SAN-134

Despite evidence of possible glucagonotropic effects, the role of the gut hormone glucagon-like peptide 2 (GLP-2) in glucose metabolism is unclear.

This work aimed to evaluate the effect of exogenous GLP-2 on plasma glucagon levels during hypoglycemia, euglycemia, and hyperglycemia in healthy male volunteers.

A randomized, double-blind, placebo-controlled, crossover study was conducted with supportive ex vivo human islet experiments. Participants included 10 lean, healthy men, median (interquartile range) aged 22 (21-23) years, with body mass index of 23.5 (23.3-23.8) and glycated hemoglobin A1c of 4.8 (4.6-5.1)% (29 (26.5-32.5) mmol/mol). During 6 separate study days, GLP-2 (6 pmol/kg/min for 10 minutes and 2 pmol/kg/min for the following 90 minutes) and placebo (saline), respectively, were infused intravenously during insulin-induced hypoglycemia (∼2.5 mmol/L), euglycemia (∼5 mmol/L), or hyperglycemia (∼10 mmol/L). Primary outcome was baseline-subtracted area under the curve for plasma glucagon, and secondary outcomes were serum insulin and C-peptide concentrations. Exploratory outcomes included norepinephrine, growth hormone, and bone homeostatic markers carboxy-terminal collagen crosslinks (CTX) and procollagen type I amino-terminal propeptide (PINP).

During GLP-2 infusions, steady-state plasma GLP-2 concentrations were 50-fold higher than during placebo. Compared to placebo, GLP-2 increased glucagon secretion slightly during euglycemia, and not during insulin-induced hypoglycemia or hyperglycemia. Ex vivo, GLP-2 did not affect glucagon secretion from isolated human islets. GLP-2 did not affect circulating concentrations of insulin, C-peptide, growth hormone, norepinephrine, or CTX during hypoglycemia, euglycemia, or hyperglycemia. GLP-2 decreased PINP during euglycemia and hyperglycemia.

Exogenous GLP-2 increased glucagon secretion slightly during euglycemia and not during insulin-induced hypoglycemia or hyperglycemia in healthy young men.

Growth outcomes in children with intestinal failure (IF) after weaning from parenteral nutrition (PN) may be modified by primary diagnosis and interventions aimed at achieving enteral tolerance. We evaluated growth after weaning by diagnosis and intestinal transplant status and during treatment with the glucagon‐like peptide‐2 analog teduglutide.

A two‐center retrospective review was conducted on children diagnosed with IF at age <12 months. The z scores for weight and length/height were examined up to 5 years after PN weaning and in children who received teduglutide for >6 months. Data were reported as median and interquartile range (IQR).

A total of 362 children (58% male and 72% White) were reviewed; 41% (n = 150) weaned from PN at age 1.5 years (IQR = 0.96–3). Weight and length/height data were available for 144 children; 46 received an intestinal transplant. Median weight and length/height z scores at weaning were −1.15 (IQR = −2.09 to −0.39) and −1.89 (IQR = −2.9 to −1.02), respectively. In those not transplanted, z scores remained stable (± 0.5 change). Children with small bowel atresia experienced accelerated linear growth (> +0.5 change) beginning in year 3. Most children transplanted experienced growth acceleration beginning in year 2. Fourteen children received teduglutide (median = 840 [IQR = 425–1530] days), and growth remained stable throughout treatment. Five were weaned from PN within 1 year.

We observed stable growth with limited catch‐up after PN weaning, with minimal variation by diagnosis, and during teduglutide therapy. Children who received an intestinal transplant experienced acceleration in weight and linear growth after weaning.