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
| Autor: | Palle Jeppesen, Jens J. Holst, P. B. Mortensen, Bolette Hartmann, Rahim M. Naimi, C. Askov-Hansen, Christopher F. Brandt, K.B. Madsen |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Short Bowel Syndrome Insulin pump endocrine system medicine.medical_specialty Physiology Clinical Biochemistry Infusions Subcutaneous Biochemistry Glucagon Gastroenterology Intestinal absorption Food-Drug Interactions Cellular and Molecular Neuroscience Endocrinology Internal medicine Glucagon-Like Peptide 2 medicine Humans Aged Dose-Response Relationship Drug Gastric emptying business.industry digestive oral and skin physiology Middle Aged Glucagon-like peptide-2 Short bowel syndrome medicine.disease Stomach emptying Intestinal Absorption Blood chemistry Female business hormones hormone substitutes and hormone antagonists |
| Zdroj: | Regulatory Peptides. 184:47-53 |
| ISSN: | 0167-0115 |
| DOI: | 10.1016/j.regpep.2013.03.023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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