Gip Gene Expression After Bariatric Surgery

Erin Moran-Atkin, MD, Fred Brody, MD MBA, Sidney Fu, MD PhD. The George Washington University Medical Center

Introduction: Following bariatric surgery, type 2 diabetes (T2D) may resolve quickly and correlates closely with incretin serum levels. One of these incretins, gastric inhibitory polypeptide (GIP), is produced in the duodenum and jejunum and increases following bariatric surgery; especially after Roux-en-Y gastric bypass (RYGB). This study analyzes GIP gene expression following bariatric surgery in order to clarify the potential pathophysiology between incretins and the resolution of T2D.

Method: The study includes 14 morbidly obese patients (9T2D and 5 non diabetic) that underwent bariatric surgery including gastric banding and RYGB. Nine patients (5 T2D; 4 non diabetic) underwent a gastric band and 5 patients (4 T2D; 1 non diabetic) underwent a RYGB. Preoperative blood was drawn the day of surgery and postoperative samples were collected at approximately three months. All blood samples were collected in PAXgene tubes to stabilize mRNA expression. Total RNA was extracted and purified, then cDNA was synthesized. Finally, real time quantitative PCR was used to quantify gene expression. Results were analyzed using Student’s t-test with a p<0.05 significant.

Results: At three months postoperatively, T2D completely resolved or significantly improved in 7 T2D (77.8%) patients. Four patients (2 RYGB and 2 gastric band) had discontinued all subcutaneous or oral medications. Three patients (2 RYGB and 1 gastric band) had discontinued subcutaneous insulin but remained on reduced levels of oral hypoglycemic agents. The remaining 2 T2D (22.2%) patients did not show any resolution of diabetes at 3 months postoperatively. Both of these patients underwent a gastric band. Postoperative GIP gene expression for all bariatric patients decreased 1.2 (p= 0.06) fold. However, the diabetic RYGB patients showed a 0.5 (p=0.38) fold increase in gene expression versus a 1.9 (p=0.08) fold decrease for gastric band patients.

Conclusion: This study represents one of the first analyses of GIP gene expression as opposed to serum levels following bariatric surgery. Although results are not statistically significant, the trend in gene expression on diabetic patients after RYGB seams to indicate that the resolution of DM in this group may be closely related to the incretin GIP. The anatomical differences secondary to a RYGB may account for the differences in gene expression versus a gastric band. Of note, patient accrual continues in order to discern the postoperative gene expression for GIP in a larger cohort. Regardless, this study begins to unravel the genomic elements that may comprise the foregut hypothesis regarding resolution of T2D.