Glucagon‐like Peptide 2 Concentrations Vary in Zambian Children During Diarrhoea, in Malnutrition and Seasonally

Abstract

Objectives Glucagon-like peptide 2 (GLP-2) is a 33 amino acid peptide hormone released from enteroendocrine L-cells following nutrient ingestion. It has been shown to exert trophic effects on the gut. We set out to measure GLP-2 concentrations in blood in children with diarrhoea and malnutrition. Methods GLP-2 levels were measured in blood samples collected from 5 different groups of children (n = 324) at different time points: those with acute diarrhoea, during illness and 3 weeks after recovery; persistent diarrhoea and severe acute malnutrition; controls contemporaneous for diarrhoea; stunted children from the community; and controls contemporaneous for the stunted children. Stool biomarkers and pathogen analysis were carried out on the children with stunting. Results GLP-2 concentrations were higher during acute diarrhoea (median 3.1 ng/mL, interquartile range 2.1, 4.4) than on recovery (median 1.8, interquartile range 1.4, 3.1; P = 0.001), but were not elevated in children with persistent diarrhoea and severe acute malnutrition. In stunted children, there was a progressive decline in GLP-2 levels from 3.2 ng/mL (1.9, 4.9) to 1.0 (0.0, 2.0; P < 0.001) as the children became more stunted. Measures of seasonality (rainfall, temperature, Food Price Index, and Shiga toxin-producing Escherichia coli ) were found to be significantly associated with GLP-2 concentrations in multivariable analysis. We also found a correlation between stool inflammatory biomarkers and GLP-2. Conclusions In diarrhoea, GLP-2 levels increased in acute but not persistent diarrhoea. Malnutrition was associated with reduced concentrations. GLP-2 displayed seasonal variation consistent with variations in nutrient availability.

Potential determinants of low circulating glucagon‐like peptide 2 concentrations in Zambian children with non‐responsive stunting

“…We have also shown that in children with diarrhoea, GLP‐2 levels are elevated in acute but not persistent diarrhoea. In malnutrition and enteropathy, GLP‐2 levels progressively declined as the children's growth became more stunted (Amadi et al., 2017 ; Besa et al., 2020 ). We set out to test the hypothesis that reduced circulating GLP‐2 levels in children with environmental enteropathy and stunting is attributable to small intestinal EEC loss or reduced function, assessed by immunostaining, transcriptomic and genomic analysis.…”