Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon

Abstract

Background & Aims: Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a terminal ileum and colon who have functional short-bowel syndrome with severe malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no postprandial secretion of GLP-2. Methods: Balance studies were performed before and after treatment with GLP-2, 400 g subcutaneously twice a day for 35 days, in 8 patients (4 -17 years from last bowel resection; 6 with Crohn's disease). Four patients received home parenteral nutrition (mean residual jejunum, 83 cm), and 4 did not (mean ileum resection, 106 cm). Biopsy specimens were taken from jejunal/ileal stomas, transit was measured by scintigraphy, and body composition was measured by dual-energy x-ray absorptiometry. Results: Treatment with GLP-2 improved the intestinal absorption of energy 3.5% ؎ 4.0% (mean ؎ SD) from 49.9% to 53.4% (P ‫؍‬ 0.04), wet weight 11% ؎ 12% from 25% to 36% (P ‫؍‬ 0.04), and nitrogen 4.7% ؎ 5.4% from 47.4% to 52.1% (P ‫؍‬ 0.04). Body weight increased 1.2 ؎ 1.0 kg (P ‫؍‬ 0.01), lean body mass increased 2.9 ؎ 1.9 kg (P ‫؍‬ 0.004), fat mass decreased 1.8 ؎ 1.3 kg (P ‫؍‬ 0.007), and 24-hour urine creatinine excretion increased (P ‫؍‬ 0.02). The time to 50% gastric emptying of solids increased 30 ؎ 16 minutes from 89 to 119 minutes (P < 0.05). Small bowel transit time was not changed. Crypt depth and villus height were increased in 5 and 6 patients, respectively. Conclusions: Treatment with GLP-2 improves intestinal absorption and nutritional status in short-bowel patients with impaired postprandial GLP-2 secretion in whom the terminal ileum and the colon have been resected.

Nutrient intake from habitual oral diet in patients with severe short bowel syndrome living in the southeastern United States

“…The net intestinal macronutrient absorption values in our subjects are within the range of those reported in other studies of PN-dependent SBS patients (12)(13)(14)(15)(16). This broad range of nutrient absorption is related to the remaining small bowel length but also to the underlying disease and the anatomy of remnant intestine.…”

Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005

“…GLP-2 has since been shown to function as an important growth factor for the gut [22], and is currently being evaluated as a therapeutic agent for intestinal insufficiency [23]. Having established radioimmunoassays for the glucagon-like peptides, we were now able to study the insulin-stimulating effect of a peptide that we isolated from gut extracts on the basis of its GLP-1 immunoreactivity.…”

Randomised controlled trial of colostrum to improve intestinal function in patients with short bowel syndrome

“…However, in a similar setting, it has been possible to demonstrate significant improvements in intestinal function employing other treatment modalities, and therefore, the effects of colostrum seem to be so modest that the clinical relevance is negligible. 20,21,43 In fact, two of the eight patients showed a negative value for relative improvement of intestinal absorption; the other six had improvements, though mainly minor, in the magnitude of 2-3%, and one patient improved his relative absorption with 11% from 47 to 58%.…”

“…Anti-diarrhoeals 13,14 reduce intestinal motility, whereas antisecretory agents [15][16][17] reduce upper GI secretions, but their effect on macronutrient absorption remains to be established. 18 Stimulation of remnant bowel adaptation with growth hormone 19 or glucagon-like peptide 2 (GLP-2) 20 has improved energy and wet weight absorption in patients with intestinal insufficiency or failure that were already well adapted, 21 probably mediated by local release of growth factors such as insulin-like growth factor 1. 22 In this context, colostrum, the first milk produced after birth in mammals, has interesting properties in addition to its normal role to stimulate growth and maturation of the newborn gut.…”