Ghrelin In Children With Intestinal Failure Receiving Longterm Parenteral Nutrition

Introduction: In children with intestinal failure (IF), increasing enteral nutrition (EN) has sometimes proved impossible, partly due to abnormalities in gastrointestinal motility. Ghrelin is a gut-derived peptide hormone that stimulates appetite and food intake and is involved in the regulation of gastrointestinal motility. Therefore, we expected low ghrelin levels in children receiving parenteral nutrition (PN). We aimed to evaluate acylated ghrelin (AG) levels in children with IF receiving PN, to test our hypothesis that ghrelin could be used as a biomarker for appetite and tolerance for EN. Methods: In this prospective multicenter study, children with IF receiving home PN for >6 months, with ≥1 ghrelin measurements, were included. Plasma AG levels were measured with ELISA assay. Since there are no reference values, AG levels were compared with the median AG level in healthy control subjects within the same age range and measured using an identical assay protocol from Kuppens et al (2015).(1) AG levels from children with motility disorders were compared with the remaining patients (with enteropathies and short bowel syndrome) with Mann-Whitney U tests. The correlation between AG levels and percentage of energy intake provided by EN (%EN) was assessed with Spearman’s rho (rs). Results: Sixty-eight ghrelin samples from 21 IF patients were analysed. Median AG level in children with IF was >2x higher than in healthy control subjects (207.8 vs 82.4 pg/ml). No significant differences in AG levels were found between patients with motility disorders (n=10) and the remaining patients (n=11) (median AG: 195.4 vs 293.2 pg/ml, respectively, p=0.387). Taking all ghrelin measurements together, a weak but significant correlation between AG and %EN was found (rs=0.260, p=0.032) in which lower AG levels corresponded with higher %EN. Conclusions: Surprisingly, children with IF had higher AG levels than healthy peers. Interventional studies are needed to support the theory that there may be ghrelin insensitivity in these children receiving long-term PN as a result of starving the gut or because of intravenous glucose infusions.