Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic E ect

Abstract

Abstract: Liraglutide has shown favourable e_ects 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 e_ect 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 e_ect 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.