Aims/hypothesis

Type 2 diabetes mellitus is known to contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, identifying HFpEF in individuals with type 2 diabetes early on is often challenging due to a limited array of biomarkers. This study aims to investigate specific biomarkers associated with the progression of HFpEF in individuals with type 2 diabetes, for the purpose of enabling early detection and more effective management strategies.

Methods

Blood samples were collected from individuals with type 2 diabetes, both with and without HFpEF, for proteomic analysis. Plasma integrin α1 (ITGA1) levels were measured and compared between the two groups. Participants were further categorised based on ITGA1 levels and underwent detailed transthoracic echocardiography at baseline and during a median follow-up period of 30 months. Multivariable linear and Cox regression analyses were conducted separately to assess the associations between plasma ITGA1 levels and changes in echocardiography indicators and re-hospitalisation risk. Additionally, proteomic data for the individuals’ left ventricles, from ProteomeXchange database, were analysed to uncover mechanisms underlying the change in ITGA1 levels in HFpEF.

Results

Individuals with type 2 diabetes and HFpEF showed significantly higher plasma ITGA1 levels than the individuals with type 2 diabetes without HFpEF. These elevated ITGA1 levels were associated with left ventricular remodelling and impaired diastolic function. Furthermore, during a median follow-up of 30 months, multivariable analysis revealed that elevated ITGA1 levels independently correlated with deterioration of both diastolic and systolic cardiac functions. Additionally, higher baseline plasma ITGA1 levels independently predicted re-hospitalisation risk (HR 2.331 [95% CI 1.387, 3.917], p=0.001). Proteomic analysis of left ventricular myocardial tissue provided insights into the impact of increased ITGA1 levels on cardiac fibrosis-related pathways and the contribution made by these changes to the development and progression of HFpEF.

Conclusions/interpretation

ITGA1 serves as a biomarker for monitoring cardiac structural and functional damage, can be used to accurately diagnose the presence of HFpEF, and can be used to predict potential deterioration in cardiac structure and function as well as re-hospitalisation for individuals with type 2 diabetes. Its measurement holds promise for facilitating risk stratification and early intervention to mitigate the adverse cardiovascular effects associated with diabetes.

Data availability

The proteomic data of left ventricular myocardial tissue from individuals with type 2 diabetes, encompassing both those with and without HFpEF, is available from the ProteomeXchange database at http://proteomecentral.proteomexchange.org.

Graphical Abstract

中文翻译：

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2 型糖尿病中 ITGA1 水平升高：对心脏功能损伤的影响

目标/假设

已知 2 型糖尿病会导致射血分数保留的心力衰竭 (HFpEF) 的发生。然而，由于生物标志物数量有限，早期识别 2 型糖尿病患者的 HFpEF 通常具有挑战性。本研究旨在调查与 2 型糖尿病患者 HFpEF 进展相关的特定生物标志物，以实现早期检测和更有效的管理策略。

方法

从患有或不患有 HFpEF 的 2 型糖尿病患者采集血样，用于蛋白质组分析。测量并比较两组之间的血浆整合素α1（ITGA1）水平。参与者根据 ITGA1 水平进一步分类，并在基线和中位随访 30 个月期间接受详细的经胸超声心动图检查。分别进行多变量线性和Cox回归分析，以评估血浆ITGA1水平与超声心动图指标变化和再住院风险之间的关联。此外，还分析了 ProteomeXchange 数据库中个体左心室的蛋白质组数据，以揭示 HFpEF 中 ITGA1 水平变化的机制。

结果

患有 HFpEF 的 2 型糖尿病患者的血浆 ITGA1 水平显着高于患有 HFpEF 的 2 型糖尿病患者。 ITGA1 水平升高与左心室重构和舒张功能受损有关。此外，在中位 30 个月的随访期间，多变量分析显示，ITGA1 水平升高与心脏舒张和收缩功能恶化独立相关。此外，较高的基线血浆 ITGA1 水平独立预测再住院风险（HR 2.331 [95% CI 1.387, 3.917]，p = 0.001）。左心室心肌组织的蛋白质组学分析提供了关于 ITGA1 水平升高对心脏纤维化相关途径的影响以及这些变化对 HFpEF 发生和进展的贡献的见解。

结论/解释

ITGA1 作为监测心脏结构和功能损伤的生物标志物，可用于准确诊断 HFpEF 的存在，并可用于预测 2 型糖尿病患者心脏结构和功能的潜在恶化以及再住院情况。其测量有望促进风险分层和早期干预，以减轻与糖尿病相关的不良心血管影响。

数据可用性

2 型糖尿病患者（包括患有和不患有 HFpEF 的患者）左心室心肌组织的蛋白质组数据可从 ProteomeXchange 数据库获取，网址为：http://proteomecentral.proteomexchange.org。

图形概要