Endocrinology and Metabolism最新文献

{"title":"The Severity of Diabetes and the Risk of Diabetic Foot Amputation: A National Cohort Study.","authors":"Jin Yu, Ji-Hyun Kim, Bongseong Kim, Kyungdo Han, Seung Hwan Lee, Mee Kyoung Kim","doi":"10.3803/EnM.2024.2266","DOIUrl":"10.3803/EnM.2024.2266","url":null,"abstract":"<p><strong>Backgruound: </strong>This study aimed to assess whether markers of diabetes severity could serve as predictors for foot amputation risk among patients with type 2 diabetes mellitus.</p><p><strong>Methods: </strong>We analyzed data from the nationally representative Korean National Health Insurance System database, tracking 2,544,077 patients with type 2 diabetes mellitus who participated in routine health check-ups between 2009 and 2012, with followup extending through the end of 2018. The parameters used to define the diabetes severity score encompassed diabetes duration, insulin usage, the number of oral glucose-lowering medications, the presence of chronic kidney disease, diabetic retinopathy, and cardiovascular disease. Each factor was assigned one point, yielding a cumulative severity score ranging from 0 to 6.</p><p><strong>Results: </strong>The risk of diabetic foot amputation was predominantly predicted by insulin therapy, diabetic retinopathy, and a prolonged duration of diabetes. The hazard ratios for foot amputation increased with the severity score as follows: 2.31 (95% confidence interval [CI], 2.15 to 2.47) for a score of 1, 4.73 (95% CI, 4.42 to 5.07) for a score of 2, 8.86 (95% CI, 8.24 to 9.53) for a score of 3, 16.95 (95% CI, 15.60 to 18.4) for a score of 4, 23.98 (95% CI, 21.25 to 27.05) for a score of 5, and 37.87 (95% CI, 28.93 to 49.57) for a score of 6.</p><p><strong>Conclusion: </strong>Specific markers of advanced diabetes effectively identified patients at an elevated risk for diabetic foot amputation.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"574-582"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between the Triglyceride-Glucose Index and Cardiovascular Risk and Mortality across Different Diabetes Durations: A Nationwide Cohort Study.","authors":"Jeongeun Kwak, Kyung-Do Han, Eun Young Lee, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Jeongmin Lee","doi":"10.3803/EnM.2024.2205","DOIUrl":"10.3803/EnM.2024.2205","url":null,"abstract":"<p><strong>Backgruound: </strong>We aimed to assess the association between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) risk and mortality in a large cohort of diabetes patients.</p><p><strong>Methods: </strong>A retrospective cohort study of 1,090,485 participants from the Korean National Health Insurance Service database was conducted. Participants were stratified into TyG quartiles.</p><p><strong>Results: </strong>Higher TyG index quartiles were significantly associated with an increased CVD risk and mortality risk. In fully adjusted models, participants in the highest TyG quartile (Q4) had an 18% higher risk of CVD (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.13 to 1.23) and a 16% higher risk of mortality (HR, 1.16; 95% CI, 1.11 to 1.23) compared to those in the lowest quartile (Q1). The association was particularly pronounced in patients with fasting glucose ≥126 mg/dL (CVD [HR, 1.33; 95% CI, 1.29 to 1.37], mortality [HR, 1.23; 95% CI, 1.20 to 1.26]; P for interaction <0.001). Patients with a diabetes duration of ≥10 years showed the strongest association between the TyG index and CVD risk (HR, 1.44; 95% CI, 1.38 to 1.50), while the mortality risk was particularly elevated in those with a diabetes duration of less than 5 years (HR, 1.23; 95% CI, 1.18 to 1.30). Subgroup analyses revealed stronger associations between TyG index and CVD risk in younger participants, non-obese individuals, and non-smokers.</p><p><strong>Conclusion: </strong>The TyG index is a significant predictor of CVD and mortality in diabetic patients, particularly in those with poor glycemic control or longer disease duration.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"548-560"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Effectiveness of Pravastatin in Korean Patients with Dyslipidemia Based on the Cardiovascular Risk Classification: Pooled Analysis of Four Observational Studies.","authors":"In-Kyung Jeong, Hyuk-Sang Kwon, Dae Jung Kim, Sin Gon Kim","doi":"10.3803/EnM.2024.2200","DOIUrl":"10.3803/EnM.2024.2200","url":null,"abstract":"<p><strong>Backgruound: </strong>Despite their efficacy, statin-related adverse events (AEs) may interfere with statin treatment and contribute to negative outcomes in patients with cardiovascular diseases. In this study, we evaluated the safety and effectiveness of pravastatin in Korea.</p><p><strong>Methods: </strong>Pooled data were collected from four multicenter prospective observational studies conducted in Korea between 2011 and 2020. Finally, 7,334 and 2,022 participants were included in the safety and effectiveness analyses, respectively. Overall safety, particularly muscle-related, incidence of new-onset diabetes mellitus (DM), changes in fasting plasma glucose and hemoglobin A1c level, achievement of target low-density lipoprotein cholesterol (LDL-C) level, and changes in LDL-C level were analyzed.</p><p><strong>Results: </strong>At week 24, after 20 or 40 mg pravastatin treatment, safety results showed that AEs and adverse drug reactions (ADRs) were 8.7% and 1.3%, respectively, and that muscle-related AEs and ADRs were 0.5% and 0.3%, respectively, with no statistically significant difference in risk factors for statin-associated muscle symptoms. No patients developed DM during the study period. Additionally, at week 24, the achievement rates of target LDL-C levels were 87.9%, 78.4%, 57.8%, and 11.6% in low-, moderate-, high-, and very high-risk groups, respectively.</p><p><strong>Conclusion: </strong>This study found that 20 or 40 mg pravastatin had minimal side effects and was safe for use in real-world clinical settings in Korea. Specifically, these doses effectively achieved the target LDL-C levels in patients with dyslipidemia in low-, moderate-, and high-risk groups for atherosclerotic cardiovascular disease (ASCVD). These results demonstrate that pravastatin can be safely administered continuously to patients with low-, moderate-, and high-risk ASCVD in a real-world clinical setting.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"598-609"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-Glucose Cotransporter-2 Inhibitor Enhances Hepatic Gluconeogenesis and Reduces Lipid Accumulation via AMPK-SIRT1 Activation and Autophagy Induction.","authors":"Si Woo Lee, Hyunki Park, Minyoung Lee, Hyangkyu Lee, Eun Seok Kang","doi":"10.3803/EnM.2024.2223","DOIUrl":"10.3803/EnM.2024.2223","url":null,"abstract":"<p><strong>Backgruound: </strong>Sodium-glucose cotransporter type 2 (SGLT2) inhibitors, such as dapagliflozin, are primarily used to lower glucose in type 2 diabetes. Recent studies suggest broader metabolic effects, particularly in the liver. This study explores the molecular mechanisms by which dapagliflozin influences hepatic glucose and lipid metabolism, hypothesizing that it activates the 5'-adenosine monophosphate-activated protein kinase (AMPK)-sirtuin 1 (Sirt1) pathway to promote gluconeogenesis and reduce lipid accumulation via autophagy.</p><p><strong>Methods: </strong>HepG2 hepatocellular carcinoma cells were treated with dapagliflozin, and Western blotting, quantitative reverse transcription polymerase chain reaction, and fluorescence microscopy were used to assess gluconeogenic enzyme expression and autophagy. In vivo, mice with liver-specific autophagy related 7 (Atg7) deletion and those on a high-fat diet were used to evaluate glucose regulation, lipid metabolism, and autophagy.</p><p><strong>Results: </strong>Dapagliflozin significantly increased expression of gluconeogenic enzymes like phosphoenolpyruvate carboxykinase (PEPCK) in HepG2 cells and enhanced autophagic flux, evidenced by increased light chain 3B (LC3B)-II levels and autophagosome formation. AMPK-Sirt1 activation was confirmed as the underlying mechanism. Additionally, dapagliflozin reduced fatty acid synthesis by suppressing enzymes such as acetyl-CoA carboxylase and fatty acid synthase, while promoting fatty acid degradation via carnitine palmitoyltransferase 1α (CPT1α) upregulation. In high-fat diet mice, dapagliflozin increased hepatic gluconeogenesis and reduced lipid accumulation, though serum cholesterol and triglyceride levels were unaffected.</p><p><strong>Conclusion: </strong>Dapagliflozin enhances hepatic gluconeogenesis and reduces steatosis by activating the AMPK-Sirt1 pathway and promoting autophagy. These findings suggest that SGLT2 inhibitors could offer therapeutic benefits for managing hepatic lipid disorders, beyond glycemic control.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"583-597"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Proteomics and Machine Learning Analysis to Distinguish Follicular Adenoma and Follicular Thyroid Carcinoma from Indeterminate Thyroid Nodules.","authors":"Hee-Sung Ahn, Eyun Song, Chae A Kim, Min Ji Jeon, Yu-Mi Lee, Tea-Yon Sung, Dong Eun Song, Jiyoung Yu, Ji Min Shin, Yeon-Sook Choi, Kyunggon Kim, Won Gu Kim","doi":"10.3803/EnM.2024.2208","DOIUrl":"10.3803/EnM.2024.2208","url":null,"abstract":"<p><strong>Backgruound: </strong>The preoperative diagnosis of follicular thyroid carcinoma (FTC) is challenging because it cannot be readily distinguished from follicular adenoma (FA) or benign follicular nodular disease (FND) using the sonographic and cytological features typically employed in clinical practice.</p><p><strong>Methods: </strong>We employed comprehensive proteomics and machine learning (ML) models to identify novel diagnostic biomarkers capable of classifying three subtypes: FTC, FA, and FND. Bottom-up proteomics techniques were applied to quantify proteins in formalin-fixed, paraffin-embedded (FFPE) thyroid tissues. In total, 202 FFPE tissue samples, comprising 62 FNDs, 72 FAs, and 68 FTCs, were analyzed.</p><p><strong>Results: </strong>Close spectrum-spectrum matching quantified 6,332 proteins, with approximately 9% (780 proteins) differentially expressed among the groups. When applying an ML model to the proteomics data from samples with preoperative indeterminate cytopathology (n=183), we identified distinct protein panels: five proteins (CNDP2, DNAAF5, DYNC1H1, FARSB, and PDCD4) for the FND prediction model, six proteins (DNAAF5, FAM149B1, RPS9, TAGLN2, UPF1, and UQCRC1) for the FA model, and seven proteins (ACTN4, DSTN, MACROH2A1, NUCB1, SPTAN1, TAGLN, and XRCC5) for the FTC model. The classifiers' performance, evaluated by the median area under the curve values of the random forest models, was 0.832 (95% confidence interval [CI], 0.824 to 0.839) for FND, 0.826 (95% CI, 0.817 to 0.835) for FA, and 0.870 (95% CI, 0.863 to 0.877) for FTC.</p><p><strong>Conclusion: </strong>Quantitative proteome analysis combined with an ML model yielded an optimized multi-protein panel that can distinguish FTC from benign subtypes. Our findings indicate that a proteomic approach holds promise for the differential diagnosis of FTC.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"623-636"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"68Ga-DOTATOC PET/CT in the Localization of Pituitary Tumors in Cushing's Disease.","authors":"Kyungwon Kim, Dongwoo Kim, Min-Ho Lee, Yae Won Park, Sung Soo Ahn, Ju Hyung Moon, Eui Hyun Kim, Sun Ho Kim, Cheol Ryong Ku, Eun Jig Lee","doi":"10.3803/EnM.2024.2249","DOIUrl":"10.3803/EnM.2024.2249","url":null,"abstract":"<p><strong>Backgruound: </strong>This study aimed to determine the value of 68Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) in localizing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas.</p><p><strong>Methods: </strong>In this retrospective cohort study, we enrolled 30 patients with Cushing's disease and positive ACTH immunoreactivity. All patients underwent 68Ga-DOTATOC PET/CT and pituitary magnetic resonance imaging (MRI) before transsphenoidal adenomectomy.</p><p><strong>Results: </strong>Twenty-five patients showed 68Ga-DOTATOC uptake in their pituitary glands on PET/CT. Median age, pre-operative ACTH levels, pre-operative cortisol, and tumor size on MRI were comparable irrespective of DOTATOC uptake. 68Ga-DOTATOC PET/CT showed a 77% success rate for localizing adenomas, which was not statistically different from that of MRI. The ACTH level in the successful localization group was significantly higher than that in the failed group (84.41 pg/mL vs. 37.26 pg/mL, P=0.001). The ACTH level was statistically significant predictor of successful localization using 68Ga-DOTATOC PET/CT (P=0.013). The area under the curve was 0.932 with a cutoff of 53.86 pg/mL for ACTH levels to determine successful localization. Pre-operative ACTH levels above 53.86 pg/mL showed the best diagnostic accuracy in predicting the success of localizing adenomas (sensitivity, 91.3%; specificity, 85.7%). Mean and maximum standardized uptake value of adenoma negatively correlated to pre-operative ACTH level.</p><p><strong>Conclusion: </strong>Plasma ACTH level is a favorable predictor for the successful localization and negative correlation with 68Ga-DOTATOC uptake of corticotroph adenomas in 68Ga-DOTATOC PET/CT. 68Ga-DOTATOC PET/CT did not improve tumor localization for Cushing's disease compared with MRI alone.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"637-647"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Risk for Hepatic Fibrosis in 476,124 Korean Adults: A Cross-Sectional Study.","authors":"Da Yeon Lee, Ji-Hee Ko, Han-Na Jang, Sun Joon Moon, Hye-Mi Kwon, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Eun-Jung Rhee","doi":"10.3803/EnM.2024.2281","DOIUrl":"10.3803/EnM.2024.2281","url":null,"abstract":"<p><p>As the new terminology of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD) has emerged, the clinical significance of MASLD is increasing. This cross-sectional study analyzed 476,124 health checkup participants (2002-2022) to compare hepatic fibrosis risks across MASLD, MetALD, non-alcoholic fatty liver disease (NAFLD), and metabolic dysfunction-associated fatty liver disease (MAFLD). Steatotic liver was identified via ultrasonography, and fibrosis risk was assessed using aspartate aminotransferase to platelet ratio index and NAFLD fibrosis score. The prevalence of NAFLD, MAFLD, MASLD, and MetALD was 30.1%, 32.3%, 29.8%, and 3.0%, respectively, with a 27.9% overlap among three conditions. Participants with steatotic liver were predominantly male, with higher glucose, lipids, liver enzymes, and homeostasis model assessment of insulin resistance levels. Three disease definitions largely overlapped, with MASLD and NAFLD being very similar, while participants with MAFLD and MetALD showed increased fibrosis risk (clinical trial registration number: 2024-11-050).</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"648-652"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antilipolytic Insulin Sensitivity Indices Measured during an Oral Glucose Challenge: Associations with Insulin-Glucose Clamp and Central Adiposity in Women without Diabetes.","authors":"Foued Naimi, Christophe Richer Dit Laflèche, Marie-Claude Battista, André C Carpentier, Jean-Patrice Baillargeon","doi":"10.3803/EnM.2024.2129","DOIUrl":"10.3803/EnM.2024.2129","url":null,"abstract":"<p><strong>Backgruound: </strong>Tissue overexposure to non-esterified fatty acids (NEFA) contributes to the development of metabolic conditions, with insulin-mediated suppression of lipolysis being an important mechanism in limiting this overexposure. We investigated which dynamic NEFA insulin-suppression indices derived from the oral glucose tolerance test (OGTT) were best associated with those derived from the insulin-glucose clamp, as well as with central adiposity and glucoregulatory parameters.</p><p><strong>Methods: </strong>This cross-sectional study recruited 29 women without diabetes, 15 healthy women, and 14 women with polycystic ovary syndrome. The OGTT indices of NEFA insulin-suppression were the decremental NEFA area under the curve, negative log-linear NEFA slope, percentage of NEFA suppression (%NEFAsupp) and time to suppress NEFA levels by 50% (T50NEFA). The indices derived from the two-step euglycemic-hyperinsulinemic clamp (low-dose insulin step) were delta NEFA and %NEFAsupp.</p><p><strong>Results: </strong>Among the OGTT and clamp indices, T50NEFA[OGTT] and %NEFAsupp[clamp] showed the closest associations in both subgroups (r=-0.58). Additionally, T50NEFA correlated significantly in all women with waist circumference (r=0.64), body fat percentage (r=0.60), fasting insulinemia (r=0.53), and M-value insulin sensitivity index (r=-0.45). Similarly, %NEFAsupp[clamp] correlated significantly in all women with waist circumference (r=-0.57), body fat percentage (r=-0.54), fasting insulinemia (r=-0.55), and M-value insulin sensitivity index (r=0.51). T50NEFA and %NEFAsupp[clamp] also correlated with other anthropometric and metabolic parameters associated with lipotoxicity.</p><p><strong>Conclusion: </strong>For dynamic testing of NEFA insulin-suppression in women, T50NEFA was the OGTT-derived index best correlated with a clamp index (%NEFAsupp). These indices were also the most closely associated with anthropometric and glucoregulatory parameters. Thus, the OGTT-derived T50NEFA appears valid for assessing dynamic antilipolytic insulin action.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"561-573"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exendin-4(1-32)K-Capric Acid, a Glucagon-Like Peptide-1 Receptor Agonist, Suppresses Food Intake via Arcuate Pro-Opiomelanocortin Neurons.","authors":"Sujin Yoo, Eun-Seon Yoo, Jae Il Kim, Jong-Woo Sohn","doi":"10.3803/EnM.2024.2185","DOIUrl":"10.3803/EnM.2024.2185","url":null,"abstract":"<p><strong>Backgruound: </strong>Glucagon-like peptide-1 (GLP-1) is an incretin known for its anti-obesity effects, and several effective drugs targeting GLP-1 receptors (GLP-1Rs) have recently been developed to treat obesity. Although GLP-1Rs are expressed by various populations of central neurons, it is still unclear which specific populations mediate the anti-obesity effects of GLP-1R agonists.</p><p><strong>Methods: </strong>In this study, we utilized the previously reported GLP-1R agonist, exendin-4(1-32)K-capric acid (Ex-4c), and conducted whole-cell patch-clamp recordings, immunohistochemistry experiments, and in vivo food intake measurements.</p><p><strong>Results: </strong>Our findings indicate that the appetite-suppressing effects of Ex-4c depend on pro-opiomelanocortin (POMC) neurons. Fos immunochemistry experiments and whole-cell patch-clamp recordings showed that Ex-4c activated POMC neurons in the arcuate nucleus of the hypothalamus. Additionally, we observed that Ex-4c stimulated GLP-1Rs and activated the protein kinase A (PKA)- dependent signaling pathway, which in turn closed putative adenosine triphosphate-sensitive K+ (KATP) channels, leading to the depolarization of POMC neurons.</p><p><strong>Conclusion: </strong>Our results demonstrate that the appetite-suppressing effects of Ex-4c are mediated through the activation of arcuate POMC neurons. Furthermore, the PKA-dependent closure of putative KATP conductance is identified as the cellular mechanism responsible for the activation of POMC neurons.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"434-447"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medullary Thyroid Carcinoma Detected by Routine Health Screening Had Better Clinical Outcome and Survival.","authors":"Ji Hyun Yoo, Da Eun Leem, Bo Ram Kim, Tae Hyuk Kim, Sun Wook Kim, Jae Hoon Chung","doi":"10.3803/EnM.2024.2214","DOIUrl":"10.3803/EnM.2024.2214","url":null,"abstract":"<p><strong>Backgruound: </strong>The benefits of early detection in medullary thyroid carcinoma (MTC) are not well established. This study investigates the impact of early detection of MTC on clinical outcomes.</p><p><strong>Methods: </strong>This retrospective study evaluated 144 patients diagnosed with MTC at Samsung Medical Center between 1995 and 2019, classified as asymptomatic (mostly detected through routine health check-ups, including ultrasonography, calcitonin, or carcinoembryonic antigen levels) and symptomatic. Initial treatment response, final clinical outcomes, and cancer-specific survival were compared.</p><p><strong>Results: </strong>MTC was diagnosed in 104 (72.2%) asymptomatic and 40 (27.8%) symptomatic patients. The symptomatic group showed a significantly larger primary tumor size, more frequent lateral neck lymph node metastasis, more advanced tumor, node, metastasis (TNM) staging, and higher pre- and postoperative serum calcitonin levels. For initial treatment response, the proportion of excellent responders was significantly higher in the asymptomatic group (71.2% vs. 40.0%), while that of patients with biochemical incomplete response (37.5% vs. 26.9%) and structural incomplete response (22.5% vs. 1.9%) was significantly higher in the symptomatic group (all P<0.001). For the final clinical outcomes, the rate of patients with no evidence of disease was higher in the asymptomatic group (67.3% vs. 30.0%), while the rate of patients with structurally identifiable disease was higher in the symptomatic group (45.0% vs. 7.7%) (P<0.001 for both). The symptomatic group had significantly poorer cancer-specific survival than the asymptomatic group (log-rank P=0.023).</p><p><strong>Conclusion: </strong>Compared with late diagnosis through symptomatic presentation, early diagnosis in asymptomatic patients results in significantly better initial treatment response, final clinical outcomes, and cancer-specific survival in patients with MTC.</p>","PeriodicalId":11636,"journal":{"name":"Endocrinology and Metabolism","volume":" ","pages":"414-420"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}