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

TY - JOUR

T1 - Augmented GLP-1 Secretion as Seen After Gastric Bypass May Be Obtained by Delaying Carbohydrate Digestion

AU - Martinussen, Christoffer

AU - Bojsen-Møller, Kirstine Nyvold

AU - Dirksen, Carsten

AU - Svane, Maria Saur

AU - Kristiansen, Viggo Bjerregaard

AU - Hartmann, Bolette

AU - Holst, Jens Juul

AU - Madsbad, Sten

PY - 2019/6/19

Y1 - 2019/6/19

N2 - 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.

AB - 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.

U2 - 10.1210/jc.2018-02661

DO - 10.1210/jc.2018-02661

M3 - Journal article

C2 - 30844053

SN - 0021-972X

VL - 104

SP - 3233

EP - 3244

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -