A dose-equivalent comparison of the effects of continuous subcutaneous glucagon-like peptide 2 (GLP-2) infusions versus meal related GLP-2 injections in the treatment of short bowel syndrome (SBS) patients

TY - JOUR

T1 - A dose-equivalent comparison of the effects of continuous subcutaneous glucagon-like peptide 2 (GLP-2) infusions versus meal related GLP-2 injections in the treatment of short bowel syndrome (SBS) patients

AU - Naimi, R M

AU - Madsen, K B

AU - Askov-Hansen, C

AU - Brandt, C F

AU - Hartmann, B

AU - Holst, Jens Juul

AU - Mortensen, P B

AU - Jeppesen, P B

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/6/10

Y1 - 2013/6/10

N2 - Objective: Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth. Short bowel syndrome (SBS) patients with distal intestinal resections have attenuated endogenous GLP-2 secretion, which may contribute to their rapid gastric emptying, gastric hypersecretion and poor intestinal adaptation, whereas SBS patients with preserved terminal ileum and colon, who have a constantly elevated GLP-2 secretion, seem to do better in these respects. This study compared effects of continuous, subcutaneous (s.c.), exogenous GLP-2 infusion (CONT-GLP-2) versus three daily s.c. GLP-2 injections (TID-GLP-2) on intestinal absorption in SBS patients. Design: Eight SBS patients (5 F, 3 M; 60. ±. 7. years; remnant small bowel 111. ±. 62. cm; 1 with 50% colon) were studied. In an open-label, sequential study, the 72-hour baseline admission was followed by two dose-equivalent, 21-day, dosing regimens; CONT-GLP-2, providing 1.0. mg/day by a MiniMed insulin pump and TID-GLP-2, providing 0.33. mg injections in relation to three meals, separated by a washout period of at least 3. weeks. During admissions, the intestinal absorption was evaluated by analysing a double portion of the diet, faecal and urinary excretions. Post-absorptive plasma citrulline, reflecting enterocyte mass, was measured by HPLC. Results: Compared to baseline, both GLP-2 dosing regimens reduced diarrhoea (CONT-GLP-2: 749. ±. 815. g/d and TID-GLP-2: 877. ±. 1004. g/d, p. = 0.01) and increased wet weight absorption (CONT-GLP-2: 19. ±. 19% and TID-GLP-2: 25. ±. 21%, p. = 0.003). Significant increases in plasma citrulline (CONT-GLP-2: 7.5. ±. 7. μmol/L and TID-GLP-2, 12.7. ±. 8. μmol/L; p. = 0.001) suggesting intestinotrophic effects in relation to GLP-2 treatment, are followed by increases in relative absorption of energy, carbohydrate and fat. No significant difference was seen on any of the absorptive parameters measured between the two dosing regimens. Conclusion: Both GLP-2 regimens significantly reduced diarrhoea in SBS patients, but a significant difference between continuous GLP-2 administration and TID injections could not be detected in a study of this size.

AB - Objective: Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth. Short bowel syndrome (SBS) patients with distal intestinal resections have attenuated endogenous GLP-2 secretion, which may contribute to their rapid gastric emptying, gastric hypersecretion and poor intestinal adaptation, whereas SBS patients with preserved terminal ileum and colon, who have a constantly elevated GLP-2 secretion, seem to do better in these respects. This study compared effects of continuous, subcutaneous (s.c.), exogenous GLP-2 infusion (CONT-GLP-2) versus three daily s.c. GLP-2 injections (TID-GLP-2) on intestinal absorption in SBS patients. Design: Eight SBS patients (5 F, 3 M; 60. ±. 7. years; remnant small bowel 111. ±. 62. cm; 1 with 50% colon) were studied. In an open-label, sequential study, the 72-hour baseline admission was followed by two dose-equivalent, 21-day, dosing regimens; CONT-GLP-2, providing 1.0. mg/day by a MiniMed insulin pump and TID-GLP-2, providing 0.33. mg injections in relation to three meals, separated by a washout period of at least 3. weeks. During admissions, the intestinal absorption was evaluated by analysing a double portion of the diet, faecal and urinary excretions. Post-absorptive plasma citrulline, reflecting enterocyte mass, was measured by HPLC. Results: Compared to baseline, both GLP-2 dosing regimens reduced diarrhoea (CONT-GLP-2: 749. ±. 815. g/d and TID-GLP-2: 877. ±. 1004. g/d, p. = 0.01) and increased wet weight absorption (CONT-GLP-2: 19. ±. 19% and TID-GLP-2: 25. ±. 21%, p. = 0.003). Significant increases in plasma citrulline (CONT-GLP-2: 7.5. ±. 7. μmol/L and TID-GLP-2, 12.7. ±. 8. μmol/L; p. = 0.001) suggesting intestinotrophic effects in relation to GLP-2 treatment, are followed by increases in relative absorption of energy, carbohydrate and fat. No significant difference was seen on any of the absorptive parameters measured between the two dosing regimens. Conclusion: Both GLP-2 regimens significantly reduced diarrhoea in SBS patients, but a significant difference between continuous GLP-2 administration and TID injections could not be detected in a study of this size.

U2 - 10.1016/j.regpep.2013.03.023

DO - 10.1016/j.regpep.2013.03.023

M3 - Journal article

C2 - 23501043

SN - 0167-0115

VL - 184

SP - 47

EP - 53

JO - Regulatory Peptides

JF - Regulatory Peptides

IS - 10

ER -