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Dapagliflozin lowers blood pressure via regulating the sympathetic neural activity in the paraventricular nucleus of hypothalamus in normal mice. 达格列净通过调节正常小鼠下丘脑室旁核交感神经活动降低血压。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-23 eCollection Date: 2026-01-01 DOI: 10.3389/fendo.2026.1689167
Meiyuan Dong, Zhimin Xu, Ligang Zhou, Song Wen

Background and aims: The risk of heart failure (HF) is significantly higher in patients with type 2 diabetes mellitus (T2DM). Recent studies have shown that an imbalance in the sympathetic nervous system (SNS) is a target for sodium-glucose cotransporter-2 inhibitors (SGLT-2i), which have been proven to reduce the risk of adverse HF outcomes in several clinical trials. However, the specific central mechanisms involved remain unclear. Therefore, our research investigates how dapagliflozin (DAPA) regulates blood pressure through SNS and explores the central neural and endocrinological pathways by which DAPA, an SGLT-2i, influences SNS activity and its impact on the cardiovascular system in the treatment of HF in T2DM.

Material and methods: Twenty-one male C57BL/6 mice aged 8-10 weeks were randomly divided into three groups (n = 7 each): control (CTRL), DAPA, and DAPA-Cyanine 3 (DAPA-Cy3). Blood pressure (BP), heart rate (HR), and blood glucose (BG) were measured after a single dose of treatment. DAPA-Cy3 was designed to assess its ability to cross the blood-brain barrier (BBB). Additionally, histological co-localization analyses of immunoreactivity for c-Fos, neuronal nitric oxide synthase (nNOS), corticotropin-releasing hormone (CRH), and vasopressin (VP) across groups were performed to explore how SGLT-2 inhibitors regulate the central sympathetic nervous system (SNS).

Results: 1) DAPA significantly reduced both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in mice, without notably affecting the heart rate (HR); 2) SGLT-2 was found to be extensively expressed in the central nervous system (CNS), especially in the hypothalamus and brainstem; 3) DAPA-Cy3 was able to cross the blood-brain barrier (BBB) and disperse throughout the brain; and 4) DAPA clearly influenced the activity of specific neurons expressing nNOS, CRH, and VP in the hypothalamus.

Conclusion: DAPA, as an SGLT-2 inhibitor, crosses the BBB and binds to the innate SGLT-2 in the hypothalamus and brainstem of mice. This significantly influences the tone of the SNS through indirect regulation by modulating nNOS, CRH, and VP, which are believed to be the upstream regulatory points of SGLT-2 in interacting with the SNS.

背景和目的:2型糖尿病(T2DM)患者发生心力衰竭(HF)的风险显著增高。最近的研究表明,交感神经系统(SNS)失衡是钠-葡萄糖共转运蛋白-2抑制剂(SGLT-2i)的靶点,在一些临床试验中已被证明可以降低心衰不良结局的风险。然而,具体的核心机制仍不清楚。因此,我们的研究探讨了dapagliflozin (DAPA)如何通过SNS调节血压,并探讨了DAPA和SGLT-2i在治疗T2DM心衰过程中影响SNS活性及其对心血管系统的中枢神经和内分泌途径。材料与方法:8 ~ 10周龄雄性C57BL/6小鼠21只,随机分为对照组(CTRL)、DAPA组和DAPA- cyanine 3组(DAPA- cy3),每组7只。单剂量治疗后测量血压(BP)、心率(HR)和血糖(BG)。DAPA-Cy3旨在评估其穿越血脑屏障(BBB)的能力。此外,我们还对各组c-Fos、神经元一氧化氮合酶(nNOS)、促肾上腺皮质激素释放激素(CRH)和加压素(VP)的免疫反应性进行了组织学共定位分析,以探讨SGLT-2抑制剂如何调节中枢交感神经系统(SNS)。结果:1)DAPA可显著降低小鼠收缩压(SBP)和舒张压(DBP),对心率(HR)无显著影响;2) SGLT-2广泛表达于中枢神经系统(CNS),尤其是下丘脑和脑干;3) DAPA-Cy3能够穿过血脑屏障(BBB)并分散到整个大脑;4) DAPA明显影响下丘脑表达nNOS、CRH和VP的特定神经元的活性。结论:DAPA作为SGLT-2抑制剂,通过血脑屏障与小鼠下丘脑和脑干的先天SGLT-2结合。这通过间接调节nNOS、CRH和VP来显著影响SNS的音调,这些被认为是SGLT-2与SNS相互作用的上游调控点。
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引用次数: 0
Potential role of glucagon like peptide 1 in taste receptors. 胰高血糖素样肽1在味觉受体中的潜在作用。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-23 eCollection Date: 2025-01-01 DOI: 10.3389/fendo.2025.1683419
Jose Luis Eduardo Doval-Caballero, Aldo Ferreira-Hermosillo, Genesis Dinora Eugenio-Ponce, Manuel Ramon García-Sáenz, Raúl Ibarra-Salce, Andrea Patricia Tenorio-Rojo, Eduardo Salif Luna-Avila, Paulo César Gete-Palacios, Fernando Pérez-Hernández, Eduardo Rojas-Milán, Luis Angel López-Cruz, César Alejandro Méndez-Hernández

The perception of taste is a complex physiological process that extends far beyond the simple detection of flavor molecules, serving as a critical interface between nutrient sensing, metabolic regulation, and feeding behavior. Emerging evidence reveals that this process is profoundly modulated by endocrine and neuromodulatory systems, creating a sophisticated gut-brain-taste axis that integrates peripheral gustatory signals with central homeostatic and hedonic mechanisms. Hormones such as glucagon-like peptide-1, leptin, ghrelin, and CCK not only regulate appetite and energy balance but also directly influence taste receptor expression and function in the tongue and gastrointestinal tract. Concurrently, neuromodulators like dopamine, serotonin, and norepinephrine fine-tune taste sensitivity at both peripheral (taste buds) and central (reward circuitry) levels, linking chemosensation to motivational states. These interactions are further complicated by metabolic conditions such as obesity and diabetes, where hormonal resistance (e.g., leptin, insulin) and neurotransmitter dysregulation contribute to altered taste preferences and compulsive eating behaviors.

味觉是一个复杂的生理过程,远远超出了对风味分子的简单检测,它是营养感知、代谢调节和摄食行为之间的关键接口。越来越多的证据表明,这一过程受到内分泌和神经调节系统的深刻调节,形成了一个复杂的肠-脑-味觉轴,将外周味觉信号与中枢稳态和享乐机制结合起来。胰高血糖素样肽-1 (glucagon-like peptide-1)、瘦素(leptin)、胃饥饿素(ghrelin)、CCK等激素不仅调节食欲和能量平衡,还直接影响舌头和胃肠道味觉受体的表达和功能。同时,像多巴胺、血清素和去甲肾上腺素这样的神经调节剂在外围(味蕾)和中枢(奖励回路)水平微调味觉敏感性,将化学感觉与动机状态联系起来。肥胖和糖尿病等代谢状况使这些相互作用进一步复杂化,其中激素抵抗(如瘦素、胰岛素)和神经递质失调导致味觉偏好改变和强迫饮食行为。
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引用次数: 0
Editorial: Unraveling immune metabolism: single-cell & spatial transcriptomics illuminate disease dynamics. 编辑:解开免疫代谢:单细胞和空间转录组学阐明疾病动力学。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-23 eCollection Date: 2026-01-01 DOI: 10.3389/fendo.2026.1779505
Yejun Tan, Yafeng Zhu, Zhengtao Liu
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引用次数: 0
The triglyceride-glucose index as an independent associate of severe tubulointerstitial fibrosis and a predictor of renal survival in IgA nephropathy. 甘油三酯-葡萄糖指数作为严重小管间质纤维化的独立关联和IgA肾病肾生存的预测因子。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-23 eCollection Date: 2026-01-01 DOI: 10.3389/fendo.2026.1754033
Guijing Tang, Anni Wang, Xingyu Zhu, Danyan Yu, Hongyu Chen, Xue Jiang, Hong Liu

Background: To investigate the association of the triglyceride-glucose (TyG) index with severe tubular atrophy/interstitial fibrosis (T2 lesions) and renal outcomes in patients with IgA nephropathy (IgAN).

Methods: We retrospectively analyzed 1,791 biopsy-proven IgAN patients between October 2014 and September 2024. Receiver operating characteristic (ROC) curve analysis assessed TyG index performance for predicting T2 lesions. Multivariable logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between the TyG index and T2 lesions. Renal survival was evaluated using Kaplan-Meier analysis and Multivariable Cox regression analysis.

Results: Among 1,791 enrolled IgAN patients, 122 (6.8%) exhibited T2 lesions. The TyG index showed predictive value for T2 lesions (AUC = 0.699, 95%CI: 0.656-0.741), with an optimal cut-off of 8.69 (specificity 64.5%, sensitivity 65.6%). After 1:1 PSM, the high-TyG group (>8.69) had a higher prevalence of severe tubulointerstitial lesions, elevated BMI, serum creatinine, 24-hour urinary protein, lower eGFR (all P < 0.001), and a higher incidence of the primary endpoint (P = 0.020). Multivariable logistic regression confirmed that a high TyG index (TyG>8.69) was independently associated with T2 lesions (OR = 2.365, 95% CI: 1.104-5.062, P = 0.027). RCS analysis indicated a linear dose-response relationship (P for overall<0.001;P for nonlinearity=0.082). Kaplan-Meier analysis showed significantly worse renal survival in the high-TyG group both before and after matching (log-rank=13.59, P<0.001 after matching). Multivariable Cox regression identified a high TyG index as an independent predictor of adverse renal outcomes (HR = 1.561, 95% CI: 1.046-2.330, P = 0.029).

Conclusion: The TyG index is independently associated with severe tubulointerstitial damage and poor renal survival in IgAN, with a value >8.69 effectively identifying high-risk patients for progressive renal injury.

背景:探讨甘油三酯-葡萄糖(TyG)指数与IgA肾病(IgAN)患者严重小管萎缩/间质纤维化(T2病变)和肾脏预后的关系。方法:回顾性分析2014年10月至2024年9月期间1791例活检证实的IgAN患者。受试者工作特征(ROC)曲线分析评估TyG指数预测T2病变的表现。采用多变量logistic回归和限制性三次样条(RCS)模型评估TyG指数与T2病变之间的关系。采用Kaplan-Meier分析和多变量Cox回归分析评估肾脏生存。结果:1791例IgAN患者中,122例(6.8%)出现T2病变。TyG指数对T2病变具有预测价值(AUC = 0.699, 95%CI: 0.656-0.741),最佳临界值为8.69(特异性64.5%,敏感性65.6%)。1:1 PSM后,高tyg组(bbb8.69)有更高的严重管间质病变患病率,BMI、血清肌酐、24小时尿蛋白升高,eGFR降低(均P < 0.001),主要终点发生率更高(P = 0.020)。多变量logistic回归证实高TyG指数(TyG>8.69)与T2病变独立相关(OR = 2.365, 95% CI: 1.104 ~ 5.062, P = 0.027)。结论:IgAN患者TyG指数与肾小管间质严重损害和肾生存差独立相关,其值>8.69可有效识别进行性肾损伤高危患者。
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引用次数: 0
Low HDL cholesterol is associated with elevated TNFR1 and TNFR2 levels in early diabetic kidney disease. 在早期糖尿病肾病中,低HDL胆固醇与TNFR1和TNFR2水平升高相关。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-23 eCollection Date: 2026-01-01 DOI: 10.3389/fendo.2026.1716843
Jianfang Su, Jing Su, Wei Wang, Jie Pan, Xianhui Zhang

Background: Early diabetic kidney disease (DKD) remains difficult to diagnose accurately since microalbuminuria lacks sensitivity and specificity. Tumor necrosis factor receptors (TNFRs), especially TNFR1 and TNFR2, have emerged as potential markers of renal inflammation and injury. Dyslipidemia, particularly reduced high-density lipoprotein cholesterol (HDL), is associated with the inflammatory milieu in type 2 diabetes mellitus (T2DM).

Objective: To investigate the association of serum TNFR1 and TNFR2 with early renal injury in T2DM and to determine the impact of HDL on TNFRs levels.

Methods: A cross-sectional study was conducted in 258 T2DM patients (135 with normoalbuminuria, 123 with microalbuminuria) and 100 age- and sex-matched healthy controls. Serum TNFR1, TNFR2, lipid profile, fasting blood glucose (FBG), and estimated glomerular filtration rate (eGFR) were measured. Group differences were analyzed, and correlation and multivariable regression analyses were performed to identify determinants of TNFR levels.

Results: Both TNFR1 and TNFR2 were significantly higher in patients with microalbuminuria compared with healthy controls (P < 0.001). TNFR1 levels increased progressively from healthy controls to normoalbuminuric and microalbuminuric groups, showing the strongest associations with UACR, eGFR, diabetes duration, and HDL. In multivariable regression, HDL emerged as the most significant negative predictor of both TNFR1 and TNFR2, independent of glycemic measures and other metabolic factors. Age was also independently associated with higher TNFR concentrations.

Conclusion: Serum TNFR1 and TNFR2 are a sensitive biomarker for early renal injury in T2DM. Importantly, low HDL is independently associated with elevated TNFR1 levels, suggesting that lipid metabolism, beyond glucose control, plays a critical role in DKD progression. Monitoring HDL levels and targeting dyslipidemia may aid in the early prevention and intervention of DKD.

背景:由于微量白蛋白尿缺乏敏感性和特异性,早期糖尿病肾病(DKD)仍然难以准确诊断。肿瘤坏死因子受体(TNFRs),尤其是TNFR1和TNFR2,已经成为肾脏炎症和损伤的潜在标志物。血脂异常,特别是高密度脂蛋白胆固醇(HDL)的降低,与2型糖尿病(T2DM)的炎症环境有关。目的:探讨血清TNFR1和TNFR2与T2DM早期肾损伤的关系,并探讨HDL对TNFR1水平的影响。方法:对258例T2DM患者(正常蛋白尿135例,微量蛋白尿123例)和100例年龄和性别匹配的健康对照进行横断面研究。测定血清TNFR1、TNFR2、血脂、空腹血糖(FBG)和肾小球滤过率(eGFR)。分析组间差异,并进行相关和多变量回归分析,以确定TNFR水平的决定因素。结果:微量白蛋白尿患者的TNFR1和TNFR2均显著高于健康对照组(P < 0.001)。从健康对照组到正常蛋白尿组和微量蛋白尿组,TNFR1水平逐渐升高,显示出与UACR、eGFR、糖尿病病程和HDL的最强关联。在多变量回归中,HDL成为TNFR1和TNFR2最显著的负预测因子,独立于血糖测量和其他代谢因素。年龄也与较高的TNFR浓度独立相关。结论:血清TNFR1和TNFR2是T2DM早期肾损伤的敏感生物标志物。重要的是,低HDL与TNFR1水平升高独立相关,这表明脂质代谢在血糖控制之外,在DKD进展中起关键作用。监测HDL水平和针对血脂异常可能有助于早期预防和干预DKD。
{"title":"Low HDL cholesterol is associated with elevated TNFR1 and TNFR2 levels in early diabetic kidney disease.","authors":"Jianfang Su, Jing Su, Wei Wang, Jie Pan, Xianhui Zhang","doi":"10.3389/fendo.2026.1716843","DOIUrl":"10.3389/fendo.2026.1716843","url":null,"abstract":"<p><strong>Background: </strong>Early diabetic kidney disease (DKD) remains difficult to diagnose accurately since microalbuminuria lacks sensitivity and specificity. Tumor necrosis factor receptors (TNFRs), especially TNFR1 and TNFR2, have emerged as potential markers of renal inflammation and injury. Dyslipidemia, particularly reduced high-density lipoprotein cholesterol (HDL), is associated with the inflammatory milieu in type 2 diabetes mellitus (T2DM).</p><p><strong>Objective: </strong>To investigate the association of serum TNFR1 and TNFR2 with early renal injury in T2DM and to determine the impact of HDL on TNFRs levels.</p><p><strong>Methods: </strong>A cross-sectional study was conducted in 258 T2DM patients (135 with normoalbuminuria, 123 with microalbuminuria) and 100 age- and sex-matched healthy controls. Serum TNFR1, TNFR2, lipid profile, fasting blood glucose (FBG), and estimated glomerular filtration rate (eGFR) were measured. Group differences were analyzed, and correlation and multivariable regression analyses were performed to identify determinants of TNFR levels.</p><p><strong>Results: </strong>Both TNFR1 and TNFR2 were significantly higher in patients with microalbuminuria compared with healthy controls (<i>P</i> < 0.001). TNFR1 levels increased progressively from healthy controls to normoalbuminuric and microalbuminuric groups, showing the strongest associations with UACR, eGFR, diabetes duration, and HDL. In multivariable regression, HDL emerged as the most significant negative predictor of both TNFR1 and TNFR2, independent of glycemic measures and other metabolic factors. Age was also independently associated with higher TNFR concentrations.</p><p><strong>Conclusion: </strong>Serum TNFR1 and TNFR2 are a sensitive biomarker for early renal injury in T2DM. Importantly, low HDL is independently associated with elevated TNFR1 levels, suggesting that lipid metabolism, beyond glucose control, plays a critical role in DKD progression. Monitoring HDL levels and targeting dyslipidemia may aid in the early prevention and intervention of DKD.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1716843"},"PeriodicalIF":4.6,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12875942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141633","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}
引用次数: 0
Periovulatory neurohormone dynamics reveal an association between secretoneurin and GnRH across the mouse estrous cycle. 排卵期神经激素动力学揭示了分泌神经素和GnRH在小鼠发情周期中的关联。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-23 eCollection Date: 2025-01-01 DOI: 10.3389/fendo.2025.1708570
Chunyu Lu, Di Peng, Kevin B Smith, Chinelo Uju, Suraj Unniappan, Paula Duarte-Guterman, Nafissa Ismail, Vance L Trudeau

Introduction: Surge release of luteinizing hormone (LH) from the pituitary is essential for fertility, as it triggers ovulation. Secretoneurin (SN), a conserved peptide derived from secretogranin-2, stimulates LH release, but its relationship to periovulatory changes in classical reproductive hormones remains unclear.

Methods: We measured fluctuations of two reproductive steroids and three peptides in the hypothalamus, pituitary, and ovary of female mice during the periovulatory period using a novel nano LC-MS/MS protocol. Immunohistochemistry for SN and GnRH was performed on brain samples. GT1-7 GnRH neuronal cells were exposed to various doses of SN and processed for PCR determination of Gnrh1 mRNA levels. A subset of these samples was subjected to RNA sequencing for pathway analysis.

Results: P4, E2, AVP, GnRH1, and SN varied across the cycle, whereas OXT was relatively stable. Ovarian P4 was highest at proestrus, while E2 peaked at diestrus. Hypothalamic P4 was elevated at diestrus, whereas pituitary P4 remained low and variable. AVP peaked at proestrus in both the hypothalamus and pituitary. SN levels were highest in the hypothalamus and pituitary at proestrus. GnRH1 increased in the hypothalamus and pituitary at proestrus but was undetectable in ovary. Regression analysis revealed a moderate positive association between hypothalamic SN and GnRH1. SN-immunoreactive fibers were found near GnRH neurons in the median and medial preoptic areas. In vitro, SN increased Gnrh1 mRNA in GT1-7 cells in a time- and dose-dependent manner. RNA sequencing after 6 h SN treatment highlights key signaling cascades including MAPK, transcriptional regulation, and calcium signaling pathways. Six upregulated TFs predicted to bind to the mouse Gnrh1 promoter were also linked to significant enrichment in ribosome-related processes, protein synthesis, and cellular component organization pathways.

Conclusion: These findings identify a periovulatory association between SN and GnRH1 and provide a foundation for targeted studies needed to test causality in the mammalian reproductive neuroendocrine network.

从垂体中释放的促黄体生成素(LH)对生育是必不可少的,因为它触发排卵。分泌神经蛋白(Secretoneurin, SN)是一种由分泌颗粒蛋白-2衍生的保守肽,可刺激LH释放,但其与传统生殖激素的排卵期变化的关系尚不清楚。方法:采用一种新型纳米LC-MS/MS方法,测定了雌性小鼠下丘脑、垂体和卵巢中两种生殖激素和三种肽在排卵期的波动。对脑标本进行SN和GnRH免疫组化。将GT1-7 GnRH神经元细胞暴露于不同剂量的SN中,用PCR方法检测Gnrh1 mRNA水平。这些样本的一个子集进行RNA测序进行途径分析。结果:P4、E2、AVP、GnRH1和SN在整个周期内变化,而OXT相对稳定。卵巢P4在发情前期最高,E2在发情后期最高。下丘脑P4在衰竭时升高,而垂体P4保持低水平和可变。AVP在发情期下丘脑和垂体均达到峰值。SN在发情期下丘脑和垂体中含量最高。GnRH1在发情期下丘脑和垂体中升高,而在卵巢中未检测到。回归分析显示下丘脑SN与GnRH1呈正相关。在中间和内侧视前区GnRH神经元附近发现sn免疫反应纤维。在体外,SN对GT1-7细胞Gnrh1 mRNA的表达呈时间和剂量依赖性。SN处理6小时后的RNA测序突出了包括MAPK、转录调控和钙信号通路在内的关键信号级联。预测与小鼠Gnrh1启动子结合的6个上调tf也与核糖体相关过程、蛋白质合成和细胞组分组织途径的显著富集有关。结论:本研究发现SN与GnRH1之间存在排卵期相关性,为进一步研究哺乳动物生殖神经内分泌网络的因果关系奠定了基础。
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引用次数: 0
Total cholesterol, high-density lipoprotein, and glucose (CHG) index and diabetic retinopathy in middle-aged and elderly Chinese adults with diabetes: a cross-sectional study. 中国中老年糖尿病患者的总胆固醇、高密度脂蛋白和葡萄糖(CHG)指数与糖尿病视网膜病变的横断面研究
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-22 eCollection Date: 2025-01-01 DOI: 10.3389/fendo.2025.1682279
Yingpin Cao, Yuqin He, Jiaqian Zhu, Yong Han

Objective: Evidence regarding the association between the total cholesterol, high-density lipoprotein, and glucose (CHG) index and diabetic retinopathy (DR) remains limited. This study aimed to explore the relationship between CHG and the prevalence of DR and evaluate its discriminative ability for DR.

Methods: This cross-sectional study analyzed data from 1,909 individuals with diabetes mellitus (DM), aged 45-90 years, whose information was collected between August and December 2011. To determine the association between CHG and DR, binary logistic regression models were employed. The discriminative ability of CHG for DR was assessed using receiver operating characteristic (ROC) analysis. Additionally, a series of sensitivity analyses and subgroup analyses were conducted.

Results: After multivariable adjustment, binary logistic regression analysis showed that each 0.1-unit increase in CHG was associated with a 14.2% higher prevalence of DR (OR = 1.142; 95% CI: 1.081-1.206). Additionally, CHG demonstrated the highest area under the curve (AUC) for discriminating DR (0.6673, 95% CI: 0.6287-0.7059), outperforming triglyceride-glucose body mass index (TyG-BMI, 0.4958, 95% CI: 0.4548-0.5368), triglyceride to high-density lipoprotein cholesterol ratio (THR, 0.5118, 95% CI: 0.4704-0.5532), and triglyceride-glucose index (TyG, 0.5720, 95% CI: 0.5314-0.6125). Sensitivity analysis and subgroup analyses further confirmed the reliability of these results.

Conclusion: This study demonstrates that elevated CHG is independently and positively associated with DR in adults with DM. Moreover, CHG shows a certain discriminative ability for DR and may have potential utility in DR assessment.

目的:关于总胆固醇、高密度脂蛋白和葡萄糖(CHG)指数与糖尿病视网膜病变(DR)之间关系的证据仍然有限。本研究旨在探讨CHG与DR患病率之间的关系,并评价CHG对DR的判别能力。方法:采用横断面研究方法,对2011年8 - 12月收集的1,909例年龄在45-90岁的糖尿病(DM)患者的资料进行分析。为了确定CHG与DR之间的关系,采用了二元逻辑回归模型。采用受试者工作特征(ROC)分析评估CHG对DR的判别能力。此外,还进行了一系列敏感性分析和亚组分析。结果:经多变量调整后,二元logistic回归分析显示,CHG每增加0.1个单位,DR患病率增加14.2% (OR = 1.142; 95% CI: 1.081 ~ 1.206)。此外,CHG在区分DR方面显示出最高的曲线下面积(AUC) (0.6673, 95% CI: 0.6287-0.7059),优于甘油三酯-葡萄糖体重指数(TyG- bmi, 0.4958, 95% CI: 0.4548-0.5368),甘油三酯与高密度脂蛋白胆固醇比值(THR, 0.5118, 95% CI: 0.4704-0.5532)和甘油三酯-葡萄糖指数(TyG, 0.5720, 95% CI: 0.5314-0.6125)。敏感性分析和亚组分析进一步证实了这些结果的可靠性。结论:本研究表明CHG升高与成人糖尿病患者DR存在独立且正相关的关系,CHG对DR有一定的判别能力,可能在DR评估中有潜在的应用价值。
{"title":"Total cholesterol, high-density lipoprotein, and glucose (CHG) index and diabetic retinopathy in middle-aged and elderly Chinese adults with diabetes: a cross-sectional study.","authors":"Yingpin Cao, Yuqin He, Jiaqian Zhu, Yong Han","doi":"10.3389/fendo.2025.1682279","DOIUrl":"10.3389/fendo.2025.1682279","url":null,"abstract":"<p><strong>Objective: </strong>Evidence regarding the association between the total cholesterol, high-density lipoprotein, and glucose (CHG) index and diabetic retinopathy (DR) remains limited. This study aimed to explore the relationship between CHG and the prevalence of DR and evaluate its discriminative ability for DR.</p><p><strong>Methods: </strong>This cross-sectional study analyzed data from 1,909 individuals with diabetes mellitus (DM), aged 45-90 years, whose information was collected between August and December 2011. To determine the association between CHG and DR, binary logistic regression models were employed. The discriminative ability of CHG for DR was assessed using receiver operating characteristic (ROC) analysis. Additionally, a series of sensitivity analyses and subgroup analyses were conducted.</p><p><strong>Results: </strong>After multivariable adjustment, binary logistic regression analysis showed that each 0.1-unit increase in CHG was associated with a 14.2% higher prevalence of DR (OR = 1.142; 95% CI: 1.081-1.206). Additionally, CHG demonstrated the highest area under the curve (AUC) for discriminating DR (0.6673, 95% CI: 0.6287-0.7059), outperforming triglyceride-glucose body mass index (TyG-BMI, 0.4958, 95% CI: 0.4548-0.5368), triglyceride to high-density lipoprotein cholesterol ratio (THR, 0.5118, 95% CI: 0.4704-0.5532), and triglyceride-glucose index (TyG, 0.5720, 95% CI: 0.5314-0.6125). Sensitivity analysis and subgroup analyses further confirmed the reliability of these results.</p><p><strong>Conclusion: </strong>This study demonstrates that elevated CHG is independently and positively associated with DR in adults with DM. Moreover, CHG shows a certain discriminative ability for DR and may have potential utility in DR assessment.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1682279"},"PeriodicalIF":4.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141553","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}
引用次数: 0
Circulating thyroid hormones and metabolites in children with autism spectrum disorder. 自闭症谱系障碍儿童循环甲状腺激素和代谢物。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-22 eCollection Date: 2025-01-01 DOI: 10.3389/fendo.2025.1716586
Michael Hancock, Rui Zhang, Suzanne J Brown, Conchita Boyder, Shelby Mullin, Purdey J Campbell, Scott G Wilson, Ee Mun Lim, Andrew J O Whitehouse, John P Walsh

Context: Thyroid hormones affect neurological development and function, but detailed studies of thyroid hormones and metabolites in autism are lacking.

Objective: To characterize thyroid function and metabolism in autistic children.

Methodology: This cross-sectional study compared 788 autistic children (mean age 7.6 ± 3.9 years, 78% male) with 301 non-autistic children (mean age 7.8 ± 4.0 years, 48% male; comprising 215 (71.4%) non-autistic siblings of participants and 86 (28.6%) unrelated individuals). Plasma TSH, free T4 (FT4) and free T3 (FT3) were measured by automated immunoassay, and total T4, total T3 and thyroid hormone metabolites by customized liquid chromatography-tandem mass spectrometry (LCMS/MS). Regression analyses were adjusted for age and sex.

Results: TSH concentrations were similar in autistic and non-autistic children (median 2.3 vs 2.1 mU/L, P = 0.64). FT4 was significantly lower in autistic children (18.4 vs 18.7 pmol/L, P = 0.0003), as was FT3 (7.0 vs 7.1pmol/L, P<0.0001), with no significant difference in the FT4:FT3 ratio (P = 0.24). Total T4 was lower in autistic children (178 vs 194 nmol/L, P = 0.0026, as was total T3 (2.2 vs 2.4 nmol/L, P = 0.018), with no significant difference in the T4:T3 ratio (P = 0.099). Two metabolites were significantly lower in autistic children: 3,5-T2 (0.010 vs 0.021 nmol/L, P<0.0001) and 3,3'-T2 (0.12 vs 0.16 nmol/L, P<0.0001), whereas T0 levels were higher (1.5 vs 1.1 nmol/L, P = 0.028).

Conclusions: Circulating thyroid hormones and metabolites differ between autistic and non-autistic children, although the observed differences are small. The study demonstrates the utility of LCMS/MS for in-depth characterization of thyroid hormone economy, with potentially wide applications.

背景:甲状腺激素影响神经发育和功能,但缺乏对自闭症中甲状腺激素及其代谢物的详细研究。目的:了解自闭症儿童甲状腺功能和代谢的特点。方法:本横断面研究比较了788名自闭症儿童(平均年龄7.6±3.9岁,78%为男性)和301名非自闭症儿童(平均年龄7.8±4.0岁,48%为男性;包括215名(71.4%)参与者的非自闭症兄弟姐妹和86名(28.6%)非亲属个体)。采用自动免疫分析法测定血浆TSH、游离T4 (FT4)和游离T3 (FT3),采用定制的液相色谱-串联质谱法(LCMS/MS)测定总T4、总T3和甲状腺激素代谢物。根据年龄和性别调整了回归分析。结果:自闭症儿童和非自闭症儿童的TSH浓度相似(中位数2.3 vs 2.1 mU/L, P = 0.64)。自闭症儿童的FT4显著降低(18.4 vs 18.7 pmol/L, P = 0.0003), FT3显著降低(7.0 vs 7.1pmol/L, P)。结论:自闭症儿童和非自闭症儿童的循环甲状腺激素和代谢物存在差异,尽管观察到的差异很小。该研究证明了LCMS/MS在深入表征甲状腺激素经济性方面的实用性,具有潜在的广泛应用前景。
{"title":"Circulating thyroid hormones and metabolites in children with autism spectrum disorder.","authors":"Michael Hancock, Rui Zhang, Suzanne J Brown, Conchita Boyder, Shelby Mullin, Purdey J Campbell, Scott G Wilson, Ee Mun Lim, Andrew J O Whitehouse, John P Walsh","doi":"10.3389/fendo.2025.1716586","DOIUrl":"10.3389/fendo.2025.1716586","url":null,"abstract":"<p><strong>Context: </strong>Thyroid hormones affect neurological development and function, but detailed studies of thyroid hormones and metabolites in autism are lacking.</p><p><strong>Objective: </strong>To characterize thyroid function and metabolism in autistic children.</p><p><strong>Methodology: </strong>This cross-sectional study compared 788 autistic children (mean age 7.6 ± 3.9 years, 78% male) with 301 non-autistic children (mean age 7.8 ± 4.0 years, 48% male; comprising 215 (71.4%) non-autistic siblings of participants and 86 (28.6%) unrelated individuals). Plasma TSH, free T4 (FT4) and free T3 (FT3) were measured by automated immunoassay, and total T4, total T3 and thyroid hormone metabolites by customized liquid chromatography-tandem mass spectrometry (LCMS/MS). Regression analyses were adjusted for age and sex.</p><p><strong>Results: </strong>TSH concentrations were similar in autistic and non-autistic children (median 2.3 vs 2.1 mU/L, P = 0.64). FT4 was significantly lower in autistic children (18.4 vs 18.7 pmol/L, P = 0.0003), as was FT3 (7.0 vs 7.1pmol/L, P<0.0001), with no significant difference in the FT4:FT3 ratio (P = 0.24). Total T4 was lower in autistic children (178 vs 194 nmol/L, P = 0.0026, as was total T3 (2.2 vs 2.4 nmol/L, P = 0.018), with no significant difference in the T4:T3 ratio (P = 0.099). Two metabolites were significantly lower in autistic children: 3,5-T2 (0.010 vs 0.021 nmol/L, P<0.0001) and 3,3'-T2 (0.12 vs 0.16 nmol/L, P<0.0001), whereas T0 levels were higher (1.5 vs 1.1 nmol/L, P = 0.028).</p><p><strong>Conclusions: </strong>Circulating thyroid hormones and metabolites differ between autistic and non-autistic children, although the observed differences are small. The study demonstrates the utility of LCMS/MS for in-depth characterization of thyroid hormone economy, with potentially wide applications.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1716586"},"PeriodicalIF":4.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141430","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}
引用次数: 0
The gut-brain axis mediates precocious puberty induced by environmentally relevant low-dose endocrine-disrupting chemical mixtures. 肠脑轴介导由环境相关的低剂量内分泌干扰化学混合物引起的性早熟。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-22 eCollection Date: 2025-01-01 DOI: 10.3389/fendo.2025.1728811
Hui Wu, Guo Wei, Shuo Huang, Lingyu Wan, Qin Xu, Congfu Huang

Background: The global rise in precocious puberty (PP) is increasingly linked to exposure to endocrine-disrupting chemicals (EDCs). However, the mechanisms by which environmentally relevant, low-dose mixtures of EDCs influence PP remain inadequately explained by direct endocrine disruption.

Objective: This systematic review evaluates a novel hypothesis: that disruption of the gut-brain axis (GBA) serves as a pivotal mechanism in EDC mixture-induced PP.

Methods: We synthesized evidence from 87 studies (45 human, 32 animal, 10 in vitro) following PRISMA 2020 guidelines. An exploratory Random Forest analysis was employed to identify key mediators and estimate the relative contribution of the GBA pathway.

Results: Perinatal exposure to low-dose EDC mixtures consistently induced gut dysbiosis, characterized by reduced microbial diversity (Shannon Δ = -1.8), a 40% decrease in Lactobacillus, and a 1.5-fold increase in Bacteroides. This dysbiosis was linked to impaired production of butyrate (↓50%) and secondary bile acids, increased intestinal permeability (FITC-dextran ↑80%), and systemic inflammation (IL-6 ↑1.8-fold). Fecal microbiota transplantation from PP donors into germ-free mice recapitulated early pubertal onset, supporting a causal role for gut microbiota. Exploratory modeling suggested that mediators within the GBA pathway could be associated with a large share (approximately 68%) of the model-internal variance explanation for PP risk at low experimental doses (≤1 μg/kg/day), indicating its potential prominence over direct endocrine disruption in this analysis. Significant synergistic effects (Synergy Index > 2.3) were observed under mixture exposures.

Conclusion: This review identifies the GBA as a critical and previously underappreciated mechanism for low-dose EDC mixture-induced precocious puberty in a dose-dependent manner. Our findings underscore the need for regulatory paradigms and future research to integrate this pathway when assessing the risks of complex, real-world chemical mixtures.

背景:全球性早熟(PP)的增加越来越多地与暴露于内分泌干扰化学物质(EDCs)有关。然而,与环境相关的低剂量EDCs混合物影响PP的机制仍然无法通过直接内分泌干扰来充分解释。目的:本系统综述评估了一个新的假设:肠脑轴(GBA)的破坏是EDC混合物诱导的pp的关键机制。方法:我们根据PRISMA 2020指南合成了87项研究(45项人,32项动物,10项体外)的证据。采用探索性随机森林分析来确定关键中介并估计大湾区通路的相对贡献。结果:围产期暴露于低剂量的EDC混合物持续诱导肠道生态失调,其特征是微生物多样性减少(Shannon Δ = -1.8),乳酸菌减少40%,拟杆菌增加1.5倍。这种生态失调与丁酸酯(50%)和次级胆汁酸的生成受损、肠通透性增加(fitc -葡聚糖↑80%)和全身炎症(IL-6↑1.8倍)有关。将PP供体的粪便微生物群移植到无菌小鼠中,再现了早期青春期,支持肠道微生物群的因果作用。探索性建模表明,在低实验剂量(≤1 μg/kg/天)下,GBA通路中的介质可能与PP风险的模型内部方差解释的很大一部分(约68%)相关,表明其在本分析中比直接内分泌干扰更重要。在混合暴露下观察到显著的协同效应(协同指数> 2.3)。结论:本综述确定GBA是低剂量EDC混合物诱导性早熟的一个关键机制,并且以剂量依赖的方式被低估。我们的研究结果强调了在评估复杂的、现实世界的化学混合物的风险时,需要监管范式和未来的研究来整合这一途径。
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引用次数: 0
Association between sleep apnea-specific novel hypoxic metrics and disturbances in glucose and lipid metabolism. 睡眠呼吸暂停特异性新型低氧指标与糖脂代谢紊乱之间的关系。
IF 4.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-22 eCollection Date: 2025-01-01 DOI: 10.3389/fendo.2025.1691429
Yujiao Zhang, Jiaqi Cai, Meirong Liu, Yan Wang, Haiyan Zhao, Jing Zhang

Objective: Obstructive sleep apnea (OSA) has been linked to disturbances in glucose and lipid metabolism. The independent association between sleep apnea-specific novel hypoxic metrics and metabolic dysregulation in OSA, however, remains unclear.

Methods: Anthropometric and polysomnographic data were obtained from OSA patients treated. Novel hypoxic indices-percentage of sleep time with the duration of respiratory events causing desaturation (pRED_3p) and sleep breathing impairment index (SBII)-were derived from the SpO2 channel. Biochemical parameters were simultaneously assessed. Multiple linear regression models were applied to examine independent associations of pRED_3p, SBII, and apnea-hypopnea index (AHI) with glucose and lipid profiles. Logistic regression was further performed to estimate odds ratios (ORs) for abnormal glucose and lipid parameters across quartiles of pRED_3p, SBII, and AHI.

Results: After controlling for confounding variables, pRED_3p demonstrated significant associations with fasting blood glucose (FBG) (β=0.122), fasting insulin (FIN) (β=0.410), HOMA-IR (β=0.325), total cholesterol (TC) (β=0.309), triglycerides (TG) (β=0.173), low-density lipoprotein cholesterol (LDL-C) (β=0.260), TC/HDL-C (β=0.182), TG/HDL-C (β=0.121), LDL-C/HDL-C (β=0.195), AI (β=0.182), LCI (β=0.663), visceral adiposity index (VAI) (β=0.115), and lipid accumulation product (LAP) (β=0.139). SBII was independently related to FBG (β=0.079), FIN (β=0.240), HOMA-IR (β=0.191), TC (β=0.179), TG (β=0.115), LDL-C (β=0.139), LDL-C/HDL-C (β=0.081), LCI (β=0.093), and LAP (β=0.098), all with p<0.05. In quartile-based comparisons, higher pRED_3p categories corresponded to progressively increased ORs for elevated FBG (2.372, 4.054, and 4.131), hyperinsulinemia (5.789, 22.644, and 26.188), high HOMA-IR (6.655, 36.637, and 43.807), hypercholesterolemia (2.751, 7.109, and 9.607), hypertriglyceridemia (1.976, 4.248, and 4.412), and elevated LDL-C (3.593, 8.050, and 12.048). Similarly, higher SBII quartiles were associated with increased ORs for elevated FBG (1.863, 3.819, and 3.874), hyperinsulinemia (5.002, 25.085, and 25.942), high HOMA-IR (5.879, 35.603, and 51.799), hypercholesterolemia (3.074, 7.297, and 8.867), hypertriglyceridemia (1.963, 4.101, and 4.757), and elevated LDL-C (3.627, 7.684, and 11.515). All linear trends were positive (p<0.001).

Conclusion: pRED_3p and SBII were associated not only with established glucose and lipid metabolism parameters-including elevated FBG, FIN, HOMA-IR, hypercholesterolemia, hypertriglyceridemia, and elevated LDL-C-but also with composite lipid indices, exhibiting consistent linear trends. Greater OSA severity corresponded to more marked disturbances in glucose and lipid metabolism. These novel hypoxic metrics may serve as predictive indicators for metabolic dysregulation in OSA.

目的:阻塞性睡眠呼吸暂停(OSA)与糖脂代谢紊乱有关。然而,睡眠呼吸暂停特异性新型低氧指标与OSA代谢失调之间的独立关联尚不清楚。方法:对接受治疗的OSA患者进行人体测量和多导睡眠图分析。新的缺氧指标-睡眠时间与引起去饱和的呼吸事件持续时间的百分比(pRED_3p)和睡眠呼吸障碍指数(SBII)-从SpO2通道导出。同时评估生化参数。应用多元线性回归模型检验pRED_3p、SBII和呼吸暂停低通气指数(AHI)与葡萄糖和脂质谱的独立关联。进一步进行Logistic回归来估计pRED_3p、SBII和AHI四分位数中异常葡萄糖和脂质参数的比值比(ORs)。结果:在控制混杂变量后,pRED_3p与空腹血糖(FBG) (β=0.122)、空腹胰岛素(FIN) (β=0.410)、HOMA-IR (β=0.325)、总胆固醇(TC) (β=0.309)、甘油三酯(TG) (β=0.173)、低密度脂蛋白胆固醇(LDL-C) (β=0.260)、TC/HDL-C (β=0.182)、TG/HDL-C (β=0.121)、LDL-C/HDL-C (β=0.195)、AI (β=0.182)、LCI (β=0.663)、内脏脂肪指数(VAI) (β=0.115)、脂质积累产物(LAP) (β=0.139)有显著相关性。教室是独立与光纤光栅(β= 0.079),鳍(β= 0.240),HOMA-IR(β= 0.191),TC(β= 0.179),TG(β= 0.115),低密度脂蛋白(β= 0.139),低密度脂蛋白胆固醇/高密度脂蛋白胆固醇(β= 0.081),LCI(β= 0.093),和圈(β= 0.098),p0.05。在基于四分位数的比较中,较高的pRED_3p类别对应于FBG升高(2.372、4.054和4.131)、高胰岛素血症(5.789、22.644和26.188)、高HOMA-IR(6.655、36.637和43.807)、高胆固醇血症(2.751、7.109和9.607)、高甘油三酯血症(1.976、4.248和4.412)和LDL-C升高(3.593、8.050和12.048)的or逐渐增加。同样,较高的SBII四分位数与FBG升高(1.863、3.819和3.874)、高胰岛素血症(5.002、25.085和25.942)、高HOMA-IR(5.879、35.603和51.799)、高胆固醇血症(3.074、7.297和8.867)、高甘油三酯血症(1.963、4.101和4.757)和LDL-C升高(3.627、7.684和11.515)的or升高相关。所有线性趋势均为正(p0.001)。结论:pRED_3p和SBII不仅与既定的糖脂代谢参数(包括FBG、FIN、HOMA-IR、高胆固醇血症、高甘油三酯血症和ldl - c升高)相关,而且与复合脂质指标相关,呈一致的线性趋势。OSA严重程度越高,糖脂代谢紊乱越明显。这些新的缺氧指标可以作为OSA代谢失调的预测指标。
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