Background

Diabetes mellitus is a chronic multisystem disease with a high global prevalence, including in Saudi Arabia. The Glucagon-like Peptide (GLP-1) receptor agonist liraglutide is known to lower glucose levels, reduce weight and improve cardiovascular outcome. However, mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear.

Methods

In the present study, a 2D-DIGE MALDI-TOF mass spectrometric approach combined with bioinformatics and network pathway analysis explore the plasma proteomic profile. The study involved 20 patients with T2DM with mean age of 54.4 ± 9.5 years and Hemoglobin A1c (HbA1c) between 8% and 11% (inclusive).

Results

A statistically significant change (p < .006) was observed in HbA1c with no significant changes in body weight, renal function, or markers of dyslipidemia post-treatment with liraglutide. 2 D-DIGE gel analysis identified significant changes (⩾1.5-fold change, Analysis of variance (ANOVA), p ⩽ 0.05) in 72 proteins, (62 down and 10 up) in liraglutide pre-treatment compared to the post-treatment state. Proteins identified in our study were found to regulate metabolic processes including acute phase response proteins, enzymes, apolipoproteins with involvement of the inflammatory signaling pathways, NF-κB, AKT, and p38 MAPK

Conclusion

Liraglutide treatment decreased levels of acute phase response that to reduce the systemic chronic inflammatory state and oxidative stress, and eventually improve the cardio-metabolic profile in these patients.

中文翻译：

---

血浆蛋白质组学显示利拉鲁肽治疗后 2 型糖尿病患者的心脏代谢状况得到改善

背景

糖尿病是一种慢性多系统疾病，全球流行率很高，包括在沙特阿拉伯。众所周知，胰高血糖素样肽 (GLP-1) 受体激动剂利拉鲁肽可降低葡萄糖水平、减轻体重并改善心血管结局。然而，利拉鲁肽治疗 2 型糖尿病 (T2DM) 患者获益的潜在机制仍不清楚。

方法

在本研究中，2D-DIGE MALDI-TOF 质谱方法结合生物信息学和网络通路分析探索血浆蛋白质组学特征。该研究涉及 20 名 T2DM 患者，平均年龄为 54.4 ± 9.5 岁，血红蛋白 A1c (HbA1c) 介于 8% 和 11%（含）之间。

结果

观察到 HbA1c 有统计学意义的变化 ( p < .006)，而利拉鲁肽治疗后体重、肾功能或血脂异常标志物没有显着变化。2 D-DIGE 凝胶分析确定了利拉鲁肽预处理与治疗后状态相比，72 种蛋白质（62 下降和 10 上升）的显着变化（1.5 倍变化，方差分析 (ANOVA)，p  0.05） . 在我们的研究中发现的蛋白质可以调节代谢过程，包括急性期反应蛋白、酶、参与炎症信号通路的载脂蛋白、NF-κB、AKT 和 p38 MAPK

结论

利拉鲁肽治疗降低了急性期反应水平，从而减少全身慢性炎症状态和氧化应激，并最终改善这些患者的心脏代谢特征。