Effects of Meal Size on the Release of GLP-1 and PYY After Roux-en-Y Gastric Bypass Surgery in Obese Subjects With or Without Type 2 Diabetes

Changes in gastrointestinal peptide release may play an important role in improving glucose control and reducing body weight following Roux-en-Y gastric bypass (RYGB), but the impact of low caloric intake on gut peptide release post-surgery has not been well characterized. The purpose of this study was to assess the relationships between low caloric intake and gut peptide release and how they were altered by RYGB. Obese females including ten normoglycemic (ON) and ten with type 2 diabetes mellitus (T2DM) (OD) were studied before, 1 week, and 3 months after RYGB. Nine lean, normoglycemic women were studied for comparison. Subjects were given three separate mixed meal challenges (MMCs; 75, 150, and 300 kcal). Plasma glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were analyzed. Prior to surgery, only minimal increases in GLP-1 and PYY were observed in response to the MMCs. After surgery, the peak GLP-1 concentration was progressively elevated in response to increasing meal sizes. The meal sizes had a statistically significant impact on elevation of GLP-1 incremental areas under the curve (ΔAUC) in both ON and OD at 1 week and 3 months post-surgery visits (p < 0.05 for all comparisons). The PYY ∆AUC was also significantly increased in a meal size-dependent manner in both ON and OD at both post-surgery visits (p < 0.05 for all comparisons). Meal sizes as small as 75–300 kcal, which cause minimal stimulation in GLP-1 or PYY release in the subjects before RYGB, are sufficient to provide statistically significant, meal size-dependent increases in the peptides post-RYGB both acutely and after meaningful weight loss occurred.