Background & Aims: Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a terminal ileum and colon who have functional short-bowel syndrome with severe malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no postprandial secretion of GLP-2. Methods: Balance studies were performed before and after treatment with GLP-2, 400 g subcutaneously twice a day for 35 days, in 8 patients (4 -17 years from last bowel resection; 6 with Crohn's disease). Four patients received home parenteral nutrition (mean residual jejunum, 83 cm), and 4 did not (mean ileum resection, 106 cm). Biopsy specimens were taken from jejunal/ileal stomas, transit was measured by scintigraphy, and body composition was measured by dual-energy x-ray absorptiometry. Results: Treatment with GLP-2 improved the intestinal absorption of energy 3.5% ؎ 4.0% (mean ؎ SD) from 49.9% to 53.4% (P ؍ 0.04), wet weight 11% ؎ 12% from 25% to 36% (P ؍ 0.04), and nitrogen 4.7% ؎ 5.4% from 47.4% to 52.1% (P ؍ 0.04). Body weight increased 1.2 ؎ 1.0 kg (P ؍ 0.01), lean body mass increased 2.9 ؎ 1.9 kg (P ؍ 0.004), fat mass decreased 1.8 ؎ 1.3 kg (P ؍ 0.007), and 24-hour urine creatinine excretion increased (P ؍ 0.02). The time to 50% gastric emptying of solids increased 30 ؎ 16 minutes from 89 to 119 minutes (P < 0.05). Small bowel transit time was not changed. Crypt depth and villus height were increased in 5 and 6 patients, respectively. Conclusions: Treatment with GLP-2 improves intestinal absorption and nutritional status in short-bowel patients with impaired postprandial GLP-2 secretion in whom the terminal ileum and the colon have been resected.
Extracorporeal albumin dialysis (ECAD) may improve severe hepatic encephalopathy (HE) in patients with advanced cirrhosis via the removal of protein or non-protein-bound toxins. A prospective, randomized, controlled, multicenter trial of the efficacy, safety, and tolerability of ECAD using molecular adsorbent recirculating system (MARS) was conducted in such patients. Patients were randomized to ECAD and standard medical therapy (SMT) or SMT alone. ECAD was provided daily for 6 hours for 5 days or until the patient had a 2-grade improvement in HE. HE grades (West Haven criteria) were evaluated every 12 hours using a scoring algorithm. The primary endpoint was the difference in improvement proportion of HE between the 2 groups. A total of 70 subjects [median age, 53; 56% male; 56% HE grade 3; 44% HE grade 4; median model for end-stage liver disease (MELD) 32 (11-50) and CPT 13 (10-15)] were enrolled in 8 tertiary centers. Patients were randomized to ECAD ؉ SMT (n ؍ 39) or SMT alone (n ؍ 31). Groups were matched in demographics and clinical variables. The improvement proportion of HE was higher in ECAD (mean, 34%; median, 30%) versus the SMT group (mean, 18.9%; median, 0%) (P ؍ 0.044) and was reached faster and more frequently than in the SMT group (P ؍ 0.045). H epatic encephalopathy (HE) is a complex neuropsychiatric syndrome commonly seen in patients with advanced liver disease. HE arises from the effects of circulating toxins on cerebral functions. Putative toxic molecules accumulate in patients with liver decompensation because of increased production, portal-systemic shunting, or lack of hepatic detoxification. 1 Patients with advanced cirrhosis and a superimposed acute liver injury often decompensate and present with manifestations of hepatic failure, including worsening HE and coma. 2 .Current therapy for HE includes the use of nonabsorbable disaccharides or poorly absorbable antibiotics, as proposed more than 3 decades ago. 3 However, standard therapy is less effective in patients with severe degrees of liver failure. 4,5 Under these circumstances, the concept of supporting the failing liver for a time while correcting the precipitating event might help patients recover from HE or be stabilized until they receive a liver transplant. 6 Extracorporeal albumin dialysis (ECAD) using the molecular adsorbent recirculating system (MARS) is a new method of hemodiafiltration whereby blood is dialyzed against an albumin-containing solution across a high-flux membrane. 7 The technique allows combined removal of albumin-bound and water-soluble toxins. [8][9][10][11][12] In uncontrolled trials of ECAD using the MARS device, patients had a reduction in ammonia levels, clear-
In this prospective study of patients with fulminant hepatic failure (FHF), we tested the hypothesis that arterial hyperammonemia results in cerebral accumulation of the osmotic active amino acids glutamine and alanine, processes that were expected to correlate with intracranial pressure (ICP). By using in vivo brain microdialysis technique together with ICP monitoring in 17 FHF patients (10 females/7 males; median age 49 (range 18 to 66) years), we found that arterial ammonia concentration correlated to brain content of glutamine (r=0.47; P<0.05) but not to alanine. A persisting high arterial ammonia concentration (above 200 micromol/L) characterized patients who developed high ICP (n=8) while patients who did not experience surges of increased ICP (n=9) had a decline in the ammonia level (P<0.05). Moreover, brain glutamine and alanine concentrations were higher at baseline and increased further in patients who developed intracranial hypertension compared with patients who experienced no surges of high ICP. Brain glutamine concentration increased 32% from baseline to 6536 (697 to 9712) micromol/L (P<0.05), and alanine 44% from baseline to 104 (81 to 381) micromol/L (P<0.05). Brain concentration of glutamine (r=0.59, P<0.05), but not alanine, correlated to ICP. Also arterial ammonia concentration correlated to ICP (r=0.73, P<0.01). To conclude, this study shows that persistence of arterial hyperammonemia is associated with profound changes in the cerebral concentration of glutamine and alanine. The elevation of brain glutamine concentration correlated to ICP in patients with FHF.
A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.
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