Diabetologia最新文献_第3页

Type 1 diabetes screening: reframing the debate from paternalism to partnership. 1型糖尿病筛查：重新定义从家长式作风到伙伴关系的辩论。

IF 8.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-23 DOI: 10.1007/s00125-025-06654-6

Andrea E Scaramuzza,Dario Iafusco,Valentino Cherubini

引用次数: 0

Type 1 diabetes screening: building a clinician-patient partnership for early care of chronic beta cell failure. 1型糖尿病筛查：为慢性β细胞衰竭的早期护理建立临床-患者伙伴关系。

IF 8.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-23 DOI: 10.1007/s00125-025-06656-4

Roberto Mallone,Aude Bandini

引用次数: 0

Glycaemic, appetite and circadian benefits of a dairy-enriched diet with high-protein breakfast and early daytime-restricted carbohydrate intake in type 2 diabetes: a randomised crossover trial. 2型糖尿病患者采用高蛋白早餐和限制碳水化合物摄入的富含乳制品饮食对血糖、食欲和昼夜节律的益处：一项随机交叉试验

IF 8.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-23 DOI: 10.1007/s00125-025-06658-2

Shani Tsameret,Oren Froy,Yael Matz,Zohar Landau,Orit Twito,Julio Wainstein,Natalie Avital-Cohen,Nava Chapnik,Daniela Jakubowicz

AIMS/HYPOTHESISThe circadian timing of food intake and the composition of dietary protein sources may jointly influence metabolic regulation. Our aim was to examine the effects of a dairy-enriched vs non-dairy isoenergetic diet with structured meal timing on circadian clock gene expression, glycaemic management and appetite regulation in individuals with type 2 diabetes.METHODSIn a randomised, crossover trial, 25 participants with type 2 diabetes and HbA1c ≥48 mmol/mol (6.5%), treated either with stable doses (≥3 months) of oral glucose-lowering agents or managed by diet, followed two 4 week dietary phases, one including dairy-based protein sources (YesMilk) and one excluding them (NoMilk), with a 3-4 week washout. Participants were randomly assigned to one of two intervention sequences using simple randomisation (coin flip), either starting with the YesMilk diet followed by the NoMilk diet, or vice versa. Due to the open-label design, allocation was not concealed from investigators or participants. The study was powered for the primary outcome of circadian clock gene expression in peripheral blood mononuclear cells. Secondary outcomes included glycaemic indices derived from continuous glucose monitoring (CGM) and appetite scores. The study was conducted via the Diabetes Unit at Wolfson Medical Center, Israel.RESULTSTwenty-nine individuals were screened; 25 met eligibility criteria and were randomised to YesMilk or NoMilk dietary interventions in a crossover design. Thirteen participants began with the YesMilk dairy diet, all of whom completed both phases. Of the 12 who began with the NoMilk diet, six completed the study. Nineteen participants completed both intervention phases. Compared with the NoMilk phase, the YesMilk diet upregulated BMAL1 (+1.8-fold, p=0.0003), REV-ERBα (also known as NRD1D1) (+2.2-fold, p<0.001) and CRY1 (+1.4-fold, p=0.03), with higher PER1 expression (p=0.01 between diets at 4 weeks). Glycaemic variables improved under the YesMilk diet, with fasting glucose reduced by ~1.7 mmol/l, glucose management indicator reduced by 0.7%, and time in range increased by 9% compared with baseline (all p<0.05). Hunger and sweet craving scores decreased by 15-20% (p<0.05).CONCLUSIONS/INTERPRETATIONA dairy-enriched diet aligned with structured meal timing enhanced circadian clock gene expression and improved glycaemic and appetite-related variables in individuals with type 2 diabetes. These findings support a mechanistic link between dietary protein source, circadian regulation and metabolic health, warranting confirmation in larger, long-term studies.TRIAL REGISTRATIONClincalTrials.gov NCT03772067 FUNDING: The Israeli Ministry of Health provided funding.

目的/假设食物摄入的昼夜节律时间和膳食蛋白质来源的组成可能共同影响代谢调节。我们的目的是研究富含乳制品和非乳制品等能饮食对2型糖尿病患者生物钟基因表达、血糖管理和食欲调节的影响。方法：在一项随机交叉试验中，25名HbA1c≥48 mmol/mol（6.5%）的2型糖尿病患者，接受稳定剂量（≥3个月）口服降糖药治疗或饮食管理，遵循两个为期4周的饮食阶段，一个包括基于乳制品的蛋白质来源（YesMilk），另一个不包括乳制品（nommilk），并有3-4周的洗脱期。通过简单的随机化（掷硬币），参与者被随机分配到两个干预序列中的一个，要么从YesMilk饮食开始，然后是nommilk饮食，反之亦然。由于开放标签设计，分配没有对研究人员或参与者隐藏。该研究为外周血单核细胞中生物钟基因表达的主要结果提供了动力。次要结局包括由连续血糖监测（CGM）得出的血糖指数和食欲评分。这项研究是通过以色列沃尔夫森医疗中心的糖尿病部门进行的。结果共筛查29例；25例符合资格标准，在交叉设计中随机分为YesMilk或nommilk饮食干预组。13名参与者从YesMilk乳制品饮食开始，他们都完成了两个阶段。在开始使用无牛奶饮食的12人中，有6人完成了研究。19名参与者完成了两个干预阶段。与nommilk期相比，YesMilk饲粮上调了BMAL1（+1.8倍，p=0.0003）、rev - erba（也称为NRD1D1）（+2.2倍，p<0.001）和CRY1(+1.4倍，p=0.03)，并在第4周提高了PER1的表达（p=0.01）。YesMilk日粮改善了血糖指标，与基线相比，空腹血糖降低了~1.7 mmol/l，血糖管理指标降低了0.7%，范围时间增加了9%（均p<0.05）。饥饿感和甜食渴望得分降低了15-20% （p<0.05）。结论/解释：在2型糖尿病患者中，富含乳制品的饮食与结构化的进餐时间相一致，可增强生物钟基因表达，并改善血糖和食欲相关变量。这些发现支持膳食蛋白质来源、昼夜节律调节和代谢健康之间的机制联系，需要在更大规模的长期研究中得到证实。资助：以色列卫生部提供资金。

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引用次数: 0

Blood DNA methylation markers are associated with diabetic kidney disease progression in type 1 diabetes. 血液DNA甲基化标记物与1型糖尿病肾病进展相关

IF 10.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-22 DOI: 10.1007/s00125-025-06661-7

Anna Syreeni, Emma H Dahlström, Laura J Smyth, Claire Hill, Stefan Mutter, Valma Harjutsalo, Zhuo Chen, Rama Natarajan, Andrzej S Krolewski, Joel N Hirschhorn, Jose C Florez, Alexander P Maxwell, Per-Henrik Groop, Amy Jayne McKnight, Niina Sandholm

Aims/hypothesis: DNA methylation has been shown to be associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we conducted epigenome-wide association studies (EWASs) on early- and late-stage DKD progression using DNA methylation data obtained by analysing baseline blood samples from participants in the Finnish Diabetic Nephropathy Study type 1 diabetes cohort.

Methods: We included 403 individuals with normal AER (early-stage progression group) and 372 individuals with severe albuminuria (late-stage progression group), and followed up DKD progression, defined as a decrease in eGFR to <60 ml/min per 1.73 m² in the early-stage progression group, and end-stage kidney disease (ESKD) in the late-stage group. Replication was conducted in two type 1 diabetes cohorts in addition to publicly available EWAS summary statistics from diabetes and general population cohorts. Significant loci were further characterised by integration with genetic and proteomic data.

Results: We identified 11 methylation sites associated with DKD progression (p<9.4 × 10^-8). Methylation at cg01730944 near the podocyte-specific gene CDKN1C and three other CpGs associated with early-stage DKD progression were independent of baseline eGFR, whereas late-stage progression CpGs were strongly associated with eGFR. The identified lead ESKD risk locus cg17944885 (chr19p13.2, p=2.6 × 10^-17) and several novel methylation sites associated with late-stage DKD progression were supported by the results of previous studies. Proteomic analysis of cis proteins identified potential target genes for two CpGs: cg14999724 methylation was associated with PRG3 and PRG2, and cg12272104 was associated with BSG, FSTL3 and PALM. Furthermore, UK Biobank data show associations between these proteins and severe kidney endpoints. Finally, survival models that included methylation markers in addition to clinical risk factors significantly improved the identification of individuals at risk of early-stage DKD progression.

Conclusions/interpretation: The current study detected 11 loci associated with DKD progression, identifying methylation changes predictive of early-stage DKD progression in type 1 diabetes for the first time. Future research is needed to establish prognostic DNA methylation markers for DKD progression.

目的/假设：DNA甲基化已被证明与肾功能和糖尿病肾病（DKD）相关，但缺乏前瞻性研究。因此，我们通过分析芬兰糖尿病肾病研究1型糖尿病队列参与者的基线血液样本获得的DNA甲基化数据，对早期和晚期DKD进展进行了全表观基因组关联研究（EWASs）。方法：我们纳入了403例AER正常（早期进展组）和372例重度蛋白尿（晚期进展组），并随访了DKD进展，定义为早期进展组eGFR降至2，晚期组为终末期肾病（ESKD）。在两个1型糖尿病队列中进行了重复研究，此外还有来自糖尿病和普通人群队列的公开EWAS汇总统计数据。通过整合遗传和蛋白质组学数据进一步表征了重要的位点。结果：我们确定了11个与DKD进展相关的甲基化位点（p-8）。足细胞特异性基因CDKN1C附近c01730944位点的甲基化和其他三个与早期DKD进展相关的CpGs与基线eGFR无关，而晚期进展CpGs与eGFR密切相关。已确定的ESKD铅风险位点cg17944885 （chr19p13.2, p=2.6 × 10-17）和几个与晚期DKD进展相关的新甲基化位点得到了先前研究结果的支持。顺式蛋白的蛋白质组学分析确定了两个CpGs的潜在靶基因：cg14999724甲基化与PRG3和PRG2相关，cg12272104甲基化与BSG、FSTL3和PALM相关。此外，英国生物银行的数据显示，这些蛋白与严重的肾脏终点之间存在关联。最后，除临床危险因素外，包括甲基化标志物的生存模型显著提高了早期DKD进展风险个体的识别。结论/解释：目前的研究检测到11个与DKD进展相关的位点，首次确定了1型糖尿病早期DKD进展的甲基化变化。未来的研究需要建立DKD进展的预后DNA甲基化标记物。

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引用次数: 0

Torsten Deckert, 7 March 1928-19 November 2025. 托斯滕·德克特，1928年3月7日- 2025年11月19日。

IF 8.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-22 DOI: 10.1007/s00125-025-06657-3

Bo Feldt-Rasmussen,Knut Borch-Johnsen,Jørn Nerup,Oluf Pedersen

引用次数: 0

Uncovering distinct predictors of diabetes distress and depressive symptoms in a longitudinal survival analysis of incidence and remission: indication for diverging aetiological paths. 在发病率和缓解的纵向生存分析中揭示糖尿病窘迫和抑郁症状的不同预测因素：不同病因路径的指征

IF 8.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-22 DOI: 10.1007/s00125-026-06666-w

Gina Lehmann,Dominic Ehrmann,Birgit Olesen,Lilli-Sophie Priesterroth,Bernhard Kulzer,Thomas Haak,Norbert Hermanns

AIMS/HYPOTHESISThe aim of the study was to examine the course of diabetes distress and depressive symptoms and their predictors of incidence and remission in individuals with type 1 and type 2 diabetes.METHODSData were collected every 6 months over a 24 month period. Participants (n=654) completed measures of diabetes distress (Problem Areas in Diabetes Scale) and depressive symptoms (Patient Health Questionnaire 8). Cox proportional hazards models were applied to examine predictors of incidence and remission, considering demographic, clinical and psychosocial factors. All predictors were assessed at baseline, except for HbA1c, which was modelled as a time-varying covariate.RESULTSDiabetes distress showed cumulative incident cases in 21% of the sample and a remission rate of 70% across 24 months. For depressive symptoms, cumulative 24 month incidence was 33% and remission was 67%. The median onset time was 18 months for diabetes distress and 24 months for depressive symptoms; the median remission time for both was 6 months. Higher HbA1c (HR=1.02, p=0.022), female gender (male gender HR=0.55, p=0.043), long-term complications (HR=2.11, p=0.009) and a history of anxiety disorders (HR=2.57, p=0.029) significantly predicted the incidence of diabetes distress, while no predictors were associated with remission. For depressive symptoms, higher HbA1c (HR=1.03, p<0.001), prior depression (HR=2.63, p=0.001) and eating disorders (HR=2.20, p=0.044) predicted incidence. Remission was significantly associated only with older age (HR=1.02, p=0.045).CONCLUSIONS/INTERPRETATIONSuboptimal glycaemic outcomes predicted both diabetes distress and depression; however, diabetes distress was associated with anxiety disorders, whereas depressive symptoms were linked to prior depression and eating disorders, hinting at distinct aetiologies.

目的/假设本研究的目的是研究1型和2型糖尿病患者的糖尿病痛苦和抑郁症状的病程及其发病率和缓解的预测因素。方法每6个月收集一次数据，为期24个月。参与者（n=654）完成了糖尿病困扰（糖尿病问题领域量表）和抑郁症状（患者健康问卷8）的测量。考虑人口统计学、临床和社会心理因素，应用Cox比例风险模型检查发病率和缓解的预测因子。除HbA1c作为时变协变量建模外，所有预测因子均在基线时进行评估。结果：在24个月的时间里，21%的样本出现了糖尿病困扰的累积事件，缓解率为70%。对于抑郁症状，24个月的累计发生率为33%，缓解率为67%。糖尿病窘迫的中位发病时间为18个月，抑郁症状的中位发病时间为24个月；两组患者的中位缓解时间均为6个月。较高的HbA1c （HR=1.02, p=0.022）、女性（男性HR=0.55, p=0.043）、长期并发症（HR=2.11, p=0.009）和焦虑症史（HR=2.57, p=0.029）显著预测糖尿病窘迫的发生率，而没有预测因素与缓解相关。对于抑郁症状，较高的HbA1c （HR=1.03, p<0.001）、既往抑郁（HR=2.63, p=0.001）和饮食失调（HR=2.20, p=0.044）预测发病率。缓解仅与年龄相关（HR=1.02, p=0.045）。结论/解释：次优血糖结局可预测糖尿病窘迫和抑郁；然而，糖尿病困扰与焦虑症有关，而抑郁症状与先前的抑郁症和饮食失调有关，这暗示了不同的病因。

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引用次数: 0

Beta cell function and mass in individuals with and without remission of type 2 diabetes after Roux-en-Y gastric bypass. Roux-en-Y胃旁路治疗后伴有和未伴有缓解的2型糖尿病患者的β细胞功能和质量

IF 10.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-20 DOI: 10.1007/s00125-025-06659-1

Sevilay Tokgöz, Laura N Deden, Adrianne Hofboer, Rick I Meijer, Eric J Hazebroek, Arianne C van Bon, Bastiaan E de Galan, Cees J Tack, Marti Boss, Martin Gotthardt

Aims/hypothesis: In people with type 2 diabetes and obesity, Roux-en-Y gastric bypass (RYGB) can induce remission of diabetes. While RYGB has been reported to improve beta cell function in individuals with type 2 diabetes, it is unclear whether this is accompanied by changes in beta cell mass. In this explorative proof-of-concept study, we compared beta cell mass, measured by [⁶⁸Ga]Ga-NODAGA-exendin-4 positron emission tomography/computed tomography (PET/CT) imaging, between individuals achieving remission of type 2 diabetes following RYGB and those not achieving remission.

Methods: Individuals with (n=8) and without (n=9) remission of type 2 diabetes up to 4 years after RYGB were injected with 100 ± 5.6 MBq of [⁶⁸Ga]Ga-NODAGA-exendin-4 to quantify beta cell mass using PET/CT imaging. Beta cell function was determined by the AUC for C-peptide and the ratio between the AUC for C-peptide and AUC for glucose obtained from a combined arginine stimulation test (ARGT) and OGTT. Acquired variables are expressed as mean ± SD or median (IQR) based on normality.

Results: Individuals with remission of type 2 diabetes had a shorter diabetes duration than those without remission. After RYGB, beta cell function was higher in individuals with remission of type 2 diabetes than individuals without remission, based on both ARGTs (AUC_C-peptide/fasting glucose 1.1 ± 0.41 vs 0.32 ± 0.16 nmol × min/mmol, p=0.001) and OGTTs (AUC_C-peptide:AUC_glucose 0.15 [0.11-0.24] vs 0.032 [0.023-0.054], p=0.005). In contrast, beta cell mass did not differ between individuals with or without remission of type 2 diabetes (3.6 [3.4-5.4] vs 3.8 [1.9-4.5] kBq/MBq, p=0.87) and did not correlate with beta cell function or body weight parameters. HOMA2-%B, also representing beta cell function, was better in the remission group and significantly improved in these individuals after RYGB, whereas it remained unchanged in non-remitters.

Conclusions/interpretation: Individuals with remission of type 2 diabetes after RYGB have better beta cell function than those not achieving remission, but the groups did not differ with respect to beta cell mass. Our preliminary data argue against a stimulating effect of RYGB on beta cell mass, although revival of non-functional (so-called dormant) beta cells is a possible explanation for remission.

Trial registration: ClinicalTrials.gov NCT02542059.

目的/假设：在2型糖尿病和肥胖患者中，Roux-en-Y胃旁路术（RYGB）可以诱导糖尿病缓解。虽然有报道称RYGB可以改善2型糖尿病患者的β细胞功能，但尚不清楚这是否伴随着β细胞质量的变化。在这项探索性的概念验证研究中，我们比较了RYGB治疗后2型糖尿病缓解者和未缓解者之间的β细胞质量，通过[68Ga]Ga-NODAGA-exendin-4正电子发射断层扫描/计算机断层扫描（PET/CT）成像测量。方法：2型糖尿病患者（n=8）和2型糖尿病患者（n=9）在RYGB治疗后4年内均有缓解，分别注射100±5.6 MBq的[68Ga]Ga-NODAGA-exendin-4，通过PET/CT成像量化β细胞质量。β细胞功能由c肽的AUC以及精氨酸刺激试验（ARGT）和OGTT联合获得的c肽AUC与葡萄糖AUC之比确定。根据正态性，获得的变量表示为平均值±SD或中位数（IQR）。结果：2型糖尿病缓解的个体比没有缓解的个体糖尿病持续时间短。RYGB后，2型糖尿病缓解者的β细胞功能高于无缓解者，基于argt （aucc -肽/空腹血糖1.1±0.41 vs 0.32±0.16 nmol × min/mmol, p=0.001）和ogtt （aucc -肽：auc葡萄糖0.15 [0.11-0.24]vs 0.032 [0.023-0.054], p=0.005）。相反，β细胞质量在2型糖尿病缓解或未缓解的个体之间没有差异（3.6 [3.4-5.4]vs 3.8 [1.9-4.5] kBq/MBq, p=0.87），并且与β细胞功能或体重参数无关。同样代表β细胞功能的HOMA2-%B在缓解组中表现更好，并且在RYGB后显着改善，而在非缓解组中保持不变。结论/解释：RYGB后2型糖尿病缓解的个体比未达到缓解的个体具有更好的β细胞功能，但两组在β细胞质量方面没有差异。我们的初步数据反对RYGB对β细胞质量的刺激作用，尽管非功能性（所谓的休眠）β细胞的复苏可能是缓解的一种解释。试验注册：ClinicalTrials.gov NCT02542059。

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引用次数: 0

Prospective comparison of WBC SPECT/CT and conventional MRI for diagnosing osteomyelitis and monitoring treatment response in diabetic foot infections. WBC SPECT/CT与常规MRI在糖尿病足感染中诊断骨髓炎和监测治疗效果的前瞻性比较

IF 8.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-18 DOI: 10.1007/s00125-025-06652-8

Orhan K Öz,Amber M Sherwood,Peter A Crisologo,Amanda L Killeen,Kavita Bhavan,Javier La Fontaine,Katie L Rubitschung,Helena Hwang,Robert W Haley,Lawrence A Lavery

AIMS/HYPOTHESISOsteomyelitis is a common complication of diabetic foot ulcers and a leading cause of lower limb amputations globally. Accurate diagnosis of diabetic foot osteomyelitis (DFO) is essential for effective infection management and improving prognosis. This study aimed to compare the performance of white blood cell (WBC)-single photon emission computed tomography (SPECT)/computed tomography (CT) and conventional MRI in the initial diagnosis of DFO and in detecting residual infection during treatment monitoring, using bone biopsy as the reference standard.METHODSIn this prospective clinical study, 47 patients with foot wounds suspicious for DFO underwent 99mTc-WBC SPECT/CT and MRI, followed by bone biopsy. After receiving a standard course of antibiotics, 20 patients returned for post-treatment imaging and a repeat biopsy. All imaging studies and histopathology were blindly interpreted as positive or negative for DFO. Biopsies were considered positive if either bone cultures or histopathology indicated osteomyelitis. Imaging results were evaluated against biopsy to determine the diagnostic performance of each method before and after treatment.RESULTSFor initial DFO diagnosis, WBC SPECT/CT demonstrated sensitivity, specificity, positive predictive value and negative predictive value of 85%, 79%, 90% and 69%, respectively, while MRI yielded corresponding values of 73%, 43%, 75% and 40%. Following antibiotic therapy, WBC SPECT/CT and MRI shared identical sensitivities, specificities, positive predictive values and negative predictive values of 75%, 75%, 43% and 92%.CONCLUSIONS/INTERPRETATIONWBC SPECT/CT exhibits greater sensitivity and specificity than MRI at initial diagnosis. However, after treatment, WBC SPECT/CT and MRI perform equivalently in determining therapeutic response. Our results indicate WBC SPECT/CT is a viable, if not superior, method for primary non-invasive assessment of suspected DFO. To our knowledge, this is the first study to use paired bone biopsy to validate imaging in diabetic foot infections both before and after antibiotic intervention.

目的/假设等骨髓炎是糖尿病足溃疡的常见并发症，也是全球下肢截肢的主要原因。准确诊断糖尿病足骨髓炎（DFO）对于有效的感染管理和改善预后至关重要。本研究以骨活检为参考标准，比较白细胞(WBC)-单光子发射计算机断层扫描(SPECT)/计算机断层扫描（CT）和常规MRI在DFO的初步诊断和治疗监测中检测残留感染的性能。方法在本前瞻性临床研究中，对47例疑似足部创伤的患者行99mTc-WBC SPECT/CT和MRI检查，并行骨活检。在接受标准疗程的抗生素治疗后，20名患者返回进行治疗后成像和重复活检。所有影像学检查和组织病理学都被盲目地解释为DFO的阳性或阴性。如果骨培养或组织病理学显示骨髓炎，则活检呈阳性。将影像学结果与活检相比较，以确定治疗前后每种方法的诊断性能。结果WBC SPECT/CT对DFO初步诊断的敏感性、特异性、阳性预测值和阴性预测值分别为85%、79%、90%和69%，而MRI的相应值分别为73%、43%、75%和40%。抗生素治疗后，白细胞SPECT/CT和MRI的敏感性、特异性、阳性预测值和阴性预测值相同，分别为75%、75%、43%和92%。结论/解释白细胞SPECT/CT在初始诊断时比MRI具有更高的敏感性和特异性。然而，治疗后，白细胞SPECT/CT和MRI在确定治疗反应方面表现相同。我们的结果表明，WBC SPECT/CT是一种可行的方法，如果不是优越的，原发性无创评估疑似DFO的方法。据我们所知，这是第一个使用配对骨活检来验证抗生素干预前后糖尿病足感染成像的研究。

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引用次数: 0

Sex steroids, SHBG and type 2 diabetes in women: what do we really know? 女性的性类固醇、SHBG和2型糖尿病：我们到底知道什么？

IF 8.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-15 DOI: 10.1007/s00125-025-06647-5

Nicolette J D Verhoog,Donita Africander,Karl-Heinz Storbeck

Androgens and oestrogens differentially regulate metabolic processes that impact the development of type 2 diabetes in women. The biological actions of these sex steroids are, however, dependent on their bioavailability, which is regulated by their carrier protein sex hormone-binding globulin (SHBG). However, SHBG itself plays a role in the risk of developing type 2 diabetes, independent of the sex steroid. The molecular mechanisms underlying the effects of androgens, oestrogens and SHBG in the pathogenesis of type 2 diabetes in women are complex and multifaceted, spanning various insulin-sensitive tissues. This review explores the current knowledge on these topics and provides a mechanistic framework that integrates current experimental and clinical findings, providing insights into sex steroid-specific pathways and the sex steroid-independent effects of SHBG. Finally, the review highlights the need for further studies using appropriate models to delineate the relationship between androgens, 17β-oestradiol, SHBG and type 2 diabetes, with a view to translating these findings to improve women's health.

雄激素和雌激素对影响女性2型糖尿病发展的代谢过程有不同的调节作用。然而，这些性类固醇的生物学作用取决于它们的生物利用度，而生物利用度是由它们的载体蛋白性激素结合球蛋白（SHBG）调节的。然而，SHBG本身在发生2型糖尿病的风险中起作用，独立于性类固醇。雄激素、雌激素和SHBG在女性2型糖尿病发病机制中的作用的分子机制是复杂和多方面的，涉及多种胰岛素敏感组织。这篇综述探讨了目前关于这些主题的知识，并提供了一个整合当前实验和临床发现的机制框架，提供了对性类固醇特异性途径和性类固醇非依赖性SHBG效应的见解。最后，该综述强调需要进一步研究，使用适当的模型来描述雄激素、17β-雌二醇、SHBG和2型糖尿病之间的关系，以期将这些发现转化为改善女性健康。

引用次数: 0

Teplizumab treatment for stage 2 type 1 diabetes: a real-world evaluation of metabolic and immunological outcomes. Teplizumab治疗2期1型糖尿病：代谢和免疫结果的真实世界评估

IF 8.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2026-01-15 DOI: 10.1007/s00125-025-06646-6

Kagan E Karakus,Lexie Chesshir,Sonya Walker,Erin E Baschal,Kristen A McDaniel,Taylor M Triolo,Andrea K Steck,Brigitte I Frohnert,Peter A Gottlieb,Aaron W Michels,Kimber M Simmons

AIMS/HYPOTHESISThis is the first real-world prospective observational study of teplizumab use following approval by the United States Food and Drug Administration in individuals with stage 2 type 1 diabetes. We examined whether glycaemic responses observed in controlled trials were reproduced in real-world practice and explored immunological biomarkers associated with treatment.METHODSChildren and adults with stage 2 type 1 diabetes were prospectively followed in the Early Type 1 Diabetes Clinic at the Barbara Davis Center. Individuals who received teplizumab between April 2023 and February 2025 (n=30) were compared with an untreated group (n=10). Key assessments included OGTTs, HbA1c measurements and continuous glucose monitoring (CGM) data, collected before and after treatment. Longitudinal metabolic data were available for up to 22 treated participants, with follow-up assessments occurring between 2 and 13 months after treatment. Changes in Epstein-Barr virus (EBV) and islet antigen-targeting T cell receptor (TCR) β chains were measured longitudinally from genomic DNA via a PCR-based targeted TCR sequencing assay.RESULTSAmong treated individuals followed up between 2 and 6 months after treatment, OGTT 2 h glucose improved (10.7 ± 2.1 to 8.8 ± 2.8 mmol/l, p=0.007), as did HbA1c (40 ± 4 to 39 ± 6 mmol/mol [5.8 ± 0.4% to 5.7 ± 0.5%], p=0.044). In addition, 67% had a stable or reduced CGM time ≥7.8 mmol/l. CD4 preproinsulin-specific TCRs declined after treatment, with no change in the untreated group. These reductions correlated with higher C-peptide AUC (r=-0.656, p=0.013). EBV TCR sequences were similar before and after teplizumab treatment.CONCLUSIONS/INTERPRETATIONTeplizumab can be safely and effectively administered in clinical practice. Early glycaemic improvements and reductions in CD4 preproinsulin-specific TCRs suggest that post-treatment immunological changes may serve as biomarkers to guide early-stage intervention.

目的/假设：这是美国食品和药物管理局批准teplizumab用于2期1型糖尿病患者后的首个真实世界的前瞻性观察性研究。我们检查了对照试验中观察到的血糖反应是否在现实世界的实践中重现，并探索了与治疗相关的免疫生物标志物。方法对Barbara Davis中心早期1型糖尿病诊所的2期1型糖尿病儿童和成人进行前瞻性随访。在2023年4月至2025年2月期间接受teplizumab治疗的个体（n=30）与未治疗组（n=10）进行比较。主要评估包括治疗前后收集的ogtt、HbA1c测量和连续血糖监测（CGM）数据。22名接受治疗的参与者的纵向代谢数据可用，随访评估在治疗后2至13个月之间进行。采用基于pcr的靶向TCR测序方法，从基因组DNA纵向测定eb病毒（EBV）和胰岛抗原靶向T细胞受体(TCR) β链的变化。结果治疗后随访2 ~ 6个月，OGTT 2 h血糖改善（10.7±2.1 ~ 8.8±2.8 mmol/l, p=0.007），糖化血红蛋白改善（40±4 ~ 39±6 mmol/mol[5.8±0.4% ~ 5.7±0.5%],p=0.044）。此外，67%的患者CGM时间稳定或缩短≥7.8 mmol/l。治疗后，CD4前胰岛素特异性tcr下降，未治疗组无变化。这些降低与较高的c肽AUC相关（r=-0.656, p=0.013）。EBV TCR序列在替普利单抗治疗前后相似。结论/解释teplizumab在临床实践中是安全有效的。早期血糖改善和CD4前胰岛素特异性tcr的降低表明，治疗后的免疫变化可能作为指导早期干预的生物标志物。

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引用次数: 0