Endocrinology and metabolism (Seoul, Korea)最新文献

{"title":"Impact of Fatty Liver Index on Cardiovascular Disease and Mortality across Alcohol Consumption Levels in Young Adults.","authors":"Byung-Hun Han, Joonyub Lee, Hun-Sung Kim, Jae-Hyoung Cho, Kyungdo Han, Seung-Hwan Lee","doi":"10.3803/EnM.2025.2710","DOIUrl":"https://doi.org/10.3803/EnM.2025.2710","url":null,"abstract":"<p><strong>Background: </strong>The fatty liver index (FLI) is widely used as a surrogate marker for metabolic dysfunction-associated steatotic liver disease, but its predictive value among individuals who consume alcohol remains uncertain. We aimed to investigate the association between FLI and the risk of cardiovascular disease (CVD) and mortality in young adults by alcohol consumption status.</p><p><strong>Methods: </strong>Using the Korean National Health Information Database, we identified 6,487,686 individuals aged 20-39 years who underwent health examinations between 2009 and 2012. FLI was calculated using body mass index, waist circumference, triglycerides, and γ-glutamyl transferase, and categorized as <30, 30-59, or ≥60. Alcohol consumption was classified as non-drinking, mild, moderate, or heavy using sex-specific thresholds. Risks of CVD-including myocardial infarction (MI) and stroke-and all-cause mortality were evaluated using multivariable Cox proportional hazards models.</p><p><strong>Results: </strong>During a mean follow-up of 13.3 years, 49,399 MI, 29,842 stroke, and 53,330 deaths were identified. The risk of CVD and mortality increased stepwise across higher FLI categories in all alcohol consumption groups. Compared with participants with FLI <30, the adjusted hazard ratios (95% confidence intervals [CIs]) for composite outcome among those with FLI ≥60 were 1.72 (95% CI, 1.67 to 1.77) in non-drinkers, 1.41 (95% CI, 1.38 to 1.43) in mild drinkers, 1.19 (95% CI, 1.15 to 1.24) in moderate drinkers, and 1.20 (95% CI, 1.12 to 1.30) in heavy drinkers. The association was strongest among non-drinkers (P for interaction <0.0001).</p><p><strong>Conclusion: </strong>FLI is a useful and practical indicator for predicting CVD and mortality in young adults, regardless of alcohol intake, with the highest predictive performance in non-drinkers.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Disparity in Suicide Mortality among Patients with Type 2 Diabetes: A Nationwide Population-Based Cohort Study.","authors":"Chaiho Jeong, Bongseong Kim, Dae Jong Oh, Tae-Seo Sohn, Kyungdo Han, Hyuk-Sang Kwon","doi":"10.3803/EnM.2025.2669","DOIUrl":"https://doi.org/10.3803/EnM.2025.2669","url":null,"abstract":"<p><strong>Background: </strong>Suicide represents a major public health concern in South Korea. Patients with type 2 diabetes mellitus (T2DM) are at higher risk for psychological distress and suicide. Although the male-to-female suicide mortality ratio in the general population has remained about 2.3, the specific differences in suicide mortality by sex among individuals with T2DM are not well characterized.</p><p><strong>Methods: </strong>We performed a nationwide cohort study utilizing the Korean National Health Insurance Service database, identifying 2,526,769 adults with T2DM who underwent health screening from 2015 to 2016. Participants were monitored until the occurrence of suicide or the study endpoint.</p><p><strong>Results: </strong>During a median follow-up of 6.0 years, 5,584 suicide deaths occurred (0.30% in men vs. 0.10% in women). Men exhibited a significantly elevated risk of suicide mortality compared to women (adjusted hazard ratio [HR], 2.88; 95% confidence interval [CI], 2.66 to 3.12). The largest disparity was observed in the ≥80 age group (HR, 3.60; 95% CI, 2.88 to 4.51). However, this sex disparity in suicide mortality was reduced among current smokers and heavy alcohol consumers. Among non-smokers, the HR comparing men to women was 3.51 (95% CI, 3.22 to 3.83), while among current smokers, it was 1.73 (95% CI, 1.40 to 2.14). Similarly, the HR among non-drinkers was 3.04 (95% CI, 2.79 to 3.31), compared with 1.36 (95% CI, 0.85 to 2.18) among heavy drinkers.</p><p><strong>Conclusion: </strong>Men with T2DM had a significantly higher risk of suicide mortality than women, exceeding the sex disparity seen in the general population, with the gap further influenced by age and lifestyle factors.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Senescence in Skeletal Muscle Aging.","authors":"Yang Li, Huating Wang","doi":"10.3803/EnM.2025.2816","DOIUrl":"https://doi.org/10.3803/EnM.2025.2816","url":null,"abstract":"<p><p>Cellular senescence is increasingly recognized as a pivotal mechanism driving skeletal muscle aging and the development of sarcopenia, a condition characterized by the progressive loss of muscle mass, strength, and function. This review synthesizes recent evidence detailing the accumulation of senescent cells in aged skeletal muscle, including muscle stem cells (MuSCs), fibro-adipogenic progenitors (FAPs), immune cells, endothelial cells, and even post-mitotic myofibers. Senescence in these cell types impairs regenerative signaling, disrupts niche homeostasis, and propagates chronic inflammation. Emerging therapeutic strategies, termed senotherapeutics, aim to counteract these effects through senolytics (which eliminate senescent cells) and senomorphics (which modulate the senescence-associated secretory phenotype), as promising interventions to restore muscle function and delay sarcopenia. We will also discuss the remaining challenges and future directions for studying senescence in skeletal muscle.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Tumor Bilaterality and Multifocality in Predicting Recurrence of Papillary Thyroid Carcinoma: A Retrospective Cohort Study.","authors":"Eunji Kim, Jun Hyun Park, Ji-Young Park, Jin Hyang Jung, Sang-Woo Lee","doi":"10.3803/EnM.2025.2607","DOIUrl":"https://doi.org/10.3803/EnM.2025.2607","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the prognostic value of bilaterality and multifocality in papillary thyroid carcinoma (PTC) recurrence, aiming to inform optimal surgical strategies.</p><p><strong>Methods: </strong>In this retrospective cohort, 1,966 patients who underwent total thyroidectomy for PTC (2011-2014) were categorized into four groups according to tumor multifocality and bilaterality confirmed by postoperative histopathology: group 1, unilateral solitary; group 2, unilateral multifocal; group 3, bilateral solitary; group 4, bilateral multifocal. Clinicopathologic features and clinical outcomes were compared across these groups.</p><p><strong>Results: </strong>Group 4 exhibited the highest prevalence of BRAFV600E positivity, nodal metastases, and recurrence. Both bilaterality and multifocality were associated with more aggressive clinicopathologic characteristics. Recurrence risk increased with the number of tumor foci, with the odds ratio (OR) significantly elevated for more than five foci. Satellite pattern was strongly linked to recurrence (OR, 19.49; P<0.001). While tumor multifocality (≥5 foci) and bilaterality were associated with recurrence in univariate analyses, these associations were not independent after adjustment. Kaplan-Meier analysis demonstrated the lowest recurrence-free survival (RFS) in group 4. Patients with bilateral disease had significantly lower RFS than those with unilateral disease (P=0.003), whereas multifocality did not significantly affect RFS compared to solitary disease (P=0.095).</p><p><strong>Conclusion: </strong>Tumor bilaterality, multifocality (≥5 foci), and satellite pattern were associated with aggressive features and higher recurrence risk. Although not independent predictors, these factors may serve as useful surrogate markers of aggressive disease biology and help guide personalized surgical strategies in patients with PTC.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the Role of Vitamin D in Fracture Prevention in the Era of Mega-Trials.","authors":"Sung Hye Kong","doi":"10.3803/EnM.2029.2938","DOIUrl":"https://doi.org/10.3803/EnM.2029.2938","url":null,"abstract":"<p><p>For decades, vitamin D has been a cornerstone of preventive medicine. However, recent large-scale randomized controlled trials have failed to replicate the broad benefits previously observed in epidemiological studies, particularly with respect to fracture and fall prevention in vitamin D-replete populations. Moreover, growing evidence suggesting an increased fall risk associated with highdose bolus administration has necessitated a re-evaluation of safety assumptions. This review synthesizes these discordant findings to propose a framework grounded in precision medicine. We explore the 'divergent threshold' hypothesis, whereby a serum 25-hydroxyvitamin D level of 20 to 30 ng/mL may be sufficient for skeletal health, whereas a higher threshold of 40 to 50 ng/mL appears necessary to achieve metabolic benefits, such as diabetes prevention in non-obese individuals. Ultimately, we advocate a shift away from a 'one-size-fits-all' paradigm toward targeted strategies that maximize efficacy while minimizing the risks associated with excess supplementation.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-Derived Fat Fraction and Metabolic Parameters in Predicting Panvascular Disease Risk in Metabolic Dysfunction-Associated Steatotic Liver Disease Patients: A Prospective Study.","authors":"Xiangyu Qiu, Lanqing Huang, Huize Jiang, Xiahui Ren, Min Tang, Tianhui Yan, Le Xu, Chong Pei, Lei Hu","doi":"10.3803/EnM.2025.2524","DOIUrl":"https://doi.org/10.3803/EnM.2025.2524","url":null,"abstract":"<p><strong>Background: </strong>Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of panvascular disease (PD). Noninvasive markers for early risk stratification are needed. We evaluated whether ultrasound-derived fat fraction (UDFF) improves the prediction of PD occurrence in MASLD patients.</p><p><strong>Methods: </strong>In this prospective cohort, 525 adults with MASLD were enrolled between October 2022 and December 2023 and followed for 6 months for PD occurrence. Baseline UDFF and clinical/metabolic variables were collected. Multivariable logistic regression analyses reported standardized coefficients (per-standard deviation [SD] β) and odds ratios (ORs) per 1-SD (OR). A decision tree model was constructed to explore differences across metabolic subgroups, including obesity, hypertension, diabetes, and multiple metabolic abnormalities. Discriminative performance was compared using the area under the curve (AUC; DeLong test).</p><p><strong>Results: </strong>Body mass index (BMI), systolic blood pressure (SBP), homeostasis model assessment of insulin resistance (HOMA-IR), and UDFF were each associated with increased PD risk. In the multivariable model, the strongest standardized effects were observed for UDFF (β=3.28; OR, 2.10; 95% confidence interval [CI], 1.45 to 2.75) and BMI (β=1.87; OR, 1.68; 95% CI, 1.25 to 2.34), followed by SBP (β=1.33; OR, 1.15; 95% CI, 1.03 to 1.26). HOMA-IR (β=0.96; OR, 1.65; 95% CI, 1.30 to 2.15), age (β=0.56; OR, 1.06; 95% CI, 1.01 to 1.12), and liver stiffness measurement (β=0.14; OR, 1.03; 95% CI, 1.01 to 1.07) also showed smaller but significant associations. The decision tree model reflected similar patterns and achieved higher discrimination than logistic regression (AUC 0.85 vs. 0.80, P<0.05).</p><p><strong>Conclusion: </strong>UDFF is a key predictor of PD risk in MASLD patients, underscoring the importance of risk stratification for early intervention and personalized management strategies.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAZ WW Domain-Mediated Regulation of Gluconeogenesis and Tumorigenesis in Hepatocellular Carcinoma through Interaction with the Glucocorticoid Receptor.","authors":"Hongxiang Huang, Jinhong Chen, Xingyu Tao, Peiyuan Zhong, Yanqiu Meng, Sujuan Peng, Wanying Luo, Zhiyong He, Shuai Luo, Xie Zhu, Zhihui Lu, Li Chen, Yangyang Liu","doi":"10.3803/EnM.2025.2471","DOIUrl":"https://doi.org/10.3803/EnM.2025.2471","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC.</p><p><strong>Methods: </strong>TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays.</p><p><strong>Results: </strong>TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression.</p><p><strong>Conclusion: </strong>TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GYG1 as a Dual Biomarker of Glucagon-Like Peptide-1 Receptor Agonist Weight-Loss Response: Findings from an Integrative Multi-Omics Substudy of a Phase II Trial.","authors":"Lijun Li, Mengyu Hou, Qiannan Gao, Liyuan Zhao, Ruihua Dong","doi":"10.3803/EnM.2025.2641","DOIUrl":"10.3803/EnM.2025.2641","url":null,"abstract":"<p><strong>Background: </strong>The global obesity crisis requires precision biomarkers to overcome treatment resistance. We investigated circulating multi-omics signatures for predicting and monitoring glucagon-like peptide-1 receptor agonist (GLP-1RA) (GZR18) response, addressing gaps in personalized obesity therapy.</p><p><strong>Methods: </strong>We conducted longitudinal multi-omics profiling (proteomics, metabolomics, and lipidomics) of 221 plasma samples from 25 participants (n=25) treated with GZR18 at nine time points over 30 weeks (four samples could not be tested due to hemolysis). High-resolution mass spectrometry quantified molecular features alongside clinical body mass index (BMI) trajectories. Theil-Sen regression modeled baseline predictors (BMI slope Z), while linear regression analysis identified longitudinal biomarkers (%BMI change). Significant candidates (P<0.05) underwent gene set enrichment analysis (GSEA; Kyoto Encyclopedia of Genes and Genomes [KEGG] pathways) and STRING network integration, with dual-response biomarkers validated through correlation and trajectory analyses.</p><p><strong>Results: </strong>GZR18-treated obese patients exhibited a dose-dependent reduction in BMI, with 48 mg biweekly producing the steepest declines (Z<-0.4 vs. placebo: Z=-0.22, P<0.001). We identified glycogenin 1 (GYG1) as a dual-function biomarker (coefficient=2.0 for prediction, P<0.05 for monitoring) and as a central network hub. Lipidomic (phosphatidylinositol 18:2-18:2) and metabolomic (oxoglutaric acid) markers predicted baseline response, while proteomic (insulin like growth factor binding protein 2 [IGFBP2]) and lipidomic (phosphatidylcholine 18:0-20:3) profiles tracked longitudinal efficacy (P<0.05). Adipocytokine signaling governed the initial response (normalized enrichment score >1.8), while starch/sucrose metabolism modulated ongoing efficacy through integrated molecular networks.</p><p><strong>Conclusion: </strong>This study establishes GYG1 as a clinically actionable, dual-function biomarker for GLP-1RA therapy in obesity, linking baseline prediction and real-time monitoring of treatment response through integrated multi-omics profiling. Our findings highlight convergent metabolic pathways driving therapeutic efficacy and provide a precision-medicine framework for optimizing obesity pharmacotherapy through blood-based molecular signatures.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Knowledge on Atypical Parathyroid Tumors and Emerging Strategies for Risk Stratification.","authors":"Hye-Sun Park, Milim Kim, Jong Ju Jeong, Namki Hong, Yumie Rhee","doi":"10.3803/EnM.2025.2846","DOIUrl":"10.3803/EnM.2025.2846","url":null,"abstract":"<p><p>Atypical parathyroid tumors (APTs) are an uncommon subset of parathyroid neoplasms that carry substantial clinical relevance because of their histological and clinical resemblance to parathyroid cancer. Despite this importance, the diagnosis of APTs remains persistently challenging, even for experienced pathologists. Their histopathological features overlap extensively with those of parathyroid cancer, and at present, no specific immunohistochemical markers are available that can reliably distinguish between these entities. Moreover, the clinical manifestations of APTs are indistinguishable from those of parathyroid adenomas or true parathyroid cancer. A major concern is the uncertain malignant potential of APTs, which contributes to difficulties in prognostic prediction and the absence of standardized surveillance guidelines. Although most published studies suggest a benign clinical course for the majority of APTs, these conclusions are frequently limited by relatively short follow-up durations. This limitation is underscored by several case reports describing recurrence or metastatic disease in patients initially diagnosed with APTs, subsequently prompting reclassification as parathyroid cancer. Recent advances in molecular technologies, particularly RNA sequencing and genomic profiling, have facilitated novel approaches to risk assessment and prognostic evaluation in APTs. This review aims to provide a comprehensive overview of the diagnosis, clinical manifestations, and current molecular strategies used to assess the malignant potential of APTs.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"14-25"},"PeriodicalIF":4.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919634","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":"Distinct Pituitary-Adrenal Responses to Hypoglycemia in Type 1 and Type 2 Diabetes.","authors":"Yun Hu, Reng-Na Yan, Ting-Ting Cai, Xiao-Wei Zhu, Jian-Hua Ma, Bo Ding","doi":"10.3803/EnM.2025.2479","DOIUrl":"10.3803/EnM.2025.2479","url":null,"abstract":"<p><strong>Backgruound: </strong>Hypoglycemia remains a major barrier to optimal glycemic control in diabetes. Counter-regulatory hormonal responses, particularly those involving the pituitary and adrenal systems, play a central role in mitigating hypoglycemia, yet differences between diabetes subtypes are not well characterized. We aimed to investigate pituitary-target gland responses to hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM).</p><p><strong>Methods: </strong>We enrolled drug-naive patients with newly diagnosed T2DM or T1DM, along with controls who did not have diabetes. Participants with diabetes received insulin pump therapy until normoglycemia was achieved. Hyperinsulinemic euglycemic-hypoglycemic clamps were then performed in all participants. Hormonal profiles of the pituitary-adrenal axis and C-peptide were serially measured during the clamps.</p><p><strong>Results: </strong>During hypoglycemic clamps, C-peptide, thyroid-stimulating hormone, estradiol, and testosterone decreased, whereas prolactin, adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) increased significantly according to repeatedmeasures analysis of variance (ANOVA) (P<0.05 for all). Compared to controls and T2DM, patients with T1DM exhibited elevated basal GH (P=0.002) and an exaggerated GH response to hypoglycemia (P=0.002), with earlier onset and sustained elevation. In contrast, patients with T2DM showed higher ACTH (P=0.024) and cortisol (P=0.043) levels during hypoglycemia compared to controls and T1DM. Relative to the T1DM group, the T2DM group demonstrated lower testosterone and higher estradiol levels during hypoglycemia (P<0.001 for both).</p><p><strong>Conclusion: </strong>Distinct diabetes subtypes demonstrate divergent pituitary-adrenal counter-regulatory responses to hypoglycemia, suggesting unique pathogenic mechanisms contributing to glycemic variability. The exaggerated GH response in T1DM may aggravate glucose fluctuations, whereas elevated ACTH and cortisol in T2DM could perpetuate insulin resistance.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"162-173"},"PeriodicalIF":4.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663462","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}