IRCCS, Scientific Institute of Telese Terme (BN), Salvatore Maugeri Foundation, Telese Terme, Italy.
Eur J Clin Invest. 2015 Feb;45(2):187-95. doi: 10.1111/eci.12395.
Diabetes mellitus (DM) is associated with impaired prognosis in patients with heart failure (HF), but pathogenic mechanisms are unclear. In the failing heart, elevated β-adrenergic receptor (β-AR) activation by catecholamines causes G-protein-coupled receptor kinase-2 (GRK2) upregulation which is responsible for β-AR signalling dysfunction. Importantly, GRK2 expression, measured in peripheral lymphocytes of HF patients, correlates with levels of this kinase in the failing myocardium reflecting the loss of hemodynamic function. Moreover, HF-related GRK2 protein overexpression promotes insulin resistance by interfering with insulin signalling. The aim of this study was to assess lymphocyte GRK2 protein levels in HF patients with and without DM.
Patients with a diagnosis of HF were enrolled in the study. All subjects underwent a complete clinical examination (including NYHA functional class assessment and echocardiography) and blood draw for serum N-terminal pro-brain natriuretic peptide (NT-proBNP), lymphocyte GRK2 and plasma norepinephrine (NE) levels. Demographic data including age, sex, medications, cardiovascular risk factors and presence of comorbidities were also collected.
Two hundred and sixty-eight patients with HF (left ventricular ejection fraction [LVEF] 30.6 ± 7.6%) with and without DM were enrolled. No differences between the two groups were found in terms of demography, HF aetiology, LVEF, NYHA class, NE and NT-proBNP. GRK2 was significantly higher in patients with DM compared to non-DM. At multivariate linear regression analysis, LVEF, NE, NT-proBNP and diabetes came out to be independent predictors of GRK2 levels in the overall study population.
In HF patients, DM is associated with significantly more elevated lymphocyte GRK2 protein levels, likely reflecting more compromised cardiac β-AR signalling/function, despite similar hemodynamic status and neuro-hormonal activation compared to patients without DM. These findings contribute to explain the negative prognostic impact of DM in patients with HF.
糖尿病（DM）与心力衰竭（HF）患者的预后受损有关，但发病机制尚不清楚。在衰竭的心脏中，儿茶酚胺引起的β-肾上腺素能受体（β-AR）激活导致 G 蛋白偶联受体激酶-2（GRK2）上调，这是导致β-AR 信号功能障碍的原因。重要的是，HF 患者外周淋巴细胞中 GRK2 的表达与衰竭心肌中这种激酶的水平相关，反映了血液动力学功能的丧失。此外，HF 相关的 GRK2 蛋白过度表达通过干扰胰岛素信号转导促进胰岛素抵抗。本研究旨在评估伴或不伴 DM 的 HF 患者淋巴细胞 GRK2 蛋白水平。
招募了诊断为 HF 的患者参加本研究。所有患者均接受了完整的临床检查（包括 NYHA 功能分级评估和超声心动图）和血液采集，以测量血清 N 端脑利钠肽前体（NT-proBNP）、淋巴细胞 GRK2 和血浆去甲肾上腺素（NE）水平。还收集了人口统计学数据，包括年龄、性别、药物、心血管危险因素和合并症。
共纳入 268 例 HF 患者（左心室射血分数 [LVEF] 30.6±7.6%），伴或不伴 DM。两组在人口统计学、HF 病因、LVEF、NYHA 分级、NE 和 NT-proBNP 方面无差异。DM 组患者的 GRK2 明显高于非 DM 组。多元线性回归分析显示，LVEF、NE、NT-proBNP 和糖尿病是总体研究人群中 GRK2 水平的独立预测因素。
在 HF 患者中，DM 与淋巴细胞 GRK2 蛋白水平显著升高相关，这可能反映了心脏β-AR 信号转导/功能受损更严重，尽管与无 DM 患者相比，血液动力学状态和神经激素激活相似。这些发现有助于解释 DM 对 HF 患者的不良预后影响。
