Preoperative plasma miR-144-3p to predict persistent type 2 diabetes after gastric bypass - a pilot proof-of-concept study.

Although RYGB induces substantial metabolic benefits, remission of type 2 diabetes mellitus (T2DM) is not universal, creating a clinical challenge in identifying patients unlikely to achieve glycemic success. This prospective observational cohort study investigated whether preoperative circulating microRNAs (miRNAs) predict persistent T2DM after Roux-en-Y gastric bypass (RYGB) in women with obesity. Twenty-eight women were assessed preoperatively and at 3, 12, and 60 months after surgery. According to ADA criteria, patients were classified as responders (R; n = 18) or non-responders (NR; n = 10). Plasma collected preoperatively and at 3 months was analyzed for circulating miRNAs. Preoperative screening was conducted using TaqMan Low Density Array (n = 17), followed by RT-qPCR validation in the full cohort (n = 28). In the screening phase, NR patients showed higher preoperative miR-144-3p expression (p = 0.033), which also correlated inversely with plasma insulin (p = 0.018). During validation, elevated preoperative miR-144-3p predicted persistent T2DM with an AUC of 0.771 (p = 0.023) and 100 % specificity. Additionally, a post hoc exploratory analysis showed that R patients who relapsed at 5 years had higher miR-144-3p levels at 3 months than those maintaining remission (p < 0.0001). Overall, these findings identify preoperative miR-144-3p as a candidate biomarker for predicting persistent T2DM after RYGB.