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

Abstract

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.

Upregulation of intestinal glucose transporters after Roux-en-Y gastric bypass to prevent carbohydrate malabsorption

“…This is in contrast to the responses to an oral glucose drink after RYGB, characterized by a higher early peak level and earlier return to baseline due to the presumed rapid GI transit (30,31). In the current study, the higher early peak was more sustained in response to the constant intra-duodenal glucose infusion.…”

Roles of the Gut in Glucose Homeostasis

“…Of note, increased intestinal gluconeogenesis was proposed to account for some of the changes in glucose homeostasis after gastric bypass in rats (33) (i.e., the increased intestinal gluconeogenesis would inhibit hepatic glucose production). On the other hand, increased glucose combustion within the hypertrophied gut after gastric bypass in rodents has also been suggested as an explanation (34); however, glucose kinetics after bypass in humans do not seem to be consistent with this hypothesis (21). Lactase insufficiency is, of course, limiting for lactose absorption in many adults, and the extent to which this may represent a problem in bariatric/metabolic surgery is well worth study.…”

“…Absorption after surgery is extremely rapid, and complete absorption is obtained more rapidly than in individuals who do not undergo this surgery (Fig. 2) (21). Even when rapid emptying of glucose from the gastric pouch is bypassed by infusing at a controlled rate directly into the small intestine, absorption of glucose is more rapid than in healthy control subjects (39).…”

“…These processes are highly regulated by insulin. The liver is the main target for insulin action (44), and postprandially, hepatic glucose production is effectively shut down, whereas hepatic glucose uptake is enhanced (21). However, a considerable part of the absorbed glucose passes through the liver so that there is a rise in plasma glucose concentration.…”

“…With rising insulin concentrations and increased insulin-stimulated translocation of GLUT-4, peripheral glucose transport is further enhanced. Thus, after gastric bypass surgery, glucose deposition is greatly accelerated and may overshoot the rate of absorption whereby glucose concentrations fall below fasting levels (21). Indeed, in most patients who undergo bypass surgery, there is a pronounced decrease in plasma glucose concentrations after a glucose load, and in some, there is significant hypoglycemia (46), which may worsen as insulin resistance diminishes with progressive weight loss.…”