Serum fasting GLP-1 and GLP-2 associate with intestinal adaptation in pediatric onset intestinal failure

Abstract

Glukagon-like-peptide-1 (GLP-1) and -2 (GLP-2), produced by intestinal L-cells, are key hormones regulating intestinal transit, secretion, absorption, and mucosal growth. We evaluated naïve fasting serum GLP-1 and GLP-2 levels in pediatric intestinal failure (IF). Fifty-five IF patients with median age 4.2 (IQR 1.3-12) years and 47 matched healthy controls underwent measurement of fasting serum GLP-1 and GLP-2. Serum GLP-2 [19.9 (13.8-27.9) vs 11.6 (7.0-18.6) ng/mL, P<0.001], but not GLP-1 [6.1 (4.0-15.7) vs 6.4 (3.9-10.7) ng/mL, P=0.976], levels were increased in IF patients. Serum GLP-2 concentrations were higher in patients with small bowel-colic continuity [21.1 (15.0-30.7) ng/mL] compared to patients with an endostomy [10.4 (6.6-17.9) ng/mL, P=0.028], whereas no association with preservation of ileum or ileocecal valve was observed. During PN delivery, GLP-2 inversely associated with remaining small bowel length (r=-0.500, P=0.041) and frequency of PN infusions (r=-0.549, P=0.042). Serum GLP-1 levels were lower in patients receiving PN currently [4.1 (2.8-5.1)] compared to patients, who had weaned off PN [6.5 (5.1-21.1), P=0.005], and correlated positively with duration of PN (r=0.763, P=0.002) and negatively with percentage parenteral energy requirement (r=-0.716, P=0.006). In pediatric IF, serum GLP-2 levels increase in patients with small bowel-colic continuity proportionally to the length of resected small intestine. Increase in serum GLP-1 and GLP-2 levels paralleled reducing requirement for parenteral support. These findings support regulation of intestinal adaption by GLP-2 and GLP-1 in children with IF.