNA attenuated the reducing effect of dulaglutide on TG content and its increasing effect on regulation of fatty acid oxidation.</p><p><strong>Conclusion: </strong>These results suggest that dulaglutide could be used therapeutically for improving nonalcoholic fatty liver disease, and its effect could be mediated in part via upregulation of FAM3A expression through a GLP-1R-dependent pathway.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"74-83"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/aa/enm-2021-1293.PMC8901965.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenal Morphology as an Indicator of Long-Term Disease Control in Adults with Classic 21-Hydroxylase Deficiency.","authors":"Taek Min Kim,&nbsp;Jung Hee Kim,&nbsp;Han Na Jang,&nbsp;Man Ho Choi,&nbsp;Jeong Yeon Cho,&nbsp;Sang Youn Kim","doi":"10.3803/EnM.2021.1278","DOIUrl":"https://doi.org/10.3803/EnM.2021.1278","url":null,"abstract":"Background Monitoring adults with classical 21-hydroxylase deficiency (21OHD) is challenging due to variation in clinical and laboratory settings. Moreover, guidelines for adrenal imaging in 21OHD are not yet available. We evaluated the relationship between adrenal morphology and disease control status in classical 21OHD. Methods This retrospective, cross-sectional study included 90 adult 21OHD patients and 270 age- and sex-matched healthy controls. We assessed adrenal volume, width, and tumor presence using abdominal computed tomography and evaluated correlations of adrenal volume and width with hormonal status. We investigated the diagnostic performance of adrenal volume and width for identifying well-controlled status in 21OHD patients (17α-hydroxyprogesterone [17-OHP] <10 ng/mL). Results The adrenal morphology of 21OHD patients showed hypertrophy (45.6%), normal size (42.2%), and hypotrophy (12.2%). Adrenal tumors were detected in 12 patients (13.3%). The adrenal volume and width of 21OHD patients were significantly larger than those of controls (18.2±12.2 mL vs. 7.1±2.0 mL, 4.7±1.9 mm vs. 3.3±0.5 mm, P<0.001 for both). The 17-OHP and androstenedione levels were highest in patients with adrenal hypertrophy, followed by those with normal adrenal glands and adrenal hypotrophy (P<0.05 for both). Adrenal volume and width correlated positively with adrenocorticotropic hormone, 17-OHP, 11β-hydroxytestosterone, progesterone sulfate, and dehydroepiandrosterone sulfate in both sexes (r=0.33–0.95, P<0.05 for all). For identifying well-controlled patients, the optimal cut-off values of adrenal volume and width were 10.7 mL and 4 mm, respectively (area under the curve, 0.82–0.88; P<0.001 for both). Conclusion Adrenal volume and width may be reliable quantitative parameters for monitoring patients with classical 21OHD.","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"124-137"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/61/enm-2021-1278.PMC8901969.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Repositioning Using Temporal Trajectories of Accompanying Comorbidities in Diabetes Mellitus.","authors":"Namgi Park,&nbsp;Ja Young Jeon,&nbsp;Eugene Jeong,&nbsp;Soyeon Kim,&nbsp;Dukyong Yoon","doi":"10.3803/EnM.2021.1275","DOIUrl":"https://doi.org/10.3803/EnM.2021.1275","url":null,"abstract":"<p><strong>Background: </strong>Most studies of systematic drug repositioning have used drug-oriented data such as chemical structures, gene expression patterns, and adverse effect profiles. As it is often difficult to prove repositioning candidates' effectiveness in real-world clinical settings, we used patient-centered real-world data for screening repositioning candidate drugs for multiple diseases simultaneously, especially for diabetic complications.</p><p><strong>Methods: </strong>Using the National Health Insurance Service-National Sample Cohort (2002 to 2013), we analyzed claims data of 43,048 patients with type 2 diabetes mellitus (age ≥40 years). To find repositioning candidate disease-drug pairs, a nested case-control study was used for 29 pairs of diabetic complications and the drugs that met our criteria. To validate this study design, we conducted an external validation for a selected candidate pair using electronic health records.</p><p><strong>Results: </strong>We found 24 repositioning candidate disease-drug pairs. In the external validation study for the candidate pair cerebral infarction and glycopyrrolate, we found that glycopyrrolate was associated with decreased risk of cerebral infarction (hazard ratio, 0.10; 95% confidence interval, 0.02 to 0.44).</p><p><strong>Conclusion: </strong>To reduce risks of diabetic complications, it would be possible to consider these candidate drugs instead of other drugs, given the same indications. Moreover, this methodology could be applied to diseases other than diabetes to discover their repositioning candidates, thereby offering a new approach to drug repositioning.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"65-73"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0d/ce/enm-2021-1275.PMC8901955.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}