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, while this may not apply after RYGB.

DESIGN: Single-blinded, randomized, crossover study.

SETTING: Hvidovre Hospital, Denmark.

PARTICIPANTS: 10 RYGB- and 10 unoperated matched subjects.

INTERVENTIONS: 4 separate days with ingestion of different carbohydrate loads, either rapidly/proximally digested (glucose+fructose; sucrose) or slowly/distally digested (isomaltulose; sucrose+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 3-fold (p=0.02) and PYY 9-fold (p=0.08) compared with sucrose in unoperated subjects but had 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+acarbose when compared to 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.