Johanna Iturrino, Michael Camilleri, Andres Acosta, Jessica O'Neill, Duane Burton, Jithinraj Edakkanambeth Varayil, Paula J Carlson, Alan R Zinsmeister, Ryan Hurt
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Other mechanisms may also play a role in effects of GLP-2 agonists.</p><p><strong>Aim: </strong>To measure effects of a GLP-2 agonist, teduglutide (TED), compared with placebo (PLA) on gastric emptying (GE), overall gut transit, fluid balance, intestinal monosaccharide absorption, and permeability in patients with SBS on home PN (HPN).</p><p><strong>Materials and methods: </strong>In 8 adults with SBS on HPN, we compared daily subcutaneous TED (0.05 mg/kg) and PLA (crossover design, each treatment 7 days with a 14-day washout) on gut transit, intestinal absorption, and permeability after oral mannitol (200 mg) and lactulose (1 g), as well as stool weight and urine volume over 8 hours. Analysis used the paired t test.</p><p><strong>Results: </strong>Of 8 patients, 4 were men, with a mean ± SD age of 54 ± 1 years, body mass index of 25 ± 4 kg/m<sup>2</sup>, residual small intestine of 63 ± 12 cm, and 25% ± 15% of residual colon. The overall gut transit (% emptied at 6 hours) was 53.4% ± 15% for TED vs 62.4% ± 15.2% for PLA (P = .075), with no effect on GE (P = .74). TED increased urine mannitol excretion at 0-2 hours (16.2 ± 3.6 mg TED vs 11.3 ± 2.2 mg PLA, P = .20) and 0-8 hours (32.7 ± 5.9 mg PLA vs 48.8 ± 8.9 mg TED, P = .17). There were no differences in urine lactulose excretion or lactulose/mannitol ratio (0.024 ± 0.005 TED vs 0.021 ± 0.005 PLA). Over 8 hours, TED (vs PLA) numerically reduced stool weight (mean ± SEM, 77 ± 18 g TED vs 106 ± 43 g PLA, P = .42) and increased urine volume (408.9 ± 52.2 mL TED vs 365.7 ± 57.3 mL PLA, P = .34).</p><p><strong>Conclusion: </strong>Seven-day TED treatment in 8 participants suggests beneficial effects on fluid balance and monosaccharide absorption, and it retarded overall gut transit with no effects on GE or mucosal permeability. Larger, longer, mechanistic studies of TED in SBS are warranted. This trial was registered at clinicaltrials.gov as NCT02099084.</p>","PeriodicalId":520701,"journal":{"name":"JPEN. 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引用次数: 24
摘要
背景:胰高血糖素样肽2 (GLP-2)激动剂可减少短肠综合征(SBS)患者对肠外营养(PN)的需求;迄今为止评估的机制主要集中在GLP-2激动剂的肠营养作用上，如增加残肠的吸收能力和增加瓜氨酸水平。其他机制也可能在GLP-2激动剂的作用中发挥作用。目的:比较GLP-2激动剂teduglutide (TED)与安慰剂(PLA)对SBS患者家庭PN (HPN)胃排空(GE)、整体肠道转运、液体平衡、肠道单糖吸收和通透性的影响。材料和方法:在8名接受HPN治疗的SBS患者中，我们比较了每日皮下TED (0.05 mg/kg)和PLA(交叉设计，每次治疗7天，14天洗脱期)在口服甘露醇(200 mg)和乳果糖(1 g)后的肠道转运、肠道吸收和通透性，以及8小时的粪便重量和尿量。分析采用配对t检验。结果:8例患者中，男性4例，平均±SD年龄54±1岁，体重指数25±4 kg/m2，小肠残余63±12 cm，结肠残余25%±15%。TED组总体肠道转运率(6小时排空率)为53.4%±15%，而PLA组为62.4%±15.2% (P = 0.075)，对GE无影响(P = 0.74)。TED在0-2小时(16.2±3.6 mg TED vs 11.3±2.2 mg PLA, P = 0.20)和0-8小时(32.7±5.9 mg PLA vs 48.8±8.9 mg TED, P = 0.17)增加尿甘露醇排泄。尿乳果糖排泄量和乳果糖/甘露醇比值(0.024±0.005 TED vs 0.021±0.005 PLA)无差异。在8小时内，TED(与PLA相比)在数值上减少了粪便重量(平均±SEM, 77±18 g TED vs 106±43 g PLA, P = 0.42)并增加了尿量(408.9±52.2 mL TED vs 365.7±57.3 mL PLA, P = 0.34)。结论:8名受试者接受为期7天的TED治疗，对体液平衡和单糖吸收有有益的影响，并延缓了整体肠道运输，但对GE或粘膜通透性没有影响。有必要对SBS中TED进行更大规模、更长时间的机制研究。该试验在clinicaltrials.gov注册为NCT02099084。
Acute Effects of a Glucagon-Like Peptide 2 Analogue, Teduglutide, on Gastrointestinal Motor Function and Permeability in Adult Patients With Short Bowel Syndrome on Home Parenteral Nutrition.
Background: Glucagon-like peptide 2 (GLP-2) agonists decrease the need for parenteral nutrition (PN) in short bowel syndrome (SBS); mechanisms evaluated to date have focused on the intestinotrophic effect of GLP-2 agonists such as increased absorptive capacity of the remnant intestine and increased citrulline levels. Other mechanisms may also play a role in effects of GLP-2 agonists.
Aim: To measure effects of a GLP-2 agonist, teduglutide (TED), compared with placebo (PLA) on gastric emptying (GE), overall gut transit, fluid balance, intestinal monosaccharide absorption, and permeability in patients with SBS on home PN (HPN).
Materials and methods: In 8 adults with SBS on HPN, we compared daily subcutaneous TED (0.05 mg/kg) and PLA (crossover design, each treatment 7 days with a 14-day washout) on gut transit, intestinal absorption, and permeability after oral mannitol (200 mg) and lactulose (1 g), as well as stool weight and urine volume over 8 hours. Analysis used the paired t test.
Results: Of 8 patients, 4 were men, with a mean ± SD age of 54 ± 1 years, body mass index of 25 ± 4 kg/m2, residual small intestine of 63 ± 12 cm, and 25% ± 15% of residual colon. The overall gut transit (% emptied at 6 hours) was 53.4% ± 15% for TED vs 62.4% ± 15.2% for PLA (P = .075), with no effect on GE (P = .74). TED increased urine mannitol excretion at 0-2 hours (16.2 ± 3.6 mg TED vs 11.3 ± 2.2 mg PLA, P = .20) and 0-8 hours (32.7 ± 5.9 mg PLA vs 48.8 ± 8.9 mg TED, P = .17). There were no differences in urine lactulose excretion or lactulose/mannitol ratio (0.024 ± 0.005 TED vs 0.021 ± 0.005 PLA). Over 8 hours, TED (vs PLA) numerically reduced stool weight (mean ± SEM, 77 ± 18 g TED vs 106 ± 43 g PLA, P = .42) and increased urine volume (408.9 ± 52.2 mL TED vs 365.7 ± 57.3 mL PLA, P = .34).
Conclusion: Seven-day TED treatment in 8 participants suggests beneficial effects on fluid balance and monosaccharide absorption, and it retarded overall gut transit with no effects on GE or mucosal permeability. Larger, longer, mechanistic studies of TED in SBS are warranted. This trial was registered at clinicaltrials.gov as NCT02099084.
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