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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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引用次数: 0
Italian guidelines for the treatment of type 1 diabetes. 意大利1型糖尿病治疗指南。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-06 DOI: 10.1007/s00592-025-02569-1
Basilio Pintaudi, Daniela Bruttomesso, Angela Girelli, Liliana Indelicato, Edoardo Mannucci, Andrea Pizzini, Valentina Anelli, Elisabetta L Romeo, Riccardo Schiaffini, Federico Spandonaro, Antonio Migliore, Massimiliano Orso, Daniela D'Angela, Barbara Polistena, Katja Speese, Rita Stara, Giovanni Targher, Marilena Vitale, Riccardo Candido
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引用次数: 0
Metrics in pregnancy: is it the time for new glycaemic goals for pregnant women with type 1 diabetes? An experience with advanced hybrid closed loop. 妊娠期指标:是时候为1型糖尿病孕妇制定新的血糖目标了吗?先进混合闭环的经验。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-06 DOI: 10.1007/s00592-025-02590-4
O Bitterman, R Fresa, A Napoli

Introduction: Recommended pregnancy specific Time in Range (TIR) 63-140 mg/dl is a quite wide range and, even if the goal of > 70% is achieved, the specific targets for fasting and mean glycaemia, which are much lower than 140 mg/dl, could not be complied. This case series aimed to explore the performance of an Advanced Hybrid closed Loop (AHCL) in pregnancy on a stricter glycaemic range.

Methods: We collected retrospective data about recommended glucose metrics and an hypothetic TITR 63-95 mg/dl, more suitable for fasting periods, from 11 type 1 diabetes patients, using Medtronic MiniMed™ 780G, with glucose target 100 mg/dl and Active Insulin Time 2 h, from preconceptional phase until delivery.

Results: TIR 63-140 mg/dl quickly improved throughout pregnancy, with progressively improving HbA1c and no significant changes in Time Below Range (TBR). TITR 63-95 mg/dl was 26% in the 1st trimester, 20% in the 2nd and 30% in the 3rd, corresponding to 6, 5 and 7 h per day, less than the hypothetic 8/24 hours of fasting. TAR > 140 reduced more compared to TAR > 95, reflecting a greater improve in postprandial values than in fasting.

Conclusions: Although the AHCL Medtronic MiniMed™ 780G helped improving glycaemic control during pregnancy, our patients spent very few hours in the range 63-95 mg/dl, probably because they did not reach fasting glucose goals. A stricter TIR may be hypothesized for pregnant women too, as an additional goal along with TIR 63-140 mg/dl, but studies are needed to explore the consequences on maternal and fetal outcomes.

推荐妊娠特定时间范围(TIR) 63-140 mg/dl是一个相当宽的范围,即使达到bbb70 %的目标,也不能满足比140 mg/dl低得多的空腹和平均血糖的特定目标。本病例系列旨在探讨先进的混合闭环(AHCL)的性能在妊娠更严格的血糖范围。方法:我们收集了11例1型糖尿病患者的回顾性数据,包括推荐的血糖指标和假设的TITR 63-95 mg/dl,更适合禁食期,使用美敦力MiniMed™780G,血糖目标为100 mg/dl,活性胰岛素时间为2小时,从孕前到分娩。结果:TIR 63-140 mg/dl在整个妊娠期间迅速改善,HbA1c逐渐改善,TBR无显著变化。TITR 63-95 mg/dl在妊娠前三个月为26%,妊娠后三个月为20%,妊娠后三个月为30%,分别为每天6、5和7小时,低于假设的禁食8/24小时。与TAR > 95相比,TAR > 140降低得更多,这反映出餐后值比禁食有更大的改善。结论:虽然AHCL美敦力MiniMed™780G有助于改善妊娠期间的血糖控制,但我们的患者在63-95 mg/dl范围内停留的时间很短,可能是因为他们没有达到空腹血糖目标。对于孕妇,也可以假设一个更严格的TIR,作为TIR 63-140 mg/dl的额外目标,但需要研究来探索对孕产妇和胎儿结局的影响。
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引用次数: 0
Preliminary real-world observational data on A8 TouchCare use in adults with type 1 diabetes 成人1型糖尿病患者使用A8 TouchCare的初步现实世界观察数据
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-06 DOI: 10.1007/s00592-025-02589-x
Nicolò Diego Borella, Anna Corsi, Cristiana Scaranna, Roberto Trevisan, Giuseppe Lepore
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引用次数: 0
Development and validation of a risk predictive nomogram for carotid intima-media thickening in patients with type 2 diabetes 2型糖尿病患者颈动脉内膜-中膜增厚风险预测图的建立和验证。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-18 DOI: 10.1007/s00592-025-02584-2
Yongqi Zheng, Luni Tuo, Jie Xiao, Runzi Ling, Lei Yan

Aim

Carotid intima-media thickness (CIMT) serves as a valuable cardiovascular risk marker in type 2 diabetes mellitus (T2DM). We aimed to develop and validate a nomogram incorporating novel indicators, including the triglyceride-glucose (TyG) index, to predict CIMT thickening in T2DM.

Methods

In this retrospective study of 804 patients with T2DM, we employed least absolute shrinkage and selection operator regression followed by stepwise regression for predictor selection. Six machine learning models were evaluated, with model selection based on the area under the receiver operating characteristic curve (AUROC). The optimal model was used to develop the nomogram, assessed using AUROC, calibration curves, decision curve analysis (DCA), and SHapley Additive exPlanations (SHAP) for feature importance.

Results

Independent predictors of CIMT thickening in T2DM included age, body mass index, current smoking status, regular exercise habits, glycated hemoglobin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and TyG index. Logistic regression demonstrated excellent predictive performance and was selected for nomogram development. The predictive model showed strong discriminative ability and good calibration in both the training and testing datasets. DCA confirmed its clinical utility across relevant risk thresholds, with SHAP analysis identifying age as the most influential predictor.

Conclusions

This study developed and validated a nomogram integrating routine clinical parameters and novel indicators, including the TyG index, to assess the risk of CIMT thickening in T2DM patients. This nomogram provides an evidence-based tool to help clinicians identify high-risk patients and guide early therapeutic interventions.

目的:颈动脉内膜-中膜厚度(CIMT)是2型糖尿病(T2DM)有价值的心血管危险指标。我们的目的是开发和验证包含新指标的nomogram,包括甘油三酯-葡萄糖(TyG)指数,以预测T2DM患者的CIMT增厚。方法:在804例T2DM患者的回顾性研究中,我们采用最小绝对收缩和选择算子回归,然后采用逐步回归来选择预测因子。对六种机器学习模型进行了评估,模型选择基于接收者工作特征曲线下面积(AUROC)。使用最优模型建立nomogram,并使用AUROC、校准曲线、决策曲线分析(DCA)和SHapley Additive explanation (SHAP)对特征重要性进行评估。结果:T2DM患者CIMT增厚的独立预测因素包括年龄、体重指数、吸烟状况、有规律的运动习惯、糖化血红蛋白、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和TyG指数。逻辑回归显示出良好的预测性能,并被选中进行nomogram开发。该预测模型在训练数据集和测试数据集上均表现出较强的判别能力和较好的校准能力。DCA证实了其在相关风险阈值上的临床应用,SHAP分析确定年龄是最具影响力的预测因子。结论:本研究开发并验证了一种整合常规临床参数和新指标(包括TyG指数)的nomogram方法,用于评估T2DM患者CIMT增厚的风险。这张nomogram图提供了一种基于证据的工具,帮助临床医生识别高危患者并指导早期治疗干预。
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引用次数: 0
Low bone morphogenic protein-2 in diabetes patients with peripheral neuropathy is a correlated risk factor for the development of Charcot arthropathy 糖尿病合并周围神经病变患者骨形态发生蛋白-2水平低是Charcot关节病发生的相关危险因素。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-17 DOI: 10.1007/s00592-025-02573-5
Jean Cassuto, Agnetha Folestad, Martin Ålund, Susanne Asteberg, Jan Göthlin

Aims

Diabetes patients with peripheral neuropathy run increased risk of developing Charcot arthropathy (Charcot), often associated with foot fractures. Bone morphogenic proteins (BMPs) are among the most important regulators of bone homeostasis and fracture repair but have not been investigated in the pathophysiology of Charcot. The current study aims to address this issue.

Methods

Sixteen patients diagnosed with active Charcot were treated with total contact cast (TCC) and monitored during 24 months (M) with repeated plain radiographs and magnetic resonance imaging (MRI). Plasma was sampled at 9 occasions and analyzed for BMP-1, BMP-2, BMP-3, BMP-4, BMP-6, BMP-7 and BMP-9 as well as for basal laboratory data. Fifteen diabetes patients with peripheral neuropathy and fifteen healthy participants without diabetes served as controls.

Results

All Charcot patients had pathologically low BMP-2 level at inclusion which remained suppressed throughout the 2-year follow-up as defined by being lower than 2 standard deviations (SD) of BMP-2 in healthy controls (p < 0.001) and in diabetes patients with neuropathy without Charcot (p < 0.002). BMP-2 did not differ between the control groups. BMP-7 in Charcot patients increased significantly 6–12 months following TCC treatment. Other BMPs showed no significant differences between the groups at any point during the follow-up.

Conclusions

Low BMP-2 in diabetes patients with neuropathy is associated with increased risk of developing Charcot fractures due to the critical role of BMP-2 for the initiation of bone repair. BMP-7 appears to partly compensate for the lack of response by other osteogenic BMPs during fracture repair in Charcot patients.

目的:伴有周围神经病变的糖尿病患者发生Charcot关节病(Charcot)的风险增加,通常与足部骨折相关。骨形态发生蛋白(BMPs)是骨稳态和骨折修复中最重要的调节因子之一,但尚未在Charcot的病理生理学中进行研究。本研究旨在解决这一问题。方法:对16例确诊为活动性Charcot的患者进行全接触铸型(TCC)治疗,随访24个月(M),反复进行x线平片和磁共振成像(MRI)检查。9次抽取血浆,分析BMP-1、BMP-2、BMP-3、BMP-4、BMP-6、BMP-7和BMP-9以及基础实验室数据。15例伴有周围神经病变的糖尿病患者和15例无糖尿病的健康受试者作为对照。结果:所有Charcot患者在纳入研究时的病理BMP-2水平均较低,在2年随访期间,该水平均低于健康对照组BMP-2的2个标准差(SD) (p)。结论:伴有神经病变的糖尿病患者的低BMP-2与Charcot骨折的风险增加有关,因为BMP-2在骨修复的启动中起着关键作用。在Charcot患者骨折修复过程中,BMP-7似乎部分补偿了其他成骨bmp缺乏反应。
{"title":"Low bone morphogenic protein-2 in diabetes patients with peripheral neuropathy is a correlated risk factor for the development of Charcot arthropathy","authors":"Jean Cassuto,&nbsp;Agnetha Folestad,&nbsp;Martin Ålund,&nbsp;Susanne Asteberg,&nbsp;Jan Göthlin","doi":"10.1007/s00592-025-02573-5","DOIUrl":"10.1007/s00592-025-02573-5","url":null,"abstract":"<div><h3>Aims</h3><p>Diabetes patients with peripheral neuropathy run increased risk of developing Charcot arthropathy (Charcot), often associated with foot fractures. Bone morphogenic proteins (BMPs) are among the most important regulators of bone homeostasis and fracture repair but have not been investigated in the pathophysiology of Charcot. The current study aims to address this issue.</p><h3>Methods</h3><p>Sixteen patients diagnosed with active Charcot were treated with total contact cast (TCC) and monitored during 24 months (M) with repeated plain radiographs and magnetic resonance imaging (MRI). Plasma was sampled at 9 occasions and analyzed for BMP-1, BMP-2, BMP-3, BMP-4, BMP-6, BMP-7 and BMP-9 as well as for basal laboratory data. Fifteen diabetes patients with peripheral neuropathy and fifteen healthy participants without diabetes served as controls.</p><h3>Results</h3><p>All Charcot patients had pathologically low BMP-2 level at inclusion which remained suppressed throughout the 2-year follow-up as defined by being lower than 2 standard deviations (SD) of BMP-2 in healthy controls (<i>p</i> &lt; 0.001) and in diabetes patients with neuropathy without Charcot (<i>p</i> &lt; 0.002). BMP-2 did not differ between the control groups. BMP-7 in Charcot patients increased significantly 6–12 months following TCC treatment. Other BMPs showed no significant differences between the groups at any point during the follow-up.</p><h3>Conclusions</h3><p>Low BMP-2 in diabetes patients with neuropathy is associated with increased risk of developing Charcot fractures due to the critical role of BMP-2 for the initiation of bone repair. BMP-7 appears to partly compensate for the lack of response by other osteogenic BMPs during fracture repair in Charcot patients.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 1","pages":"123 - 131"},"PeriodicalIF":2.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00592-025-02573-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Modified cut-off value of the urine albumin-to-creatinine ratio is helpful for identifying patients at high risk for chronic kidney disease in prediabetes 修改后的尿白蛋白与肌酐比值临界值有助于鉴别糖尿病前期慢性肾脏疾病的高危患者。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-17 DOI: 10.1007/s00592-025-02518-y
Jing Liu, Liu Yang, Jinli Wu, Lili You, Li Yan, Meng Ren

Background

Prediabetes is associated with higher risk of chronic kidney disease (CKD), however studies investigating the prognostic index for incident CKD in patients with prediabetes are lacking. Thus, the present study aims to find the risk factors for CKD in prediabetic population.

Methods

We included 1220 prediabetic participants without CKD in the REACTION study and examined the associations of clinical indicators with CKD incidence with 3.6 years of follow-up using logistic regression analyses. To explore the nonlinear relationship between the Urine Albumin-To-Creatinine Ratio (UACR) and the hazard ratio (HR) of CKD, a Restricted Cubic Spline (RCS) analysis was conducted. Logistic regression analysis was employed to assess the association between UACR categories and the risk of CKD incidence.

Results

There were 78 (6.4%) individuals developed CKD, and elevated UACR was observed in patients who developed CKD. UACR was an independent risk factor of CKD after adjusting for covariates and RCS presented an association between elevated UACR and higher risk of CKD incidence. UACR cutoff points of 7.54 mg/g overall was associated with the risk of CKD progression. In comparison to a UACR range of 0-7.54 mg/g (B1), those who falling within the ranges of 7.54–14.95 (B2), 14.95–22.36 (B3), and 22.36-30 (B4), exhibited a significantly increased risk of CKD development. eGFR below the threshold of 81.64 mL/min/1.73m2 was significantly associated with an increased risk of CKD characterized by impaired glomerular filtration.

Conclusion

In conclusion, the novel UACR cutoff of 7.54 mg/g serves as an effective tool to identify individuals at high risk of developing CKD-ACR during the prediabetes stage.

背景:前驱糖尿病与慢性肾脏疾病(CKD)的高风险相关,然而研究前驱糖尿病患者发生CKD的预后指标缺乏。因此,本研究旨在发现糖尿病前期人群CKD的危险因素。方法:我们在REACTION研究中纳入了1220名无CKD的糖尿病前期参与者,并通过3.6年的随访使用logistic回归分析来检查临床指标与CKD发病率的关系。为探讨尿白蛋白与肌酐比值(UACR)与CKD危险比(HR)之间的非线性关系,采用限制性三次样条(RCS)分析。采用Logistic回归分析评估UACR分类与CKD发病风险之间的关系。结果:有78人(6.4%)发展为CKD,在CKD患者中观察到UACR升高。调整协变量后,UACR是CKD的独立危险因素,RCS显示UACR升高与CKD发病率升高之间存在关联。总体UACR临界值为7.54 mg/g与CKD进展风险相关。与0-7.54 mg/g (B1)的UACR范围相比,那些落在7.54-14.95 (B2), 14.95-22.36 (B3)和22.36-30 (B4)范围内的人,CKD发展的风险显着增加。eGFR低于阈值81.64 mL/min/1.73m2与以肾小球滤过受损为特征的CKD风险增加显著相关。综上所述,新的UACR临界值7.54 mg/g可作为识别糖尿病前期CKD-ACR高风险个体的有效工具。
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引用次数: 0
Retinopathy and nephropathy in type 1 diabetes: role of HbA1c and blood pressure variability 1型糖尿病视网膜病变和肾病:HbA1c和血压变异性的作用
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-17 DOI: 10.1007/s00592-025-02575-3
Pavel Fatulla, Johnny Ludvigsson, Henrik Imberg, Thomas Nyström, Marcus Lind

Aims

To examine the association between within-person variability in glycated hemoglobin A1c (HbA1c) and blood pressure (BP) with retinopathy and nephropathy in type 1 diabetes (T1D).

Methods

This nationwide cohort included 9,358 individuals from the Swedish National Diabetes Register with T1D <5 years at inclusion (1998–2017) and ≥8 years follow-up. Variability in HbA1c, systolic BP (SBP), and diastolic BP (DBP) was calculated as updated SDs. Associations with microvascular complications were analyzed using logistic regression with generalized estimating equations, adjusted for demographic and clinical covariates.

Results

Mean age at inclusion was 14.2 years, mean diabetes duration 1.2 years, and 44% were female. Over 10.7 years’ follow-up, retinopathy developed in 33% and nephropathy in 9.3%. SBP variability was significantly associated with pre-proliferative or proliferative retinopathy (aOR 1.13, 95% CI 1.00–1.27) and proliferative retinopathy/ laser photocoagulation (1.23, 1.04–1.45), as well as with any albuminuria (1.15, 1.08–1.23) and macroalbuminuria (1.29, 1.15–1.45). DBP variability was associated with any albuminuria (1.11, 1.03–1.19) and macroalbuminuria (1.28, 1.10–1.50). HbA1c variability was associated with any retinopathy (1.14, 1.08–1.20) and any albuminuria (1.12, 1.03–1.21).

Conclusions

Beyond mean levels, higher variability in HbA1c and BP is associated with retinopathy and nephropathy. Stable BP control in patients with established retinopathy may be important to prevent progression to sight-threatening stages.

目的:研究1型糖尿病(T1D)患者糖化血红蛋白A1c (HbA1c)和血压(BP)的个体变异与视网膜病变和肾病的关系。方法:该全国性队列包括来自瑞典国家糖尿病登记的9358例T1D患者。结果:纳入时的平均年龄为14.2岁,平均糖尿病病程为1.2年,44%为女性。在10.7年的随访中,视网膜病变发生率为33%,肾病发生率为9.3%。收缩压变异性与增殖性或增殖性视网膜病变(aOR 1.13, 95% CI 1.00-1.27)、增殖性视网膜病变/激光光凝(1.23,1.04-1.45)以及任何蛋白尿(1.15,1.08-1.23)和大量蛋白尿(1.29,1.15-1.45)显著相关。DBP变异性与任何蛋白尿(1.11,1.03-1.19)和巨量蛋白尿(1.28,1.10-1.50)相关。HbA1c变异性与视网膜病变(1.14,1.08-1.20)和蛋白尿(1.12,1.03-1.21)相关。结论:在平均水平之外,HbA1c和BP的较高变异性与视网膜病变和肾病相关。稳定的血压控制在已确定的视网膜病变患者可能是重要的,以防止进展到视力威胁阶段。
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引用次数: 0
Expression of long non-coding RNAs MALAT1, MEG3, and XIST in gestational diabetes mellitus: a cross-sectional study 长链非编码rna MALAT1、MEG3和XIST在妊娠糖尿病中的表达:一项横断面研究
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-10 DOI: 10.1007/s00592-025-02581-5
Bishal Kumar Dey, Sudipta Banerjee, Pieu Adhikary, Subhankar Chowdhury, Sanchita Roy, Subesha Basu Roy, Rana Bhattacharjee

Background and aims

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first identified during pregnancy that does not meet the criteria for overt diabetes. Its pathophysiology shares key features with type 2 diabetes mellitus (T2D), including insulin resistance and inflammation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are implicated in T2D. This study investigates the gene expression of lncRNAs in GDM and explores their association with insulin resistance and proinflammatory cytokines.

Materials and methods

This cross-sectional study included 25 GDM and 36 non-GDM (NGDM) participants from a tertiary care antenatal clinic. GDM was diagnosed using a 75 g oral glucose tolerance test (OGTT) based on the International Association of Diabetes and Pregnancy Study Groups criteria. MALAT1, MEG3, and XIST were selected for analysis due to their reported involvement in T2D. Their gene expression levels were quantified using real-time PCR, while serum concentrations of proinflammatory cytokines (TNF-α, IL-6, IL-1β) and glycemic markers (C-peptide, fasting insulin) were measured using ELISA.

Results

MALAT1, MEG3, and XIST were significantly downregulated in the GDM group compared to the NGDM group (p < 0.01). In the GDM group, all three lncRNAs showed a significant negative correlation with Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) (MALAT1: r = -0.44, p = 0.03; MEG3: r = -0.46, p = 0.04; XIST: r = -0.45, p = 0.04). Additionally, MALAT1 gene expression negatively correlated with IL-6 (r = -0.49, p = 0.03) and TNF-α (r = -0.48, p = 0.04). MEG3 and XIST gene expression negatively correlated with IL-1β (r = -0.51 and − 0.50, p = 0.03 for both) and TNF-α (r = -0.47 and − 0.52, p = 0.04 and 0.03, respectively).

Conclusion

MALAT1, MEG3, and XIST are downregulated in GDM, and their gene expression levels are negatively correlated with insulin resistance and select proinflammatory cytokines. These findings suggest a potential role for lncRNA downregulation in GDM pathogenesis, warranting further investigation.

背景和目的:妊娠期糖尿病(GDM)被定义为妊娠期间首次发现的葡萄糖耐受不良,但不符合显性糖尿病的标准。其病理生理特征与2型糖尿病(T2D)相似,包括胰岛素抵抗和炎症。新出现的证据表明,长链非编码rna (lncRNAs)与T2D有关。本研究研究了lncRNAs在GDM中的基因表达,并探讨了它们与胰岛素抵抗和促炎细胞因子的关系。材料和方法:本横断面研究包括来自三级保健产前诊所的25名GDM和36名非GDM (NGDM)参与者。根据国际糖尿病和妊娠研究小组的标准,使用75克口服葡萄糖耐量试验(OGTT)诊断GDM。我们选择MALAT1、MEG3和XIST进行分析,因为有报道称它们与T2D有关。采用实时荧光定量PCR法检测各组基因表达水平,ELISA法检测血清促炎因子(TNF-α、IL-6、IL-1β)和血糖指标(c肽、空腹胰岛素)浓度。结果:与NGDM组相比,GDM组MALAT1、MEG3、XIST显著下调(p)。结论:MALAT1、MEG3、XIST在GDM中下调,且其基因表达水平与胰岛素抵抗和选择性促炎因子呈负相关。这些发现提示lncRNA下调在GDM发病机制中的潜在作用,值得进一步研究。
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引用次数: 0
Incidence and causes of major amputation in patients with diabetic foot ulcers: data from a retrospective study 糖尿病足溃疡患者主要截肢的发生率和原因:来自回顾性研究的数据。
IF 2.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-04 DOI: 10.1007/s00592-025-02577-1
Marco Meloni, Luigi Uccioli, Aikaterini Andreadi, Laura Giurato, Valeria Ruotolo, Maria Romano, Alessandro Minasi, Ermanno Bellizzi, Federico Rolando Bonanni, Martina Salvi, Alfonso Bellia, Davide Lauro

Aim

The study aimed to evaluate the rate and causes of major amputation in patients with diabetic foot syndrome.

Methods

The current study is a retrospective observational study including consecutive patients referred to a tertiary-level diabetic foot service from January 2020 to November 2023 due to a new diabetic foot problem requiring hospital admission. All patients had been managed by a multi-disciplinary diabetic foot team (MDFT) through a pre-set limb salvage protocol including the management of peripheral arterial disease, infection, foot offloading, and comorbidities. At 1 year of follow-up, the following outcomes measures were evaluated: rate of major amputation, clinical characteristics of amputees, and causes of major amputation.

Results

Overall, 1226 patients referring for a diabetic foot problem and requiring hospitalization were screened for the study. Among them, 30 (2.4%) patients experienced major amputation. Amputees had 69.9±10.7 years, the majority were male (73.3%) with a prevalence of type 2 diabetes (93.3%) and a long diabetes duration (25.2±9.8 years). They showed several comorbidities such as ischaemic heart disease (83.3%), heart failure (46.7%), end-stage-renal-disease (26.7%), and in addition high rate of peripheral arterial disease (PAD) (86.7%), infected wounds (98.3%), and osteomyelitis (90%). Major amputation was mainly related to untreatable limb ischemia (failure of revascularization procedure) in 56.7% of cases, calcaneus osteomyelitis and necrotizing fasciitis in 16.7% of cases, and tarsal osteomyelitis in 10% of cases.

Conclusions

The rate of major amputation was very low in this population managed by a MDFT. PAD was the main cause of major amputation.

目的:探讨糖尿病足综合征患者主要截肢的发生率及原因。方法:本研究是一项回顾性观察性研究,纳入了从2020年1月至2023年11月因新的糖尿病足问题需要住院的三级糖尿病足服务的连续患者。所有患者均由多学科糖尿病足小组(MDFT)通过预先设定的肢体保留方案进行管理,包括外周动脉疾病、感染、足部卸载和合并症的管理。在1年的随访中,评估了以下指标:大截肢率、截肢者的临床特征和大截肢的原因。结果:总的来说,1226例糖尿病足问题和需要住院治疗的患者被筛选为研究。其中大截肢30例(2.4%)。截肢者平均年龄为69.9±10.7岁,男性居多(73.3%),2型糖尿病患病率(93.3%),糖尿病病程较长(25.2±9.8年)。他们表现出一些合并症,如缺血性心脏病(83.3%)、心力衰竭(46.7%)、终末期肾病(26.7%),此外外周动脉疾病(PAD)(86.7%)、伤口感染(98.3%)和骨髓炎(90%)的高发率。大截肢主要与无法治愈的肢体缺血(血运重建手术失败)有关(56.7%),跟骨髓炎和坏死性筋膜炎占16.7%,跗骨骨髓炎占10%。结论:在该人群中,经MDFT治疗的大截肢率非常低。外周动脉是导致大面积截肢的主要原因。
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Acta Diabetologica
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