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

J Clin Endocrinol Metab. 2019 Aug 1;104(8):3233-3244. doi: 10.1210/jc.2018-02661.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02879955.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbohydrate Metabolism*
  • Cross-Over Studies
  • Digestion*
  • Female
  • Gastric Bypass*
  • Gastric Inhibitory Polypeptide / blood
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood*
  • Humans
  • Male
  • Middle Aged
  • Peptide YY / blood
  • Single-Blind Method

Substances

  • Peptide YY
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon

Associated data

  • ClinicalTrials.gov/NCT02879955