Cardiovascular Diabetology最新文献_第7页

Association of nonalcoholic fatty liver disease with new-onset atrial fibrillation stratified by age groups 按年龄组划分的非酒精性脂肪肝与新发心房颤动的关系

IF 9.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-12 DOI: 10.1186/s12933-024-02408-7

Eun Ju Cho, Goh Eun Chung, Jeong-Ju Yoo, Yuri Cho, Kyu Na Lee, Dong Wook Shin, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Su Jong Yu

The association between nonalcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) has been inconsistent, and the impact of hepatic fibrosis on this relationship remains uncertain. We investigated the association between NAFLD and the risk of new-onset AF across different age groups. A total of 3,179,582 participants from the 2009 Korean National Health Screening Program were divided into five groups based on NAFLD status: no NAFLD (fatty liver index [FLI] < 30); grade 1 NAFLD without advanced fibrosis (FLI 30–59 & BARD < 2); grade 1 NAFLD with advanced fibrosis (FLI 30–59 & BARD ≥ 2); grade 2 NAFLD without advanced fibrosis (FLI ≥ 60 & BARD < 2); and grade 2 NAFLD with advanced fibrosis (FLI ≥ 60 & BARD ≥ 2). The primary outcome was incident AF. During the median follow-up of 9.3 years, 62,542 patients were diagnosed with new-onset AF. In the age- and sex-adjusted model, the risk of new-onset AF increased across NAFLD grades and fibrosis categories: grade 1 NAFLD without advanced fibrosis (hazard ratio [HR] 1.120, 95% confidence interval [CI]: 1.081–1.161); grade 1 NAFLD with advanced fibrosis (HR 1.275, 95% CI 1.251–1.300); grade 2 NAFLD without advanced fibrosis (HR 1.305, 95% CI: 1.252–1.360); and grade 2 NAFLD with advanced fibrosis (HR 1.627, 95% CI: 1.586–1.670). In the multivariate model, the excess risk of AF in patients with NAFLD and advanced fibrosis remained significant, even in participants aged 20–39 years. Patients with NAFLD had a higher risk of new-onset AF, which increased progressively with NAFLD severity, particularly in those aged 20–29 years.

非酒精性脂肪肝（NAFLD）与心房颤动（AF）之间的关系并不一致，肝纤维化对这种关系的影响仍不确定。我们研究了非酒精性脂肪肝与不同年龄组新发房颤风险之间的关系。根据非酒精性脂肪肝状态，我们将 2009 年韩国国民健康检查计划的 3,179,582 名参与者分为五组：无非酒精性脂肪肝（脂肪肝指数[FLI] < 30）；1级非酒精性脂肪肝，无晚期纤维化（FLI 30-59，BARD < 2）；1级非酒精性脂肪肝，有晚期纤维化（FLI 30-59，BARD ≥ 2）；2级非酒精性脂肪肝，无晚期纤维化（FLI ≥ 60，BARD < 2）；2级非酒精性脂肪肝，有晚期纤维化（FLI ≥ 60，BARD ≥ 2）。主要结果是发生房颤。在中位随访 9.3 年期间，有 62542 名患者被诊断为新发房颤。在年龄和性别调整模型中，新发房颤的风险随非酒精性脂肪肝等级和纤维化类别的不同而增加：无晚期纤维化的1级非酒精性脂肪肝（危险比[HR]1.120，95%置信区间[CI]：1.081-1.161）；1级非酒精性脂肪肝伴晚期纤维化（HR 1.275，95% CI 1.251-1.300）；2级非酒精性脂肪肝无晚期纤维化（HR 1.305，95% CI：1.252-1.360）；2级非酒精性脂肪肝伴晚期纤维化（HR 1.627，95% CI：1.586-1.670）。在多变量模型中，即使在20-39岁的参与者中，非酒精性脂肪肝和晚期纤维化患者发生房颤的超额风险仍然显著。非酒精性脂肪肝患者新发房颤的风险较高，且随着非酒精性脂肪肝严重程度的增加而逐渐增加，尤其是在20-29岁的患者中。

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引用次数: 0

Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays 将红细胞作为儿童肥胖与胰岛素抵抗串联过程中代谢紊乱的敏感而可靠的传感器：观察研究、体内挑战测试和体外孵化试验的发现

IF 9.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-11 DOI: 10.1186/s12933-024-02395-9

Álvaro González-Domínguez, Otto Savolainen, Jesús Domínguez-Riscart, Rikard Landberg, Alfonso Lechuga-Sancho, Raúl González-Domínguez

Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals’ metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.

虽然胰岛素抵抗（IR）是儿童肥胖症最常见、最具病理相关性的并发症之一，但它在调节和加重肥胖症病理生理学方面的作用尚未完全阐明。为了更深入地了解儿童肥胖与 IR 之间的相互作用，我们采用了综合实验设计，将观察数据、体内挑战测试（即口服葡萄糖耐量测试）和体外检测（即用胰岛素培养红细胞）结合起来，研究对象包括肥胖合并 IR 的儿童、肥胖合并 IR 的儿童以及健康对照组，并收集他们的血浆和红细胞样本进行代谢组学分析。在内源性、微生物和环境决定因素的相互影响下，合并有红外症的儿童表现出更严重的代谢紊乱，包括能量平衡失调、氨基酸代谢、氧化应激、类固醇激素和胆汁酸的合成、膜脂组成，以及与饮食、内分泌干扰物暴露和肠道微生物群相关的暴露相关代谢物的差异。此外，挑战测试和体内外试验显示，红外热反应对个体的代谢灵活性有有害影响，这反映在对高胰岛素血症做出反应时，在全身和红细胞水平上调节平衡的能力减弱。因此，我们首次证明，红细胞中代谢物的改变是可靠而灵敏的生物标志物，可用于揭示红外热与儿童肥胖症代谢的复杂性。这项研究强调，要更准确地了解与肥胖相关的分子机制，就必须解决个体间的变异因素，如是否存在合并症等。

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引用次数: 0

Mendelian randomization analysis reveals causal effects of blood lipidome on gestational diabetes mellitus 孟德尔随机分析揭示血脂组对妊娠糖尿病的因果效应

IF 9.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-11 DOI: 10.1186/s12933-024-02429-2

Yao Dong, An-qun Hu, Bai-xue Han, Meng-ting Cao, Hai-yan Liu, Zong-guang Li, Qing Li, Ying-jie Zheng

Observational studies have revealed associations between maternal lipid metabolites and gestational diabetes mellitus (GDM). However, whether these associations are causal remain uncertain. To evaluate the causal relationship between lipid metabolites and GDM. A two-sample Mendelian randomization (MR) analysis was performed based on summary statistics. Sensitivity analyses, validation analyses and reverse MR analyses were conducted to assess the robustness of the MR results. Additionally, a phenome-wide MR (Phe-MR) analysis was performed to evaluate potential side effects of the targeted lipid metabolites. A total of 295 lipid metabolites were included in this study, 29 of them had three or more instrumental variables (IVs) suitable for sensitivity analyses. The ratio of triglycerides to phosphoglycerides (TG_by_PG) was identified as a potential causal biomarker for GDM (inverse variance weighted (IVW) estimate: odds ratio (OR) = 2.147, 95% confidential interval (95% CI) 1.415–3.257, P = 3.26e−4), which was confirmed by validation and reverse MR results. Two other lipid metabolites, palmitoyl sphingomyelin (d18:1/16:0) (PSM(d18:1/16:0)) (IVW estimate: OR = 0.747, 95% CI 0.583–0.956, P = 0.021) and triglycerides in very small very low-density lipoprotein (XS_VLDL_TG) (IVW estimate: OR = 2.948, 95% CI 1.197–5.215, P = 0.015), were identified as suggestive potential biomarkers for GDM using a conventional cut-off P-value of 0.05. Phe-MR results indicated that lowering TG_by_PG had detrimental effects on two diseases but advantageous effects on the other 13 diseases. Genetically predicted elevated TG_by_PG are causally associated with an increased risk of GDM. Side-effect profiles indicate that TG_by_PG might be a target for GDM prevention, though caution is advised due to potential adverse effects on other conditions.

观察性研究发现，母体脂质代谢物与妊娠糖尿病（GDM）之间存在关联。然而，这些关联是否是因果关系仍不确定。为了评估血脂代谢物与妊娠糖尿病之间的因果关系，我们进行了一项双样本孟德尔随机研究。根据汇总统计进行了双样本孟德尔随机化（MR）分析。进行了敏感性分析、验证分析和反向 MR 分析，以评估 MR 结果的稳健性。此外，还进行了全表型 MR（Phe-MR）分析，以评估目标脂质代谢物的潜在副作用。本研究共纳入了 295 个脂质代谢物，其中 29 个代谢物有三个或三个以上适合进行敏感性分析的工具变量 (IV)。甘油三酯与磷酸甘油比值（TG_by_PG）被确定为 GDM 的潜在因果生物标志物（逆方差加权（IVW）估计值：比值比（OR）= 2.147，95% 置信区间（95% CI）为 1.415-3.257，P = 3.26e-4），验证和反向 MR 结果证实了这一点。另外两种脂质代谢物棕榈酰鞘磷脂（d18:1/16:0）（PSM(d18:1/16:0)）（IVW 估计值：OR = 0.747，95% CI 0.583-0.956，P = 0.021）和极小极低密度脂蛋白中的甘油三酯（XS_VLDL_TG）（IVW 估计值：OR = 2.948，95% CI 1.197-5.215，P = 0.015）被确定为 GDM 的提示性潜在生物标志物，常规临界 P 值为 0.05。Phe-MR结果表明，降低TG_by_PG对两种疾病不利，但对其他13种疾病有利。基因预测的 TG_by_PG 升高与 GDM 风险增加有因果关系。副作用分析表明，TG_by_PG 可能是预防 GDM 的靶点，但由于可能对其他疾病产生不利影响，建议谨慎使用。

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引用次数: 0

The role of body composition in left ventricular remodeling, reverse remodeling, and clinical outcomes for heart failure with mildly reduced ejection fraction: more knowledge to the “obesity paradox” 身体成分在左心室重塑、反向重塑和射血分数轻度降低型心力衰竭临床预后中的作用："肥胖悖论 "的更多知识

IF 9.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-11 DOI: 10.1186/s12933-024-02430-9

Kang Fu, Youran Dong, Zhiyuan Wang, Junlin Teng, Congyi Cheng, Cong Su, Xiaoping Ji, Huixia Lu

Although the “obesity paradox” is comprehensively elucidated in heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), the role of body composition in left ventricular (LV) remodeling, LV reverse remodeling (LVRR), and clinical outcomes is still unclear for HF with mildly reduced ejection fraction (HFmrEF). Our study is a single-centre, prospective, and echocardiography-based study. Consecutive HFmrEF patients, defined as HF patients with a left ventricular ejection fraction (LVEF) between 40 and 49%, between January 2016 to December 2021 were included. Echocardiography was re-examined at 3-, 6-, and 12-month follow-up to assess the LVRR dynamically. Body mass index (BMI), fat mass, fat-free mass, percent body fat (PBF), CUN-BAE index, and lean mass index (LMI) were adopted as anthropometric parameters in our study to assess body composition. The primary outcome was LVRR, defined as: (1) a reduction higher than 10% in LV end-diastolic diameter index (LVEDDI), or a LVEDDI < 33 mm/m2, (2) an absolute increase of LVEF higher than 10 points compared with baseline echocardiogram, or a follow-up LVEF ≥50%. The secondary outcome was a composite of re-hospitalization for HF or cardiovascular death. A total of 240 HFmrEF patients were enrolled in our formal analysis. After 1-year follow-up based on echocardiography, 113 (47.1%) patients developed LVRR. Patients with LVRR had higher fat mass (21.7 kg vs. 19.3 kg, P = 0.034) and PBF (28.7% vs. 26.6%, P = 0.047) compared with those without. The negative correlation between anthropometric parameters and baseline LVEDDI was significant (all P < 0.05). HFmrEF patients with higher BMI, fat mass, PBF, CUN-BAE index, and LMI had more pronounced and persistent increase of LVEF and decline in LV mass index (LVMI). Univariable Cox regression analysis revealed that higher BMI (HR 1.042, 95% CI 1.002–1.083, P = 0.037) and fat mass (HR 1.019, 95% CI 1.002–1.036, P = 0.026) were each significantly associated with higher cumulative incidence of LVRR for HFmrEF patients, while this relationship vanished in the adjusted model. Mediation analysis indicated that the association between BMI and fat mass with LVRR was fully mediated by baseline LV dilation. Furthermore, higher fat mass (aHR 0.957, 95% CI 0.917–0.999, P = 0.049) and PBF (aHR 0.963, 95% CI 0.924–0.976, P = 0.043) was independently associated with lower risk of adverse clinical events. Body composition played an important role in the LVRR and clinical outcomes for HFmrEF. For HFmrEF patients, BMI and fat mass was positively associated with the cumulative incidence of LVRR, while higher fat mass and PBF predicted lower risk of adverse clinical events but not LMI.

虽然 "肥胖悖论 "已在射血分数降低型心力衰竭（HFrEF）和射血分数保留型心力衰竭（HFpEF）中得到全面阐明，但对于射血分数轻度降低型心力衰竭（HFmrEF），身体成分在左心室重塑、左心室反向重塑（LVRR）和临床预后中的作用仍不清楚。我们的研究是一项基于超声心动图的单中心、前瞻性研究。研究纳入了2016年1月至2021年12月期间连续就诊的HFmrEF患者，定义为左室射血分数（LVEF）在40%至49%之间的HF患者。在随访3个月、6个月和12个月时再次进行超声心动图检查，以动态评估左心室射血分数（LVRR）。本研究采用体重指数（BMI）、脂肪量、无脂肪量、体脂百分比（PBF）、CUN-BAE 指数和瘦体重指数（LMI）作为人体测量参数来评估身体组成。主要结果是 LVRR，定义为(1）左心室舒张末期直径指数（LVEDDI）下降超过 10%，或 LVEDDI < 33 mm/m2；（2）与基线超声心动图相比，LVEF 绝对值增加超过 10 个点，或随访 LVEF ≥50%。次要结果是因心房颤动再次住院或心血管死亡的复合结果。共有 240 名 HFmrEF 患者参与了我们的正式分析。根据超声心动图进行为期一年的随访后，113 例（47.1%）患者出现了 LVRR。与无 LVRR 的患者相比，LVRR 患者的脂肪量（21.7 千克对 19.3 千克，P = 0.034）和 PBF（28.7% 对 26.6%，P = 0.047）更高。人体测量参数与基线 LVEDDI 之间存在显著的负相关（所有 P 均小于 0.05）。BMI、脂肪量、PBF、CUN-BAE 指数和 LMI 较高的 HFmrEF 患者 LVEF 的增加和 LV 质量指数（LVMI）的下降更为明显和持久。单变量 Cox 回归分析显示，较高的体重指数（HR 1.042，95% CI 1.002-1.083，P = 0.037）和脂肪量（HR 1.019，95% CI 1.002-1.036，P = 0.026）均与 HFmrEF 患者较高的 LVRR 累积发生率显著相关，而这种关系在调整模型中消失。中介分析表明，BMI 和脂肪量与 LVRR 的关系完全由基线 LV 扩张中介。此外，较高的脂肪量（aHR 0.957，95% CI 0.917-0.999，P = 0.049）和 PBF（aHR 0.963，95% CI 0.924-0.976，P = 0.043）与较低的不良临床事件风险独立相关。身体成分对 LVRR 和 HFmrEF 的临床结局起着重要作用。对于 HFmrEF 患者来说，体重指数和脂肪量与 LVRR 的累积发生率呈正相关，而较高的脂肪量和 PBF 可预测较低的不良临床事件风险，但不能预测 LMI。

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引用次数: 0

Triglyceride-glucose index correlates with the occurrence and prognosis of acute myocardial infarction complicated by cardiogenic shock: data from two large cohorts 甘油三酯-葡萄糖指数与急性心肌梗死并发心源性休克的发生和预后的相关性：来自两个大型队列的数据

IF 9.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-11 DOI: 10.1186/s12933-024-02423-8

Huiruo Liu, Liangshan Wang, Xing Zhou, Hong Wang, Xing Hao, Zhongtao Du, Chenglong Li, Xiaotong Hou

Triglyceride-glucose (TyG) index, a dependable indicator of insulin resistance, has been identified as a valid marker regarding multiple cardiovascular diseases. Nevertheless, the correlation of TyG index with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains uncertain. Our study aims for elucidating this relationship by comprehensively analyzing two large-scale cohorts. Utilizing records from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care IV, the link between TyG and the incidence and prognosis of AMICS was assessed multicentrally and retrospectively by logistic and correlation models, as well as restricted cubic spline (RCS). Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were employed to balance the potential confounders. Subgroup analyses were performed according to potential modifiers. Overall, 5208 AMI patients, consisting of 375 developing CS were finally included. The TyG index exhibited an apparently higher level in AMI populations developing CS than in those who did not experienced CS [9.2 (8.8–9.7) vs. 9.0 (8.5–9.5)], with a moderate discrimination ability to recognize AMICS from the general AMI (AUC: 0.604). Logistic analyses showed that the TyG index was significantly correlated with in-hospital and ICU mortality. RCS analysis demonstrated a linear link between elevated TyG and increased risks regarding in-hospital and ICU mortality in the AMICS population. An increased mortality risk remains evident in PSM-, OW- and IPTW-adjusted populations with higher TyG index who have undergone CS. Correlation analyses demonstrated an apparent link between TyG index and APS score. Subgroup analyses presented a stable link between elevated TyG and mortality particularly in older age, females, those who are overweight or hypertensive, as well as those without diabetes. Elevated TyG index was related to the incidence of CS following AMI and higher mortality risks in the population with AMICS. Our findings pointed a previously undisclosed role of TyG index in regard to AMICS that still requires further validation.

甘油三酯-葡萄糖（TyG）指数是胰岛素抵抗的可靠指标，已被确定为多种心血管疾病的有效标志物。然而，TyG 指数与急性心肌梗死并发心源性休克（AMICS）的相关性仍不确定。我们的研究旨在通过全面分析两个大规模队列来阐明这种关系。利用 eICU 协作研究数据库和重症监护医学信息市场 IV 的记录，通过逻辑和相关模型以及受限立方样条曲线（RCS），多中心和回顾性地评估了 TyG 与 AMICS 发病率和预后之间的关系。为了平衡潜在的混杂因素，采用了倾向评分匹配（PSM）、逆概率治疗加权（IPTW）和重叠加权（OW）。根据潜在的调节因素进行了分组分析。最终共纳入了 5208 名 AMI 患者，其中包括 375 名 CS 患者。发生 CS 的 AMI 患者的 TyG 指数明显高于未发生 CS 的患者[9.2 (8.8-9.7) vs. 9.0 (8.5-9.5)]，在识别 AMICS 和一般 AMI 方面具有中等辨别能力（AUC：0.604）。逻辑分析表明，TyG指数与院内死亡率和重症监护室死亡率显著相关。RCS分析表明，在AMICS人群中，TyG指数升高与住院和重症监护室死亡率风险增加之间存在线性关系。在 PSM、OW 和 IPTW 调整后的人群中，TyG 指数较高且接受过 CS 的患者的死亡风险仍明显增加。相关分析表明，TyG指数与APS评分之间存在明显联系。亚组分析显示，TyG指数升高与死亡率之间存在稳定联系，尤其是在老年人、女性、超重或高血压患者以及无糖尿病患者中。TyG指数升高与急性心肌梗死后的CS发病率和AMICS人群较高的死亡率风险有关。我们的研究结果表明，TyG指数在AMICS中的作用之前尚未披露，仍需进一步验证。

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引用次数: 0

MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression 脂肪组织源性外泌体包裹的 MiRNA-132/212 会加剧动脉粥样硬化的进展

IF 9.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-09 DOI: 10.1186/s12933-024-02404-x

Bei Guo, Tong-Tian Zhuang, Chang-Chun Li, Fuxingzi Li, Su-Kang Shan, Ming-Hui Zheng, Qiu-Shuang Xu, Yi Wang, Li-Min Lei, Ke-Xin Tang, Wenlu Ouyang, Jia-Yue Duan, Yun-Yun Wu, Ye-Chi Cao, Muhammad Hasnain Ehsan Ullah, Zhi-Ang Zhou, Xiao Lin, Feng Wu, Feng Xu, Xiao-Bo Liao, Ling-Qing Yuan

Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.

肥胖者的内脏脂肪组织是一个独立的心血管风险指标。然而，脂肪组织是否会通过其分泌的外泌体影响动脉粥样硬化等常见心血管疾病，目前仍不清楚。我们分离了饮食诱导肥胖小鼠脂肪组织分泌的外泌体，以研究它们对动脉粥样硬化进展的影响及其相关机制。对动脉粥样硬化斑块内皮细胞凋亡、血管平滑肌细胞（VSMC）的增殖和迁移进行了评估。使用 GraphPad Prism 9.0 和适当的统计检验分析统计意义。我们证明，脂肪组织源性外泌体（AT-EX）通过促进斑块内皮细胞凋亡、增殖和 VSMCs 迁移，加剧了动脉粥样硬化的进展。在AT-EX货物中检测到了MicroRNA-132/212（miR-132/212）。从机理上讲，富含miR-132/212的AT-EX通过靶向G蛋白亚基α12加剧棕榈酸诱导的内皮细胞凋亡，并通过靶向体外磷酸酶和天丝同源物增强血小板衍生生长因子BB型诱导的VSMC增殖和迁移。重要的是，褪黑素能降低外泌体 miR-132/212 的水平，从而减轻 AT-EX 促进动脉粥样硬化的影响。这些数据揭示了脂肪组织源性外泌体调节动脉粥样硬化进展的病理机制，并确定 miR-132/212 为动脉粥样硬化的潜在诊断和治疗靶点。

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引用次数: 0

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults 在一个以年轻健康成年人为主的样本中，内皮功能与皮肤高级糖化终产物（AGEs）积累之间的关系

IF 9.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-09 DOI: 10.1186/s12933-024-02428-3

Juanita J. Fewkes, Aimee L. Dordevic, Margaret Murray, Gary Williamson, Nicole J. Kellow

In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium. A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4–36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates. FMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001. Higher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers. The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.

在患有慢性疾病的人群中，皮肤自发荧光（SAF）是衡量身体组织中长期荧光高级糖化终产物（AGEs）积累的一种指标，它与使用血流介导的扩张（FMD）测量的血管内皮功能有关。本研究的主要目的是量化普通人群中成年人血管内皮功能与 AGEs 组织积累之间的关系，以确定 SAF 是否可用作预测血管内皮早期损伤的标志物。该研究对 125 名参与者（中位年龄：28.5 岁，IQR：24.4-36.0；54% 为女性）进行了横断面研究。内皮功能通过空腹 FMD 进行测量。使用 AGE 阅读器测量皮肤 AGEs（SAF）。此外，还测量了参与者的人体测量、血压和血液生物标志物。通过多变量回归分析评估了两者之间的关联，并对重要的协变量进行了调整。FMD与SAF（ρ = -0.50，P < 0.001）和实际年龄（ρ = -0.51，P < 0.001）成反比。在多变量分析中，SAF、实际年龄和男性性别与 FMD 减少独立相关（分别为 B [95% CI]；-2.60 [-4.40, -0.80]；-0.10 [-0.16, -0.03]；1.40 [0.14, 2.67]），多变量模型调整 R2 = 0.31，P < 0.001。在以年轻人为主的健康人群中，通过 SAF 测量的较高皮肤 AGE 水平与较低的 FMD 值相关。此外，年龄较大的男性参与者的 FMD 值明显较低，这与内皮功能受损有关。这些结果表明，在出现任何动脉结构性病理生理学或典型的心血管疾病风险标记物之前，SAF 这种简单而廉价的标记物可用来预测内皮功能受损。该研究已在澳大利亚-新西兰临床试验注册中心进行了前瞻性注册（ACTRN12621000821897），并同时以相同的 ID 编号进入了世界卫生组织国际临床试验注册平台。

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引用次数: 0

High proportion of undiagnosed diabetes in patients surgically treated for infrarenal abdominal aortic aneurysm: findings from the multicentre Norwegian Aortic Aneurysm and Diabetes (ABANDIA) Study 接受手术治疗的肾下腹主动脉瘤患者中未确诊糖尿病的比例很高：挪威主动脉瘤和糖尿病多中心研究（ABANDIA）的结果

IF 9.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-09 DOI: 10.1186/s12933-024-02421-w

J. Wesche, T. Bakken, M. Vetrhus, K. O. Hufthammer, L. Aa Nyroenning, H. Fagertun, I. Saethre, B. H. Wold, C. Lyng, E. M. Pettersen, I. S. Kjellsen, E. T. Gubberud, S. Kiil, H. Loose, M. T. Helgeland, M. E. Altreuther, E. Mattsson, T. Jonung, I. D. Hjellestad

The aim was to investigate the total prevalence of known and undiagnosed diabetes mellitus (DM), and the association of DM with perioperative complications following elective, infrarenal, open surgical (OSR) or endovascular (EVAR), Abdominal Aortic Aneurysm (AAA) repair. In this Norwegian prospective multicentre study, 877 patients underwent preoperative screening for DM by HbA1c measurements from November 2017 to December 2020. Diabetes was defined as screening detected HbA1c ≥ 48 mmol/mol (6.5%) or previously diagnosed diabetes. The association of DM with in-hospital complications, length of stay, and 30-day mortality rate were evaluated using adjusted and unadjusted logistic regression models. The total prevalence of DM was 15% (95% CI 13%,17%), of which 25% of the DM cases (95% CI 18%,33%) were undiagnosed upon admission for AAA surgery. The OSR to EVAR ratio was 52% versus 48%, with similar distribution among DM patients, and no differences in the prevalence of known and undiagnosed DM in the EVAR versus the OSR group. Total 30-day mortality rate was 0.6% (5/877). Sixty-six organ-related complications occurred in 58 (7%) of the patients. DM was not statistically significantly associated with a higher risk of in-hospital organ-related complications (OR 1.23, 95% CI 0.57,2.39, p = 0.57), procedure-related complications (OR 1.48, 95% CI 0.79,2.63, p = 0.20), 30-day mortality (p = 0.09) or length of stay (HR 1.06, 95% CI 0.88,1.28, p = 0.54). According to post-hoc-analyses, organ-related complications were more frequent in patients with newly diagnosed DM (n = 32) than in non-DM patients (OR 4.92; 95% CI 1.53,14.3, p = 0.005). Twenty-five percent of all DM cases were undiagnosed at the time of AAA surgery. Based on post-hoc analyses, undiagnosed DM seems to be associated with an increased risk of organ related complications following AAA surgery. This study suggests universal DM screening in AAA patients to reduce the number of DM patients being undiagnosed and to improve proactive diabetes care in this population. The results from post-hoc analyses should be confirmed in future studies.

该研究旨在调查已知和未确诊糖尿病（DM）的总患病率，以及DM与择期、肾下、开放手术（OSR）或血管内（EVAR）腹主动脉瘤（AAA）修复术围手术期并发症的关联。在这项挪威前瞻性多中心研究中，877 名患者在 2017 年 11 月至 2020 年 12 月期间通过 HbA1c 测量接受了糖尿病术前筛查。糖尿病的定义是筛查出的 HbA1c ≥ 48 mmol/mol（6.5%）或既往诊断为糖尿病。采用调整和未调整的逻辑回归模型评估了糖尿病与院内并发症、住院时间和30天死亡率的关系。DM的总患病率为15%（95% CI为13%,17%），其中25%的DM病例（95% CI为18%,33%）在入院接受AAA手术时未被确诊。OSR与EVAR的比例为52%对48%，DM患者的分布情况相似，EVAR组与OSR组已知和未确诊的DM患病率没有差异。30天总死亡率为0.6%（5/877）。58名患者（7%）出现了66例器官相关并发症。DM与较高的院内器官相关并发症风险（OR 1.23，95% CI 0.57,2.39，p = 0.57）、手术相关并发症（OR 1.48，95% CI 0.79,2.63，p = 0.20）、30天死亡率（p = 0.09）或住院时间（HR 1.06，95% CI 0.88,1.28，p = 0.54）无明显统计学相关性。根据事后分析，与非糖尿病患者相比，新确诊的糖尿病患者（n = 32）更容易出现器官相关并发症（OR 4.92; 95% CI 1.53,14.3，p = 0.005）。所有DM病例中有25%在接受AAA手术时尚未确诊。根据事后分析，未确诊的DM似乎与AAA手术后器官相关并发症的风险增加有关。本研究建议对 AAA 患者进行 DM 普查，以减少未确诊的 DM 患者人数，并改善该人群的糖尿病前瞻性护理。事后分析的结果应在今后的研究中得到证实。

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引用次数: 0

Fully automated epicardial adipose tissue volume quantification with deep learning and relationship with CAC score and micro/macrovascular complications in people living with type 2 diabetes: the multicenter EPIDIAB study. 利用深度学习进行全自动心外膜脂肪组织体积量化以及与 2 型糖尿病患者 CAC 评分和微/大血管并发症的关系：多中心 EPIDIAB 研究。

IF 8.5 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-03 DOI: 10.1186/s12933-024-02411-y

Bénédicte Gaborit, Jean Baptiste Julla, Joris Fournel, Patricia Ancel, Astrid Soghomonian, Camille Deprade, Adèle Lasbleiz, Marie Houssays, Badih Ghattas, Pierre Gascon, Maud Righini, Frédéric Matonti, Nicolas Venteclef, Louis Potier, Jean François Gautier, Noémie Resseguier, Axel Bartoli, Florian Mourre, Patrice Darmon, Alexis Jacquier, Anne Dutour

Background: The aim of this study (EPIDIAB) was to assess the relationship between epicardial adipose tissue (EAT) and the micro and macrovascular complications (MVC) of type 2 diabetes (T2D).

Methods: EPIDIAB is a post hoc analysis from the AngioSafe T2D study, which is a multicentric study aimed at determining the safety of antihyperglycemic drugs on retina and including patients with T2D screened for diabetic retinopathy (DR) (n = 7200) and deeply phenotyped for MVC. Patients included who had undergone cardiac CT for CAC (Coronary Artery Calcium) scoring after inclusion (n = 1253) were tested with a validated deep learning segmentation pipeline for EAT volume quantification.

Results: Median age of the study population was 61 [54;67], with a majority of men (57%) a median duration of the disease 11 years [5;18] and a mean HbA1c of7.8 ± 1.4%. EAT was significantly associated with all traditional CV risk factors. EAT volume significantly increased with chronic kidney disease (CKD vs no CKD: 87.8 [63.5;118.6] vs 82.7 mL [58.8;110.8], p = 0.008), coronary artery disease (CAD vs no CAD: 112.2 [82.7;133.3] vs 83.8 mL [59.4;112.1], p = 0.0004, peripheral arterial disease (PAD vs no PAD: 107 [76.2;141] vs 84.6 mL[59.2; 114], p = 0.0005 and elevated CAC score (> 100 vs < 100 AU: 96.8 mL [69.1;130] vs 77.9 mL [53.8;107.7], p < 0.0001). By contrast, EAT volume was neither associated with DR, nor with peripheral neuropathy. We further evidenced a subgroup of patients with high EAT volume and a null CAC score. Interestingly, this group were more likely to be composed of young women with a high BMI, a lower duration of T2D, a lower prevalence of microvascular complications, and a higher inflammatory profile.

Conclusions: Fully-automated EAT volume quantification could provide useful information about the risk of both renal and macrovascular complications in T2D patients.

研究背景本研究（EPIDIAB）旨在评估心外膜脂肪组织（EAT）与2型糖尿病（T2D）微血管和大血管并发症（MVC）之间的关系：该研究是一项多中心研究，旨在确定降糖药物对视网膜的安全性，研究对象包括筛查出糖尿病视网膜病变（DR）的 2 型糖尿病患者（n = 7200），并对 MVC 进行了深入的表型分析。对纳入后接受心脏 CT 进行 CAC（冠状动脉钙化）评分的患者（n = 1253）进行了测试，并使用经过验证的深度学习分割管道对 EAT 体积进行量化：研究人群的中位年龄为 61 [54;67]，男性占多数（57%），中位病程为 11 年 [5;18]，平均 HbA1c 为 7.8 ± 1.4%。EAT 与所有传统的冠心病风险因素都有明显关联。慢性肾脏病（CKD vs 无 CKD：87.8 [63.5;118.6] vs 82.7 mL [58.8;110.8], p = 0.008）、冠状动脉疾病（CAD vs 无 CAD：112.2 [82.7;133.3] vs 83.8 mL [59.4;112.1]，p = 0.0004；外周动脉疾病（PAD vs 无 PAD：107 [76.2;141] vs 84.6 mL[59.2;114]，p = 0.0005）；CAC 评分升高（> 100 vs 结论：CAC 评分升高可能是由于外周动脉疾病所致）：全自动 EAT 容量定量可提供有关 T2D 患者肾脏和大血管并发症风险的有用信息。

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引用次数: 0

Metabolically "extremely unhealthy" obese and non-obese people with diabetes and the risk of cardiovascular adverse events: the Silesia Diabetes - Heart Project. 代谢 "极不健康 "的肥胖和非肥胖糖尿病患者与心血管不良事件的风险：西里西亚糖尿病-心脏项目。

IF 8.5 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology

Pub Date : 2024-09-03 DOI: 10.1186/s12933-024-02420-x

Oliwia Janota, Marta Mantovani, Hanna Kwiendacz, Krzysztof Irlik, Tommaso Bucci, Steven H M Lam, Bi Huang, Uazman Alam, Giuseppe Boriani, Mirela Hendel, Julia Piaśnik, Anna Olejarz, Aleksandra Włosowicz, Patrycja Pabis, Wiktoria Wójcik, Janusz Gumprecht, Gregory Y H Lip, Katarzyna Nabrdalik

Background: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia).

Methods: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1-2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese "extremely unhealthy"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1-2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese "extremely unhealthy"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke.

Results: 2105 people with DM were included [median age 60 (IQR 45-70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06-13.47, respectively). On interaction analysis, in "extremely unhealthy" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (P_int=0.824), but more pronounced in individuals aged < 65 years compared to older adults (P_int= 0.028).

Conclusion: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an "extremely unhealthy" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach.

背景：非肥胖糖尿病（DM）患者越来越多。然而，他们的心血管风险（CV），尤其是合并心血管-肾脏-代谢（CKM）疾病时的心血管风险，却鲜为人知。本研究旨在根据肥胖和合并症（高血压、慢性肾病和血脂异常）的存在情况，分析糖尿病患者发生重大心血管不良事件的风险：我们分析了参加前瞻性西里西亚糖尿病心脏项目（NCT05626413）的人员。根据是否存在不同的临床风险因素（肥胖和慢性肾脏病合并症），这些人被分为 6 个类别：(i) 第 1 组：非肥胖，无 CKM 合并症；(ii) 第 2 组：非肥胖，有 1-2 个 CKM 合并症；(iii) 第 3 组：非肥胖，有 3 个 CKM 合并症（非肥胖 "极不健康"）；(iv) 第 4 组：(v) 第 5 组：有 1-2 项 CKM 合并症的肥胖者；以及 (vi) 第 6 组：有 3 项 CKM 合并症的肥胖者（肥胖者 "极不健康"）。主要结果是冠心病死亡、心肌梗死、新发心力衰竭和缺血性脑卒中的综合结果。结果：2105 名糖尿病患者被纳入研究[中位年龄 60 岁（IQR 45-70），48.8% 为女性]。第 1 组和第 6 组发生主要综合结果的风险较高（aHR 4.50，95% CI 1.20-16.88；aHR 3.78，95% CI 1.06-13.47）。交互分析显示，在 "极度不健康 "人群中，肥胖和非肥胖人群的慢性肾功能不全并发症对不良事件风险的影响是一致的（Pint=0.824），但在高龄人群中更为明显（Pint=0.028）：结论：非肥胖和肥胖的糖尿病患者以及患有 3 种相关慢性肾功能不全并发症的患者都是 "极度不健康 "的表型，发生心血管不良事件的风险最高。这些结果凸显了利用跨学科方法对糖尿病患者进行风险分层以进行风险因素管理的重要性。

{"title":"Metabolically \"extremely unhealthy\" obese and non-obese people with diabetes and the risk of cardiovascular adverse events: the Silesia Diabetes - Heart Project.","authors":"Oliwia Janota, Marta Mantovani, Hanna Kwiendacz, Krzysztof Irlik, Tommaso Bucci, Steven H M Lam, Bi Huang, Uazman Alam, Giuseppe Boriani, Mirela Hendel, Julia Piaśnik, Anna Olejarz, Aleksandra Włosowicz, Patrycja Pabis, Wiktoria Wójcik, Janusz Gumprecht, Gregory Y H Lip, Katarzyna Nabrdalik","doi":"10.1186/s12933-024-02420-x","DOIUrl":"10.1186/s12933-024-02420-x","url":null,"abstract":"Background: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia).Methods: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1-2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese \"extremely unhealthy\"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1-2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese \"extremely unhealthy\"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke.Results: 2105 people with DM were included [median age 60 (IQR 45-70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06-13.47, respectively). On interaction analysis, in \"extremely unhealthy\" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (Pint=0.824), but more pronounced in individuals aged < 65 years compared to older adults (Pint= 0.028).Conclusion: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an \"extremely unhealthy\" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach.","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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