Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome
Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome
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DOI：
10.1530/eje-08-0462
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发表时间：
2008-10-01
影响因子：
5.8
通讯作者：
Chanoine, Jean-Pierre
中科院分区：
文献类型：
--
作者：
De Waele, Kathleen;Ishkanian, Stacey L.;Chanoine, Jean-Pierre
目的：Ghrelin主要由胃分泌，并以酰化和去酰化Ghrelin的形式循环。酰化（但不脱酰基）的ghrelin刺激食欲。这两个浓度升高普拉德-威利综合征（PWS），这表明生长激素释放肽可能有助于这些科目的暴食症和超重。我们评估了长效奥曲肽（Oct）是否能降低PWS青少年的酰化和去酰化ghrelin浓度、体重、食欲和对食物的强迫行为。设计：一项为期56周的前瞻性、随机、交叉试验。9例PWS受试者（年龄14.6（10.8-18.9）岁，体重指数（BMI）Z评分+1.9（0.6-03））接受Oct（30 mg）或生理盐水i.m.每4周进行一次，共16周，并在24周的洗脱期后转换为另一种治疗。Oct导致酰化（-53%）和去酰化（-54%）空腹ghrelin浓度降低（P < 0.05），但对BMI无显著影响。OCT对肽YY浓度、食欲或对食物的强迫行为没有显著影响。在两名受试者中，OCT导致胰岛素样生长因子-1浓度降低、HbA 1c升高和血糖一过性升高。三名受试者开发胆结石。结论：在PWS青少年中，OCT治疗引起生长激素释放肽浓度长期下降，但没有改善体重或食欲。进一步的干预研究，旨在澄清胃饥饿素在PWS中的作用，应集中在管理的具体抑制剂胃饥饿素分泌或胃饥饿素受体的活性，不干扰其他食欲调节肽。
Objective: Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but no desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader-Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreased acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.Design: A 56-week prospective, randomized, cross-over trial.Methods: Nine subjects with PWS (age 14.6 (10.8-18.9) years, body mass index (BMI) Z-score + 1.9 (0.6-03) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period.Results: Eight subjects completed the study. Oct caused a decrease in both acylated (-53%) and desacyl (-54%) fasting ghrelin concentrations(P < 0.05) but did not significantly affect BMI. Oct had no significant effect on peptide YY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in insulin-like growth factor-1 concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones.Conclusions: Oct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Further intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.