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 μg 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.