Frontiers in Endocrinology最新文献

{"title":"Comparative effects of different exercise modalities and doses on lipid metabolism in patients with type 2 diabetes mellitus: a systematic review with Bayesian dose-response network meta-analysis.","authors":"Jing Liu, Runjie Shi, Wenhui Fu, Ming Zhang","doi":"10.3389/fendo.2026.1947147","DOIUrl":"10.3389/fendo.2026.1947147","url":null,"abstract":"<p><strong>Objective: </strong>This review aimed to determine whether the effects of structured exercise on triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) differed according to exercise modality and weekly training volume in adults with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>Seven electronic databases were searched from inception to 18 December 2025. Randomized controlled trials were eligible when they enrolled adults with T2DM, evaluated a structured exercise intervention, and reported TG or LDL-C outcomes. Comparative effects across exercise categories were then estimated with a Bayesian random-effects network model. Weekly exercise volume was converted to MET-min/week and further examined using model-based dose-response network meta-analysis.</p><p><strong>Results: </strong>Seventy RCTs comprising 5,317 adults with T2DM met the eligibility criteria. The TG analysis was based on 68 trials and 5,216 participants, whereas the LDL-C analysis included 61 trials and 4,473 participants. In the Bayesian network model, all active exercise modalities were associated with greater reductions in TG and LDL-C than the non-exercise control condition. Among the included modalities, high-intensity interval training (HIIT) produced the most favorable estimate for TG reduction (MD = -0.48 mmol/L, 95% CrI: -0.67, -0.30; SUCRA = 92.53%), while combined aerobic and resistance exercise (CE) showed the highest ranking for LDL-C improvement (MD = -0.46 mmol/L, 95% CrI: -0.63, -0.29; SUCRA = 85.45%). Dose-response modeling indicated that the lipid-lowering effects did not increase in a strictly linear manner across weekly exercise volume. The 95% CrIs remained below zero at approximately 1100-1500 MET-min/week for TG and 950-1500 MET-min/week for LDL-C.</p><p><strong>Conclusions: </strong>The lipid response to exercise varied according to both training modality and weekly volume. HIIT generated the most favorable estimate for TG, whereas combined exercise showed the leading estimate for LDL-C. The identified dose intervals may provide quantitative reference points for exercise planning, but they should not be treated as fixed prescriptions because certainty of evidence, physical capacity, adherence, treatment background, and safety differ among patients.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD420261412956, identifier CRD420261412956.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1947147"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237519","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":"Antihyperglycemic and pancreatic tissue-preserving effects of <i>L. sativum</i> oil in streptozotocin-induced diabetic rats: exploratory analysis of PDX-1 and GCK.","authors":"Fatimah A Al-Saeed, Nadiyah M Alabdallah","doi":"10.3389/fendo.2026.1963673","DOIUrl":"10.3389/fendo.2026.1963673","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus constitutes a major global health burden. <i>L. sativum</i> has long been employed in traditional medicine for glycemic management, an effect attributed to its rich phytochemical constituents, including flavonoids, phenolic acids, and glucosinolates. This study investigated the ameliorative effects of <i>L. sativum</i> oil against streptozotocin-induced type 1 diabetes in rats, with particular emphasis on pancreatic and duodenal homeobox 1 (PDX-1) and glucokinase (GCK) gene expression.</p><p><strong>Methods: </strong>A total of 48 young male Wistar rats were randomly divided into four experimental groups (n = 12 per group): a control group (CG), a streptozotocin-induced type 1 diabetic group (SG; 60 mg/kg, single intraperitoneal injection), a diabetic group treated with <i>L. sativum</i> oil group (S+<i>LS</i>G; 250 mg/kg/day, oral gavage), and a healthy group receiving <i>L. sativum</i> oil alone (LSG; 250 mg/kg/day).</p><p><strong>Results: </strong>In this study, the SG exhibited significant hyperglycemia, hypoinsulinemia, and dyslipidemia compared to the CG (P < 0.01). Treatment of diabetic rats with <i>L. sativum</i> oil (S+LSG) markedly attenuated these metabolic abnormalities, lowering blood glucose to 146.33 mg/dL, raised insulin to 15.51 µIU/mL, and improving the lipid profile relative to the SG. Histological analysis indicated severe islet atrophy, extensive cytoplasmic vacuolation, and interstitial fibrosis in the SG group, while the S+LSG group displayed notable architectural improvement and preserved islet integrity. Analysis of serum oxidative stress markers revealed that the SG exhibited significantly reduced (P < 0.01) activities of glutathione (GPx), superoxide dismutase (SOD), and catalase (CAT) compared to the CG. Furthermore, treatment with <i>L. sativum</i> (S+LSG) significantly restored these enzyme activities to GPx, SOD, and CAT. In contrast, serum MDA levels were markedly elevated in the SG relative to the CG, and were partially reduced in the S+LSG. Gene expression analysis revealed significant downregulated in the PDX-1 (0.802-fold) and GCK (0.779-fold) in the SG compared to CG (P < 0.01). Treatment with <i>L. sativum</i> oil in the diabetic rats (S+LSG) resulted in partial restoration (PDX 1: 0.830-fold and GCK: 0.840-fold); however, these changes were not statistically significant relative to SG.</p><p><strong>Conclusion: </strong><i>L. sativum</i> oil may effectively alleviate hyperglycemia, preserve pancreatic tissue architecture, and enhance antioxidant defense mechanisms in streptozotocin-induced diabetic rats.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1963673"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237401","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":"Pembrolizumab-induced fulminant type 1 diabetes mellitus: a case report and literature review.","authors":"Shujun Sun, Liang Su, Xiaojing Ma, Jianxin Dou","doi":"10.3389/fendo.2026.1958726","DOIUrl":"10.3389/fendo.2026.1958726","url":null,"abstract":"<p><p>As pembrolizumab has been widely used in the immunotherapy of various solid tumors such as melanoma and lung cancer, reports of pembrolizumab-related adverse drug events have gradually attracted attention; however, cases of pembrolizumab-induced fulminant type 1 diabetes mellitus (FT1DM) remain rare. This article reports a case of a young male patient with clear cell renal cell carcinoma (ccRCC) and suspected pulmonary metastases, who had a prior history of hypothyroidism and no family history of diabetes. After 22 cycles of pembrolizumab treatment, the patient developed lethargy and marked metabolic acidosis. The patient had markedly elevated blood glucose with an HbA1c of 6.7% and extremely low C-peptide levels. Given the history of pembrolizumab treatment, the patient was diagnosed with immune checkpoint inhibitor-associated FT1DM. His condition improved after fluid resuscitation and insulin therapy, and he was subsequently discharged. The patient continued treatment with the same agent for another three cycles before permanent discontinuation. Given the rarity of pembrolizumab-associated FT1DM, we further reviewed the literature. A literature search identified 32 confirmed cases of pembrolizumab-associated FT1DM, which were included in the analysis. The 32 reported cases mainly involved lung cancer and melanoma, with FT1DM onset ranging from 1 to 24 treatment cycles. GADA-positive patients tended to develop FT1DM earlier. Thyroid dysfunction occurred before or concurrently with FT1DM in 90% of cases. One case of pituitary dysfunction and one case of adrenal dysfunction both occurred after FT1DM onset. These findings suggest that metabolic monitoring should continue throughout pembrolizumab therapy, and that subsequent endocrine dysfunction should be monitored after FT1DM. Pembrolizumab-associated FT1DM requires long-term insulin therapy. Whether to continue or resume pembrolizumab should be decided individually after DKA resolution and glycemic stabilization.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1958726"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237472","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":"Serum miRNA expression profile in responders to acupuncture treatment for diminished ovarian reserve: a study protocol for a nested case-control study.","authors":"Dongxue An, Li Yang, Jiashan Li, Tian Hang, Lingyu Qi, Jiaxi Meng, Chenchen Su, Quanying Zhang, Ge Lu, Binbin Wang, Yigong Fang, Huanfang Xu","doi":"10.3389/fendo.2026.1972018","DOIUrl":"10.3389/fendo.2026.1972018","url":null,"abstract":"<p><strong>Objective: </strong>Diminished ovarian reserve (DOR) leads to subfertility, infertility, and premature menopause, significantly compromising women's reproductive health. Although clinical evidence supports the effectiveness of acupuncture in improving ovarian reserve, treatment responses vary considerably among DOR patients, and the factors associated with favorable outcomes remain unclear. Serum microRNAs may serve as potential biomarkers for distinguishing acupuncture responders, warranting further investigation.</p><p><strong>Design and methods: </strong>This prospective nested case-control study will enroll women with DOR who undergo acupuncture treatment. Treatment response will be evaluated based on changes in anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), serum follicle stimulating hormone (FSH) levels and clinical pregnancy. According to their response, participants demonstrating greater improvement will be assigned to the experimental group (responders), while non-responders will be matched in a 1:1 ratio to form the control group. Serum microRNA profiles from both groups will be analyzed using high-throughput sequencing to identify differentially expressed microRNAs. Candidate microRNAs will subsequently be validated via real-time quantitative PCR (RT-qPCR), and receiver operating characteristic (ROC) curve analysis will be performed to evaluate their predictive value for acupuncture treatment response.</p><p><strong>Discussion: </strong>This is the first clinical study to characterize the serum miRNA expression profiles of DOR patients who benefit from acupuncture. The findings are expected to provide evidence supporting the precise identification of acupuncture-responsive individuals within this patient population.</p><p><strong>Study protocol registration: </strong>https://itmctr.ccebtcm.org.cn/mgt/project/view/-4614215526207679163, identifier ITMCTR2025000004.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1972018"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237413","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":"Size-dependent heterogeneity in the associations of C-TIRADS ultrasound features with malignancy in thyroid nodules.","authors":"Dongming Guo, Yonghua Xu, Xianying Liao, Haiqing Huang, Yuxia Zhai, Haitao Li, Zhihui Lin, Jiajia Wang, Zhe Chen","doi":"10.3389/fendo.2026.1844286","DOIUrl":"10.3389/fendo.2026.1844286","url":null,"abstract":"<p><strong>Aim: </strong>To investigate whether the associations between Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) ultrasound features and malignancy vary according to thyroid nodule size.</p><p><strong>Methods: </strong>This two-center retrospective cohort study included 3726 thyroid nodules, which were categorized according to maximum diameter as ≤1 cm or >1 cm. Extreme gradient boosting models and SHapley Additive exPlanations (SHAP) were used for exploratory visualization of the contributions of individual ultrasound features to malignancy prediction in the overall cohort and the two size subgroups. Multivariable Firth logistic regression was used to estimate the adjusted associations between the C-TIRADS features and malignancy. Single-feature interaction models were constructed to assess whether nodule size modified these associations. The discriminative performance of the original C-TIRADS model and the interaction model was compared using the area under the receiver operating characteristic curve (AUC). Center-adjusted sensitivity analyses were also performed.</p><p><strong>Results: </strong>Vertical orientation and solid composition showed greater contributions to malignancy prediction and stronger associations with malignancy in nodules ≤1 cm, whereas microcalcification and ill-defined/irregular margin or extrathyroidal extension showed stronger associations with malignancy in nodules >1 cm. Significant feature-by-size interactions were identified for vertical orientation, solid composition, microcalcification, and ill-defined/irregular margin or extrathyroidal extension, whereas no significant interactions were observed for markedly hypoechoic or comet-tail artifact. The interaction model showed a modest but statistically significant improvement in discriminative performance compared with the original C-TIRADS model (AUC 0.918 vs. 0.911, <i>P</i> < 0.001). The center-adjusted sensitivity analyses yielded consistent findings.</p><p><strong>Conclusion: </strong>The associations between C-TIRADS ultrasound features and malignancy exhibit significant size-dependent heterogeneity. In nodules ≤1 cm, vertical orientation and solid composition may indicate a substantially higher likelihood of malignancy and therefore warrant particularly careful clinical evaluation, whereas microcalcification and ill-defined/irregular margin or extrathyroidal extension may be more informative for malignancy assessment in nodules >1 cm. Considering nodule size when interpreting individual C-TIRADS features may improve diagnostic discrimination.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1844286"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237353","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":"Liraglutide reduces lipid accumulation in human orbital fibroblasts in Graves' orbitopathy.","authors":"Chih-Wei Shih, Shyang-Rong Shih, Yi-Hsuan Wei, Chia-Hung Lin, Shu-Lang Liao, Ting-An Chou, I Chu, Hou-Jen Chen, Neng-Li Liao, Feng-Chiao Tsai","doi":"10.3389/fendo.2026.1914378","DOIUrl":"10.3389/fendo.2026.1914378","url":null,"abstract":"<p><p>Graves' orbitopathy (GO) is characterized by proliferation and differentiation of orbital fibroblasts. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic disorders and have been reported to modulate cell proliferation and differentiation. The present study aimed to examine the effects of GLP-1RAs on key fibroblast-mediated pathogenic processes relevant to GO using human orbital fibroblasts. Orbital fibroblasts were isolated from patients with GO and non-GO controls. Cells were treated with the GLP-1RAs liraglutide (100 nM) or semaglutide (200 nM). Fibroblast proliferation was assessed by nuclear counting, lipid accumulation was evaluated by Oil Red O staining of oil droplets, and myofibroblastic differentiation was assessed by α-smooth muscle actin (α-SMA) immunostaining. Hyaluronan production was measured by ELISA. <i>GLP1R</i> mRNA expression was examined using reverse transcription quantitative PCR. Among the outcomes assessed, liraglutide significantly reduced lipid accumulation in GO-derived orbital fibroblasts, whereas semaglutide showed a nonsignificant trend in the same direction. Neither liraglutide nor semaglutide significantly altered lipid accumulation in non-GO fibroblasts. Importantly, neither GLP-1RA increased fibroblast proliferation, TGF-β-induced myofibroblastic differentiation, or IL-1β-induced hyaluronan production in GO or non-GO fibroblasts under the tested conditions. <i>GLP1R</i> mRNA was not reliably detected, and the underlying mechanism remains uncertain. Taken together, this <i>in vitro</i> study showed a significant reduction in lipid accumulation following liraglutide treatment in GO-derived orbital fibroblasts, while semaglutide showed a trend in the same direction that did not reach statistical significance. Neither agent enhanced fibroblast proliferation, myofibroblastic differentiation, or hyaluronan production under the tested conditions. These findings suggest a potentially favorable biological profile of liraglutide in GO and warrant further studies to clarify the underlying mechanisms and assess its clinical relevance, particularly in patients with metabolic comorbidities.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1914378"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237443","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":"Predicting cumulative live birth after IVF with growth hormone supplementation: the role of pretreatment duration and machine learning-based models.","authors":"Yufeng Chen, Ziyi Dai, Peiyu Wang, Chang Liu","doi":"10.3389/fendo.2026.1967517","DOIUrl":"10.3389/fendo.2026.1967517","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the association between growth hormone (GH) pretreatment duration and cumulative live birth (CLB), identify key prognostic factors, and develop predictive models using logistic regression (LR) and machine learning (ML) algorithms among women undergoing <i>in vitro</i> fertilization (IVF) with GH supplementation.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of women undergoing IVF/intracytoplasmic sperm injection (ICSI) with GH between February 2015 and June 2023 at a single tertiary center. Five models were developed: LR, random forest (RF), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and support vector machine (SVM). Performance was assessed with cross-validation and bootstrap resampling. AUROC and Brier scores evaluated discrimination and calibration.</p><p><strong>Results: </strong>Among 1,782 women, 763 (42.82%) achieved at least one live birth. Maternal age, anti-Müllerian hormone (AMH), antral follicle count (AFC), the assisted reproductive technology (ART) cycle number, and GH duration were significant predictors. LR performed best (AUROC 0.782; Brier 0.187), showing strong calibration and interpretability. ML models had moderate discrimination but inferior calibration. AMH, AFC, and GH duration were key predictors across all methods.</p><p><strong>Conclusions: </strong>Both logistic regression and machine learning effectively predicted CLB after GH-pretreated IVF, but LR provided favorable discrimination, calibration, and interpretability. GH pretreatment ≥2 months was independently associated with higher odds of cumulative live birth.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1967517"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237469","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 of current HbA1c with concurrent multiorgan screening abnormalities and the incremental value of routine clinical characteristics in type 2 diabetes: a single-center cross-sectional study in Wenzhou, China.","authors":"Chengcheng Ye, Huahua Peng, Xinxin Wang, Yongsheng Wang","doi":"10.3389/fendo.2026.1974690","DOIUrl":"10.3389/fendo.2026.1974690","url":null,"abstract":"<p><strong>Background: </strong>Glycated hemoglobin A1c (HbA1c) is central to glycemic management but mainly reflects recent average glycemia rather than long-term cumulative exposure or existing organ abnormalities. We assessed whether adding age, sex, diabetes duration, body mass index (BMI), and systolic blood pressure to HbA1c improved the identification of concurrent vascular, renal, and peripheral nerve abnormalities in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>This was a single-center cross-sectional analysis of a prospectively maintained clinical registry at a standardized metabolic disease management center. Adults with T2DM assessed between January 10, 2022, and April 30, 2026, were included, and each patient contributed one standardized visit selected for analysis (the index assessment). The primary outcome was a screening abnormality in at least two of three organ domains: vascular, renal, and peripheral nerve. We used multivariable logistic regression to estimate adjusted cross-sectional associations and 20 repeats of stratified fivefold cross-validation to assess the discrimination and calibration of three prespecified nested models.</p><p><strong>Results: </strong>The analysis included 674 patients with a mean age of 52.6 years, of whom 62.9% were men. Among them, 342 (50.7%) had abnormalities in at least two organ domains. Of the 112 patients with current HbA1c <7.0%, 44 (39.3%) had multiorgan abnormalities. Current HbA1c was not clearly associated with the outcome after adjustment (adjusted odds ratio [OR] per 1-percentage-point increase, 1.04; 95% confidence interval [CI], 0.96-1.13), whereas age, diabetes duration, and systolic blood pressure were independently associated with it. The cross-validated area under the receiver operating characteristic curve (AUC) was 0.523 (95% CI, 0.479-0.568) for HbA1c alone and 0.775 (95% CI, 0.740-0.810) after age, sex, diabetes duration, BMI, and systolic blood pressure were added. The difference in AUC was 0.251 (95% CI, 0.195-0.304).</p><p><strong>Conclusions: </strong>A single current HbA1c measurement had limited discriminatory ability for concurrent clustering of multiorgan screening abnormalities in adults with T2DM. Adding age, sex, diabetes duration, BMI, and systolic blood pressure to HbA1c substantially improved discrimination of this clustering phenotype. Age, diabetes duration, and systolic blood pressure were independently associated with multiorgan abnormalities.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1974690"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237495","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 an interpretable machine learning model for predicting early acute kidney injury and altered consciousness in cardiac surgery patients admitted to the intensive care unit: a retrospective study.","authors":"Shu Yang, Jing Luo, Lianzheng Ma, Dongxiao Huang, Minmin Zhu, Linlin Cai","doi":"10.3389/fendo.2026.1959304","DOIUrl":"10.3389/fendo.2026.1959304","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) and altered consciousness are common and serious complications following cardiac surgery, both associated with increased morbidity and mortality in the intensive care unit (ICU). Early prediction of these complications is essential for timely intervention. We aimed to develop and validate an interpretable machine learning model for predicting early AKI and altered consciousness risk in this population.</p><p><strong>Methods: </strong>We retrospectively extracted data from the MIMIC-IV database. Adult patients who underwent cardiac surgery within 24 h before ICU admission were included. The primary outcome was early AKI defined by KDIGO criteria within 48 h after ICU admission. The secondary outcome was altered consciousness within 24 h after ICU admission, defined as a Glasgow Coma Scale (GCS) score ≤12. A comprehensive set of candidate variables was screened using four feature selection methods (LassoCV, mRMR, mutual information, and <i>F</i>-test) with a voting strategy. Eight machine learning models were developed and compared. SHapley Additive exPlanations (SHAP) values were used to interpret the best-performing model. External validation was performed using data from cardiac surgery patients at Wuxi No.2 People's Hospital between 1 January 2020 and 31 December 2025.</p><p><strong>Result: </strong>A total of 5,288 patients were included, with an AKI incidence of 76.2% (4,031/5,288) and an altered consciousness incidence of 22.8% (1,206/5,288). For the primary outcome of AKI, the XGBoost model achieved a training AUC of 0.787 (95% CI: 0.770-0.804) and an internal test AUC of 0.659 (95% CI: 0.629-0.688). For the secondary outcome of altered consciousness, the XGBoost model achieved an internal test AUC of 0.951 (95% CI: 0.936-0.963). Calibration curve and decision curve analysis confirmed good calibration and clinical utility for both models. SHAP analysis identified SpO₂, age, APSIII score, creatinine, and white blood cell count as the top 5 most important predictors for AKI. External validation was performed in an independent cohort of 395 cardiac surgery ICU patients from Wuxi No.2 People's Hospital, in whom the incidence of AKI and altered consciousness was 28.1% and 67.3%, respectively. The models retained acceptable discrimination in this external cohort (AKI: AUC 0.764, 95% CI: 0.711-0.818; altered consciousness: AUC 0.679, 95% CI: 0.615-0.737).</p><p><strong>Conclusion: </strong>We developed interpretable XGBoost-based prediction models for both early AKI and altered consciousness risk in cardiac surgery patients admitted to the ICU. The models exhibited excellent discrimination, calibration, and clinical utility, which may facilitate early identification of high-risk patients and guide personalized interventions.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1959304"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237422","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 of clonal hematopoiesis of indeterminate potential with cardiovascular mortality in cardiovascular-kidney-metabolic syndrome: a large prospective cohort study.","authors":"Zehao Zhao, Changsheng Ma, Libo Zhao, Xiliang Zhao, Quan Li, Yaodong Ding, Yang Zhang, Li Lin, Wenjie Wang, Jiayi Han, Yingxuan Bai, Tianyi Wang, Yong Zeng","doi":"10.3389/fendo.2026.1910361","DOIUrl":"10.3389/fendo.2026.1910361","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular-kidney-metabolic (CKM) syndrome represents a progressive pathophysiological continuum. While clonal hematopoiesis of indeterminate potential (CHIP) is known to increase the risk of CKM disease onset and adverse prognoses, its overall and stage-specific impacts on cardiovascular mortality within the CKM framework, alongside the circulating proteomic mechanisms mediating this excess risk, remain largely unknown.</p><p><strong>Methods: </strong>Participants from the UK Biobank with available CHIP data across the CKM syndrome continuum were included. The primary outcome was cardiovascular mortality. Kaplan-Meier curves and multivariable Cox proportional hazards models were utilized to evaluate the incremental risk conferred by CHIP. Sensitivity and subgroup analyses were conducted to ascertain result robustness. Within UKB Pharma Proteomics Project (UKB-PPP), circulating proteins jointly associated with CHIP and cardiovascular mortality were identified, followed by functional enrichment and mediation analyses to elucidate the underlying mechanisms.</p><p><strong>Results: </strong>During a median follow-up of 16.5 years, 6,515 cardiovascular deaths were recorded among 288,384 participants across CKM stages 1-4. Across all varying CKM stages, individuals harboring Large CHIP exhibited a significantly higher risk of cardiovascular mortality compared to the non-CHIP group (all log-rank P < 0.05). Following multivariable adjustment, Large CHIP emerged as an independent risk factor for cardiovascular mortality (hazard ratio, 1.24; 95% confidence interval, 1.09-1.40), with subgroup analyses confirming consistent effects regardless of CKM stage or established cardiometabolic and renal diseases. Proteomic profiling, corroborated by UKB-PPP, revealed that the mechanisms driving this excess risk predominantly involve immune-inflammatory dysregulation and tissue structural remodeling. This pathway was highlighted by critical downstream mediators, including the structural component DSC2 (mediating 34.3% of the risk) and key immune-regulatory receptors such as VSIG4 (33.1%) and CD300C (29.2%).</p><p><strong>Conclusions: </strong>CHIP is an independent risk factor for cardiovascular mortality across all stages of CKM syndrome. Mechanistically, CHIP exacerbates this adverse outcome primarily by driving systemic inflammation, immune dysregulation, and aberrant tissue remodeling.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1910361"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13684865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237483","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}