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Insulin resistance assessed by estimated glucose disposal rate and risk of atherosclerotic cardiovascular diseases incidence: the multi-ethnic study of atherosclerosis. 通过估计葡萄糖处置率评估胰岛素抵抗与动脉粥样硬化性心血管疾病发病风险:动脉粥样硬化多种族研究。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02437-2
Jiayi Yi, Chao Qu, Xiang Li, Hai Gao

Background: To investigate the relationship between estimated glucose disposal rate (eGDR), a surrogate indicator of insulin resistance, and atherosclerotic cardiovascular diseases (ASCVD) incidence risk.

Methods: This prospective cohort study utilized data from the 6026 participants from the Multi-Ethnic Study of Atherosclerosis. The eGDR (mg/kg/min) was computed as 21.158 - (0.09 × waist circumference [cm]) - (3.407 × hypertension [yes/no]) - (0.551 × HbA1c [%]). The population was categorized into four subgroups according to the quartiles (Q) of eGDR. Cox proportional hazard models were applied to assess the associations between eGDR and ASCVD incidence, and restricted cubic spine (RCS) was employed to examine the dose-response relationship.

Results: The mean age of participants was 63.6 ± 10.1 years, comprising 3163 (52.5%) women. Over a median follow-up duration of 14.1 years, 565 (9.4%) developed ASCVD, including 256 (4.2%) myocardial infarctions, 234 (3.9%) strokes, and 358 (5.9%) fatal coronary heart disease. Compared to the lowest quartile, the adjusted hazard ratios (95% confidence intervals) for incident ASCVD for Q2-Q4 were 0.87 (0.68-1.10), 0.63 (0.47-0.84), and 0.43 (0.30-0.64), respectively. Per 1 standard deviation increase in eGDR was associated with a 30% (HR: 0.70, 95% CI 0.60-0.80) risk reduction of ASCVD, with the subgroup analyses indicating that age and hypertension modified the association (P for interaction < 0.05). RCS analysis indicated a significant and linear relationship between eGDR and ASCVD incidence risk.

Conclusion: eGDR level was negatively associated with incident ASCVD risk in a linear fashion among the general population. Our findings may contribute to preventive measures by improving ASCVD risk assessment.

背景:目的:研究作为胰岛素抵抗替代指标的估计葡萄糖排泄率(eGDR)与动脉粥样硬化性心血管疾病(ASCVD)发病风险之间的关系:这项前瞻性队列研究利用了多种族动脉粥样硬化研究(Multi-Ethnic Study of Atherosclerosis)6026 名参与者的数据。eGDR (mg/kg/min) 的计算公式为 21.158 - (0.09 × 腰围 [cm]) - (3.407 × 高血压 [是/否]) - (0.551 × HbA1c [%])。根据 eGDR 的四分位数 (Q) 将人群分为四个亚组。采用Cox比例危险模型评估eGDR与ASCVD发病率之间的关系,并采用限制性立方体脊柱(RCS)检验剂量-反应关系:参与者的平均年龄为 63.6 ± 10.1 岁,其中女性 3163 人(52.5%)。在14.1年的中位随访期间,565人(9.4%)患上了ASCVD,包括256人(4.2%)心肌梗死、234人(3.9%)中风和358人(5.9%)致命性冠心病。与最低四分位数相比,Q2-Q4发生ASCVD的调整危险比(95%置信区间)分别为0.87(0.68-1.10)、0.63(0.47-0.84)和0.43(0.30-0.64)。eGDR每增加1个标准差,ASCVD风险就会降低30%(HR:0.70,95% CI 0.60-0.80),亚组分析表明,年龄和高血压会改变这种关联(P为交互作用 结论:在普通人群中,eGDR水平与ASCVD发病风险呈线性负相关。我们的研究结果可能有助于通过改进 ASCVD 风险评估来采取预防措施。
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引用次数: 0
Evidence of a bi-directional relationship between heart failure and diabetes: a strategy for the detection of glucose abnormalities and diabetes prevention in patients with heart failure. 心力衰竭与糖尿病之间双向关系的证据:检测心力衰竭患者血糖异常和预防糖尿病的策略。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02436-3
Paul Valensi

Prevalence of heart failure (HF) and diabetes are markedly increasing globally. In a population of HF patients, approximately 40% have diabetes which is associated with a more severe HF, poorer cardiovascular outcomes and higher hospitalization rates for HF than HF patients without diabetes. Similar trends were shown in HF patients with prediabetes. In addition, the association between HF and renal function decline was demonstrated in patients with or without diabetes. However, the exact prevalence of dysglycemia in HF patients requires further investigation aiming to clarify the most accurate test to detect dysglycemia in this population. The relationship between HF and diabetes is complex and probably bidirectional. In one way, patients with diabetes have a more than two-fold risk of developing incident HF with reduced or preserved ejection fraction than those without diabetes. In the other way, patients with HF, when compared with those without HF, show an increased risk for the onset of diabetes due to several mechanisms including insulin resistance (IR), which makes HF emerging as a precursor for diabetes development. This article provides epidemiological evidence of undetected dysglycemia (prediabetes or diabetes) in HF patients and reviews the pathophysiological mechanisms which favor the development of IR and the risks associated with these disorders in HF patients. This review also offers a discussion of various strategies for the prevention of diabetes in HF patients, based first on fasting plasma glucose and HbA1c measurement and if normal on an oral glucose tolerance test as diagnostic tools for prediabetes and unknown diabetes that should be performed more extensively in those patients. It discusses the implementation of diabetes prevention measures and well-structured management programs for HF patients who are generally overweight or obese, as well as current pharmacotherapeutic options for prediabetes, including sodium-glucose cotransporter 2 inhibitors which are among the pillars of HF treatment and which recently showed a benefit in the reduction of incident diabetes in HF patients. Thus, there is an urgent need of routine screening for dysglycemia in all HF patients, which should contribute to reduce the incidence of diabetes and to treat earlier diabetes when already present.

在全球范围内,心力衰竭(HF)和糖尿病的发病率正在明显上升。在心力衰竭患者中,约有 40% 患有糖尿病,与无糖尿病的心力衰竭患者相比,糖尿病患者的心力衰竭程度更严重,心血管预后更差,住院率更高。患有糖尿病前期的高血压患者也有类似的趋势。此外,无论是否患有糖尿病,高血压与肾功能衰退之间的关系都得到了证实。然而,高血压患者中血糖异常的确切发病率还需要进一步调查,以明确在这一人群中检测血糖异常的最准确测试方法。心房颤动与糖尿病之间的关系很复杂,而且可能是双向的。一方面,与非糖尿病患者相比,糖尿病患者发生射血分数降低或保留的心房颤动的风险是后者的两倍多。另一方面,由于胰岛素抵抗(IR)等多种机制,与无高血压的患者相比,高血压患者罹患糖尿病的风险增加,这使得高血压成为糖尿病发病的前兆。本文提供了高血脂患者未被发现的血糖异常(糖尿病前期或糖尿病)的流行病学证据,并回顾了有利于高血脂患者发生 IR 的病理生理机制以及与这些疾病相关的风险。本综述还讨论了预防 HF 患者糖尿病的各种策略,首先基于空腹血浆葡萄糖和 HbA1c 测量,如果正常,则基于口服葡萄糖耐量试验,作为糖尿病前期和未知糖尿病的诊断工具,应在这些患者中更广泛地开展。报告还讨论了如何对体重普遍超重或肥胖的高血压患者实施糖尿病预防措施和结构合理的管理方案,以及目前针对糖尿病前期的药物治疗方案,包括钠-葡萄糖共转运体 2 抑制剂,该药物是高血压治疗的支柱之一,最近的研究显示,该药物可有效减少高血压患者的糖尿病发病率。因此,迫切需要对所有高血压患者进行血糖异常常规筛查,这将有助于降低糖尿病的发病率,并在糖尿病已经出现时尽早治疗。
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引用次数: 0
Construction of machine learning diagnostic models for cardiovascular pan-disease based on blood routine and biochemical detection data. 基于血常规和生化检测数据构建心血管泛疾病机器学习诊断模型。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02439-0
Zhicheng Wang, Ying Gu, Lindan Huang, Shuai Liu, Qun Chen, Yunyun Yang, Guolin Hong, Wanshan Ning

Background: Cardiovascular disease, also known as circulation system disease, remains the leading cause of morbidity and mortality worldwide. Traditional methods for diagnosing cardiovascular disease are often expensive and time-consuming. So the purpose of this study is to construct machine learning models for the diagnosis of cardiovascular diseases using easily accessible blood routine and biochemical detection data and explore the unique hematologic features of cardiovascular diseases, including some metabolic indicators.

Methods: After the data preprocessing, 25,794 healthy people and 32,822 circulation system disease patients with the blood routine and biochemical detection data were utilized for our study. We selected logistic regression, random forest, support vector machine, eXtreme Gradient Boosting (XGBoost), and deep neural network to construct models. Finally, the SHAP algorithm was used to interpret models.

Results: The circulation system disease prediction model constructed by XGBoost possessed the best performance (AUC: 0.9921 (0.9911-0.9930); Acc: 0.9618 (0.9588-0.9645); Sn: 0.9690 (0.9655-0.9723); Sp: 0.9526 (0.9477-0.9572); PPV: 0.9631 (0.9592-0.9668); NPV: 0.9600 (0.9556-0.9644); MCC: 0.9224 (0.9165-0.9279); F1 score: 0.9661 (0.9634-0.9686)). Most models of distinguishing various circulation system diseases also had good performance, the model performance of distinguishing dilated cardiomyopathy from other circulation system diseases was the best (AUC: 0.9267 (0.8663-0.9752)). The model interpretation by the SHAP algorithm indicated features from biochemical detection made major contributions to predicting circulation system disease, such as potassium (K), total protein (TP), albumin (ALB), and indirect bilirubin (NBIL). But for models of distinguishing various circulation system diseases, we found that red blood cell count (RBC), K, direct bilirubin (DBIL), and glucose (GLU) were the top 4 features subdividing various circulation system diseases.

Conclusions: The present study constructed multiple models using 50 features from the blood routine and biochemical detection data for the diagnosis of various circulation system diseases. At the same time, the unique hematologic features of various circulation system diseases, including some metabolic-related indicators, were also explored. This cost-effective work will benefit more people and help diagnose and prevent circulation system diseases.

背景:心血管疾病又称循环系统疾病,仍然是全球发病率和死亡率的主要原因。诊断心血管疾病的传统方法通常既昂贵又耗时。因此,本研究的目的是利用易于获取的血常规和生化检测数据,构建用于诊断心血管疾病的机器学习模型,并探索心血管疾病的独特血液学特征,包括一些代谢指标:经过数据预处理后,25794 名健康人和 32822 名循环系统疾病患者的血常规和生化检测数据被用于我们的研究。我们选择了逻辑回归、随机森林、支持向量机、极梯度提升(XGBoost)和深度神经网络来构建模型。最后,使用 SHAP 算法对模型进行解释:XGBoost构建的循环系统疾病预测模型性能最佳(AUC:0.9921 (0.9911-0.9930); Acc: 0.9618 (0.9588-0.9645); Sn:0.9690(0.9655-0.9723);Sp:0.9526(0.9477-0.9572);PPV:0.9631(0.9592-0.9668);NPV:0.9600(0.9556-0.9644);MCC:0.9224(0.9165-0.9279);F1 评分:0.9661(0.9634-0.9686))。大多数区分各种循环系统疾病的模型也具有良好的性能,其中区分扩张型心肌病和其他循环系统疾病的模型性能最好(AUC:0.9267 (0.8663-0.9752)).SHAP 算法对模型的解释表明,生化检测特征对循环系统疾病的预测做出了重要贡献,如钾(K)、总蛋白(TP)、白蛋白(ALB)和间接胆红素(NBIL)。但在区分各种循环系统疾病的模型中,我们发现红细胞计数(RBC)、K、直接胆红素(DBIL)和葡萄糖(GLU)是细分各种循环系统疾病的前 4 个特征:本研究利用血常规和生化检测数据中的 50 个特征构建了多个模型,用于诊断各种循环系统疾病。结论:本研究利用血常规和生化检测数据中的 50 个特征构建了多个模型,用于诊断各种循环系统疾病,同时还探索了各种循环系统疾病的独特血液学特征,包括一些与代谢相关的指标。这项具有成本效益的工作将造福更多的人,帮助诊断和预防循环系统疾病。
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引用次数: 0
The differential effects of dyslipidemia status and triglyceride-glucose index on left ventricular global function and myocardial microcirculation in diabetic individuals: a cardiac magnetic resonance study 血脂异常状态和甘油三酯-葡萄糖指数对糖尿病患者左心室整体功能和心肌微循环的不同影响:一项心脏磁共振研究
IF 9.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-19 DOI: 10.1186/s12933-024-02435-4
Li Jiang, Hua‑Yan Xu, Yuan Li, Ke Shi, Han Fang, Wei‑Feng Yan, Ying‑Kun Guo, Zhi-Gang Yang
It remains unclear whether the association between dyslipidemia status and triglyceride-glucose (TyG) index with myocardial damage varies in the context of type 2 diabetes mellitus (T2DM). This study aimed to determine the differential effects of dyslipidemia status and TyG index on left ventricular (LV) global function and myocardial microcirculation in patients with T2DM using cardiac magnetic resonance (CMR) imaging. A total of 226 T2DM patients and 72 controls who underwent CMR examination were included. The T2DM group was further categorized into subgroups based on the presence or absence of dyslipidemia (referred to as T2DM (DysL+) and T2DM (DysL-)) or whether the TyG index exceeded 9.06. CMR-derived LV perfusion parameters, remodeling index, and global function index (GFI) were assessed and compared among groups. A multivariable linear regression model was employed to evaluate the effects of various variables on LV myocardial microcirculation, remodeling index, and GFI. The LV GFI sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (p < 0.001), and was lower (p = 0.003) in T2DM with higher TyG index group than in lower TyG index group. The LV remodeling index was higher in higher TyG index group than in lower TyG index group (p = 0.002), but there was no significant difference in whether the subgroup was accompanied by dyslipidemia. Multivariable analysis revealed that the TyG index, but not dyslipidemia status, was independently associated with LV remodeling index (β coefficient[95% confidence interval], 0.152[0.025, 0.268], p = 0.007) and LV GFI (− 0.159[− 0.281, − 0.032], p = 0.014). For LV myocardial microcirculation, perfusion index, upslope, and max signal intensity sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (all p < 0.001). Dyslipidemia status independently correlated with perfusion index (− 0.147[− 0.272, − 0.024], p = 0.02) and upslope (− 0.200[− 0.320, 0.083], p = 0.001), while TyG index was independently correlated with time to maximum signal intensity (0.141[0.019, 0.257], p = 0.023). Both dyslipidemia status and higher TyG index were associated with further deterioration of LV global function and myocardial microvascular function in the context of T2DM. The effects of dyslipidemia and a higher TyG index appear to be differential, which indicates that not only the amount of blood lipids and glucose but also the quality of blood lipids are therapeutic targets for preventing further myocardial damage.
血脂异常状态和甘油三酯-葡萄糖(TyG)指数与心肌损伤之间的关系在2型糖尿病(T2DM)患者中是否存在差异,目前仍不清楚。本研究旨在利用心脏磁共振(CMR)成像确定血脂异常状态和 TyG 指数对 T2DM 患者左心室(LV)整体功能和心肌微循环的不同影响。共有 226 名 T2DM 患者和 72 名对照组患者接受了 CMR 检查。根据有无血脂异常(T2DM(DysL+)和 T2DM(DysL-))或 TyG 指数是否超过 9.06,将 T2DM 组进一步分为若干亚组。对CMR衍生的左心室灌注参数、重塑指数和整体功能指数(GFI)进行评估,并在各组间进行比较。采用多变量线性回归模型评估了各种变量对左心室心肌微循环、重塑指数和GFI的影响。对照组、T2DM(DysL-)组和T2DM(DysL+)组的左心室GFI依次下降(p < 0.001),TyG指数较高的T2DM组低于TyG指数较低的T2DM组(p = 0.003)。TyG指数较高组的左心室重塑指数高于TyG指数较低组(P = 0.002),但在是否伴有血脂异常的亚组中无显著差异。多变量分析显示,TyG指数与左心室重塑指数(β系数[95%置信区间],0.152[0.025, 0.268],P = 0.007)和左心室GFI(- 0.159[- 0.281, - 0.032],P = 0.014)独立相关,而与血脂异常状态无关。在左心室心肌微循环方面,对照组、T2DM(DysL-)组和T2DM(DysL+)组的灌注指数、上斜率和最大信号强度依次下降(均 p < 0.001)。血脂异常状态与灌注指数(- 0.147[- 0.272, - 0.024],p = 0.02)和上斜率(- 0.200[- 0.320, 0.083],p = 0.001)独立相关,而TyG指数与达到最大信号强度的时间独立相关(0.141[0.019, 0.257],p = 0.023)。血脂异常状态和较高的TyG指数都与T2DM背景下左心室整体功能和心肌微血管功能的进一步恶化有关。血脂异常和较高的TyG指数的影响似乎是不同的,这表明不仅血脂和血糖的数量,而且血脂的质量都是防止心肌进一步损伤的治疗目标。
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引用次数: 0
Sex inequalities in cardiovascular risk factors and their management in primary prevention in adults living with type 1 diabetes in Germany and France: findings from DPV and SFDT1 德国和法国 1 型糖尿病成人患者心血管风险因素及其一级预防管理中的性别不平等:DPV 和 SFDT1 的研究结果
IF 9.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-16 DOI: 10.1186/s12933-024-02419-4
Emmanuel Cosson, Marie Auzanneau, Gloria A. Aguayo, Wolfram Karges, Jean-Pierre Riveline, Petra Augstein, Laura Sablone, Peter Jehle, Guy Fagherazzi, Reinhard W. Holl
To evaluate whether cardiovascular risk factors and their management differ in primary prevention between adult males and females with type 1 diabetes (T1D) in two European countries in 2020–2022 and sex inequalities in achievement of standards of care in diabetes. We used 2020–2022 data of patients without a cardiovascular history in the Prospective Diabetes Follow-up registry (DPV) centres, in Germany, and the Société Francophone du Diabète– Cohorte Diabète de Type 1 cohort (SFDT1), in France. We included 2,657 participants from the DPV registry and 1,172 from the SFDT1 study. Body mass indexes were similar in females and males with similar proportions of HbA1c < 7% (DPV: 36.6 vs 33.0%, p = 0.06, respectively; SFDT1: 23.4 vs 25.7%, p = 0.41). Females were less overweight compared to men in DPV (55.4 vs 61.0%, p < 0.01) but not in SFDT1 (48.0 vs 44.9%, p = 0.33) and were less prone to smoke (DPV: 19.7 vs 25.8%, p < 0.01; SFDT1: 21.0 vs 26.0%, p = 0.07). Systolic blood pressure was lower in females than males with a higher rate of antihypertensive therapy in case of hypertension in females in DPV (70.5 vs 63.7%, p = 0.02) but not in SFDT1 (73.3 vs 68.6%, p = 0.64). In the case of microalbuminuria, ACEi-ARB were less often prescribed in women than men in DPV (21.4 vs 37.6%, p < 0.01) but not SFDT1 (73.3 vs 67.5.0%, p = 0.43). In females compared to males, HDL-cholesterol levels were higher; triglycerides were lower in both countries. In those with LDL-cholesterol > 3.4 mmol/L (DPV: 19.9 (females) vs 23.9% (males), p = 0.01; SFDT1 17.0 vs 19.2%, p = 0.43), statin therapy was less often prescribed in females than males in DPV (7.9 vs 17.0%, p < 0.01), SFDT1 (18.2 vs 21.0%, p = 0.42). In both studies, females in primary prevention have a better cardiovascular risk profile than males. We observed a high rate of therapeutic inertia, which might be higher in females for statin treatment and nephroprotection with ACEi-ARB, especially in Germany. Diabetologists should be aware of sex-specific differences in the management of cardiorenal risk factors to develop more personalized prevention strategies.
目的:评估 2020-2022 年两个欧洲国家的 1 型糖尿病(T1D)成年男性和女性患者在一级预防中的心血管风险因素及其管理是否存在差异,以及在达到糖尿病护理标准方面的性别不平等。我们使用了德国前瞻性糖尿病随访登记中心(DPV)和法国 1 型糖尿病法语协会队列(SFDT1)2020-2022 年无心血管病史患者的数据。我们纳入了 DPV 登记的 2,657 名参与者和 SFDT1 研究的 1,172 名参与者。女性和男性的体重指数相似,HbA1c 3.4 mmol/L的比例也相似(DPV:19.9(女性) vs 23.9%(男性),p = 0.01;SFDT1:17.0 vs 19.2%,p = 0.43),DPV(7.9 vs 17.0%,p < 0.01)和SFDT1(18.2 vs 21.0%,p = 0.42)中,他汀类药物的处方女性少于男性。在这两项研究中,女性一级预防者的心血管风险状况优于男性。我们观察到女性的治疗惰性较高,尤其是在德国,在他汀类药物治疗和 ACEi-ARB 肾保护方面,女性的治疗惰性可能更高。糖尿病医生应了解心肾风险因素管理中的性别差异,以制定更个性化的预防策略。
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引用次数: 0
Cardiometabolic benefits of fenofibrate in heart failure related to obesity and diabetes 非诺贝特对肥胖和糖尿病相关性心力衰竭的心脏代谢益处
IF 9.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-16 DOI: 10.1186/s12933-024-02417-6
Jiwon Park, Hangyul Song, Shinje Moon, Yumin Kim, Sungsoo Cho, Kyungdo Han, Cheol-Young Park, Sung Woo Cho, Chang-Myung Oh
Heart failure (HF) is a serious and common condition affecting millions of people worldwide, with obesity being a major cause of metabolic disorders such as diabetes and cardiovascular disease. This study aimed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, on the obese- and diabetes-related cardiomyopathy. We used db/db mice and high fat diet-streptozotocin induced diabetic mice to investigate the underlying mechanisms of fenofibrate’s beneficial effects on heart function. Fenofibrate reduced fibrosis, and lipid accumulation, and suppressed inflammatory and immunological responses in the heart via TNF signaling. In addition, we investigated the beneficial effects of fenofibrate on HF hospitalization. The Korean National Health Insurance database was used to identify 427,154 fenofibrate users and 427,154 non-users for comparison. During the 4.22-year follow-up, fenofibrate use significantly reduced the risk of HF hospitalization (hazard ratio, 0.907; 95% CI 0.824–0.998). The findings suggest that fenofibrate may be a useful therapeutic agent for obesity- and diabetes-related cardiomyopathy.
心力衰竭(HF)是一种严重的常见病,影响着全球数百万人,而肥胖是糖尿病和心血管疾病等代谢紊乱的主要原因。本研究旨在探讨过氧化物酶体增殖激活受体α(PPARα)激动剂非诺贝特对肥胖和糖尿病相关心肌病的影响。我们利用db/db小鼠和高脂饮食-链脲佐菌素诱导的糖尿病小鼠来研究非诺贝特对心脏功能产生有益影响的内在机制。非诺贝特可减少纤维化和脂质积累,并通过 TNF 信号转导抑制心脏的炎症和免疫反应。此外,我们还研究了非诺贝特对高血压住院治疗的有益影响。我们利用韩国国民健康保险数据库确定了427154名非诺贝特使用者和427154名非使用者进行对比。在4.22年的随访期间,使用非诺贝特能显著降低高血压住院风险(危险比为0.907;95% CI为0.824-0.998)。研究结果表明,非诺贝特可能是肥胖和糖尿病相关心肌病的有效治疗药物。
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引用次数: 0
MicroRNAs in diabetic macroangiopathy 糖尿病大血管病变中的微RNA
IF 9.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-16 DOI: 10.1186/s12933-024-02405-w
Guocheng Rao, Boqiang Peng, Guixiang Zhang, Xianghui Fu, Jingyan Tian, Yan Tian
Diabetic macroangiopathy is a leading cause of diabetes-related mortality worldwide. Both genetic and environmental factors, through a multitude of underlying molecular mechanisms, contribute to the pathogenesis of diabetic macroangiopathy. MicroRNAs (miRNAs), a class of non-coding RNAs known for their functional diversity and expression specificity, are increasingly recognized for their roles in the initiation and progression of diabetes and diabetic macroangiopathy. In this review, we will describe the biogenesis of miRNAs, and summarize their functions in diabetic macroangiopathy, including atherosclerosis, peripheral artery disease, coronary artery disease, and cerebrovascular disease, which are anticipated to provide new insights into future perspectives of miRNAs in basic, translational and clinical research, ultimately advancing the diagnosis, prevention, and treatment of diabetic macroangiopathy.
糖尿病大血管病变是全球糖尿病相关死亡的主要原因。遗传和环境因素通过多种潜在的分子机制,共同作用于糖尿病大血管病变的发病机制。微小核糖核酸(miRNA)是一类以功能多样性和表达特异性著称的非编码核糖核酸,它们在糖尿病和糖尿病大血管病变的发生和发展过程中的作用日益得到认可。在这篇综述中,我们将描述 miRNAs 的生物发生,并总结它们在糖尿病大血管病变(包括动脉粥样硬化、外周动脉疾病、冠状动脉疾病和脑血管疾病)中的功能,预计这将为 miRNAs 在基础、转化和临床研究中的未来前景提供新的见解,最终推动糖尿病大血管病变的诊断、预防和治疗。
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引用次数: 0
Identification of potential therapeutic targets for nonischemic cardiomyopathy in European ancestry: an integrated multiomics analysis 识别欧洲血统非缺血性心肌病的潜在治疗靶点:多组学综合分析
IF 9.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-12 DOI: 10.1186/s12933-024-02431-8
Kaijia Shi, Xu Chen, Yangyang Zhao, Peihu Li, Jinxuan Chai, Jianmin Qiu, Zhihua Shen, Junli Guo, Wei Jie
Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670–0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199–1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.
非缺血性心肌病(NISCM)是一项临床挑战,其治疗靶点有限。本研究旨在确定有希望治疗 NISCM 的药物靶点。我们利用了 deCODE 研究中的顺式-pQTLs(其中包括 35,559 名冰岛人的数据)和 FinnGen 研究中的 SNPs(其中包括 1,754 例 NISCM 病例和 340,815 例芬兰血统对照的数据)。为了估计循环血浆蛋白水平与 NISCM 风险之间的因果关系,我们进行了孟德尔随机化 (MR) 分析。对有重大关联的蛋白质进行了错误发现率(FDR)校正,然后进行了贝叶斯共定位分析。利用各种 NISCM 数据集进一步分析了前两种蛋白质 LILRA5 和 NELL1 的表达情况。人类蛋白质图谱(HPA)的描述验证了蛋白质的表达。利用比较毒物基因组学数据库(CTD)评估了环境暴露对 LILRA5 的影响,并通过分子对接确定了潜在的小分子相互作用。磁共振分析确定了 255 种与 NISCM 相关的循环血浆蛋白,其中 16 种在 FDR 校正后仍具有显著性。贝叶斯共定位分析确定 LILRA5 和 NELL1 具有显著性,PP.H4 > 0.8。在 NISCM 中,LILRA5 具有保护作用(OR = 0.758,95% CI,0.670-0.857),而 NELL1 则具有风险作用(OR = 1.290,95% CI,1.199-1.387)。在糖尿病、肥厚型、扩张型和炎症性心肌病等 NISCM 中发现 LILRA5 表达减少,而在肥厚型心肌病中 NELL1 表达增加。HPA 数据显示,正常心脏中的中性粒细胞、巨噬细胞和内皮细胞中 LILRA5 高表达,而 NELL1 表达有限。免疫浸润分析显示,糖尿病心肌病患者的中性粒细胞减少。CTD 分析确定了几种影响 LILRA5 mRNA 表达的小分子。其中,雌二醇、雌二醇-3-苯甲酸酯、钆喷酸、托泊替康和睾酮被发现能在类 Ig C2 结构域中的保守 VAL-15 或 THR-133 残基处与 LILRA5 蛋白稳定结合。这项研究以欧洲祖先队列为基础,揭示了 LILRA5 和 NELL1 是治疗 NISCM 的潜在靶点,其中 LILRA5 在糖尿病心肌病中的应用前景尤为广阔。有几种小分子与 LILRA5 相互作用,这意味着潜在的临床意义。
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引用次数: 0
Correction: GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease 更正:在心血管代谢疾病临床前小鼠模型中,GIP 受体激动可改善血脂异常和动脉粥样硬化,而与体重减轻无关
IF 9.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-12 DOI: 10.1186/s12933-024-02407-8
Stephan Sachs, Anna Götz, Brian Finan, Annette Feuchtinger, Richard D. DiMarchi, Yvonne Döring, Christian Weber, Matthias H. Tschöp, Timo D. Müller, Susanna M. Hofmann
<p><b>Correction to: Cardiovasc Diabetol (2023) 22:217</b></p><p>https://doi.org/10.1186/s12933-023-01940-2</p><p>Following publication of the original article [1], the author noticed the errors in Fig. 2 and in Results section.</p><p>The bar graph is mistakenly duplicated in “percentage of plaque area of the aortic valves” of Fig. 2E. The corrected figure is given below:</p><figure><figcaption><b data-test="figure-caption-text">Fig. 2</b></figcaption><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12933-024-02407-8/MediaObjects/12933_2024_2407_Fig2_HTML.png?as=webp" type="image/webp"/><img alt="figure 2" aria-describedby="Fig2" height="344" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12933-024-02407-8/MediaObjects/12933_2024_2407_Fig2_HTML.png" width="685"/></picture><p>Acyl-GIP ameliorates dyslipidemia and atherosclerotic plaque formation in LDLR-/- male mice. Plasma (<b>A</b>) triglycerides, (<b>B</b>) cholesterol and (<b>C</b>) lipoprotein fractions as well as (<b>D</b> and <b>E</b>) the percentage of plaque area in aortic arches and valves and along the descending aorta of male LDLR-/- mice treated daily with either vehicle or acyl-GIP via subcutaneous injections for 28 days. <i>n</i> = 7. Blood lipids were determined from sac plasma at the end of the study. Data represent means ± SEM. *<i>P</i> < 0.05, **<i>P</i> < 0.01, *** <i>P</i> < 0.001, determined by unpaired two-sided t-test</p><span>Full size image</span><svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-chevron-right-small" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></figure><p>In Result section under the heading “GIPR-agonist acyl-GIP ameliorates dyslipidemia and atherosclerotic plaque formation in male LDLR-/- mice independently of weight loss”, the last sentence should read “Most importantly, acyl-GIP treatment was accompanied by reduced atherosclerotic plaque formation within the aortic valve and a trend to decrease fat streaks along the descending aorta (Fig. 2E)“ instead of “Most importantly, acyl-GIP treatment was accompanied by reduced atherosclerotic plaque formation within the aortic valve (Fig. 2G–H) and decreased fat streaks along the descending aorta (Fig. 2I)”.</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Sachs S, Götz A, Finan B, et al. GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease. Cardiovasc Diabetol. 2023;22:217.https://doi.org/10.1186/s12933-023-01940-2</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><
创作共用 "许可协议允许以任何媒介或格式使用、共享、改编、分发和复制文章,但必须注明原作者和出处,提供指向 "创作共用 "许可协议的链接,并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出许可使用范围,您需要直接从版权所有者处获得许可。要查看该许可的副本,请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明,否则创作共用公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文Sachs, S., Götz, A., Finan, B. et al. Correction:GIP受体激动在心血管代谢疾病临床前小鼠模型中改善血脂异常和动脉粥样硬化,与体重减轻无关。Cardiovasc Diabetol 23, 341 (2024). https://doi.org/10.1186/s12933-024-02407-8Download citationPublished: 12 September 2024DOI: https://doi.org/10.1186/s12933-024-02407-8Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative.
{"title":"Correction: GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease","authors":"Stephan Sachs, Anna Götz, Brian Finan, Annette Feuchtinger, Richard D. DiMarchi, Yvonne Döring, Christian Weber, Matthias H. Tschöp, Timo D. Müller, Susanna M. Hofmann","doi":"10.1186/s12933-024-02407-8","DOIUrl":"https://doi.org/10.1186/s12933-024-02407-8","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction to: Cardiovasc Diabetol (2023) 22:217&lt;/b&gt;&lt;/p&gt;&lt;p&gt;https://doi.org/10.1186/s12933-023-01940-2&lt;/p&gt;&lt;p&gt;Following publication of the original article [1], the author noticed the errors in Fig. 2 and in Results section.&lt;/p&gt;&lt;p&gt;The bar graph is mistakenly duplicated in “percentage of plaque area of the aortic valves” of Fig. 2E. The corrected figure is given below:&lt;/p&gt;&lt;figure&gt;&lt;figcaption&gt;&lt;b data-test=\"figure-caption-text\"&gt;Fig. 2&lt;/b&gt;&lt;/figcaption&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12933-024-02407-8/MediaObjects/12933_2024_2407_Fig2_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure 2\" aria-describedby=\"Fig2\" height=\"344\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12933-024-02407-8/MediaObjects/12933_2024_2407_Fig2_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;p&gt;Acyl-GIP ameliorates dyslipidemia and atherosclerotic plaque formation in LDLR-/- male mice. Plasma (&lt;b&gt;A&lt;/b&gt;) triglycerides, (&lt;b&gt;B&lt;/b&gt;) cholesterol and (&lt;b&gt;C&lt;/b&gt;) lipoprotein fractions as well as (&lt;b&gt;D&lt;/b&gt; and &lt;b&gt;E&lt;/b&gt;) the percentage of plaque area in aortic arches and valves and along the descending aorta of male LDLR-/- mice treated daily with either vehicle or acyl-GIP via subcutaneous injections for 28 days. &lt;i&gt;n&lt;/i&gt; = 7. Blood lipids were determined from sac plasma at the end of the study. Data represent means ± SEM. *&lt;i&gt;P&lt;/i&gt; &lt; 0.05, **&lt;i&gt;P&lt;/i&gt; &lt; 0.01, *** &lt;i&gt;P&lt;/i&gt; &lt; 0.001, determined by unpaired two-sided t-test&lt;/p&gt;&lt;span&gt;Full size image&lt;/span&gt;&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/figure&gt;&lt;p&gt;In Result section under the heading “GIPR-agonist acyl-GIP ameliorates dyslipidemia and atherosclerotic plaque formation in male LDLR-/- mice independently of weight loss”, the last sentence should read “Most importantly, acyl-GIP treatment was accompanied by reduced atherosclerotic plaque formation within the aortic valve and a trend to decrease fat streaks along the descending aorta (Fig. 2E)“ instead of “Most importantly, acyl-GIP treatment was accompanied by reduced atherosclerotic plaque formation within the aortic valve (Fig. 2G–H) and decreased fat streaks along the descending aorta (Fig. 2I)”.&lt;/p&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Sachs S, Götz A, Finan B, et al. GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease. Cardiovasc Diabetol. 2023;22:217.https://doi.org/10.1186/s12933-023-01940-2&lt;/p&gt;&lt;p&gt;Article CAS PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Effects of dietary interventions and intermittent fasting on HDL function in obese individuals with T2DM: a randomized controlled trial 饮食干预和间歇性禁食对患有 T2DM 的肥胖者高密度脂蛋白功能的影响:随机对照试验
IF 9.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-12 DOI: 10.1186/s12933-024-02426-5
Anja Pammer, Anna Obermayer, Julia T. Stadler, Peter N. Pferschy, Norbert J. Tripolt, Hansjörg Habisch, Tobias Madl, Harald Sourij, Gunther Marsche
Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants’ glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070.
心血管疾病是导致 2 型糖尿病(T2DM)患者死亡的一个重要风险因素。高密度脂蛋白(HDL)具有多方面的动脉粥样硬化保护作用,并能加强血糖控制,因此被认为在维护心血管健康方面发挥着至关重要的作用。饮食干预和间歇性禁食(IF)对高密度脂蛋白功能的影响仍不确定。本研究旨在评估饮食干预和间歇性禁食作为一种安全改善血糖控制和减轻体重的策略对 T2DM 患者高密度脂蛋白功能参数的影响。在进行为期 12 周的干预之前,INTERFAST-2 研究的所有参与者(n = 41)都被标准化为统一的基础胰岛素方案,并被随机分配到 IF 组或非 IF 组。此外,所有参与者都被建议遵守促进健康饮食模式的饮食建议。IF 组(n = 19)采用隔日禁食法,在禁食日减少 75% 的卡路里摄入量。参与者的血糖水平受到持续监测。干预后还测量了其他参数:通过核磁共振波谱测量脂蛋白组成和亚类分布。高密度脂蛋白胆固醇外排能力、副氧自由基酶 1 (PON1) 活性、卵磷脂胆固醇酰基转移酶 (LCAT) 活性和胆固醇酯转移蛋白 (CETP) 活性通过细胞检测法和市售试剂盒进行评估。载脂蛋白 M(apoM)水平通过酶联免疫吸附法测定。经过 12 周的干预后,IF 方案显著提高了血清载脂蛋白 M 的水平(p = 0.0144),而非 IF 组则没有提高(p = 0.9801)。在 IF 组中,载脂蛋白 M 水平与体重下降和空腹血糖水平相关。12 周后,两组的高密度脂蛋白胆固醇外排能力均有显著增强(p < 0.0001,p = 0.0006)。值得注意的是,在 12 周的干预后,只有非 IF 组的 PON1(p = 0.0455)和 LCAT(p = 0.0117)活性明显升高。相比之下,胰岛素转换组观察到的变化未达到统计学意义。均衡饮食结合细致的胰岛素管理可改善高密度脂蛋白的多种功能指标。虽然额外的 IF 能提高载脂蛋白水平,但并不能进一步增强高密度脂蛋白功能的其他方面。该研究于2019年9月3日在德国临床试验注册中心(DRKS)注册,注册号为DRKS00018070。
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Cardiovascular Diabetology
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