Augmented GLP-1 Secretion as Seen After Gastric Bypass May Be Obtained by Delaying Carbohydrate Digestion.

CONTEXT: Exaggerated postprandial glucagon-like peptide-1 (GLP-1) secretion seems important for weight loss and diabetes remission after Roux-en-Y gastric bypass (RYGB) and may result from carbohydrate absorption in the distal small intestine.

OBJECTIVE

To investigate distal [GLP-1; peptide YY (PYY)] and proximal [glucose-dependent insulinotropic polypeptide (GIP)] gut hormone secretion in response to carbohydrates hydrolyzed at different rates. We hypothesized that slow digestion restricts proximal absorption, facilitating distal delivery of carbohydrates and thereby enhanced GLP-1 secretion in unoperated individuals, whereas this may not apply after RYGB.

DESIGN

Single-blinded, randomized, crossover study.

SETTING

Hvidovre Hospital, Hvidovre, Denmark.

PARTICIPANTS

Ten RYGB-operated patients and 10 unoperated matched subjects.

INTERVENTIONS: Four separate days with ingestion of different carbohydrate loads, either rapidly/proximally digested (glucose plus fructose; sucrose) or slowly/distally digested (isomaltulose; sucrose plus acarbose).

MAIN OUTCOME MEASURES: GLP-1 secretion (area under the curve above baseline). Secondary outcomes included PYY and GIP.

RESULTS

Isomaltulose enhanced secretion of GLP-1 nearly threefold (P = 0.02) and PYY ninefold (P = 0.08) compared with sucrose in unoperated subjects but had a modest effect after RYGB. Acarbose failed to increase sucrose induced GLP-1 secretion in unoperated subjects and diminished the responses by 50% after RYGB (P = 0.03). In both groups, GIP secretion was reduced by isomaltulose and even more so by sucrose plus acarbose when compared with sucrose intake.

CONCLUSIONS

GLP-1 secretion depends on the rate of carbohydrate digestion, but in a different manner after RYGB. Enhanced GLP-1 secretion is central after RYGB, but it may also be obtained in unoperated individuals by delaying hydrolysis of carbohydrates, pushing their digestion and absorption distally in the small intestine.