Frontiers in Endocrinology最新文献

{"title":"Analysis of 1,25-dihydroxyvitamin D genomic action in human enteroids and colonoids reveals multiple regulatory effects of vitamin D in human intestinal physiology.","authors":"Zachary K Criss, Kali Deans-Fielder, James C Fleet, Sylvia Christakos, Noah Shroyer","doi":"10.3389/fendo.2025.1538463","DOIUrl":"10.3389/fendo.2025.1538463","url":null,"abstract":"<p><strong>Introduction: </strong>The intestine has molecular and functional diversity across the proximal-distal and the crypt-villus axes, so it is imperative to determine the common and compartment-specific molecular actions of vitamin D. However, very little work on vitamin D mediated gene regulation has been done in normal human intestine. Here, we examined the impact of 1,25-dihydroxyvitamin D (1,25(OH)₂D₃) on cultures of human intestinal epithelium derived from duodenum (Dd) and distal colon (Co) biopsies of 6 subjects per tissue.</p><p><strong>Methods: </strong>Human enteroids and colonoids were cultured for 3 days to promote a stem cell phenotype (undifferentiated, Un) or to induce differentiation (Diff) and then treated with vehicle control or 1,25(OH)₂D₃ (100 nM). 24h following treatment enteroids/colonoids were collected, RNA was isolated and RNA-seq was performed using paired-end Illumina sequencing (analysis in R using DESeq2).</p><p><strong>Results and discussion: </strong>RNA-seq analysis showed that VDR mRNA is present in all four cultures tested (DdUn, DdDiff, CoUn, CoDiff) and it is not altered by 1,25(OH)₂D₃ treatment, intestinal segment, or differentiation status. 1,25(OH)₂D₃ induced the classic intestinal target genes TRPV6, ATP2B1 and CYP24A1 in all four culture groups while S100G was induced only in DdDiff. While 63 genes were vitamin D regulated across all four cultures (55 up, 8 down), we found that vitamin D regulated subgroups of genes within Dd, Co, Un, or Diff groups as well as set of genes that were unique to each culture. Functional analysis revealed several vitamin D-enriched gene ontologies or pathways including those for xenobiotic/drug metabolism in all four cultures. In differentiated cultures vitamin D induced genes were enriched for functions like regulation of barrier function through regulation of Rho GTPases and metabolism of lipids while vitamin D downregulated genes in Un groups were enriched for activities like water transport. These results provide new insight into 1,25(OH)₂D₃ genomic action in the functionally distinct compartments and segments of human intestine and suggest multiple regulatory effects of vitamin D in human intestinal physiology.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1538463"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of hypothalamic-pituitary-adrenal axis impairment and effects of hydrocortisone treatment in adults with Prader-Willi syndrome.","authors":"Magdalena Góralska, Agata Pokrzywa, Agnieszka Stańczyk, Maria Libura, Tomasz Bednarczuk","doi":"10.3389/fendo.2025.1517334","DOIUrl":"10.3389/fendo.2025.1517334","url":null,"abstract":"<p><strong>Objective: </strong>The prevalence of hypothalamic-pituitary-adrenal impairment (HPAI) in adults with Prader Willi Syndrome (PWS) remains unclear despite its clinical relevance. The aim of our study was to assess the prevalence of HPA axis impairment in adults with PWS based on the results of the high dose short synacthen test (HDSST), as well as to analyze the effects of hydrocortisone (HCT) therapy in this population.</p><p><strong>Design: </strong>Retrospective analysis.</p><p><strong>Patients: </strong>Thirty adult patients (14 men, 16 women, aged 18-28 years) with genetically confirmed PWS. Twenty-two patients (73.3%) had been adequately treated with human recombinant growth hormone (rhGH). Due to hypogonadotropic hypogonadism, all patients received hormone replacement therapy.</p><p><strong>Measurements: </strong>Physical examination included measuring height, weight and body fat percentage (using the electrical bioimpedance method). Based on HDSST results, patients were divided into two groups: with HPA axis impairment (cortisol < 500 nmol/L at 30^th minute), and AS (adrenal sufficiency; cortisol ≥ 500 nmol/L at the 30^th minute). Clinical symptoms of adrenal insufficiency (AI), body weight and body fat percentage were evaluated at baseline, after 6 and 12 months of follow-up.</p><p><strong>Results: </strong>Fourteen of the 30 patients (46.7%) showed a 30-min cortisol peak <500 nmol/L, and were assigned to the HPAI group. Peak cortisol levels at 30' and 60' were significantly lower in the HPAI group compared to the Control one, respectively (<i>P</i><0.001) Correlation analysis revealed that basal cortisol was positively correlated with cortisol levels at both 30' and 60' of the HDSST (r = 0.872, <i>P</i> < 0.001 and r = 0.829, <i>P</i> < 0.001, respectively). Fatigue, myalgia and muscle weakness occurred more often in the HPAI group than in the Control group (90.9% vs. 20%, <i>P</i>= 0.01, 90.9% vs. 0%, <i>P</i>=0.001, respectively). All symptomatic patients with HPAI received HCT treatment (10 mg/day) in two divided doses. Fatigue, myalgiaand muscle weakness improved significantly after 12 months of HCT therapy (P<0.001). No adverse effects of HCT treatment were observed, such as weight gain, body fat percentage increase or metabolic abnormalities.</p><p><strong>Conclusions: </strong>The results of our study suggest that the HPA axis should be routinely evaluated in adult patients with PWS. Short term, low-dose HCT treatment in symptomatic patients with HPAI is safe and can reduce symptoms of fatigue, myalgia and muscle weakness. However, the benefits and adverse effects of HCT treatment in this population require confirmation in prospective, placebo-controlled randomized clinical studies.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1517334"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of intravenous immunoglobulin in recurrent pregnancy loss: a retrospective analysis of patients with abnormal cellular immunity.","authors":"Jae Won Han, Jin Sol Park, Jong-Seok Kim, Sung Ki Lee","doi":"10.3389/fendo.2025.1546602","DOIUrl":"10.3389/fendo.2025.1546602","url":null,"abstract":"<p><strong>Introduction: </strong>Various causes of recurrent pregnancy loss (RPL) have been identified, but even with a detailed evaluation, almost half of the cases have unidentified etiologies. Immune imbalance is one of the proposed potential etiologies of these idiopathic RPL. To regulate abnormal cellular immunity, intravenous immunoglobulin (IVIG), a type of immunotherapy, is proposed to improve pregnancy outcomes. However, the efficacy of IVIG in RPL is still controversial.</p><p><strong>Methods: </strong>RPL was defined as women with two or more spontaneous abortions and in total, 987 RPL women visited Department of Obstetrics and Gynecology, Konyang University Hospital from January 2007 to December 2020. Only those with a full evaluation and known treatment outcome were included. Idiopathic RPL(n=215) and women with known etiology (n=251) were enrolled. Both the idiopathic and known etiology groups were subsequently stratified into subgroups based on the presence of at least one abnormal cellular immunity (n=100 and n=97, respectively). We investigated the pregnancy outcome by sorting the patients into seven subgroups depending on abnormal cellular immunity including natural killer (NK) cell level, NK cell cytotoxicity and Th1/Th2 ratio.</p><p><strong>Results: </strong>Patients with older age and higher body mass index had negative effect on pregnancy outcomes whereas the number of previous miscarriages did not show significant difference in pregnancy outcomes. Among all RPL women with at least one abnormal cellular immunity were treated with IVIG and the overall live birth rate (LBR) was 82.7%. The group which did not have IVIG treatment showed an overall LBR of 80.7%. Among the seven groups of idiopathic RPL women with abnormal cellular immunity, the group with both high NK cell level and NK cell cytotoxicity showed the highest LBR, 90.5%, and the group with both high NK cell level and Th1/Th2 ratio showed the lowest LBR, 75%.</p><p><strong>Discussion: </strong>IVIG treatment appears to improve LBRs in women with RPL and abnormal cellular immunity. These findings support the potential benefit of IVIG in selected RPL patients with immune imbalances. Further studies are needed to refine patient selection criteria and optimize treatment protocols for improving pregnancy outcomes in this population.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1546602"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in incidence, mortality, and conditional survival of anaplastic thyroid cancer over the last two decades in the USA.","authors":"Hongpeng Guo, Junjie Zhang, Yuanji Jia, Zongfeng Liu, Ying Qi, Chenglin Sun, Zhencun Cai, Ji Wu","doi":"10.3389/fendo.2025.1585679","DOIUrl":"10.3389/fendo.2025.1585679","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy, and there is currently a lack of up-to-date epidemiological data. Traditional survival analysis fails to capture the dynamic changes in prognosis for long-term survivors, while conditional survival (CS) analysis, a critical tool for adaptive risk stratification, remains underexplored in ATC.</p><p><strong>Methods: </strong>Patients diagnosed with ATC between 2000 and 2021 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Temporal trends in age-adjusted incidence and incidence-based mortality were analyzed using Joinpoint regression to calculate annual percentage changes (APCs) with 95% confidence intervals (CIs). Overall survival (OS) was estimated using the Kaplan-Meier method. CS rates were calculated using the formula: CS(y/x) = OS(y+x)/OS(x). Prognostic factors were identified using Best Subset Regression (BSR), LASSO, and univariate and multivariate Cox regression analyses, and these factors were incorporated into a CS-nomogram model. The predictive performance of the model was validated using evaluation metrics, including the area under the receiver operating characteristic curve (AUC). Point values were assigned to the model's predictive factors, and a risk stratification system was developed based on the optimal threshold of the total score.</p><p><strong>Results: </strong>From 2000 to 2021, the age-adjusted incidence of ATC increased from 0.066 to 0.077 per 100,000 (APC: 2.308%, 95% CI: 1.187-3.441), peaking at 0.119 in 2018. Mortality trends paralleled this rise, with age-adjusted mortality increasing from 0.037 to 0.051 per 100,000 (APC: 2.380%, 95% CI: 1.129-3.646). CS analysis demonstrated a progressive increase in survival rates over time, with the 24-month cumulative survival rate rising from 14.0% to 93.8%, with the most pronounced temporal changes observed in patients with distant disease. Prognostic factors identified through BSR, LASSO, and Cox regression included age, SEER stage, and treatment. A novel CS-nomogram was successfully developed and validated for dynamic real-time survival prediction, enabling identification of high- and low-risk patient groups.</p><p><strong>Conclusion: </strong>The incidence and incidence-based mortality of ATC have increased over the past few decades. The CS rates of ATC patients have dynamically improved over time. The CS-nomogram, integrating age, SEER stage, and treatment, provides clinicians with a personalized, dynamic, and real-time survival prediction tool that helps alleviate survivors' psychological distress, reduces anxiety, and optimizes precision follow-up strategies.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1585679"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ferroptosis: a novel insight into thyroid cancer therapy.","authors":"Xinyao Liu, Liangkai Wang, Xuehua Xi, Tongtong Zhou, Zhe Sun, Bo Zhang","doi":"10.3389/fendo.2025.1527693","DOIUrl":"10.3389/fendo.2025.1527693","url":null,"abstract":"<p><p>There is a continuous increase in the incidence of thyroid cancer. A deeper understanding of the molecular mechanisms of thyroid cancer could significantly improve thyroid cancer management. Newly discovered type of programmed cell death, ferroptosis, has been demonstrated to play a crucial role in many cancers. Mounting evidence shows that there is a close association between ferroptosis and thyroid cancer, which offer a promising therapeutic strategy for thyroid cancer. Ferroptosis is expected to emerge as a novel therapeutic target. Regrettably, the exact role of ferroptosis in thyroid cancer is not yet completely understood. Further, there is currently no summary of ferroptosis in thyroid cancer progression and treatment. Hence, in this review, we aim to revisit the pathological process of thyroid cancer and reveal the role of ferroptosis in thyroid cancer. In addition, we provide evidence that ferroptosis inducers could suppress the growth of thyroid cancer cells. Lastly, we discuss the potential application of ferroptosis inducers in thyroid cancer treatment, as well as possible impediments and corresponding strategies. The relationship between ferroptosis and thyroid cancer will be better understood through this review, which may offer a novel insight into thyroid cancer therapy.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1527693"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 efficacy of adjuvant Sotagliflozin therapy in patients with T1D - an update and systematic review and meta-analysis.","authors":"Yunzhen Lei, Shanshan Yao, Zhenglong Wang, Qianxian Tu, Zhengqiang Yuan, Qianfeng Jiang","doi":"10.3389/fendo.2025.1506652","DOIUrl":"10.3389/fendo.2025.1506652","url":null,"abstract":"<p><strong>Objective: </strong>This meta-analysis aims to assess the safety and efficacy of Sotagliflozin in patients with type 1 diabetes (T1D).</p><p><strong>Methods: </strong>Data on target organ protection, blood glucose levels, blood pressure, weight, insulin usage, and adverse events (AEs) associated with Sotagliflozin in the treatment of T1D were collected from databases including PubMed, Scopus, Web of Science, Embase, and the Cochrane Library. The search period extended until February 21, 2024, and included studies were restricted to randomized controlled trials (RCTs) investigating Sotagliflozin for T1D. The meta-analysis was performed using Stata 14 and RevMan 5.4.</p><p><strong>Results: </strong>A total of 12 randomized controlled trials were included in the analysis, with treatment durations ranging from 14 to 52 weeks. Sotagliflozin, when used in combination with insulin therapy, resulted in significant reductions in cardiovascular disease (CVD) risk (-6.38%; <i>95% CI:</i> -7.63 to -5.1; <i>P</i> < 0.05) and end-stage kidney disease (ESKD) risk (-5.0%; <i>95% CI:</i> -7.62 to -2.3; <i>P</i> < 0.05). Additionally, Sotagliflozin significantly reduced blood glucose, blood pressure, and body weight, with these effects showing dose- and duration-dependent trends. Regarding adverse effects, the combination of insulin and Sotagliflozin was associated with an increased incidence of genital infections (Sotagliflozin group: 8% vs. control: 2%) but a reduced risk of fractures (Sotagliflozin group: 1% vs. control: 2%). No statistically significant differences were observed between the two groups for other outcomes, including diabetic ketoacidosis (DKA), hypoglycemia, mortality, cancer, nausea, diarrhea, urinary tract infections, or liver and kidney function impairment.</p><p><strong>Conclusion: </strong>In T1D patients, Sotagliflozin adjunct therapy improves blood glycemia, stabilizes blood pressure, and reduces cardiovascular risk factors. It also shows potential in lowering fracture risk, but the risk of DKA requires further clinical validation.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/#joinuppage, identifier CRD42023467427.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1506652"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Sexual function and dysfunction in men and women with diabetes.","authors":"Adriana Coppola, Katherine Esposito, Carmine Gazzaruso","doi":"10.3389/fendo.2025.1629375","DOIUrl":"10.3389/fendo.2025.1629375","url":null,"abstract":"","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1629375"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of novel machine learning-based prognostic models and propensity score matching for comparison of surgical approaches in mucinous breast cancer.","authors":"Chunmei Chen, Jundong Wu, Yutong Fang, Yong Li, Qunchen Zhang","doi":"10.3389/fendo.2025.1557858","DOIUrl":"10.3389/fendo.2025.1557858","url":null,"abstract":"<p><p>Mucinous breast cancer (MBC) is a rare subtype of breast cancer with specific clinicopathologic and molecular features. Despite MBC patients generally having a favorable survival prognosis, there is a notable absence of clinically accurate predictive models. Patients diagnosed with MBC from the SEER database spanning 2010 to 2020 were included for analysis. Cox regression analysis was conducted to identify independent prognostic factors. Ten machine learning algorithms were utilized to develop prognostic models, which were further validated using MBC patients from two Chinese hospitals. Cox analysis and propensity score matching were applied to evaluate survival differences between MBC patients undergoing mastectomy and breast-conserving surgery (BCS). We determined that the XGBoost models were the optimal models for predicting overall survival (OS) and breast cancer-specific survival (BCSS) in MBC patients with the most accurate performance (AUC=0.833-0.948). Moreover, the XGBoost models still demonstrated robust performance in the external test set (AUC=0.856-0.911). Patients treated with BCS exhibited superior OS compared to those undergoing mastectomy (p < 0.001, HR: 0.60, 95% CI: 0.47-0.77). However, no significant difference was observed in the risk of breast cancer-related mortality. We have successfully developed 6 optimal prognostic models utilizing the XGBoost algorithm to accurately predict the survival of MBC patients. We also developed an interactive web application to facilitate the utilization of our models by clinicians or researchers. Notably, we observed a significant improvement in OS for patients undergoing BCS.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1557858"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolite perturbations in type 1 diabetes associated with metabolic dysfunction-associated steatotic liver disease.","authors":"Adeyinka Taiwo, Ronald A Merrill, Linder Wendt, Daniel Pape, Himani Thakkar, J Alan Maschek, James Cox, Scott A Summers, Bhagirath Chaurasia, Nikitha Pothireddy, Bianca B Carlson, Antonio Sanchez, Patrick Ten Eyck, Diana Jalal, Ayotunde Dokun, Eric B Taylor, William I Sivitz","doi":"10.3389/fendo.2025.1500242","DOIUrl":"10.3389/fendo.2025.1500242","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Although MASLD has been widely studied in persons with Type 2 diabetes (T2D), far less in known about the pathogenesis and severity of MASLD in Type 1 diabetes (T1D).</p><p><strong>Objectives: </strong>Determine metabolic perturbations associated with MASLD in persons with T1D.</p><p><strong>Study design: </strong>We conducted a cross-sectional study of 30 participants with T1D. Based on the results of a FibroScan, participants were stratified as cases (MASLD) or controls. Metabolomic analyses were performed on plasma obtained from all participants after an overnight (after midnight) fast.</p><p><strong>Results: </strong>17 of 30 participants were classified as cases (MASLD) and 13 as controls. Cases had higher BMI (p=<0.001) and were taking higher daily insulin doses than controls (p=0.003). Metabolomic analyses revealed that those with MASLD had elevated levels of gluconeogenic substrates pyruvate (p=0.001) and lactate (p=0.043), gluconeogenic amino acids alanine (p<0.001) and glutamate (p=0.004), phenylalanine (p=0.003), and anthranilic acid (p=0.015). Lipidomics revealed, elevated ceramides (P=0.02), diacylglycerols (p=0.0009) and triacylglycerols (P=0.0004) in MASLD group. In those with MASLD, the acylcarnitines, isovalerylcarnitine (CAR.5.0) (P=0.002) and L-Palmitoylcarnitine (CAR.16.0) (P=0.048), were elevated. Pathway analyses using MetaboAnalyst 5.0 Software revealed that, pathways including phenylalanine and tyrosine metabolism, tryptophan metabolism, glucose-alanine cycle, glutamate metabolism, and glutathione metabolism were significantly enriched in those with MASLD.</p><p><strong>Conclusion: </strong>Participants with T1D and MASLD manifest features of insulin resistance and metabolite perturbations suggesting enhanced gluconeogenesis, dysfunctional fat synthesis, and perturbed TCA cycle activity.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1500242"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial dysfunction in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: current knowledge and novel biomarkers.","authors":"Joanna Hubska, Zuzanna Roszkowska, Małgorzata Bobrowicz, Sebastian Iwaniuk, Beata Rak-Makowska, Urszula Ambroziak","doi":"10.3389/fendo.2025.1581681","DOIUrl":"10.3389/fendo.2025.1581681","url":null,"abstract":"<p><p>Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a complex endocrine disorder characterized by impaired cortisol synthesis and androgen excess. Beyond its hormonal and metabolic implications, CAH has been increasingly associated with an elevated risk of cardiovascular complications, including endothelial dysfunction, a critical precursor to atherosclerosis and a risk factor for cardiovascular and metabolic diseases. This review explores the current knowledge on endothelial function in patients with CAH, focusing on the interplay between chronic hormonal imbalance, prolonged glucocorticoid treatment, and associated metabolic disorders. We also discuss <i>in vivo</i> methods for assessing endothelial function alongside the potential utility of novel biomarkers, which may facilitate earlier identification of vascular dysfunction and stratification of cardiovascular risk. By summarizing emerging concepts in this field, we aim to highlight areas for future research and opportunities for improving long-term cardiovascular outcomes in individuals with 21OHD.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1581681"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}