Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass surgery (RYGB) improves glucose tolerance in patients with type 2 diabetes, but also changes the glucose profile in response to a meal in glucose-tolerant individuals. We hypothesised that the driving force for the changed postprandial glucose profiles after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production. METHODS: We determined glucose absorption and metabolism and the rate of lipolysis before and 3 months after RYGB in obese glucose-tolerant individuals using the double-tracer technique during a mixed meal. RESULTS: After RYGB, the postprandial plasma glucose profile changed, with a higher peak glucose concentration followed by a faster return to lower than basal levels. These changes were brought about by changes in glucose kinetics: (1) a more rapid appearance of ingested glucose in the systemic circulation, and a concomitant increase in insulin and glucagon-like peptide-1 secretion; (2) postprandial glucose disappearance was maintained at a high rate for a longer time after RYGB. Endogenous glucose production was similar before and after surgery. Postoperative glucagon secretion increased and showed a biphasic response after RYGB. Adipose tissue basal rate of lipolysis was higher after RYGB. CONCLUSIONS/INTERPRETATION: A rapid rate of absorption of ingested glucose into the systemic circulation, followed by increased insulin secretion and glucose disappearance appears to drive the changes in the glucose profile observed after RYGB, while endogenous glucose production remains unchanged. TRIAL REGISTRATION: ClinicalTrials.gov NCT01559792. FUNDING: The study was part of the UNIK program: Food, Fitness & Pharma for Health and Disease (see www.foodfitnesspharma.ku.dk ). Funding was received from the Novo Nordisk foundation and the Strategic Research Counsel for the Capital Area and Danish Research Agency. The primary investigator received a PhD scholarship from the University of Copenhagen, which was one-third funded by Novo Nordisk.