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Could the heparanase/TGF-β axis modulation be considered for the SGLT2 inhibitors cardioprotection in obesity? A hypothesis-generating report 肝素酶/TGF-β轴调节是否可以被认为是SGLT2抑制剂对肥胖的心脏保护作用?一份假设生成报告。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-25 DOI: 10.1007/s00592-025-02591-3
Angelo Di Vincenzo, Marika Crescenzi, Marnie Granzotto, Federico Capone, Fausto Cortese, Paola Fioretto, Roberto Vettor, Marco Rossato
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引用次数: 0
Investigating the role of IGF-1 in diabetic gastroparesis: a preliminary review 研究IGF-1在糖尿病性胃轻瘫中的作用:初步综述。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-24 DOI: 10.1007/s00592-025-02578-0
Yifan Lu, Wei Wei, Hao Chen, Yixuan Xie, Jie Tian, Ziming Zhao, Qibiao Wu, Xiqiao Zhou

Diabetic gastroparesis is characterized by delayed gastric emptying due to diabetes mellitus, affecting up to 50% of patients with type 1 and type 2 diabetes who have poor glycemic control, significantly impairing their quality of life. IGF-1 presents significant potential as a therapeutic target for DGP due to its neuroprotective effects and its role in inhibiting smooth muscle cell apoptosis. By promoting the survival and regeneration of interstitial cells of Cajal and reducing inflammation, IGF-1 could enhance gastrointestinal regulation, thereby improving gastric motility and alleviating DGP symptoms. Although IGF-1 has not yet been utilized as a targeted therapy for DGP, its ability to modulate key signaling pathways, such as SCF/C-Kit, PI3K/AKT, and ERK/MAPK, suggests promising therapeutic avenues. Future research should focus on investigating these mechanisms to determine IGF-1’s precise role in DGP pathophysiology and explore its clinical applications.

Graphical Abstract

糖尿病性胃轻瘫以糖尿病引起的胃排空延迟为特征,影响高达50%血糖控制不良的1型和2型糖尿病患者,显著影响其生活质量。由于其神经保护作用和抑制平滑肌细胞凋亡的作用,IGF-1作为DGP的治疗靶点具有很大的潜力。IGF-1通过促进Cajal间质细胞的存活和再生,减轻炎症,增强胃肠调节,从而改善胃动力,缓解DGP症状。虽然IGF-1尚未被用作DGP的靶向治疗,但其调节关键信号通路的能力,如SCF/C-Kit, PI3K/AKT和ERK/MAPK,表明了有希望的治疗途径。未来的研究应重点研究这些机制,以确定IGF-1在DGP病理生理中的确切作用,并探索其临床应用。
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引用次数: 0
Diagnostic performance of PAPP-A and β-hCG in early detection of gestational diabetes mellitus: a meta-analysis. pap -a和β-hCG在妊娠期糖尿病早期检测中的诊断价值:荟萃分析。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-24 DOI: 10.1007/s00592-025-02597-x
Maryam Rahimi, Ladan Haghighi, Mostafa Majidnia, Babak Ghadirzadeh, Yousef Moradi

Background: Gestational diabetes mellitus (GDM) is a common metabolic disorder that creates considerable risks regarding both maternal and fetal health. Conventional screening approaches for GDM which are typically performed in the late second trimester; frequently miss an important window for early intervention.

Methods: This meta-analysis seeks to evaluate the diagnostic accuracy of first-trimester maternal serum biomarkers, particularly pregnancy-associated plasma protein-A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG), in the prediction of GDM. This systematic review of observational studies was conducted to assess PAPP-A and/or β-hCG levels during the first trimester, examining their correlation with the subsequent diagnosis of GDM. This meta-analysis collected data from numerous studies to evaluate sensitivity, specificity, likelihood ratios and diagnostic odds ratios; alongside with developing summary receiver operating characteristic (sROC) curves.

Results: This diagnostic meta-analysis assessed 23 studies encompassing first-trimester PAPP-A and β-hCG measurements with regards to early prediction of GDM. The overall pooled sensitivity and specificity were found to be 63% (95% CI: 53-73%) and 70% (95% CI: 61-78%), alongside an AUC of 0.72 (95% CI: 0.68-0.76). Substantial heterogeneity was observed regarding both sensitivity and specificity (I² >95%). Unaccompanied PAPP-A showed a sensitivity of 67% (95% CI: 55-77%) and specificity of 66% (95% CI: 54-76%) with AUC of 0.71, while β-hCG alone exhibited low sensitivity of 29% (95% CI: 7-69%) despite a high specificity of 87% (95% CI: 64-96%) with its AUC found to be 0.71. Fagan's analysis revealed modest clinical impact; which was found to be raising post-test probability from 20% to ~ 39% after a positive result. Deek's tests suggested no major publication bias (p = 0.45 for overall, 0.41 for PAPP-A, 0.08 for β-hCG). Subgroup analyses revealed higher sensitivity levels in studies utilizing ADA criteria and in studies with smaller samples, while those with cohort designs generated more conservative estimates upon comparison with their case-control counterparts.

Conclusion: First-trimester PAPP-A and β-hCG are found to express modest diagnostic accuracy and therefore are best considered as adjuncts to early risk stratification regarding GDM. PAPP-A, as stand-alone, provides balanced though moderate levels of sensitivity and specificity, whereas β-hCG shows high specificity levels but very low sensitivity level; thus, limiting its independent predictive value. Neither biomarker is found to be sufficient as a stand-alone diagnostic tool, but both may contribute to comprehensive risk models which might inform timely intervention. Future research should emphasize standardized methodologies and validation in large, diverse populations in order to improve clinical applicability.

背景:妊娠期糖尿病(GDM)是一种常见的代谢性疾病,对母体和胎儿健康都有相当大的风险。GDM的常规筛查方法通常在妊娠中期晚期进行;经常错过早期干预的重要窗口期。方法:本荟萃分析旨在评估妊娠早期母体血清生物标志物,特别是妊娠相关血浆蛋白-a (ppap -a)和β-人绒毛膜促性腺激素(β-hCG)在预测GDM中的诊断准确性。本研究对观察性研究进行了系统回顾,以评估妊娠前三个月的pap - a和/或β-hCG水平,并检查其与随后GDM诊断的相关性。本荟萃分析收集了大量研究的数据,以评估敏感性、特异性、似然比和诊断优势比;同时还开发了接受者工作特征(sROC)曲线。结果:本诊断荟萃分析评估了23项研究,包括孕早期pap -a和β-hCG测量与早期预测GDM的关系。总体合并敏感性和特异性分别为63% (95% CI: 53-73%)和70% (95% CI: 61-78%), AUC为0.72 (95% CI: 0.68-0.76)。在敏感性和特异性方面观察到实质性的异质性(I²>95%)。无伴pap - a的敏感性为67% (95% CI: 55-77%),特异性为66% (95% CI: 54-76%), AUC为0.71,而单独使用β-hCG的敏感性为29% (95% CI: 7-69%),特异性为87% (95% CI: 64-96%), AUC为0.71。Fagan的分析显示临床影响不大;结果发现,在阳性结果后,将后验概率从20%提高到~ 39%。Deek的检验显示没有重大的发表偏倚(总体p = 0.45, PAPP-A p = 0.41, β-hCG p = 0.08)。亚组分析显示,在使用ADA标准的研究和样本较小的研究中,敏感性水平较高,而那些采用队列设计的研究与病例对照研究相比,产生了更保守的估计。结论:发现妊娠早期pap - a和β-hCG的诊断准确性不高,因此最好将其作为GDM早期风险分层的辅助手段。单独使用时,PAPP-A的敏感性和特异性平衡但中等,而β-hCG的特异性较高,但敏感性很低;从而限制了其独立的预测价值。这两种生物标志物都不足以作为单独的诊断工具,但两者都可能有助于建立全面的风险模型,从而为及时干预提供信息。未来的研究应强调标准化的方法和在大量不同人群中的验证,以提高临床适用性。
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引用次数: 0
The close relationship between inflammation and insulin resistance: a comparative perspective from a new angle. 炎症与胰岛素抵抗的密切关系:一个新的比较视角。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-15 DOI: 10.1007/s00592-025-02596-y
Xiaoyan Wang, Run Yang, Jingxiang Li, Yongqi Liang, Chenxi Jin, Yining Xu, Xianbo Wu, Mengchen Zou

Background: Excess weight is a progressive metabolic epidemic, and inflammation plays an important role in the progression of disease. Insulin resistance (IR) is an important feature of obesity, but it does not reflect systemic inflammation. Currently, there is a lack of effective clinical tools for early risk stratification and intervention in physically active people.

Methods: This was a prospective cohort of 72,262 overweight but physically active persons in the UK Biobank. The TyG was combined with hsCRP, waist circumference (WC), or body mass index (BMI) as indices of IR. Adjusted Cox regression, interaction tests, restricted cubic splines (RCS) analysis, Kaplan-Meier analysis, and Harrell's C-index were used to examine the relations and time-dependent predictive power.

Results: During 12.7 years of follow-up, 1,477 participants developed metabolic dysfunction-associated fatty liver disease (MAFLD). RCS analysis suggested TyG-hsCRP had a nonlinear positive correlations with all-cause mortality. Compared to the lowest quartile group, the corrected hazard ratio (HR) (95% confidence interval [CI]) of new-onset MAFLD in maximum quartile groups for TyG-hsCRP was 1.94(1.62-2.32), for TyG-WC was 1.78(1.44-2.18), for TyG-BMI was 1.36(1.12-1.65), and for TyG was 1.41(1.15-1.72). The relation between C-index of TyG-hsCRP and MAFLD was higher than that of other TyG indices. Similar results were observed in all-cause mortality.

Conclusion: TyG-hsCRP is superior to other indices for identifying risk of MAFLD and all-cause mortality in overweight but physically active people. Our findings suggest the importance of inflammatory metabolism and provide evidence for effectively early anti-inflammatory treatments.

背景:超重是一种进行性代谢流行病,炎症在疾病的进展中起着重要作用。胰岛素抵抗(IR)是肥胖的一个重要特征,但它并不反映全身性炎症。目前,缺乏有效的临床工具对体力活动者进行早期风险分层和干预。方法:这是一个来自英国生物银行的72,262名超重但身体活跃的人的前瞻性队列。TyG与hsCRP、腰围(WC)或体重指数(BMI)联合作为IR的指标。采用校正Cox回归、相互作用检验、限制性三次样条(RCS)分析、Kaplan-Meier分析和Harrell’s c指数检验相关性和随时间变化的预测能力。结果:在12.7年的随访期间,1477名参与者发展为代谢功能障碍相关脂肪肝(MAFLD)。RCS分析显示TyG-hsCRP与全因死亡率呈非线性正相关。与最低四分位数组相比,TyG- hscrp组新发MAFLD的校正风险比(HR)(95%可信区间[CI])为1.94(1.62-2.32),TyG- wc组为1.78(1.44-2.18),TyG- bmi组为1.36(1.12-1.65),TyG组为1.41(1.15-1.72)。TyG- hscrp c指数与MAFLD的相关性高于其他TyG指数。在全因死亡率中也观察到类似的结果。结论:TyG-hsCRP在超重但运动人群中识别MAFLD风险和全因死亡率的指标优于其他指标。我们的发现提示了炎症代谢的重要性,并为有效的早期抗炎治疗提供了证据。
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引用次数: 0
miR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5. miR-125a-5p通过靶向GSTM5促进糖尿病足溃疡正常血管生成。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-15 DOI: 10.1007/s00592-025-02594-0
Fei Huang, Yan Zhou, Hairong Wu, Feifei Ma

Background: Reduced angiogenesis is a key factor in impaired healing diabetic foot ulcers. It is critical to identifying the relevant genes that regulate angiogenesis or the relevant mechanisms that accelerate angiogenesis, which is essential for the treatment of Diabetic foot ulcers (DFU).

Methods: Direct targeting of miR-125a-5p to Glutathione S-Transferase M5 (GSTM5) was demonstrated by dual luciferase assays. MiR-125a-5p and GSTM5 were induced or silenced by HGM in endothelial cells in vitro, and the results were compared with a blank control to determine the mechanism of miR-125a-5p and GSTM5 expression levels on DFU.

Results: Initial analysis revealed distinct expression patterns of miR-125a-5p and GSTM5 between acute and chronic DFU patients. Their regulatory roles were investigated by comparing differential expression profiles in these two patient groups. We found that low expression of both in chronic DFU patients was positively correlated with changes in angiogenic markers. Inhibition of miR-125a-5p and GSTM5 in endothelial cells in vitro yielded the same results, demonstrating the promote angiogenesis of their expression on angiogenesis.

Conclusion: MiR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5.

背景:血管生成减少是糖尿病足溃疡愈合受损的关键因素。确定调节血管生成的相关基因或加速血管生成的相关机制对于糖尿病足溃疡(DFU)的治疗至关重要。方法:通过双荧光素酶测定证实miR-125a-5p直接靶向谷胱甘肽s -转移酶M5 (GSTM5)。在体外内皮细胞中,HGM诱导或沉默MiR-125a-5p和GSTM5,并将结果与空白对照进行比较,以确定MiR-125a-5p和GSTM5表达水平对DFU的影响机制。结果:初步分析显示,miR-125a-5p和GSTM5在急慢性DFU患者中的表达模式不同。通过比较这两组患者的差异表达谱来研究它们的调节作用。我们发现两者在慢性DFU患者中的低表达与血管生成标志物的变化呈正相关。体外抑制内皮细胞中miR-125a-5p和GSTM5的结果相同,表明其表达对血管生成有促进作用。结论:MiR-125a-5p通过靶向GSTM5促进糖尿病足溃疡正常血管生成。
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引用次数: 0
Nutrient intake order on metabolic outcomes in type 2 diabetes: a systematic review and meta-analysis. 营养摄入顺序对2型糖尿病代谢结局的影响:一项系统综述和荟萃分析。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-13 DOI: 10.1007/s00592-025-02586-0
Luisa M Saldarriaga-Callejas, Piyush Ratan, Eric Pasqualotto, Ticiane Bovi, Talita Trevisan

Introduction and objective: Macronutrient sequence has been proposed as a practical strategy to improve postprandial glycemia in individuals with type 2 diabetes (T2D). However, current evidence remains inconclusive. This meta-analysis aims to provide an updated evaluation of the impact of a carbohydrate-last (CL) strategy, compared to carbohydrate-first or unordered (CF) intake, on metabolic parameters in adults with T2D.

Methods: A systematic search was conducted in PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) evaluating nutrient intake order in T2D. Outcomes were analyzed using mean difference (MD) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was assessed using Cochrane's Q test and I² statistics. Analyses were conducted using R, version 4.4.2.

Results: Seventeen studies involving 389 participants were included, with 114 (29%) in a parallel design and 192 (49%) in a crossover design receiving CL. In the pooled analysis, the CL group had significantly lower postprandial glucose at 60 min (MD: -42.73 mg/dL; 95% CI: -55.51, -29.96; p < 0.01) and 120 min (MD: -13.00 mg/dL; 95% CI: -21.07, -4.94; p < 0.01), higher postprandial glucagon-like peptide-1 (GLP-1) levels (MD: 8.21 pmol/L; 95% CI: 2.34, 14.09; p < 0.01), delayed gastric emptying half-time (MD: 28.14 min; 95% CI: 16.06, 40.23; p < 0.01), and reduced glycated hemoglobin (HbA1c) at follow-up (MD: -0.16%; 95% CI: -0.31, -0.01; p = 0.04).

Conclusion: Carbohydrate-last eating pattern has been shown to improve postprandial glycemia, enhance GLP-1 secretion, and delay gastric emptying, with a minimal effect on HbA1c in individuals with mild T2D. Further research is needed to confirm its applicability in advanced disease stages and to establish long-term metabolic benefits.

简介和目的:大量营养素序列已被提出作为改善2型糖尿病(T2D)患者餐后血糖的实用策略。然而,目前的证据仍然不确定。本荟萃分析旨在提供最新的评估碳水化合物最后(CL)策略,与碳水化合物优先或无序(CF)摄入相比,对成人T2D代谢参数的影响。方法:系统检索PubMed、Embase和Cochrane Central中评估t2dm患者营养摄入顺序的随机对照试验(RCTs)。在随机效应模型下,采用95%置信区间(CI)的均值差(MD)分析结果。采用Cochrane’s Q检验和I²统计量评估异质性。使用R 4.4.2版本进行分析。结果:纳入17项研究,涉及389名参与者,其中114项(29%)为平行设计,192项(49%)为交叉设计,接受CL。在综合分析中,CL组60分钟餐后血糖显著降低(MD: -42.73 mg/dL; 95% CI: -55.51, -29.96; p结论:碳水化合物-最后进食模式已被证明可以改善餐后血糖,增强GLP-1分泌,延迟胃排空,对轻度T2D患者的HbA1c影响最小。需要进一步的研究来证实其在疾病晚期的适用性,并确定长期的代谢益处。
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引用次数: 0
Therapeutic potential of copper II oxide in treating diabetic wounds: an emerging approach for enhanced healing 氧化铜在治疗糖尿病伤口中的治疗潜力:一种促进愈合的新方法。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-07 DOI: 10.1007/s00592-025-02582-4
Subhasri Bogadi, Md Ekhtiar Uddin, Veera Venkata Satyanarayana Reddy Karri, Rahima Begum, Mohammed Abdul Kader, Shahabe S. Abullais, Md Shahin Reza, Athanasios Alexiou, Marios Papadakis

Diabetes is the most serious consequence of Type 2 Diabetes Mellitus, which affects almost all vital organs in the human body. According to the World Health Organization, 537 million adults worldwide are affected by diabetes and its complications. By 2030, this figure is expected to reach 643 million, and by 2045, it will reach 783 million. Up to 25% of diabetic patients experience the equivalent foot Ulcer (Diabetic wound). Infections result in hospitalization in more than 50% of wounds, and 20% of infections necessitate amputations. In India, people with DWs account for 80% of all non-traumatic amputations performed yearly. The rise in blood sugar levels, reflected by a chronic hyperglycemic state, is a significant contributor to the failure of the healing process. This is because the extremities do not get enough blood, which reduces oxygen. In diabetic wounds, oxidative stress plays a critical role in stabilizing Hypoxia hypoxia-inducible factor (HIF-1 α). Numerous researchers have looked into the theory that oxidative stress in a specific area causes delayed chronic diabetic wounds. Some of the existing remedies, such as hyperbaric oxygen inhalation therapy (HBO) and other topical gaseous oxygen (TGO) administration, have certain drawbacks, such as the inability to stop oxidative stress in particular regions of the wound that cannot synthesize oxygen in the target site. Therefore, it is crucial to reduce oxidative stress in chronic diabetic wounds. In this review, we focus on metal oxide-related nanoparticles such as copper II oxide, which act as an anti-oxidant activity property by lowering the oxidative stress and stabilizing Hypoxia Inducible Factor (HIF), which in turn encourages proangiogenic factors and vascular endothelial growth factors to aid in wound healing.

Graphical abstract

糖尿病是2型糖尿病最严重的后果,它影响人体几乎所有重要器官。根据世界卫生组织的数据,全世界有5.37亿成年人患有糖尿病及其并发症。到2030年,这一数字预计将达到6.43亿,到2045年,这一数字将达到7.83亿。高达25%的糖尿病患者会出现足部溃疡(糖尿病伤口)。感染导致50%以上的伤口住院,20%的感染需要截肢。在印度,每年进行的非创伤性截肢手术中,DWs患者占80%。慢性高血糖状态所反映的血糖水平升高是导致愈合过程失败的重要因素。这是因为四肢没有得到足够的血液,从而减少了氧气。在糖尿病创面中,氧化应激在稳定缺氧诱导因子(HIF-1 α)中起关键作用。许多研究人员已经研究了特定区域的氧化应激导致延迟性慢性糖尿病伤口的理论。一些现有的补救措施,如高压氧吸入疗法(HBO)和其他局部气态氧(TGO)给药,有一定的缺点,例如无法阻止伤口特定区域的氧化应激,不能在目标部位合成氧气。因此,减少慢性糖尿病创面的氧化应激至关重要。在这篇综述中,我们将重点关注金属氧化物相关纳米颗粒,如铜II氧化铜,它通过降低氧化应激和稳定缺氧诱导因子(HIF)来发挥抗氧化活性,从而促进促血管生成因子和血管内皮生长因子,帮助伤口愈合。
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引用次数: 0
In women with pre-existing diabetes, the contribution to pregnancy outcomes of gestational weight gain as defined by IOM guidelines, differs when adjustment for gestational age is used 在已有糖尿病的妇女中,根据IOM指南的定义,妊娠期体重增加对妊娠结局的贡献在使用胎龄调整时有所不同。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-07 DOI: 10.1007/s00592-025-02587-z
Xinglei Xie, Jiaming Liu, Alicia López, Apolonia García-Patterson, J. M. Adelantado, Esther López, Rosa Corcoy

Aims

To investigate the association between gestational weight gain (GWG) as per Institute of Medicine 2009 (IOM) and pregnancy outcomes in women with gestational (GDM) or preexisting diabetes mellitus (PDM), when applying or not a correction for gestational age (IOM-CGWG and IOM-GWG respectively).

Methods

We conducted a retrospective analysis of pregnant women with either GDM or PDM attended in our center. Exposure variables: IOM-GWG and IOM-CGWG. Outcome variables: Maternal and fetal/neonatal clinical outcomes. Statistics: Logistic regression with adjustment for other potential independent variables.

Results

In women with GDM, correction for gestational age did not affect the distribution of weight gain or the association with clinical outcomes (pregnancy-induced hypertension, preeclampsia, cesarean delivery, large-for-gestational age newborns (LGA), macrosomia and small-for-gestational age newborns (SGA)). In women with PDM, correction for gestational age, caused a shift in the distribution to a higher rate of excessive weight gain. In the adjusted analysis, IOM-GWG was significantly associated with cesarean delivery, preterm birth, LGA, macrosomia, SGA and neonatal respiratory distress. With IOM-CGWG, the association with preterm birth disappeared while an association with PIH emerged. Population-attributable and preventive fraction were substantial for both women with GDM and PDM.

Conclusions

We conclude that the associations of IOM-GWG and IOM-CGWG are substantial in both women with GDM and PDM, indicating an area for potential intervention. In women with PDM, the modification of associations when gestational age is accounted for is relevant, highlighting the importance of considering this variable.

目的:探讨妊娠期糖尿病(GDM)或既往存在糖尿病(PDM)的妇女在应用或不应用胎龄校正(IOM- cgwg和IOM-GWG)时妊娠体重增加(GWG)与妊娠结局的关系。方法:我们对在本中心就诊的GDM或PDM孕妇进行了回顾性分析。暴露变量:IOM-GWG和IOM-CGWG。结果变量:产妇和胎儿/新生儿临床结果。统计学:对其他潜在的自变量进行调整的逻辑回归。结果:在GDM患者中,修正胎龄不影响体重增加的分布或与临床结局(妊娠高血压、先兆子痫、剖宫产、大胎龄新生儿(LGA)、巨大儿和小胎龄新生儿(SGA))的关联。在患有PDM的女性中,对胎龄的校正导致了分布的转变,使体重过度增加的比率更高。在调整分析中,IOM-GWG与剖宫产、早产、LGA、巨大儿、SGA和新生儿呼吸窘迫显著相关。在IOM-CGWG中,与早产的关联消失,而与PIH的关联出现。GDM和PDM患者的人群归因率和预防率均较高。结论:我们得出结论,在GDM和PDM女性中,IOM-GWG和IOM-CGWG的相关性都是显著的,这表明了一个潜在的干预领域。在患有PDM的妇女中,当考虑到胎龄时,相关性的改变是相关的,强调了考虑这一变量的重要性。
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引用次数: 0
Blunted cortisol and altered antioxidant defense as biomarkers of systemic stress in hyperglycemic Zebrafish. 在高血糖斑马鱼中,钝化的皮质醇和改变的抗氧化防御作为全身应激的生物标志物。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-07 DOI: 10.1007/s00592-025-02585-1
Roseleena Minz, Praveen Kumar Sharma

Background/aim: Emerging evidence links hyperglycemia, a "hallmark of diabetes mellitus" not only to peripheral metabolic dysfunction but also to its detrimental impact on brain health, often contributing to stress-related pathologies such as depression and cognitive decline. Zebrafish, with their well-characterized vascular system and behavioral assays, offer a unique model to study the impacts of sucrose-induced hyperglycemia. This study aims to investigates the effects of sucrose-induced hyperglycemia on stress mechanisms in type 2 diabetes using the zebrafish.

Methods: Male zebrafish were divided into two groups: control, and 55.5mM sucrose immersed. Over two weeks, these were subjected to behavioural assays- the novel tank test (NTT) and the light/dark test (LDT). The NTT assessed anxiety-related behaviour by measuring the time spent in different vertical zones of a novel tank, while the light/dark test evaluated anxiety responses based on the time spent in illuminated versus dark compartments. Trajectory body coordinates and tail kinematics were quantified using ZebraZoom software to asses locomotor metrics status. Cortisol levels were measured to assess HPA axis function. Antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT), were quantified to evaluate oxidative stress.

Results: The results revealed that zebrafish exposed to sucrose exhibited significant hyperglycemia (**p < 0.01) and behavioural changes compared to those on control. Specifically, in the NTT, the hyperglycemic group demonstrated heightened anxiety-like behaviour, spending more time at the bottom zone of the tank. In the light/dark test, male zebrafish showed increased anxiety by spending more time in the dark compartment. Hyperglycemic zebrafish showed a significant blunting of the cortisol response, indicating impaired stress regulation. Additionally, SOD activity was increased, while CAT activity was decreased, suggesting an imbalance in antioxidative defense mechanisms.

Conclusion: The zebrafish system effectively models the negative impacts of sucrose-induced hyperglycemia, providing valuable insights into the stress mechanisms associated with type 2 diabetes. These findings demonstrate that hyperglycemia alters both endocrine stress response and antioxidant systems, potentially serving as biomarkers of systemic stress.

背景/目的:新出现的证据表明,作为“糖尿病的标志”的高血糖不仅与外周代谢功能障碍有关,而且还与其对大脑健康的有害影响有关,经常导致与压力相关的病理,如抑郁和认知能力下降。斑马鱼具有良好的血管系统特征和行为分析,为研究蔗糖诱导的高血糖的影响提供了独特的模型。本研究旨在利用斑马鱼研究蔗糖诱导的高血糖对2型糖尿病应激机制的影响。方法:将雄性斑马鱼分为对照组和55.5mM蔗糖浸泡组。在两周的时间里,这些老鼠接受了行为分析——新水箱测试(NTT)和光/暗测试(LDT)。NTT通过测量在新水箱的不同垂直区域中花费的时间来评估焦虑相关行为,而光/暗测试则根据在照明隔间和黑暗隔间中花费的时间来评估焦虑反应。使用ZebraZoom软件对轨迹、体坐标和尾部运动学进行量化,以评估运动指标状态。测量皮质醇水平以评估下丘脑轴功能。测定抗氧化酶,包括超氧化物歧化酶(SOD)和过氧化氢酶(CAT),以评估氧化应激。结果:结果显示,暴露于蔗糖的斑马鱼表现出显著的高血糖(**p)。结论:斑马鱼系统有效地模拟了蔗糖诱导的高血糖的负面影响,为研究2型糖尿病的应激机制提供了有价值的见解。这些发现表明,高血糖改变内分泌应激反应和抗氧化系统,可能作为全身性应激的生物标志物。
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引用次数: 0
Non-invasive biomarkers for diabetic complications: insights from corneal and retinal imaging. 糖尿病并发症的非侵入性生物标志物:来自角膜和视网膜成像的见解。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-06 DOI: 10.1007/s00592-025-02588-y
Meichun Xiao, Yunhan Chen, Xiaoxin Yan, Li Wang, Huiqin Cheng, Wenqu Chen

Background: Diabetes-related complications, such as diabetic peripheral neuropathy (DPN) and chronic kidney disease (CKD), severely affect quality of life. Early detection is crucial. This study investigates ocular imaging parameters as potential biomarkers for these conditions using corneal confocal microscopy (CCM) and optical coherence tomography angiography (OCTA).

Methods: This cross-sectional study included 76 type 2 diabetes patients (139 eyes) from Fujian Medical University Union Hospital. Participants underwent CCM to assess corneal nerve fiber density (CNFD), branching density (CNBD), and nerve fiber length (CNFL). OCTA and OCT were used to evaluate macular and peripapillary retinal vascular densities (VD) and retinal nerve fiber layer (RNFL) thickness. Laboratory tests measured sural nerve conduction velocity (SSNCV), urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). DPN and CKD were categorized using Toronto consensus criteria and UACR thresholds, respectively. Statistical analyses included Spearman correlation and ROC curve evaluations.

Results: Significant reductions in CNFD, CNBD, and CNFL were observed in the DPN + group compared to DPN- (P < 0.001, P = 0.005, P < 0.001). Corneal nerve parameters correlated positively with SSNCV (r = 0.419-0.430, P < 0.001). ROC analysis demonstrated CNFD as the most sensitive marker for detecting DPN (AUC = 0.7179, 95% CI: 0.6328-0.8031). Retinal superficial VD in the superior macular region showed the highest diagnostic performance for CKD (AUC = 0.7140, 95% CI: 0.6057-0.8223), with significant correlations between retinal VD parameters and UACR.

Conclusions: Corneal nerve parameters measured by CCM and retinal vascular parameters assessed by OCTA are promising non-invasive biomarkers for early detection and monitoring of diabetic neuropathic and microvascular disorders.

背景:糖尿病相关并发症,如糖尿病周围神经病变(DPN)和慢性肾脏疾病(CKD),严重影响生活质量。早期发现至关重要。本研究利用角膜共聚焦显微镜(CCM)和光学相干断层扫描血管造影(OCTA)研究了眼部成像参数作为这些疾病的潜在生物标志物。方法:对福建医科大学协和医院2型糖尿病患者76例(139眼)进行横断面研究。参与者接受CCM评估角膜神经纤维密度(CNFD)、分支密度(CNBD)和神经纤维长度(CNFL)。OCTA和OCT评估黄斑和乳头周围视网膜血管密度(VD)和视网膜神经纤维层(RNFL)厚度。实验室测试测量腓肠神经传导速度(SSNCV)、尿白蛋白与肌酐比值(UACR)和肾小球滤过率(eGFR)。DPN和CKD分别使用多伦多共识标准和UACR阈值进行分类。统计学分析包括Spearman相关和ROC曲线评价。结果:与DPN-相比,DPN +组CNFD、CNBD和CNFL显著降低(P)。结论:CCM测量的角膜神经参数和OCTA评估的视网膜血管参数是早期检测和监测糖尿病神经病变和微血管疾病的有希望的非侵入性生物标志物。
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Acta Diabetologica
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