Diabetes & metabolism最新文献_第4页

Are GLP-1 receptor agonists and diabetic retinopathy foes or friends? GLP-1受体激动剂和糖尿病视网膜病变是敌是友？

IF 4.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-08-18 DOI: 10.1016/j.diabet.2025.101696

Kai Liu , Shu Liu , Dong Wang , Hong Qiao

With the increasing number of patients with diabetes worldwide, the number of patients with diabetic retinopathy (DR) is also increasing, which affects the lives of patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are anti-diabetic drugs that mimic the action of endogenous glucagon-like peptide-1, which significantly improve glycemic control in patients with type 2 diabetes. GLP-1RAs can repair the blood-retinal barrier function by activating the GLP-1 receptor in retinal endothelial cells and nerve cells, inhibiting the RhoA/ROCK signaling pathway, up-regulating the tight junction protein occludin and ZO-1, and inhibiting the activation of microglia, reducing the release of pro-inflammatory factors, and reducing neuroinflammation and vascular leakage. However, some GLP-1RAs may increase the risk of DR, such as diabetic macular edema and proliferative DR, and may increase the risk of DR deterioration, especially during rapid glucose lowering. Although the new GLP-1/GIP dual-receptor agonists and GLP-1/GIP/glucagon tri-receptor agonists show comprehensive benefit potential by effectively improving body metabolism, the short-term negative effect of sudden blood glucose drop still needs to be paid attention to. For patients with moderate to severe DR, it is necessary to strengthen ophthalmic monitoring to avoid rapid blood glucose decline in the initial treatment. In the long-term treatment, metabolic benefits and retinal risks need to be weighed, and the patient's condition needs to be evaluated before treatment. Therefore, GLP-1RAs has a duality of "mechanism protection and clinical risk" on DR, and individualized treatment strategy should take into consideration drug characteristics, DR severity and glucose control.

随着全球糖尿病患者数量的不断增加，糖尿病视网膜病变（DR）患者数量也在不断增加，影响着患者的生活。胰高血糖素样肽-1受体激动剂（Glucagon-like peptide-1 receptor agonists, GLP-1RAs）是一种模拟内源性胰高血糖素样肽-1作用的降糖药物，可显著改善2型糖尿病患者的血糖控制。GLP-1RAs通过激活视网膜内皮细胞和神经细胞中的GLP-1受体，抑制RhoA/ROCK信号通路，上调紧密连接蛋白occludin和ZO-1，抑制小胶质细胞的活化，减少促炎因子的释放，减少神经炎症和血管渗漏，从而修复血视网膜屏障功能。然而，一些GLP-1RAs可能会增加DR的风险，如糖尿病性黄斑水肿和增殖性DR，并可能增加DR恶化的风险，特别是在血糖快速降低期间。虽然新型GLP-1/GIP双受体激动剂和GLP-1/GIP/胰高血糖素三受体激动剂通过有效改善机体代谢显示出综合获益潜力，但短期内血糖突然下降的负面影响仍需引起重视。对于中重度DR患者，需加强眼科监测，避免初始治疗时血糖迅速下降。在长期治疗中，需要权衡代谢益处和视网膜风险，治疗前需要评估患者的病情。因此，GLP-1RAs对DR具有“机制保护和临床风险”的双重作用，个体化治疗策略应综合考虑药物特性、DR严重程度和血糖控制情况。

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引用次数: 0

Reduced risks of colorectal cancer with GLP-1RAs in type 2 diabetes: A nationwide cohort study using a target trial emulation framework GLP-1RAs降低2型糖尿病患者患结直肠癌的风险：一项使用目标试验模拟框架的全国性队列研究

IF 4.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-08-10 DOI: 10.1016/j.diabet.2025.101695

Chih-Chien Wu , Chien-Chou Su , Yu-Ching Chang , Pei-Ting Lee , Yi-Chia Su

Aim

- Type 2 diabetes (T2D) is associated with increased risk of colorectal cancer (CRC). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce CRC risk compared to insulin therapy; however, current evidence is controversial. We aimed to evaluate the association between CRC and the use of GLP-1RAs and long-acting insulins (LAIs).

Methods

- This target trial emulation employed nationwide data from a Taiwanese T2D cohort. We identified new GLP-1RA and LAI users from 2013 to 2021, and applied propensity score (PS) matching to ensure comparable baseline characteristics. The primary outcome was CRC. Follow-up lasted until outcome occurrence, death, or study end in 2022, whichever came first. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated to assess the association between treatment and outcomes. Sensitivity analyses—including stabilized inverse probability weighting, time-dependent survival analysis, E-values, and negative control outcome analyses—were conducted to test the robustness of findings.

Results

- We included 11,726 PS-matched pairs of GLP-1RA and LAI users and found no significant baseline disparities between cohorts. Compared to LAIs, GLP-1RAs were associated with significantly reduced CRC risk (HR [95 % CI]: 0.66 [0.48–0.92]), with the association limited to the rectum (HR: 0.53 [0.28–0.92]) but not observed in the right- or left-sided colon (right, HR: 0.69 [0.41–1.19]; left, HR: 0.77 [0.44–1.33]). These findings were consistent across sensitivity analyses and among patients with varying baseline characteristics.

Conclusion

- Among patients with T2D requiring injectable glucose-lowering agents, GLP-1RA use, compared to LAIs, was associated with reduced CRC risk, particularly in the rectum.

目的- 2型糖尿病（T2D）与结直肠癌（CRC）风险增加相关。与胰岛素治疗相比，胰高血糖素样肽-1受体激动剂（GLP-1RAs）可能降低结直肠癌的风险；然而，目前的证据是有争议的。我们的目的是评估结直肠癌与GLP-1RAs和长效胰岛素（LAIs）使用之间的关系。方法：这项目标试验模拟采用了台湾t2dm队列的全国数据。我们从2013年到2021年确定了新的GLP-1RA和LAI用户，并应用倾向评分（PS）匹配来确保可比较的基线特征。主要结局为结直肠癌。随访持续到2022年结果发生、死亡或研究结束，以先到者为准。计算95%置信区间（ci）的风险比（hr），以评估治疗与结果之间的关联。进行敏感性分析，包括稳定的逆概率加权、时间相关的生存分析、e值和阴性对照结果分析，以检验结果的稳健性。结果：我们纳入了11,726对ps匹配的GLP-1RA和LAI使用者，发现队列之间没有显著的基线差异。与LAIs相比，GLP-1RAs与显著降低结直肠癌风险相关（HR [95% CI]: 0.66[0.48-0.92]），这种关联仅限于直肠（HR: 0.53[0.28-0.92]），但在左右结肠(HR: 0.69 [0.41-1.19]；左，HR: 0.77[0.44-1.33])。这些发现在敏感性分析和不同基线特征的患者中是一致的。结论：在需要注射降糖药的T2D患者中，与LAIs相比，GLP-1RA的使用与降低结直肠癌风险相关，特别是在直肠。

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引用次数: 0

Body weight trends in individuals with type 1 diabetes using automated insulin delivery vs. traditional insulin pumps 1型糖尿病患者使用自动胰岛素输送与传统胰岛素泵的体重变化趋势

IF 4.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-07-29 DOI: 10.1016/j.diabet.2025.101693

Charles Thivolet , Zoé Henry , Nathalie Bendelac , Sylvie Villar Fimbel

Objective

This study analyzed the determinants of weight gain among participants initiating an automated insulin delivery (AID) system.

Research design and methods

In this observational study, we evaluated 928 persons with type 1 diabetes initiating an insulin pump therapy, including 467 with AID, 98 with pumps with predictive low-glucose suspend (PLGS) algorithm and 363 initiating a sensor-augmented pump (SAP).

Results

After 3 months, median (95CI) TIR increased from 50.69 % [49.2–52.3] to 67.9 % [66.7–69.1] in the AID group and HbA1c levels showed a mean reduction of 0.82 %. AID resulted in equivalent body weight gain to SAP and PLGS despite significant improvements in glucose control. Multivariable analysis revealed that weight gain was linked to baseline HbA1C (P < 0.001) and age but not to the type of pump system. During follow-up, percentage increase in body weight at 12 months were similar between groups

Conclusions

In persons with T1D, AID did not increase weight gain in comparison to other pump systems.

目的：本研究分析了启动自动胰岛素输送（AID）系统的参与者体重增加的决定因素。研究设计和方法：在这项观察性研究中，我们评估了928例开始胰岛素泵治疗的1型糖尿病患者，其中467例使用AID， 98例使用预测低糖悬浮（PLGS）算法的泵，363例使用传感器增强泵（SAP）。结果：3个月后，AID组的中位（95CI） TIR从50.69%[49.2-52.3]上升至67.9% [66.7-69.1]，HbA1c水平平均下降0.82%。AID导致的体重增加与SAP和PLGS相当，尽管血糖控制有显著改善。多变量分析显示，体重增加与基线HbA1C有关

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引用次数: 0

Association between smoking status and suicide mortality in patients with type 2 diabetes: A nationwide population-based cohort study 吸烟状况与2型糖尿病患者自杀死亡率之间的关系：一项基于全国人群的队列研究

IF 4.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-07-26 DOI: 10.1016/j.diabet.2025.101692

Chaiho Jeong , Bongseong Kim , Dae Jong Oh , Tae-Seo Sohn , Kyungdo Han , Hyuk-Sang Kwon

Background

Patients with type 2 diabetes (T2D) are at greater risk of suicide due to stresses associated with disease management. Smoking adds to this burden. However, its association with suicide mortality in this population remains unclear. This study aimed to evaluate the relationship between smoking and suicide mortality in this high-risk group.

Methods

This cohort study utilized the Korean National Health Insurance Service (NHIS) database. A total of 2,524,769 participants aged ≥ 20 years with T2D who underwent national health examinations in 2015–2016 were included. Participants were followed until suicide death or the end of the study period.

Results

Over 5.8 years mean follow-up, 5,578 individuals died by suicide. Risk of suicide mortality was significantly higher—adjusted hazard ratio [95 % confidence interval]—in current smokers compared to never-smokers: 1.55 [1.44;1.67]. A dose–response pattern was observed among current smokers: 1.41 [1.22;1.63] for light smokers (<10 cigarettes/day) and 1.66 [1.52;1.81] for heavy smokers (≥20/day). In ex-smokers, only those with a smoking history of ≥ 30 years exhibited an elevated risk: 1.12 [1.02;1.24]. The association was particularly strong in women: 2.97 [2.39;3.69]; and individuals aged <65 years: 1.76 [1.61;1.92].

Conclusions

Current smoking was significantly associated with increased suicide mortality in patients with T2D, particularly among heavy smokers, women and those younger than 65 years. Long-term smoking history was also associated with elevated risk among ex-smokers.

背景：2型糖尿病（T2D）患者由于与疾病管理相关的压力而有更高的自杀风险。吸烟加重了这种负担。然而，其与该人群自杀死亡率的关系尚不清楚。本研究旨在评估吸烟与这一高危人群自杀死亡率之间的关系。方法：本队列研究利用韩国国民健康保险服务（NHIS）数据库。共纳入2015-2016年接受全国健康检查的年龄≥20岁T2D患者2,524,769例。参与者被跟踪到自杀死亡或研究期结束。结果：在5.8年的平均随访中，5578人死于自杀。与不吸烟者相比，当前吸烟者自杀死亡率的调整后危险比[95%置信区间]显著更高：1.55[1.44;1.67]。在当前吸烟者中观察到剂量-反应模式：轻度吸烟者为1.41[1.22;1.63](结论：当前吸烟与T2D患者自杀死亡率增加显著相关，特别是在重度吸烟者、女性和65岁以下的人群中。长期吸烟史也与戒烟者的风险增加有关。

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引用次数: 0

Conduction disturbances in Type 1 and Type 2 Diabetes in two large independent nationwide and international databases 1型和2型糖尿病的传导干扰在两个大型独立的全国和国际数据库。

IF 4.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-07-24 DOI: 10.1016/j.diabet.2025.101690

Lucile Accoceberry , Uazman Alam , Grégoire Fauchier , Lisa Lochon , Arnaud Bisson , Pierre Henri Ducluzeau , Gregory Y.H. Lip , Laurent Fauchier

Aim

Type 1 (T1D) and type 2 diabetes (T2D) are associated with increased cardiovascular risk, but limited data exist on their independent association with conduction disturbances. We evaluated the association between diabetes and conduction disorders, comparing T1D and T2D populations with non-diabetic controls in two independent databases.

Methods

Observational study using two large databases with matched cohorts: the French PMSI and the international TriNetX network. PMSI captures nationwide hospital admissions in France, while TriNetX includes patients from over 120 healthcare organizations worldwide. We identified > 440,000 patients with T2D from PMSI and > 900,000 patients with T2D and > 20,000 patients with T1D from TriNetX. Using 1:1 propensity score matching, these patients were matched to non-diabetic controls based on demographics and comorbidities

Results

Compared to no DM, T2D was associated with a higher risk of conduction disturbances, including atrioventricular block (HR 1.22 [1.19–1.25], PMSI; HR 1.50 [1.45–1.55], TriNetX), left bundle branch block (BBB), (HR 1.12 [1.08–1.17], PMSI; HR 1.50 [1.47–1.54], TriNetX), and right BBB (HR 1.14 [1.09–1.18], PMSI; HR 1.38 [1.34–1.43], TriNetX). Patients with T2D also had a higher risk of myocardial infarction (HR 1.29 [1.25–1.32], PMSI; HR 2.14 [2.08–2.19], TriNetX). Conversely, T1D was not associated with an increased risk of conduction disorders in the TriNetX cohort.

Conclusion

T2D is independently associated with conduction disturbances and a higher incidence of coronary events compared to no DM, whereas T1D does not appear to confer the same risk. This suggests distinct pathophysiological mechanisms and the possible need for enhanced monitoring in T2D patients.

目的：1型（T1D）和2型糖尿病（T2D）与心血管风险增加相关，但关于它们与传导障碍的独立关联的数据有限。我们评估了糖尿病和传导障碍之间的关系，在两个独立的数据库中比较了T1D和T2D人群与非糖尿病对照组。方法：观察性研究，使用两个具有匹配队列的大型数据库：法国PMSI和国际TriNetX网络。PMSI捕获法国全国范围内的医院入院情况，而TriNetX包括来自全球120多个医疗机构的患者。我们从PMSI中发现了440,000例T2D患者，从TriNetX中发现了900,000例T2D患者和20,000例T1D患者。采用1:1倾向评分匹配，根据人口统计学和合并症将这些患者与非糖尿病对照进行匹配。结果：与非DM相比，T2D与传导障碍的风险较高相关，包括房室传导阻滞(HR 1.22 [1.19-1.25]， PMSI；HR 1.50 [1.45-1.55], TriNetX)，左束支阻滞（BBB）， (HR 1.12 [1.08-1.17]， PMSI；HR 1.50 [1.47-1.54], TriNetX)，右BBB (HR 1.14 [1.09-1.18]， PMSI；HR 1.38 [1.34-1.43], TriNetX)。t2dm患者发生心肌梗死的风险也较高(HR 1.29 [1.25-1.32]， PMSI；hr2.14 [2.08-2.19]；相反，在TriNetX队列中，T1D与传导障碍风险增加无关。结论：与非DM相比，T2D与传导障碍和更高的冠状动脉事件发生率独立相关，而T1D似乎不具有相同的风险。这表明不同的病理生理机制和可能需要加强监测的T2D患者。

{"title":"Conduction disturbances in Type 1 and Type 2 Diabetes in two large independent nationwide and international databases","authors":"Lucile Accoceberry , Uazman Alam , Grégoire Fauchier , Lisa Lochon , Arnaud Bisson , Pierre Henri Ducluzeau , Gregory Y.H. Lip , Laurent Fauchier","doi":"10.1016/j.diabet.2025.101690","DOIUrl":"10.1016/j.diabet.2025.101690","url":null,"abstract":"<div><h3>Aim</h3><div>Type 1 (T1D) and type 2 diabetes (T2D) are associated with increased cardiovascular risk, but limited data exist on their independent association with conduction disturbances. We evaluated the association between diabetes and conduction disorders, comparing T1D and T2D populations with non-diabetic controls in two independent databases.</div></div><div><h3>Methods</h3><div>Observational study using two large databases with matched cohorts: the French PMSI and the international TriNetX network. PMSI captures nationwide hospital admissions in France, while TriNetX includes patients from over 120 healthcare organizations worldwide. We identified > 440,000 patients with T2D from PMSI and > 900,000 patients with T2D and > 20,000 patients with T1D from TriNetX. Using 1:1 propensity score matching, these patients were matched to non-diabetic controls based on demographics and comorbidities</div></div><div><h3>Results</h3><div>Compared to no DM, T2D was associated with a higher risk of conduction disturbances, including atrioventricular block (HR 1.22 [1.19–1.25], PMSI; HR 1.50 [1.45–1.55], TriNetX), left bundle branch block (BBB), (HR 1.12 [1.08–1.17], PMSI; HR 1.50 [1.47–1.54], TriNetX), and right BBB (HR 1.14 [1.09–1.18], PMSI; HR 1.38 [1.34–1.43], TriNetX). Patients with T2D also had a higher risk of myocardial infarction (HR 1.29 [1.25–1.32], PMSI; HR 2.14 [2.08–2.19], TriNetX). Conversely, T1D was not associated with an increased risk of conduction disorders in the TriNetX cohort.</div></div><div><h3>Conclusion</h3><div>T2D is independently associated with conduction disturbances and a higher incidence of coronary events compared to no DM, whereas T1D does not appear to confer the same risk. This suggests distinct pathophysiological mechanisms and the possible need for enhanced monitoring in T2D patients.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 6","pages":"Article 101690"},"PeriodicalIF":4.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring perceived barriers to physical activity among individuals with type 1 diabetes in the era of new technologies: An analysis from the BETTER registry 探索新技术时代1型糖尿病患者身体活动的感知障碍：来自BETTER注册表的分析

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-07-06 DOI: 10.1016/j.diabet.2025.101677

C. Guédet , L. Alexandre-Heymann , J.E. Yardley , V. Messier , V. Boudreau , T. Chahal , M. Dostie , M-E. Mathieu , A-S. Brazeau , S. Tagougui , R. Rabasa-Lhoret

Objective

We aimed to identify barriers to physical activity for people living with type 1 diabetes (PwT1D) and their relationship with sociodemographic and disease-specific factors.

Methods

- Cross-sectional study with BETTER registry participants (>14 years) who completed the BAPAD1 (Barriers to Physical Activity in T1D) questionnaire. An item with a score of 5 or more was defined as a barrier. Participants were categorized into 4 subgroups based on their insulin therapy and blood glucose monitoring modality: 1) multiple daily injections (MDI) without continuous glucose monitoring (CGM), 2) MDI with CGM, 3) continuous subcutaneous insulin infusion (CSII) with CGM, and 4) automated insulin delivery system (AID).

Results

Among 1117 participants, the main perceived barrier was fear of hypoglycemia. BAPAD1 scores were similar across all subgroups, but more individuals in the AID group perceived "fear of hypoglycemia" and "loss of control over diabetes" as barriers. Being female, having a low income or education level, being overweight or obese, taking medication for depression, younger diabetes, higher HbA1c, presence of microvascular complications, and lack of confidence in managing hypoglycemia were associated with higher BAPAD1 score.

Conclusion

Fear of hypoglycemia remains the main barrier to physical activity for PwT1D. Technological advances alone are not sufficient to reduce perceived barriers to physical activity, highlighting the need for complementary educational and behavioral interventions.

目的：-我们旨在确定1型糖尿病患者（PwT1D）的身体活动障碍及其与社会人口统计学和疾病特定因素的关系。方法：-对BETTER注册中心的参与者（> - 14岁）进行横断面研究，他们完成了BAPAD1 （T1D身体活动障碍）问卷。得分在5分或以上的项目被定义为障碍。根据胰岛素治疗和血糖监测方式将参与者分为4个亚组：1)每日多次注射（MDI）不进行连续血糖监测（CGM）， 2) MDI合并连续血糖监测（CGM）， 3)连续皮下胰岛素输注（CSII）与CGM， 4)胰岛素自动输送系统（AID）。结果：在1117名参与者中，主要的感知障碍是对低血糖的恐惧。所有亚组的BAPAD1得分相似，但AID组中更多的个体认为“害怕低血糖”和“失去对糖尿病的控制”是障碍。女性、收入或受教育程度低、超重或肥胖、服用抑郁症药物、糖尿病年轻化、HbA1c较高、存在微血管并发症以及对低血糖管理缺乏信心与较高的BAPAD1评分相关。结论：对低血糖的恐惧仍然是PwT1D患者进行体育活动的主要障碍。仅靠技术进步并不足以减少人们所认为的身体活动障碍，这突出表明需要补充教育和行为干预措施。(图1)。

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引用次数: 0

Association between continuous glucose monitoring metrics and metabolic dysfunction-associated steatotic liver disease in adults with type 1 diabetes undergoing vibration-controlled transient elastography: a multicenter cross-sectional study 在接受振动控制的瞬时弹性成像的成人1型糖尿病患者中，连续血糖监测指标与代谢功能障碍相关的脂肪变性肝病之间的关系：一项多中心横断面研究

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-07-05 DOI: 10.1016/j.diabet.2025.101684

Alessandro Mantovani , Stefano Ciardullo , Elena Sani , Alessandro Csermely , Emigela Shtembari , Ilaria Milani , Paolo Sbraccia , Gianluca Perseghin , Frida Leonetti , Giovanni Targher , Valeria Guglielmi , Danila Capoccia

Background

There is uncertainty regarding the association between continuous glucose monitoring (CGM), derived glycemic metrics, and metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with type 1 diabetes (T1D).

Methods

We consecutively enrolled 262 adult individuals with established T1D undergoing vibration-controlled transient elastography (VCTE) with liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). All participants underwent CGM. MASLD was defined as CAP ≥248 dB/m and the presence of at least one cardiometabolic risk factor. Significant liver fibrosis was defined as LSM ≥8 kPa.

Results

Participants had a mean age of 54±13 years, a mean body mass index (BMI) of 25.8 ± 5.6 kg/m² and a mean HbA1c of 7.7 ± 1.4 %. The prevalence of MASLD and significant liver fibrosis was 35.1 % (n = 92) and 4.6 % (n = 12), respectively. Using quantile regression analysis, time above range 180–250 mg/dl (TAR1) was significantly associated with increased CAP values (coefficient: 1.037; 95 % confidence interval [0.216;1.858]; P = 0.013). This association remained significant even after adjusting for age, sex, BMI, HbA1c, and total daily insulin dose. Other variables independently associated with CAP were older age, male sex, BMI, and total daily insulin dose. Using a random forest regression model, BMI was found to be the most important factor, followed by age, total daily insulin dose, and TAR1.

Conclusions

TAR1 was independently associated with increased CAP values, even after adjustment for age, BMI, sex, HbA1c, and total daily insulin dose, suggesting a potential role for glycemic variability in hepatic fat accumulation in adults with T1D.

背景：在1型糖尿病（T1D）患者中，持续血糖监测（CGM）、衍生血糖指标与代谢功能障碍相关的脂肪变性肝病（MASLD）之间的关系尚不确定。方法采用振动控制瞬态弹性成像（VCTE），结合肝刚度测量（LSM）和可控衰减参数（CAP），对262例已确定T1D的成年患者进行连续实验。所有参与者均行CGM。MASLD定义为CAP≥248 dB/m，且存在至少一种心脏代谢危险因素。LSM≥8 kPa为肝纤维化。结果参与者平均年龄54±13岁，平均体重指数（BMI） 25.8±5.6 kg/m2，平均糖化血红蛋白（HbA1c） 7.7±1.4%。MASLD和显著肝纤维化的患病率分别为35.1% （n = 92）和4.6% （n = 12）。分位数回归分析显示，180 ~ 250 mg/dl （TAR1）以上时间与CAP值升高显著相关(系数：1.037；95%置信区间[0.216;1.858]；P = 0.013)。即使在调整了年龄、性别、BMI、HbA1c和每日总胰岛素剂量后，这种相关性仍然显著。与CAP独立相关的其他变量包括年龄、男性、BMI和每日总胰岛素剂量。使用随机森林回归模型，BMI是最重要的因素，其次是年龄、每日总胰岛素剂量和TAR1。结论：即使在调整了年龄、BMI、性别、HbA1c和每日总胰岛素剂量后，star1仍与CAP值升高独立相关，提示血糖变异性在成年T1D患者肝脏脂肪积累中的潜在作用。

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引用次数: 0

Post-translational modifications of apolipoproteins as promising biomarkers for diabetes-related cardiovascular diseases: A comprehensive review 载脂蛋白翻译后修饰作为糖尿病相关心血管疾病有前景的生物标志物：综述

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-07-05 DOI: 10.1016/j.diabet.2025.101683

Chloé Chevalier , Arsênio Rodrigues Oliveira , Valentin Blanchard , Cédric Le May , Bertrand Cariou , Samy Hadjadj , Mikaël Croyal

Lipoproteins are biochemical complexes of apolipoproteins and lipids that primarily mediate the transport of lipids through the circulation, from sites of absorption or synthesis to those of use, storage, or excretion. In type 2 diabetes (T2D), disruptions in lipoprotein metabolism are key drivers of complications and strongly contribute to atherosclerotic cardiovascular disease (ASCVD). As a result, ASCVD remains the leading cause of death in T2D, with significantly higher prevalence than in non-diabetic individuals. Protein post-translational modifications (PTMs) have emerged as key contributors to organ failure mechanisms, with specific PTMs closely linked to the pathogenesis of T2D. Several reports also emphasized the value of plasma apolipoproteins for the early prediction of ASCVD in cardiometabolic diseases. Thus, apolipoproteins, and especially their structurally post-translational modified forms, offer new insights into the molecular mechanisms of lipoprotein dysfunction and may enhance the specificity of ASCVD risk stratification in T2D. This review outlines major apolipoprotein PTMs identified in T2D, many of which can now be quantified in biological samples, particularly via mass spectrometry. We also discuss their role in lipoprotein metabolism dysfunction and their potential value in assessing ASCVD risk in T2D, highlighting their growing potential as clinical biomarkers in population-based cohort studies.

脂蛋白是载脂蛋白和脂质的生化复合物，主要介导脂质的循环运输，从吸收或合成点到使用、储存或排泄点。在2型糖尿病（T2D）中，脂蛋白代谢紊乱是并发症的关键驱动因素，也是动脉粥样硬化性心血管疾病（ASCVD）的重要诱因。因此，ASCVD仍然是T2D患者死亡的主要原因，其患病率明显高于非糖尿病患者。蛋白质翻译后修饰（PTMs）已成为器官衰竭机制的关键因素，特定的PTMs与T2D的发病机制密切相关。一些报告也强调了血浆载脂蛋白在心血管代谢疾病ASCVD早期预测中的价值。因此，载脂蛋白，特别是其结构翻译后修饰形式，为脂蛋白功能障碍的分子机制提供了新的见解，并可能增强T2D中ASCVD风险分层的特异性。本文概述了在T2D中发现的主要载脂蛋白PTMs，其中许多现在可以在生物样品中定量，特别是通过质谱法。我们还讨论了它们在脂蛋白代谢功能障碍中的作用，以及它们在评估T2D患者ASCVD风险方面的潜在价值，强调了它们在基于人群的队列研究中作为临床生物标志物的潜力。

{"title":"Post-translational modifications of apolipoproteins as promising biomarkers for diabetes-related cardiovascular diseases: A comprehensive review","authors":"Chloé Chevalier , Arsênio Rodrigues Oliveira , Valentin Blanchard , Cédric Le May , Bertrand Cariou , Samy Hadjadj , Mikaël Croyal","doi":"10.1016/j.diabet.2025.101683","DOIUrl":"10.1016/j.diabet.2025.101683","url":null,"abstract":"<div><div>Lipoproteins are biochemical complexes of apolipoproteins and lipids that primarily mediate the transport of lipids through the circulation, from sites of absorption or synthesis to those of use, storage, or excretion. In type 2 diabetes (T2D), disruptions in lipoprotein metabolism are key drivers of complications and strongly contribute to atherosclerotic cardiovascular disease (ASCVD). As a result, ASCVD remains the leading cause of death in T2D, with significantly higher prevalence than in non-diabetic individuals. Protein post-translational modifications (PTMs) have emerged as key contributors to organ failure mechanisms, with specific PTMs closely linked to the pathogenesis of T2D. Several reports also emphasized the value of plasma apolipoproteins for the early prediction of ASCVD in cardiometabolic diseases. Thus, apolipoproteins, and especially their structurally post-translational modified forms, offer new insights into the molecular mechanisms of lipoprotein dysfunction and may enhance the specificity of ASCVD risk stratification in T2D. This review outlines major apolipoprotein PTMs identified in T2D, many of which can now be quantified in biological samples, particularly via mass spectrometry. We also discuss their role in lipoprotein metabolism dysfunction and their potential value in assessing ASCVD risk in T2D, highlighting their growing potential as clinical biomarkers in population-based cohort studies.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 5","pages":"Article 101683"},"PeriodicalIF":4.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GLP-1 receptor agonists, body composition, skeletal muscle and risk of sarcopaenia: from promising findings in animal models to debated concern in human studies GLP-1受体激动剂，身体成分，骨骼肌和肌少症的风险：从动物模型的有希望的发现到人类研究中有争议的问题

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-06-24 DOI: 10.1016/j.diabet.2025.101681

André J. Scheen

Background. - Glucagon-like peptide-1 (GLP-1)-based therapies induce a clinically relevant weight loss, which is associated with overall better prognosis in people with type 2 diabetes and/or clinical obesity. However, a risk of excessive reduction in fat-free mass (FFM) and skeletal muscle mass (SSM), potentially leading to sarcopaenia in at-risk patients, is currently a matter of debate as this negative effect could minimize their benefit/risk balance. Methods. - An extensive literature search to detect animal and human studies that investigated the effects of GLP-1-based therapies on changes in body composition (FFM and SMM), muscle strength, structure, and function. Results. - Favourable effects on SMM, intramuscular lipid deposition, inflammation and mitochondrial health were consistently reported in different rodent models with GLP-based therapies. However, mixed results were reported in human studies, some reported an excessive FFM/SMM loss while others arguing for a protective effect against sarcopaenia (including less myosteatosis). This controversy may result from misinterpretation of SMM derived from FFM changes and a lack of studies that properly investigate SMM, muscle function and structure in humans. Conclusion. - Maximizing fat loss while preserving lean (muscle) tissue mass and function is a central goal of modern obesity pharmacological treatments. Currently, available data preclude to have a definite conclusion about positive/negative effects of GLP-1-based therapies on muscle. Further investigations using accurate methodologies to assess not only SMM but also muscle structure, function (strength) and performance are needed to better analyse the effects of GLP-1-based therapies, especially among individuals at higher risk of sarcopaenia, older patients and frail people.

背景。-以胰高血糖素样肽-1 （GLP-1）为基础的治疗可诱导临床相关的体重减轻，这与2型糖尿病和/或临床肥胖患者的总体预后较好相关。然而，过度减少无脂肪量（FFM）和骨骼肌量（SSM）的风险，可能导致高危患者的肌少症，目前是一个有争议的问题，因为这种负面影响可能会使他们的利益/风险平衡最小化。方法。-广泛的文献检索，以检测基于glp -1的治疗对身体成分（FFM和SMM）、肌肉力量、结构和功能变化的影响的动物和人类研究。结果。-在不同的啮齿动物模型中，glp疗法对SMM、肌内脂质沉积、炎症和线粒体健康均有良好的影响。然而，在人体研究中报告了不同的结果，一些报告了过度的FFM/SMM损失，而另一些则认为对肌少症有保护作用（包括减少肌骨化病）。这一争议可能源于对源自FFM变化的SMM的误解，以及缺乏适当研究人类SMM、肌肉功能和结构的研究。结论。-最大限度地减少脂肪，同时保持瘦（肌肉）组织的质量和功能是现代肥胖药物治疗的中心目标。目前，现有的数据排除了对基于glp -1的治疗对肌肉的正面或负面影响的明确结论。为了更好地分析基于glp -1的治疗的效果，特别是在肌少症高风险人群、老年患者和体弱人群中，需要使用准确的方法进行进一步的研究，不仅要评估SMM，还要评估肌肉结构、功能（力量）和表现。

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引用次数: 0

Prediction of cardiovascular events by skin auto-fluorescence: the DIABAGE follow-up study 皮肤自身荧光预测心血管事件：DIABAGE随访研究

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-06-23 DOI: 10.1016/j.diabet.2025.101682

Jorys Bueno , Alpha M. Diallo , Stéphane Jaisson , Jenny Fontaine , Céline Lukas , Romain Barriquand , Géraldine Vitellius , Philippe Gillery , Brigitte Delemer , Sara Barraud

Aim

Advanced glycation end-products (AGEs) are known to play a role in the pathophysiology of type 1 diabetes (T1D) complications. The aim of this study was to assess the predictive value of AGEs indirectly evaluated by skin auto-fluorescence (SAF) on the occurrence of cardiovascular events (CVEs) in T1D.

Methods

We measured baseline SAF in T1D patients with at least 10 years history of diabetes and assessed incident CVEs. An optimum threshold of SAF was determined using ROC curve, and its predictive value was assessed by Cox proportional regression.

Results

The study included 179 patients, 53 % of whom were women. At baseline, the mean age was 47.7 ± 15.9 years, the mean duration of diabetes was 26.4 ± 12.2 years. Median HbA_1c was 7.7 % (7.3–8.7) and median LDL cholesterol was 2.58 mmol/l (2.14–3.07). Median follow-up was 7.4 years (6.85 - 7.7) with 34 CVEs in 24 patients.

The median SAF level was 2.7 (2.3–3.1) in patients with incident CVEs and 2.1 (1.8–2.6) in patients without CVEs. The optimum threshold of SAF to differentiate patients with or without incident CVEs was 2.2. The occurrence of CVE was predicted by the optimum SAF threshold in the unadjusted model (HR 6.46), but also after adjustment with different models (HR 3.15–5.05).

Conclusion

SAF level is higher in people living with T1D who will present CVEs. Furthermore, SAF threshold of 2.2 predicted the occurrence of CVE. If these results are confirmed, SAF could be a useful marker in cardiovascular risk stratification in T1D.

目的:。已知晚期糖基化终产物（AGEs）在1型糖尿病（T1D）并发症的病理生理中发挥作用。本研究的目的是评估皮肤自身荧光（SAF）间接评估的AGEs对T1D患者心血管事件（CVEs）发生的预测价值。方法:。我们测量了至少有10年糖尿病病史的T1D患者的基线SAF，并评估了cve的发生率。采用ROC曲线确定SAF的最佳阈值，并采用Cox比例回归评价其预测价值。结果:。该研究包括179名患者，其中53%是女性。基线时，平均年龄为47.7±15.9岁，平均糖尿病病程为26.4±12.2年。中位HbA1c为7.7%(7.3-8.7)，中位LDL胆固醇为2.58 mmol/l（2.14-3.07）。24例患者34例cve，中位随访7.4年（6.85 - 7.7）。发生cve患者的中位SAF水平为2.7(2.3-3.1)，无cve患者的中位SAF水平为2.1（1.8-2.6）。SAF区分有无cve的最佳阈值为2.2。未调整模型的最佳SAF阈值可以预测CVE的发生（HR 6.46），不同模型调整后的最佳SAF阈值也可以预测CVE的发生（HR 3.15-5.05）。结论:。出现cve的T1D患者的SAF水平较高。SAF阈值为2.2预测CVE的发生。如果这些结果得到证实，SAF可能是T1D患者心血管危险分层的有用标志物。

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引用次数: 0