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External validation and calibration of risk equations for prediction of diabetic kidney diseases among patients with type 2 diabetes in Taiwan. 用于预测台湾 2 型糖尿病患者糖尿病肾脏疾病的风险方程的外部验证和校准。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-09 DOI: 10.1186/s12933-024-02443-4
Hsuan-Yu Su, Thi Thuy Dung Nguyen, Wei-Hung Lin, Huang-Tz Ou, Shihchen Kuo

Background: Most existing risk equations for predicting/stratifying individual diabetic kidney disease (DKD) risks were developed using relatively dated data from selective and homogeneous trial populations comprising predominately Caucasian type 2 diabetes (T2D) patients. We seek to adapt risk equations for prediction of DKD progression (microalbuminuria, macroalbuminuria, and renal failure) using empiric data from a real-world population with T2D in Taiwan.

Methods: Risk equations from three well-known simulation models: UKPDS-OM2, RECODe, and CHIME models, were adapted. Discrimination and calibration were determined using the area under the receiver operating characteristic curve (AUROC), a calibration plot (slope and intercept), and the Greenwood-Nam-D'Agostino (GND) test. Recalibration was performed for unsatisfactory calibration (p-value of GND test < 0.05) by adjusting the baseline hazards of risk equations to address risk variations among patients.

Results: The RECODe equations for microalbuminuria and macroalbuminuria showed moderate discrimination (AUROC: 0.62 and 0.76) but underestimated the event risks (calibration slope > 1). The CHIME equation had the best discrimination for renal failure (AUROCs from CHIME, UKPDS-OM2 and RECODe: 0.77, 0.60 and 0.64, respectively). All three equations overestimated renal failure risk (calibration slope < 1). After rigorous updating, the calibration slope/intercept of the recalibrated RECODe for predicting microalbuminuria (0.87/0.0459) and macroalbuminuria (1.10/0.0004) risks as well as the recalibrated CHIME equation for predicting renal failure risk (0.95/-0.0014) were improved.

Conclusions: Risk equations for prediction of DKD progression in real-world Taiwanese T2D patients were established, which can be incorporated into a multi-state simulation model to project and differentiate individual DKD risks for supporting timely interventions and health economic research.

背景:现有的用于预测/分级个体糖尿病肾病(DKD)风险的大多数风险方程都是利用来自以白种人为主的 2 型糖尿病(T2D)患者的选择性同质试验人群的相对过时的数据开发的。我们试图利用台湾真实世界中 T2D 患者的经验数据,调整预测 DKD 进展(微量白蛋白尿、大量白蛋白尿和肾衰竭)的风险方程:方法:三个著名模拟模型中的风险方程:方法:改编了 UKPDS-OM2、RECODe 和 CHIME 模型中的风险方程。使用接收者操作特征曲线下面积(AUROC)、校准图(斜率和截距)和格林伍德-南-达戈斯蒂诺(GND)测试确定识别和校准。如果校准结果不理想(GND 检验结果的 p 值),则进行重新校准:微量白蛋白尿和宏观白蛋白尿的 RECODe 方程显示出中等程度的区分度(AUROC:0.62 和 0.76),但低估了事件风险(校准斜率 > 1)。CHIME 方程对肾衰竭的判别能力最强(CHIME、UKPDS-OM2 和 RECODe 的 AUROC 分别为 0.77、0.60 和 0.64)。所有三个方程都高估了肾功能衰竭风险(校准斜率):建立了预测台湾 T2D 患者 DKD 进展的风险方程,可将其纳入多状态模拟模型,预测和区分个体 DKD 风险,以支持及时干预和卫生经济学研究。
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引用次数: 0
Exposure of cumulative atherogenic index of plasma and the development of prediabetes in middle-aged and elderly individuals: evidence from the CHARLS cohort study. 血浆累积致动脉粥样硬化指数的暴露与中老年人糖尿病前期的发展:来自 CHARLS 队列研究的证据。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-30 DOI: 10.1186/s12933-024-02449-y
Yang Zou, Song Lu, Dongdong Li, Xin Huang, Chao Wang, Guobo Xie, Lihua Duan, Hongyi Yang

Background: The impact of dynamic changes in the degree of atherosclerosis on the development of prediabetes remains unclear. This study aims to investigate the association between cumulative atherogenic index of plasma (CumAIP) exposure during follow-up and the development of prediabetes in middle-aged and elderly individuals.

Methods: A total of 2,939 prediabetic participants from the first wave of the China Health and Retirement Longitudinal Study (CHARLS) were included. The outcomes for these patients, including progression to diabetes and regression to normal fasting glucose (NFG), were determined using data from the third wave. CumAIP was calculated as the ratio of the average AIP values measured during the first and third waves to the total exposure duration. The association between CumAIP and the development of prediabetes was analyzed using multivariable Cox regression and restricted cubic spline (RCS) regression.

Results: During a median follow-up period of 3 years, 15.21% of prediabetic patients progressed to diabetes, and 22.12% regressed to NFG. Among the groups categorized by CumAIP quartiles, the proportion of prediabetes progressing to diabetes gradually increased (Q1: 10.61%, Q2: 13.62%, Q3: 15.65%, Q4: 20.95%), while the proportion regressing to NFG gradually decreased (Q1: 23.54%, Q2: 23.71%, Q3: 22.18%, Q4: 19.05%). Multivariable-adjusted Cox regression showed a significant positive linear correlation between high CumAIP exposure and prediabetes progression, and a significant negative linear correlation with prediabetes regression. Furthermore, in a stratified analysis, it was found that compared to married individuals, those who were unmarried (including separated, divorced, widowed, or never married) had a relatively higher risk of CumAIP-related diabetes.

Conclusion: CumAIP is closely associated with the development of prediabetes. High CumAIP exposure not only increases the risk of prediabetes progression but also hinders its regression within a certain range. These findings suggest that monitoring and maintaining appropriate AIP levels may help prevent the deterioration of blood glucose levels.

背景:动脉粥样硬化程度的动态变化对糖尿病前期发展的影响仍不清楚。本研究旨在探讨中老年人在随访过程中血浆累积致动脉粥样硬化指数(CumAIP)暴露与糖尿病前期发展之间的关系:方法:纳入中国健康与退休纵向研究(CHARLS)第一阶段的 2939 名糖尿病前期患者。这些患者的预后,包括发展为糖尿病和恢复正常空腹血糖(NFG)的情况,是通过第三期研究的数据确定的。CumAIP的计算方法是第一波和第三波测量的AIP平均值与总暴露时间之比。采用多变量 Cox 回归和限制性立方样条曲线 (RCS) 回归分析了 CumAIP 与糖尿病前期发展之间的关系:中位随访期为 3 年,15.21% 的糖尿病前期患者发展为糖尿病,22.12% 的患者发展为 NFG。在按 CumAIP 四分位数划分的组别中,糖尿病前期发展为糖尿病的比例逐渐增加(Q1:10.61%;Q2:13.62%;Q3:15.65%;Q4:20.95%),而退变为 NFG 的比例逐渐减少(Q1:23.54%;Q2:23.71%;Q3:22.18%;Q4:19.05%)。多变量调整后的 Cox 回归显示,CumAIP 暴露高与糖尿病前期进展之间存在显著的正线性相关,而与糖尿病前期回归之间存在显著的负线性相关。此外,在分层分析中还发现,与已婚人士相比,未婚人士(包括分居、离婚、丧偶或从未结婚)罹患与CumAIP相关的糖尿病的风险相对较高:结论:CumAIP 与糖尿病前期的发展密切相关。高 CumAIP 暴露不仅会增加糖尿病前期发展的风险,还会阻碍其在一定范围内消退。这些研究结果表明,监测并维持适当的 AIP 水平有助于防止血糖水平恶化。
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引用次数: 0
N6-Methyladenosine-mediated phase separation suppresses NOTCH1 expression and promotes mitochondrial fission in diabetic cardiac fibrosis. N6-甲基腺苷介导的相分离可抑制NOTCH1的表达并促进糖尿病心脏纤维化中线粒体的分裂。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02444-3
Zhi-Yan Liu, Li-Chan Lin, Zhen-Yu Liu, Kai Song, Bin Tu, He Sun, Yang Zhou, Sui Mao, Ye Zhang, Rui Li, Jing-Jing Yang, Jian-Yuan Zhao, Hui Tao

Background: N6-methyladenosine (m6A) modification of messenger RNA (mRNA) is crucial for liquid-liquid phase separation in mammals. Increasing evidence indicates that liquid-liquid phase separation in proteins and RNAs affects diabetic cardiomyopathy. However, the molecular mechanism by which m6A-mediated phase separation regulates diabetic cardiac fibrosis remains elusive.

Methods: Leptin receptor-deficient mice (db/db), cardiac fibroblast-specific Notch1 conditional knockout (POSTN-Cre × Notch1flox/flox) mice, and Cre mice were used to induce diabetic cardiac fibrosis. Adeno-associated virus 9 carrying cardiac fibroblast-specific periostin (Postn) promoter-driven small hairpin RNA targeting Alkbh5, Ythdf2, or Notch1, and the phase separation inhibitor 1,6-hexanediol were administered to investigate their roles in diabetic cardiac fibrosis. Histological and biochemical analyses were performed to determine how Alkbh5 and Ythdf2 regulate Notch1 expression in diabetic cardiac fibrosis. NOTCH1 was reconstituted in ALKBH5- and YTHDF2-deficient cardiac fibroblasts and mouse hearts to study its effects on mitochondrial fission and diabetic cardiac fibrosis. Heart tissue samples from patients with diabetic cardiomyopathy were used to validate our findings.

Results: In mice with diabetic cardiac fibrosis, decreased Notch1 expression was accompanied by high m6A mRNA levels and mitochondrial fission. Fibroblast-specific deletion of Notch1 enhanced mitochondrial fission and cardiac fibroblast proliferation and induced diabetic cardiac fibrosis in mice. Notch1 downregulation was associated with Alkbh5-mediated m6A demethylation in the 3'UTR of Notch1 mRNA and elevated m6A mRNA levels. These elevated m6A levels in Notch1 mRNA markedly enhanced YTHDF2 phase separation, increased the recognition of m6A residues in Notch1 mRNA by YTHDF2, and induced Notch1 degradation. Conversely, epitranscriptomic downregulation rescues Notch1 expression, resulting in the opposite effects. Human heart tissues from patients with diabetic cardiomyopathy were used to validate the findings in mice with diabetic cardiac fibrosis.

Conclusions: We identified a novel epitranscriptomic mechanism by which m6A-mediated phase separation suppresses Notch1 expression, thereby promoting mitochondrial fission in diabetic cardiac fibrosis. Our findings provide new insights for the development of novel treatment approaches for patients with diabetic cardiac fibrosis.

背景:信使 RNA(mRNA)的 N6-甲基腺苷(m6A)修饰对哺乳动物的液-液相分离至关重要。越来越多的证据表明,蛋白质和 RNA 的液-液相分离会影响糖尿病心肌病。然而,m6A 介导的相分离调节糖尿病心肌纤维化的分子机制仍未确定:方法:利用瘦素受体缺陷小鼠(db/db)、心脏成纤维细胞特异性 Notch1 条件性敲除(POSTN-Cre × Notch1flox/flox)小鼠和 Cre 小鼠诱导糖尿病心脏纤维化。为了研究它们在糖尿病性心脏纤维化中的作用,研究人员给小鼠注射了携带心脏成纤维细胞特异性骨膜蛋白(Postn)启动子驱动的靶向Alkbh5、Ythdf2或Notch1的小发夹RNA的腺相关病毒9和相分离抑制剂1,6-己二醇。为确定 Alkbh5 和 Ythdf2 如何调控 Notch1 在糖尿病心脏纤维化中的表达,进行了组织学和生化分析。在ALKBH5和YTHDF2缺陷的心成纤维细胞和小鼠心脏中重组NOTCH1,以研究其对线粒体裂变和糖尿病心脏纤维化的影响。糖尿病心肌病患者的心脏组织样本被用来验证我们的研究结果:结果:在糖尿病心肌纤维化的小鼠中,Notch1表达的减少伴随着高m6A mRNA水平和线粒体裂变。成纤维细胞特异性缺失 Notch1 可增强线粒体分裂和心成纤维细胞增殖,并诱导小鼠发生糖尿病性心脏纤维化。Notch1 的下调与 Alkbh5 介导的 Notch1 mRNA 3'UTR m6A 去甲基化和 m6A mRNA 水平升高有关。Notch1 mRNA 中 m6A 水平的升高显著增强了 YTHDF2 的相分离,增加了 YTHDF2 对 Notch1 mRNA 中 m6A 残基的识别,并诱导 Notch1 降解。相反,表转录组下调可挽救 Notch1 的表达,从而产生相反的效果。来自糖尿病心肌病患者的人类心脏组织被用来验证糖尿病心脏纤维化小鼠的研究结果:我们发现了一种新的表观转录组学机制,通过这种机制,m6A 介导的相分离抑制了 Notch1 的表达,从而促进了糖尿病心脏纤维化中线粒体的裂变。我们的发现为开发糖尿病心脏纤维化患者的新型治疗方法提供了新的见解。
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引用次数: 0
Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk: a comprehensive review. 代谢功能障碍相关脂肪肝与心血管风险:综合综述。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02434-5
Haixiang Zheng, Leonardo Antonio Sechi, Eliano Pio Navarese, Gavino Casu, Gianpaolo Vidili

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), poses a significant global health challenge due to its increasing prevalence and strong association with cardiovascular disease (CVD). This comprehensive review summarizes the current knowledge on the MASLD-CVD relationship, compares analysis of how different terminologies for fatty liver disease affect cardiovascular (CV) risk assessment using different diagnostic criteria, explores the pathophysiological mechanisms connecting MASLD to CVD, the influence of MASLD on traditional CV risk factors, the role of noninvasive imaging techniques and biomarkers in the assessment of CV risk in patients with MASLD, and the implications for clinical management and prevention strategies. By incorporating current research and clinical guidelines, this review provides a comprehensive overview of the complex interplay between MASLD and cardiovascular health.

代谢功能障碍相关性脂肪性肝病(MASLD)以前被称为非酒精性脂肪肝(NAFLD),由于其发病率越来越高且与心血管疾病(CVD)密切相关,因此对全球健康构成了重大挑战。这篇综合性综述总结了当前有关 MASLD 与心血管疾病关系的知识,比较分析了脂肪肝的不同术语如何影响使用不同诊断标准进行的心血管疾病(CV)风险评估,探讨了 MASLD 与心血管疾病相关的病理生理机制、MASLD 对传统 CV 风险因素的影响、无创成像技术和生物标志物在评估 MASLD 患者 CV 风险中的作用,以及对临床管理和预防策略的影响。本综述结合了当前的研究和临床指南,全面概述了 MASLD 与心血管健康之间复杂的相互作用。
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引用次数: 0
Impact of baseline FIB-4 score on efpeglenatide benefits on cardiovascular outcomes in people with type 2 diabetes: a participant-level exploratory analysis of the AMPLITUDE-O trial. 基线 FIB-4 评分对依非格列奈对 2 型糖尿病患者心血管预后益处的影响:AMPLITUDE-O 试验参与者层面的探索性分析。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02432-7
Stefano Del Prato, Zhuoru Li, Chinthanie Ramasundarahettige, Kelley R H Branch, Carolyn S P Lam, Renato D Lopes, Richard Pratley, Julio Rosenstock, Naveed Sattar, Hertzel C Gerstein

Aims: To estimate the incidence of major adverse cardiovascular events (MACE), expanded MACE, and MACE or Death across Fibrosis- 4 score (FIB-4) categories in people with type 2 diabetes and to determine whether efpeglenatide's effect varies with increasing FIB-4 severity.

Materials and methods: AMPLITUDE-O trial data were used to estimate the relationship of FIB-4 score categories to the hazard of MACE, expanded MACE, and MACE or death. Interactions on these outcomes between baseline FIB-4 score, and between FIB-4 score and efpeglenatide were also assessed.

Results: Baseline FIB-4 score was available for 4059 participants (99.6%) allowing subdivision of the population in tertiles. During a median follow-up of 1.8 years, numerical increases in the incidence of all 3 outcomes did not change significantly across tertiles of FIB-4 score (P for trend ≥ 0.25) with negligible relationship of the score to incident outcomes (MACE HR, per 1 SD higher score, 95% CI: 1.00, 0.89-1.13). Efpeglenatide's effect on all MACE outcomes did not vary across FIB-4 tertiles (all interaction p values ≥ 0.64).

Conclusions: In high-risk people with type 2 diabetes, the degree of liver fibrosis, as estimated by FIB-4 score, was not related to incident cardiovascular outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of FIB-4 category.

目的:估算2型糖尿病患者不同纤维化4级评分(FIB-4)的主要不良心血管事件(MACE)、扩大的MACE和MACE或死亡的发生率,并确定依非格列奈的效果是否随FIB-4严重程度的增加而变化:AMPLITUDE-O试验数据用于估算FIB-4评分类别与MACE、扩大MACE和MACE或死亡风险之间的关系。还评估了基线FIB-4评分与这些结果之间的相互作用,以及FIB-4评分与依非格列奈之间的相互作用:有4059名参与者(99.6%)获得了基线FIB-4评分,因此可以对人群进行梯度细分。在1.8年的中位随访期间,FIB-4评分的3种结果发生率的数值增长在不同的分层中没有显著变化(趋势P≥0.25),评分与事件结果的关系微乎其微(MACE HR,评分每增加1 SD,95% CI:1.00,0.89-1.13)。依非格列奈对所有MACE结果的影响在不同FIB-4分级中没有差异(所有交互作用P值≥0.64):结论:在2型糖尿病高危人群中,根据FIB-4评分估算的肝纤维化程度与心血管事件结局无关。依非格列奈对这些结果的有利影响与 FIB-4 类别无关。
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引用次数: 0
Altered oxidant and antioxidant levels are associated with vascular stiffness and diabetic kidney disease in type 1 diabetes after exposure to acute and chronic hyperglycemia. 氧化剂和抗氧化剂水平的改变与 1 型糖尿病患者在急性和慢性高血糖后的血管硬化和糖尿病肾病有关。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02427-4
Krishna Adeshara, Elyse Di Marco, Marco Bordino, Daniel Gordin, Luciano Bernardi, Mark E Cooper, Per-Henrik Groop

Background: Hyperglycemia-induced oxidative stress is a well-established pathological mediator of vascular complications in diabetes. We assessed plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia in relation to vascular stiffness and varying degrees of kidney disease in type 1 diabetes individuals.

Methods: The acute hyperglycemia study included 22 type 1 diabetic individuals with normal albumin excretion rate (AER) and 13 non-diabetic controls. These individuals received an acute glucose challenge during a 120-minute hyperglycemic clamp. The chronic hyperglycemia study included 118 type 1 diabetic individuals with chronically low (n = 60) or high (n = 58) HbA1c concentrations and varying degrees of diabetic kidney disease (DKD) classified as normal, moderate, or severe albuminuria (AER). Levels of malondialdehyde (MDA), reactive oxygen metabolites (ROMs), total antioxidant capacity (TAC), biological antioxidant potential (BAP) and superoxide dismutase (SOD) were measured from plasma or serum samples in the FinnDiane study.

Results: Levels of MDA (p < 0.01) and ROMs (p < 0.01) were elevated in type 1 diabetes individuals compared to non-diabetic controls at baseline. Acute hyperglycemia further increased MDA levels (p < 0.05) and sustained the elevation of ROMs in type 1 diabetes individuals. Acute hyperglycemic challenge impaired TAC in both non-diabetic (p < 0.05) and type 1 diabetes (p < 0.01) individuals compared to baseline whereas BAP was increased (p < 0.05) with no difference observed in non-diabetic controls. There was a positive association between high circulating MDA and AIx (r2 = 0.611, p = 0.05), and between delta ROMs and delta AIx (r2 = 0.955, p = 0.014) in combined analysis of individuals with type 1 diabetes and non-diabetic controls. Type 1 diabetes individuals with varying status of DKD, showed elevated levels of ROMs in those with high HbA1c compared to their counterpart with low HbA1c (p < 0.05). Individuals with severe albuminuria showed elevated ROM levels (p < 0.01) and depressed antioxidant capacity (p < 0.01) compared to those with normal AER of comparable HbA1c concentrations.

Conclusions: Biomarkers of oxidative stress are associated with vascular stiffness and DKD following acute and chronic hyperglycemic exposure and may provide added value to HbA1c in understanding disease pathology, predicting risk and assessing the status of secondary complications of type 1 diabetes.

背景:高血糖引起的氧化应激是糖尿病血管并发症的病理介质。我们评估了血浆氧化剂和抗氧化剂水平对急性和慢性高血糖的反应,这与 1 型糖尿病患者的血管僵硬度和不同程度的肾脏疾病有关:急性高血糖研究包括22名白蛋白排泄率(AER)正常的1型糖尿病患者和13名非糖尿病对照组患者。这些人在 120 分钟高血糖钳夹期间接受了急性葡萄糖挑战。慢性高血糖研究包括 118 名 HbA1c 浓度长期偏低(n = 60)或偏高(n = 58)的 1 型糖尿病患者,他们患有不同程度的糖尿病肾病(DKD),分为正常、中度或重度白蛋白尿(AER)。芬兰迪安研究从血浆或血清样本中测量了丙二醛(MDA)、活性氧代谢物(ROMs)、总抗氧化能力(TAC)、生物抗氧化潜能(BAP)和超氧化物歧化酶(SOD)的水平:结果:MDA 水平(P氧化应激生物标志物与急性和慢性高血糖暴露后的血管僵化和糖尿病并发症有关,在了解疾病病理、预测风险和评估 1 型糖尿病继发性并发症的状况方面,氧化应激生物标志物可能比 HbA1c 更有价值。
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引用次数: 0
Effects of adipose tissues on the relationship between type 2 diabetes mellitus and reduced heart rate variability: mediation analysis. 脂肪组织对 2 型糖尿病与心率变异性降低之间关系的影响:中介分析。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02438-1
Xiaolan Ouyang, Long Peng, Zhuoshan Huang, Tongtong Wang, Jiafu Wang, Hongxing Wu, Junlin Zhong, Bingyuan Wu, Lin Wu, Yue Li, Yan Lu, Suhua Li, Xixiang Tang

Background: Type 2 diabetes mellitus (T2DM) is associated with decreased heart rate variability (HRV) with an unclear intermediate mechanism. This study aimed to conduct mediation analysis to explore the impact of various adipose tissues on the relationship between T2DM and HRV.

Methods: A total of 380 participants were enrolled for analysis, including 249 patients with T2DM and 131 non-diabetic controls. The thicknesses of four adipose tissues (subcutaneous, extraperitoneal, intraperitoneal, and epicardial) were measured by abdominal ultrasound or echocardiography respectively. HRV was assessed by 24-hour Holter for monitoring both frequency domain indices (LF, HF, and LF/HF) and time domain indices (SDNN, SDANN, SDNN index, rMSSD and pNN50). Mediation analysis was used toexamine whether adipose tissues mediated the relationship between T2DM and each index of HRV. Then, a latent variable - HRV burden - was constructed by structural equation model with selected HRV indices to comprehensively assess the whole HRV.

Results: Compared to non-diabetic controls, patients with T2DM exhibited a significant reduction in indices of HRV, and a remarkable increase in the thicknesses of extraperitoneal, intraperitoneal, and epicardial adipose tissues. Mediation analysis found significant indirect effects of T2DM on six indices of HRV, including HF, SDNN, SDANN, SDNN index, rMSSD, and pNN50, which was mediated by epicardial adipose tissue rather than other adipose tissues, with the mediation proportions of 64.21%, 16.38%, 68.33%, 24.34%, 24.10% and 30.51%, respectively. Additionally, epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV burden (24.26%), which composed by SDNN, SDNN index, rMSSD, and pNN50.

Conclusion: Epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV, which reinforces the value of targeting heart-specific visceral fat to prevent cardiac autonomic neuropathy in diabetes.

背景:2型糖尿病(T2DM)与心率变异性(HRV)下降有关,中间机制尚不清楚。本研究旨在进行中介分析,探讨各种脂肪组织对 T2DM 与心率变异性之间关系的影响:方法:共招募了 380 名参与者进行分析,其中包括 249 名 T2DM 患者和 131 名非糖尿病对照者。通过腹部超声或超声心动图分别测量了四种脂肪组织(皮下、腹膜外、腹膜内和心外膜)的厚度。心率变异通过 24 小时 Holter 监测频域指数(LF、HF 和 LF/HF)和时域指数(SDNN、SDANN、SDNN 指数、rMSSD 和 pNN50)进行评估。研究人员使用中介分析法来检验脂肪组织是否在 T2DM 与心率变异各指标之间起中介作用。然后,通过结构方程模型与选定的心率变异指数构建了一个潜变量--心率变异负担,以全面评估心率变异的整体情况:结果:与非糖尿病对照组相比,T2DM 患者的心率变异指数显著降低,腹膜外、腹膜内和心外膜脂肪组织的厚度显著增加。中介分析发现,T2DM对HF、SDNN、SDANN、SDNN指数、rMSSD和pNN50等六项心率变异指标有明显的间接影响,其中心外膜脂肪组织而非其他脂肪组织是中介,中介比例分别为64.21%、16.38%、68.33%、24.34%、24.10%和30.51%。此外,心外膜脂肪组织部分介导了 T2DM 与心率变异负荷降低之间的关系(24.26%),其中由 SDNN、SDNN 指数、rMSSD 和 pNN50 组成:心外膜脂肪组织部分介导了T2DM与心率变异性降低之间的关系,这加强了针对心脏特异性内脏脂肪预防糖尿病心脏自主神经病变的价值。
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引用次数: 0
Association of semaglutide treatment with coronary artery inflammation in type 2 diabetes mellitus patients: a retrospective study based on pericoronary adipose tissue attenuation. 塞马鲁肽治疗与 2 型糖尿病患者冠状动脉炎症的关系:基于冠状动脉周围脂肪组织衰减的回顾性研究。
IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-28 DOI: 10.1186/s12933-024-02445-2
Yanhong Li, Wenjing Yao, Tianxing Wang, Qian Yang, Kexin Song, Feifei Zhang, Fan Wang, Yi Dang

Background: The pericoronary fat attenuation index (FAI) has emerged as a novel and sensitive biomarker reflecting the degree of coronary artery inflammation. Semaglutide has been demonstrated to exert a cardiovascular protective effect independent of hypoglycemia; however, its impact on coronary artery inflammation remains elusive. This study aimed to investigate the association between semaglutide treatment and coronary artery inflammation based on FAI in patients with type 2 diabetes mellitus (T2DM).

Methods: This study enrolled 497 T2DM patients who underwent coronary computed tomography angiography (CCTA) at Hebei General Hospital, of whom 93 treated with semaglutide (Sema+) and 404 did not (Sema-). Clinical data, laboratory indicators, and CCTA parameters were collected and compared between the two groups at baseline. Propensity score matching (PSM) was used to adjust for confounders, and pericoronary FAI was compared. Multivariate linear regression models were used to analyze the association between semaglutide treatment and pericoronary FAI.

Results: Before PSM, pericoronary FAI of the LAD and LCX was lower in patients treated with semaglutide than those without semaglutide treatment. The results of the PSM analysis revealed a lower FAI in all three major coronary arteries in the Sema + group compared to the Sema- group. Multivariate linear regression analyses revealed an independent association between semaglutide treatment and reduced FAI in all three major coronary arteries. This association varied across T2DM patients of differing profiles.

Conclusion: Semaglutide treatment may be associated with lower coronary artery inflammation in patients with T2DM, which might partially explain its cardiovascular protective mechanism.

背景:冠状动脉周围脂肪衰减指数(FAI冠状动脉周围脂肪衰减指数(FAI)已成为反映冠状动脉炎症程度的一种新颖而敏感的生物标志物。塞马鲁肽已被证实具有独立于低血糖的心血管保护作用;然而,它对冠状动脉炎症的影响仍然难以捉摸。本研究旨在探讨基于FAI的2型糖尿病(T2DM)患者的塞马鲁肽治疗与冠状动脉炎症之间的关系:本研究纳入了在河北省总医院接受冠状动脉计算机断层扫描(CCTA)的497例T2DM患者,其中93例接受了塞马鲁肽治疗(Sema+),404例未接受治疗(Sema-)。研究人员收集了两组患者的临床数据、实验室指标和CCTA参数,并对两组患者的基线数据进行了比较。采用倾向评分匹配法(PSM)调整混杂因素,并比较冠状动脉周围FAI。采用多变量线性回归模型分析塞马鲁肽治疗与冠状动脉周围FAI之间的关系:结果:在PSM之前,接受过塞马鲁肽治疗的患者的LAD和LCX冠状动脉周围FAI低于未接受塞马鲁肽治疗的患者。PSM 分析结果显示,与 Sema 组相比,Sema + 组患者三条主要冠状动脉的 FAI 均较低。多变量线性回归分析显示,塞马鲁肽治疗与三大冠状动脉FAI降低之间存在独立关联。这种关联在不同类型的T2DM患者中存在差异:结论:塞马鲁肽治疗可能与 T2DM 患者冠状动脉炎症的降低有关,这可能是其心血管保护机制的部分原因。
{"title":"Association of semaglutide treatment with coronary artery inflammation in type 2 diabetes mellitus patients: a retrospective study based on pericoronary adipose tissue attenuation.","authors":"Yanhong Li, Wenjing Yao, Tianxing Wang, Qian Yang, Kexin Song, Feifei Zhang, Fan Wang, Yi Dang","doi":"10.1186/s12933-024-02445-2","DOIUrl":"https://doi.org/10.1186/s12933-024-02445-2","url":null,"abstract":"<p><strong>Background: </strong>The pericoronary fat attenuation index (FAI) has emerged as a novel and sensitive biomarker reflecting the degree of coronary artery inflammation. Semaglutide has been demonstrated to exert a cardiovascular protective effect independent of hypoglycemia; however, its impact on coronary artery inflammation remains elusive. This study aimed to investigate the association between semaglutide treatment and coronary artery inflammation based on FAI in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>This study enrolled 497 T2DM patients who underwent coronary computed tomography angiography (CCTA) at Hebei General Hospital, of whom 93 treated with semaglutide (Sema+) and 404 did not (Sema-). Clinical data, laboratory indicators, and CCTA parameters were collected and compared between the two groups at baseline. Propensity score matching (PSM) was used to adjust for confounders, and pericoronary FAI was compared. Multivariate linear regression models were used to analyze the association between semaglutide treatment and pericoronary FAI.</p><p><strong>Results: </strong>Before PSM, pericoronary FAI of the LAD and LCX was lower in patients treated with semaglutide than those without semaglutide treatment. The results of the PSM analysis revealed a lower FAI in all three major coronary arteries in the Sema + group compared to the Sema- group. Multivariate linear regression analyses revealed an independent association between semaglutide treatment and reduced FAI in all three major coronary arteries. This association varied across T2DM patients of differing profiles.</p><p><strong>Conclusion: </strong>Semaglutide treatment may be associated with lower coronary artery inflammation in patients with T2DM, which might partially explain its cardiovascular protective mechanism.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"348"},"PeriodicalIF":8.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342130","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}
引用次数: 0
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。
{"title":"Insulin resistance assessed by estimated glucose disposal rate and risk of atherosclerotic cardiovascular diseases incidence: the multi-ethnic study of atherosclerosis.","authors":"Jiayi Yi, Chao Qu, Xiang Li, Hai Gao","doi":"10.1186/s12933-024-02437-2","DOIUrl":"https://doi.org/10.1186/s12933-024-02437-2","url":null,"abstract":"<p><strong>Background: </strong>To investigate the relationship between estimated glucose disposal rate (eGDR), a surrogate indicator of insulin resistance, and atherosclerotic cardiovascular diseases (ASCVD) incidence risk.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"349"},"PeriodicalIF":8.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342144","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}
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
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Cardiovascular Diabetology
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