Changes in Blood microRNA Expression and Early Metabolic Responsiveness 21 Days Following Bariatric Surgery

Background. Early metabolic responses following bariatric surgery appear greater than the initial weight loss and coincide with remission/improvement in diabetes. We hypothesized that small noncoding microRNA changes might contribute to regulating mechanisms for weight loss and diabetes remission. Methods. 29 type 2 diabetes patients (mean BMI 46.2 kg/m2) underwent Roux-en-Y gastric bypass (RYGB) surgery. Clinical measurements and fasting blood samples were taken preoperatively and at day 21 postoperatively. Diabetes remission following bariatric surgery was defined as withdrawal of anti-diabetic medication, fasting glucose <126 mg/dl (7 mmol/L) and HbA1c <6.5%. microRNA expression was determined by quantitative polymerase chain reaction. Results. BMI decreased by 3.8 kg/m2 21 days postoperatively. Eleven of 29 RYGB (38%) had diabetes remission. Changes from pre- to post-surgery in 32 of 175 microRNAs were nominally significant (p<0.05). Following multiple comparison adjustment, changes in seven microRNAs remained significant: miR-7-5p, let-7f-5p, miR-15b-5p, let-7i-5p, miR-320c, miR-205-5p, and miR-335-5p. Four pathways were over-represented by these seven microRNAs, including diabetes and insulin resistance pathways. Only one microRNA was nominally associated with diabetes remission 21 days post-surgery (p<0.05): miR-132-3p. Conclusion. Seven microRNAs showed significant changes 21 days after bariatric surgery. Functional pathways of the altered microRNAs were associated with diabetes-, pituitary- and liver-related disease, with expression in natural killer cells, and pivotal intestinal pathology suggesting possible mechanistic roles in early diabetes responses following bariatric surgery.