Circulating Peptide YY, Weight Loss, and Glucose Homeostasis After Gastric Bypass Surgery in Morbidly Obese Subjects

In Brief Objective: To prospectively assess the relationship between circulating peptide YY (PYY), body weight, and glucose tolerance in severely obese subjects undergoing Roux-en-Y gastric bypass (RYGBP). Summary Background Data: The mechanisms accounting for the beneficial effects of RYGBP on body weight and glucose homeostasis are not well understood. Methods: Prospective study on the response of PYY to a standardized test meal (STM) and its relationship with weight loss and glucose homeostasis (fasting plasma glucose, HbA1c, HOMA-IR, HOMA-B) in nondiabetic (n = 25) and diabetic (n = 10) severely obese subjects evaluated before, and at 6 and 52 weeks after RYGBP. Results: The PYY response to a STM significantly increased (P < 0.001) already at 6 weeks at a time when subjects despite presenting a significant weight loss (−14.6% ± 1.2%) were still markedly obese. Despite massive weight loss (−43.0% ± 2.3%), no further increase in the area under the curve of PYY was observed at 52 weeks after surgery (P = 0.44). The PYY response to a STM at 6 weeks after surgery significantly correlated (r = 0.489, P < 0.05) with the percent excess weight loss at 32.5 ± 1.1 months after surgery. In contrast, no significant correlation was found between PYY and glucose homeostasis parameters in nondiabetic and diabetic patients. Conclusion: Our data support the hypothesis that an increased PYY response after meal ingestion is involved in the sustained weight loss observed after RYGBP. In contrast, our data does not support PYY being relevant in the changes in glucose homeostasis occurring after this type of bariatric surgery. This prospective study supports the hypothesis that changes in body weight occurring after Roux-en-Y gastric bypass could be explained at least in part by changes in peptide YY (PYY). In contrast, our data does not support changes in PYY as being critical for the amelioration of glucose homeostasis after this type of bariatric surgery.