Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), naïve to incretin-based therapy, were treated with liraglutide (1.2 mg/day as an add-on to metformin) for 4 months. miRNAs were quantified using real-time polymerase chain reaction. After liraglutide treatment, we found significant reductions in fasting glucose (from 9.8 ± 5.3 to 6.7 ± 1.6 mmol/L, p = 0.0042), glycosylated haemoglobin (HbA1c) (from 8.1 ± 0.8 to 6.6 ± 1.0%, p = 0.0008), total cholesterol (from 5.0 ± 1.0 to 4.0 ± 0.7 mmol/L, p = 0.0011), triglycerides (from 1.9 ± 1.0 to 1.5 ± 0.8 mmol/L, p = 0.0104) and low-density lipoprotein cholesterol (from 2.9 ± 1.2 to 2.2 ± 0.6 mmol/L, p = 0.0125), while the serum levels of miRNA-27b, miRNA-130a and miRNA-210a were significantly increased (median (interquartile range, IQR) changes: 1.73 (7.12) (p = 0.0401), 1.91 (3.64) (p = 0.0401) and 2.09 (11.0) (p = 0.0486), respectively). Since the changes in miRNAs were independent of changes in all the metabolic parameters investigated, liraglutide seems to exert a direct epigenetic effect in T2DM patients, regulating microRNAs involved in the maintenance of endothelial cell homeostasis. These changes might be implicated in liraglutide’s benefits and may represent useful targets for cardiometabolic management.

中文翻译：

---

利拉鲁肽增加2型糖尿病患者血清MicroRNA-27b，-130a和-210的水平：一种新的表观遗传学作用

除葡萄糖控制外，利拉鲁肽还对多种心脏代谢危险因素显示出有利影响。MicroRNA（miRNA）调节基因表达，导致细胞反应和功能的转录后修饰。特定的miRNA，包括miRNA-27b，miRNA-130a和miRNA-210，在心脏代谢疾病中起作用。我们旨在确定利拉鲁肽对miRNA-27b，miRNA-130a和miRNA-210血清水平的影响。25名初次接受降血糖素治疗的2型糖尿病（T2DM）受试者接受利拉鲁肽（1.2 mg /天作为二甲双胍的补充治疗）治疗4个月。使用实时聚合酶链反应对miRNA进行定量。经利拉鲁肽治疗后，我们发现空腹血糖显着降低（从9.8±5.3降至6.7±1.6 mmol / L，p= 0.0042），糖基化血红蛋白（HbA1c）（从8.1±0.8到6.6±1.0％，p = 0.0008），总胆固醇（从5.0±1.0到4.0±0.7 mmol / L，p = 0.0011），甘油三酸酯（从1.9± 1.0至1.5±0.8 mmol / L，p = 0.0104）和低密度脂蛋白胆固醇（从2.9±1.2至2.2±0.6 mmol / L，p = 0.0125），而血清miRNA-27b，miRNA-130a和miRNA-210a显着增加（中位（四分位间距，IQR）变化：1.73（7.12）（p = 0.0401），1.91（3.64）（p = 0.0401）和2.09（11.0）（p= 0.0486）。由于miRNA的变化与所研究的所有代谢参数的变化均无关，因此利拉鲁肽似乎在T2DM患者中发挥了直接的表观遗传作用，调节了参与维持内皮细胞稳态的microRNA。这些变化可能与利拉鲁肽的益处有关，可能代表了心脏代谢管理的有用目标。