Frontiers in Endocrinology最新文献

{"title":"Mechanisms of dyslipidemia-induced erectile dysfunction: a narrative review.","authors":"Dicheng Luo, Di Sun, Elena Colonnello, Li-Ping Pan, Shuang Wu, Jun Guo, Hao Wang, Jiwei Zhang","doi":"10.3389/fendo.2026.1780243","DOIUrl":"https://doi.org/10.3389/fendo.2026.1780243","url":null,"abstract":"<p><strong>Background: </strong>Dyslipidemia is strongly associated with obesity, metabolic syndrome, and atherosclerosis, and is increasingly recognized as an independent risk factor for erectile dysfunction (ED). Emerging evidence suggests lipid-specific mechanisms that may directly impair erectile function, beyond the effects of obesity.</p><p><strong>Objective: </strong>To summarize the pathophysiological mechanisms linking dyslipidemia to the development and progression of ED.</p><p><strong>Methods: </strong>A narrative review of studies published between 2000 and 2025 was conducted using PubMed, Web of Science, Scopus, and Google Scholar, including experimental, clinical, observational, and review studies.</p><p><strong>Results and conclusion: </strong>Dyslipidemia contributes to ED through multiple interconnected pathways, including vascular dysfunction, neural impairment, oxidative stress, inflammation, and endocrine alterations. These mechanisms may increase susceptibility to ED in affected patients. However, direct evidence remains limited, and confounding by coexisting metabolic, cardiovascular and neural conditions complicates interpretation. Further research is needed to clarify the independent effects of dyslipidemia and to identify potential therapeutic strategies.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1780243"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835902","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":"A metabolic-to-inflammatory pattern in cardiovascular-kidney-metabolic syndrome staging: a comparative cross-sectional study.","authors":"Teng Zhang, Zi-Yue Man, Shi-Meng Zhang, Jian-Jun Mu, Yue-Yuan Liao","doi":"10.3389/fendo.2026.1805355","DOIUrl":"https://doi.org/10.3389/fendo.2026.1805355","url":null,"abstract":"<p><strong>Background: </strong>Amid the cardiovascular-kidney-metabolic (CKM) syndrome public health crisis, this study aimed to explore differential pathological associations with established versus advanced CKM status and assess its consistency across Chinese and U.S. adults.</p><p><strong>Methods: </strong>This cross-sectional study analyzed data from two independent sources: a community survey in Shaanxi, China (n=2, 100) and the U.S. National Health and Nutrition Examination Survey (NHANES) (2011-2018; n=5, 359). Associations between three pathological axes-visceral adiposity (VA), insulin resistance/dyslipidemia pathological score (IRD-PS), and systemic low-grade inflammation pathological score (SLI-PS)-and two key CKM outcomes (established: Stages 2-4 vs. 0-1; advanced: Stages 3-4 vs. 0-2) were evaluated using Firth's penalized logistic regression to address potential quasi-complete separation in the outcome data.</p><p><strong>Results: </strong>IRD-PS exhibited the strongest association with established CKM status in both populations (Shaanxi: <i>OR</i> = 2.49, 95% <i>CI</i> 2.18, 2.86; NHANES: <i>OR</i> = 2.52, 95% <i>CI</i> 2.24, 2.82). In contrast, SLI-PS was significantly and consistently correlated with advanced CKM status (Shaanxi: <i>OR</i> = 1.11, 95% <i>CI</i> 1.03, 1.19; NHANES: <i>OR</i> = 1.07, 95% <i>CI</i> 1.01, 1.14). Statistical exploratory decomposition analysis revealed IRD-PS largely attenuated the association between VA and established CKM status, statistically accounting for 67.1% of the effect in Shaanxi and 64.5% in NHANES. In the NHANES, significant racial/ethnic heterogeneity was observed in the IRD-PS-established CKM status association (<i>P</i> for interaction < 0.001), with the strongest association in non-Hispanic Asian people (<i>OR</i> = 3.96) and the weakest in non-Hispanic Black people (<i>OR</i> = 2.03). These cross-sectional associations should be interpreted with caution.</p><p><strong>Conclusions: </strong>Our findings support a conceptual model of CKM syndrome in which metabolic dysregulation is the primary correlate of the established (Stage 2+) CKM status and in which systemic inflammation is a more prominent correlate of advanced (Stage 3+) CKM status. These findings may primarily generalize to the analyzed subsamples rather than broader general populations. Given the cross-sectional design, all findings are strictly hypothesis-generating, and the proposed stage-specific pathological pattern requires formal validation in future longitudinal cohorts.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1805355"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835425","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":"Association between prior gestational diabetes mellitus and adverse pregnancy outcomes.","authors":"Mengqing Weng, Haibing Gao, Julan Peng, Huayou Li, Lili Chen, Han Yang, Jie Wang","doi":"10.3389/fendo.2026.1826255","DOIUrl":"https://doi.org/10.3389/fendo.2026.1826255","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to examine the independent association between a history of gestational diabetes mellitus (GDM) and adverse maternal-fetal outcomes in subsequent pregnancies, with the objective of informing evidence-based clinical management strategies for this high-risk population.</p><p><strong>Methods: </strong>This retrospective study included women who delivered at Shenzhen Longhua District People's Hospital between 2015 and 2025. Participants were categorized into a PGDM group (n=332) and a non-PGDM group (n=994) based on prior history of GDM. Propensity score matching was employed to control for confounding factors, and logistic regression analysis was used to assess the association between PGDM and adverse pregnancy outcomes.</p><p><strong>Results: </strong>Pregnant women with prior GDM had significantly higher risks of cesarean delivery (32.8% vs. 26.9%), GDM recurrence (50.0% vs. 11.8%), and gestational hypertension (3.0% vs. 1.2%) (all p<0.05). Multivariate analysis indicated that a history of PGDM independently predicted GDM recurrence (OR = 7.320, 95%CI: 5.473-9.791), gestational hypertension(OR = 2.924, 95% CI: 1.154-7.405), and reduced gestational age (OR = 0.88 per week, 95% CI: 0.792-0.981), while decreasing the risk ofPostpartum Anemia (OR = 0.694, 95% CI: 0.488-0.986). Neonatal outcomes showed no differences between groups.</p><p><strong>Conclusion: </strong>A history of PGDM significantly increases the risk of GDM recurrence and gestational hypertension in subsequent pregnancies, and is associated with earlier delivery gestational age. Notably, a history of PGDM is also associated with a reduced risk of postpartum anemia.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1826255"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835569","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":"Cardiovascular and autonomic nervous system response to graded exercise in adolescents with type 1 diabetes.","authors":"Tadej Rondaij, Jakob Jesih, Klemen Dovč, Tadej Battelino, Nejka Potočnik","doi":"10.3389/fendo.2026.1813865","DOIUrl":"https://doi.org/10.3389/fendo.2026.1813865","url":null,"abstract":"<p><strong>Introduction: </strong>Type 1 diabetes (T1D) is associated with an increased risk of cardiovascular and autonomic complications. Although cardiopulmonary exercise testing (CPET) is a valuable tool for assessing cardiorespiratory function, data on physiological response to maximal exertion in adolescents with T1D remain limited and inconsistent. This study aimed to compare cardiovascular, respiratory, metabolic, and microvascular responses to CPET in adolescents with T1D and healthy peers.</p><p><strong>Methods: </strong>Sixteen participants aged 11-16 years (eight with T1D and eight healthy controls), matched for anthropometric characteristics, underwent CPET on a cycle ergometer. Respiratory gas exchange, heart rate, heart rate variability, blood pressure, blood glucose, lactate concentration, skin blood flow, skin temperature, and cutaneous vascular conductance were measured at predefined time points during rest, exercise, and recovery. Blood glucose, lactate concentration, and skin microvascular variables were assessed at rest and during recovery.</p><p><strong>Results: </strong>Adolescents with T1D demonstrated a significantly lower V̇O₂/power output slope and a higher ventilatory equivalent for oxygen at maximal effort, suggesting altered oxygen uptake efficiency. Maximal power output and maximal oxygen consumption did not differ between groups. Heart rate responses and heart rate variability were similar throughout testing. However, finger skin blood flow and cutaneous vascular conductance were significantly lower in the T1D group at rest and during recovery.</p><p><strong>Conclusion: </strong>Adolescents with T1D showed preserved cardiovascular function and comparable overall exercise capacity to healthy peers, despite subtle impairments in oxygen utilization and reduced skin microvascular function. These findings indicate that even at a young age, T1D is associated with altered metabolic, respiratory, and microvascular responses to maximal exercise. The results suggest that peripheral, rather than central mechanisms may underlie these differences, potentially involving glucose levels or synthetic insulin effects on vascular endothelium.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1813865"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835882","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":"Effects of kaempferol on bone loss in animal models of osteoporosis: a systematic review and meta-analysis.","authors":"Guangming Kang, Dechun Qu, Bo Dong, Rui Tang, Xin Liu, Shihang Cao, Dongping Wan, Haoxiang Yuan, Chuan Leng, Rui Wang, Baohui Wang","doi":"10.3389/fendo.2026.1805337","DOIUrl":"https://doi.org/10.3389/fendo.2026.1805337","url":null,"abstract":"<p><strong>Purpose: </strong>Osteoporosis remains a major global health challenge, necessitating the search for safe and effective therapeutic leads. Kaempferol, a natural flavonoid, has shown potential in bone health management. This systematic review and meta-analysis aimed to quantitatively evaluate the preclinical efficacy of kaempferol in mitigating bone loss in animal models of osteoporosis.</p><p><strong>Methods: </strong>Following PRISMA guidelines and PROSPERO registration (CRD420251273304), a comprehensive search was conducted across eight electronic databases up to January 2026. Twelve randomized controlled trials investigating kaempferol monotherapy in osteoporotic animal models (primarily OVX rats) were included. Methodological quality was assessed using SYRCLE's risk of bias tool, and meta-analysis was performed using Stata 18.0.</p><p><strong>Results: </strong>Kaempferol significantly increased femoral bone mineral density (BMD) (SMD = 2.86; 95% CI: 1.96-3.79; p < 0.001). It also significantly improved microarchitectural parameters (BV/TV, Tb.N, Tb.Th) and biomechanical properties (elastic modulus). Mechanistically, kaempferol elevated bone formation markers (P1NP), suppressed bone resorption markers (TRACP, CTX), and modulated the RANKL/OPG signaling axis. Subgroup analyses confirmed consistent osteoprotective effects across various dosages and intervention durations.</p><p><strong>Conclusion: </strong>Preclinical evidence robustly demonstrates that kaempferol effectively preserves bone mass and microarchitectural integrity while enhancing mechanical strength. These findings establish kaempferol as a promising natural bioactive candidate for osteoporosis management and provide a rigorous evidence-based foundation for its clinical translation.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/, identifier CRD420251273304.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1805337"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835918","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 autologous stem cell at different doses combined with core decompression in the treatment of osteonecrosis of the femoral head: a systematic review and network meta-analysis.","authors":"Mingjie Wei, Libo Yuan, Guocheng Feng, Baochuang Qi, Xiangwen Shi, Yongqing Xu","doi":"10.3389/fendo.2026.1720437","DOIUrl":"https://doi.org/10.3389/fendo.2026.1720437","url":null,"abstract":"<p><strong>Objective: </strong>To compare autologous stem cell (SC) at different doses combined with core decompression (CD) versus CD alone for osteonecrosis of the femoral head (ONFH), using conversion to total hip arthroplasty (THA) as the primary outcome.</p><p><strong>Methods: </strong>PubMed, Embase, Cochrane Library, Web of Science, and CNKI were systematically searched (from inception to July 2025) to identify studies comparing different SC dosages (low dose: <1×10^7; medium dose: 1×10^7-10×10^8; high dose: >1×10^8). Conventional meta-analyses were performed using Review Manager 5.3, while network meta-analyses (NMA) were conducted with Stata 16.0. Treatment efficacy was ranked using SUCRA curves. Sensitivity analyses and funnel plots were applied to assess the robustness of the findings and potential publication bias.</p><p><strong>Results: </strong>Eighteen studies involving 1,192 patients were included. Compared with CD alone, evidence from conventional meta-analysis and network meta-analysis suggested that high-dose autologous stem cell therapy (>1×10^8 cells) combined with CD was associated with a lower risk of hip failure (conversion to THA) (OR = 0.24, 95% CI: 0.12 to 0.44). The high-dose group was also associated with a lower rate of femoral head collapse (OR = 0.24, 95% CI: 0.08 to 0.74) and lower VAS score (SMD = -1.93, 95% CI: -3.64 to -0.23). However, no statistically significant advantage of the high-dose group over the low- or medium-dose groups was observed, and no clear differences in incidence of adverse events (AEs) were detected across dose categories.</p><p><strong>Conclusions: </strong>Preliminary evidence suggests that, compared with CD alone, high-dose autologous stem cell therapy (>1×10^8 cells) combined with CD is associated with a lower risk of hip failure and a lower femoral head collapse rate, with additional improvements in pain in some comparisons. However, the certainty of evidence is limited by heterogeneity in study design, follow-up, and cell dose reporting. Future studies should emphasize standardized cell processing and intervention dosing to validate the dose-response relationship and establish the optimal clinical dosage.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/display_record, identfier CRD420251154025.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1720437"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835889","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":"Prevalence of cardiovascular-kidney-metabolic syndrome in areas of Southern China where ethnic minority populations reside: a cross-sectional study.","authors":"Kehui Li, Ying Zeng, Manqiu Mo, Yunan Xu, Xiaohua Li, Yuanshan Xu, Zhiqiang Nong, Ling Pan, Rongjie Huang","doi":"10.3389/fendo.2026.1818782","DOIUrl":"https://doi.org/10.3389/fendo.2026.1818782","url":null,"abstract":"<p><strong>Introduction: </strong>Epidemiological data and the comorbidity situation of cardiovascular-kidney-metabolic disease (CKM) in ethnic minority regions of southern China are lacking. This study aimed to (1) estimate the prevalence and stage distribution of CKM syndrome and (2) identify factors associated with CKM stages and explore the interrelationships among coexisting chronic conditions in a multi-ethnic population in southern China.</p><p><strong>Methods: </strong>We analyzed data from the 2020-2021 China Cardiovascular Disease and Risk Factors Surveillance project in Guangxi. CKM syndrome was defined as the coexistence of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders. The primary outcome was CKM stage (0-4), and binary CKM variables were used in regression analyses. Prevalence was estimated using data from questionnaires, physical examinations, and laboratory tests. Regression and network analyses were conducted to examine factors associated with CKM and the interrelationships among chronic conditions.</p><p><strong>Results: </strong>Among 8,552 participants (median age 50 [IQR 36-63]; 41.9% male; 66.6% urban; 42.3% Zhuang), the age- and sex-adjusted prevalence of CKM stages 1-4 was 76.4% (95% CI: 75.5-77.3%), with 17.2% at stage 1, 57.7% at stages 2-3, and 1.4% at stage 4 (all p < 0.001). The prevalence of CKM stages 2-4 was significantly higher among males, older individuals, rural residents, and non-Zhuang populations (p < 0.05). Factors independently associated with CKM (stages 2-4) included male sex, older age, rural residence, lower education level, alcohol consumption, low fruit intake, high red meat intake, and hyperuricemia (all p < 0.05). The prevalence of individual chronic conditions was as follows: hypertension, 39.7%; non-hypertension CVD (other CVD), 1.6%; CKD, 13.8%; obesity, 12.2%; and diabetes, 12.1%. Hypertension was a central condition linking CVD, CKD, hyperuricemia, obesity, and diabetes.</p><p><strong>Conclusion: </strong>This study reveals a substantial burden of CKM stages 2-3 in Guangxi, China, affecting over half of the population, especially rural elderly men. The findings highlight the need for targeted prevention strategies focusing on modifiable factors associated with CKM in ethnic minority regions.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1818782"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835647","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":"Genomic profiling of a DICER1-wildtype thyroblastoma reveals AGK-BRAF fusion, EIF1AX duplication, and TERT promoter mutations: integrated genomic and pathway analysis.","authors":"Alberto Gualandi, Fernanda Picozzi, Annabella Di Mauro, Susi Pelotti, Imma D'Arbitrio, Pasquale De Luca, Lucia Cannella, Antonio Pizzolorusso, Alessandro Ottaiano, Annarita Peddio, Gerardo Ferrara, Salvatore Tafuto","doi":"10.3389/fendo.2026.1747919","DOIUrl":"https://doi.org/10.3389/fendo.2026.1747919","url":null,"abstract":"<p><strong>Introduction: </strong>Thyroblastoma is a rare and highly aggressive embryonal thyroid malignancy typically associated with DICER1 alterations. However, DICER1-wildtype cases remain poorly characterized at the molecular level.</p><p><strong>Methods: </strong>We report a case of aggressive thyroblastoma in a 62-year-old male, negative for canonical DICER1 RNase IIIb mutations. Comprehensive genomic profiling was performed using Oxford Nanopore long-read sequencing, followed by integrative bioinformatic and pathway-level analyses.</p><p><strong>Results: </strong>Molecular analysis revealed an alternative oncogenic signature characterized by an EIF1AX p.Lys3_Lys5dup duplication, TERT alterations (promoter C228T and coding p.C42R), and an AGK-BRAF fusion predicted to drive constitutive MAPK/ERK signaling. Functional enrichment analyses highlighted dysregulation of translational initiation, telomere maintenance, and mitogenic pathways, alongside potential immune-escape mechanisms linked to DUX4 activation. Clinically, the tumor exhibited a triphasic morphology, extensive locoregional infiltration, pulmonary metastases, and only transient response to chemotherapy.</p><p><strong>Discussion: </strong>These findings expand the molecular spectrum of thyroblastoma beyond the canonical DICER1-driven paradigm and suggest that DICER1-wildtype cases may represent a distinct biological subgroup. The identification of alterations affecting TERT and MAPK pathways highlights potential therapeutic vulnerabilities and supports the clinical value of comprehensive genomic profiling in ultra-rare thyroid malignancies.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1747919"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835916","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 a multi-center nomogram for the presence of diabetic retinopathy in patients with type 2 diabetes: incorporating homocysteine, glycemic, lipid, and renal markers.","authors":"Liming Wu, Risu Na, Ling Qiu","doi":"10.3389/fendo.2026.1822839","DOIUrl":"https://doi.org/10.3389/fendo.2026.1822839","url":null,"abstract":"<p><strong>Objective: </strong>To develop and validate a nomogram that integrates plasma homocysteine with glycemic, lipid, and renal markers for estimating the probability of prevalent diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>This multi-center retrospective study included 930 patients. A development cohort (n=651; 145 DR events, 22.3% prevalence) was recruited from Shanghai Fengxian District Central Hospital, and an independent validation cohort (n=279; 71 DR events, 25.4% prevalence) was recruited from Shanghai Xuhui District Central Hospital. The primary outcome was the presence of DR based on fundus examination. Candidate clinical variables included demographic, clinical, and laboratory data. After pre-screening for multicollinearity, Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select informative indicators. A multivariable logistic regression model was built, and a nomogram was constructed. Model performance was evaluated by discrimination (area under the curve, AUC), calibration (Brier score, calibration-in-the-large [CITL]), and clinical utility (Decision Curve Analysis, DCA).</p><p><strong>Results: </strong>Eight variables were selected for the final model: Age, T2DM Duration, Systolic Blood Pressure, HbA1c, HDL-C, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and Homocysteine. The nomogram demonstrated favorable discrimination with an AUC of 0.865 in the development cohort and maintained a stable performance with an AUC of 0.842 in the validation cohort. Calibration was adequate in both sets (development Brier score 0.132, CITL 0.02; validation Brier score 0.148, CITL 0.15). DCA showed a positive net benefit for clinical decision-making across a wide range of threshold probabilities (10% to 75%). Subgroup analyses confirmed consistent performance across different patient demographics.</p><p><strong>Conclusion: </strong>A nomogram combining homocysteine with traditional clinical and renal markers shows promising capability in assessing the probability of prevalent DR in T2DM patients. While demonstrating potential applicability for screening prioritization, these retrospective findings require further prospective validation before the tool can be routinely implemented to guide clinical management.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1822839"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835946","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":"Vesicular GABA transport expression in kisspeptin cells may contribute to the preovulatory gonadotropin surge.","authors":"Henrique Rodrigues Vieira, Estela Guidini Ferrufino, Ligia M M de Sousa, Guilherme A Alves, Marina G Martins, Jose Donato, Renata Frazao","doi":"10.3389/fendo.2026.1807596","DOIUrl":"https://doi.org/10.3389/fendo.2026.1807596","url":null,"abstract":"<p><strong>Background: </strong>The neurotransmitter gamma-aminobutyric acid (GABA) plays a vital role in the modulation of reproductive function by controlling gonadotropin-releasing hormone (GnRH) secretion. Most kisspeptin neurons, which are key regulators of GnRH neurons, coexpress GABA and other neuropeptides. However, whether the expression of the vesicular GABA transporter (Vgat) in kisspeptin cells contributes to the reproductive phenotype of mice remains unclear.</p><p><strong>Methods: </strong>Brain slices from female vesicular GABA transporter-Cre/GFP (Vgat-Cre/GFP) mice were used to assess GABAergic coexpression in kisspeptin neurons during diestrus and proestrus. Mice carrying conditional ablation of <i>Slc32a1</i> (referred to as <i>Vgat</i>) in <i>Kiss1</i>-expressing cells (Kiss1-Cre/Vgat <i>^flox/flox</i> mice) were generated to study possible effects on reproduction and metabolism.</p><p><strong>Results: </strong>50-60% of kisspeptin neurons in the anteroventral periventricular and rostral periventricular nuclei are GABAergic. However, the percentage of GABAergic kisspeptin neurons did not differ between proestrus and diestrus stages. Deletion of <i>Vgat</i> in kisspeptin cells was sufficient to downregulate <i>Gnrh1</i> and <i>Kiss1r</i> expression in the rostral periventricular region of female mice. In contrast, <i>Cartpt</i> mRNA expression in the mediobasal hypothalamus was downregulated only in male mice compared with controls. Body composition, puberty onset, and fertility were preserved in both sexes; however, female Kiss1-Cre/Vgat <i>^flox/flox</i> mice exhibited significantly lower serum luteinizing hormone levels at proestrus.</p><p><strong>Discussion: </strong>These findings indicate that <i>Vgat</i> expression in kisspeptin neurons may contribute to LH surge generation but is not essential for the onset of puberty or for the maintenance of fertility in either female or male mice.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1807596"},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835684","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}