Effects of Simple Carbohydrates on GLP-1 Responses in Gastric Bypass Patients and Matched Controls

Abstract

Exaggerated postprandial secretion of GLP-1 seems to contribute importantly to the metabolic effects of Roux-en-Y gastric bypass (RYGB). The surgery accelerates nutrient entry to the distal intestine, which is believed to augment GLP-1 secretion. In un-operated individuals, slowly digested carbohydrates are also absorbed in the distal intestine and may accordingly produce greater GLP-1 responses than rapidly absorbed ones. Our aim was to investigate GLP-1 secretion in response to isomolar (0.1385 mol) oral loads of glucose (glu) and fructose (fru), either given as separate monosaccharides (25 g glu and 25 g fru) or as disaccharides in the form of 47.5 g sucrose (suc) +/- alpha glucosidase inhibition (by acarbose (aca)) or 47.5 g isomaltulose (iso), which is slower digested than suc, on 4 separate days in 10 RYGB patients and 10 controls (CON) matched on BMI, age and sex. Glu/fru and suc induced similar glucose excursions and responses of C-peptide and GLP-1, the latter being 3-fold greater in RYGB compared to CON. Digestion of iso was slow in comparison with suc in both groups. Mean GLP-1 response (positive iAUC) to iso was ∼50% and ∼160% greater than to suc in RYGB (p=0.11) and CON (p=0.01), respectively. Aca effectively slowed suc digestion in both groups, resulting in lower peak concentrations of glucose (RYGB: 9.3 vs. 6.7 mmol/l, CON: 7.7 vs. 6.6 mmol/l) and C-peptide (RYGB: 2762 vs. 1341 pmol/l, CON: 2367 vs. 1520 pmol/l) compared with suc alone (p<0.01). Aca diminished mean suc stimulated GLP-1 secretion by ∼50% in RYGB (p<0.01), but this effect was absent in CON. The slowly absorbed disaccharide isomaltulose elicits a greater GLP-1 response than sucrose. The same effect is not evident when digestion of sucrose is inhibited by acarbose, which in RYGB diminishes sucrose induced GLP-1 secretion. Understanding the digestive processes involved in carbohydrate induced GLP-1 release after gastric bypass is an important step towards mimicking the effects of the surgery by pharmacological means. Disclosure C. Martinussen: None. K.N. Bojsen-Moller: None. C. Dirksen: None. M.S. Svane: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., AstraZeneca. Research Support; Self; Danish Diabetes Academy, Novo Nordisk Foundation. Other Relationship; Self; Antag Therapeutics. Other Relationship; Spouse/Partner; Antag Therapeutics. S. Madsbad: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Eli Lilly and Company. Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi-Aventis, Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S.