Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The “Heart OMics in AGEing” (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial. Protein biomarkers (n = 276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline and 9 months (or last visit) from HOMAGE trial participants including 217 patients with, and 310 without, diabetes. Twenty-one biomarkers were increased and five decreased in patients with diabetes compared to non-diabetics at baseline. The markers clustered mainly within inflammatory and proteolytic pathways, with granulin as the key-hub, as revealed by knowledge-induced network and subsequent gene enrichment analysis. Treatment with spironolactone in diabetic patients did not lead to large changes in biomarkers. The effects of spironolactone on NTproBNP, fibrosis biomarkers and echocardiographic measures of diastolic function were similar in patients with and without diabetes (all interaction analyses p > 0.05). Amongst patients at risk for HF, those with diabetes have higher plasma concentrations of proteins involved in inflammation and proteolysis. Diabetes does not influence the effects of spironolactone on the proteomic profile, and spironolactone produced anti-fibrotic, anti-remodelling, blood pressure and natriuretic peptide lowering effects regardless of diabetes status. Trial registration NCT02556450.

中文翻译：

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有发生心力衰竭风险的糖尿病患者的蛋白质组学机制特征：来自 HOMAGE 试验的见解

糖尿病 (DM) 患者发生心力衰竭 (HF) 的风险增加。“衰老中的心脏 OMics” (HOMAGE) 试验表明，螺内酯对高危人群的纤维化和心脏重塑具有有益作用，可能会减缓 HF 的进展。我们在 HOMAGE 试验中比较了患有和非糖尿病患者的 HF 风险患者的蛋白质组学特征。在基线和 9 个月（或最后一次访问）从 HOMAGE 试验参与者收集的血浆中测量来自 Olink®Proseek-Multiplex 心血管和炎症面板的蛋白质生物标志物（n = 276），其中包括 217 名糖尿病患者和 310 名非糖尿病患者。与基线时的非糖尿病患者相比，糖尿病患者的 21 个生物标志物增加，5 个减少。正如知识诱导网络和随后的基因富集分析所揭示的那样，这些标记物主要聚集在炎症和蛋白水解途径中，以颗粒蛋白为关键枢纽。在糖尿病患者中使用螺内酯治疗不会导致生物标志物发生大的变化。螺内酯对 NTproBNP、纤维化生物标志物和超声心动图测量舒张功能的影响在糖尿病患者和非糖尿病患者中相似（所有相互作用分析 p > 0.05）。在有 HF 风险的患者中，糖尿病患者的血浆中参与炎症和蛋白水解的蛋白质浓度较高。糖尿病不影响螺内酯对蛋白质组学特征的影响，螺内酯产生抗纤维化、抗重塑、无论糖尿病状态如何，都有降低血压和利钠肽的作用。试用注册 NCT02556450。