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

ObjectiveGhrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader–Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in...

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Veröffentlicht in:European journal of endocrinology 2008-10, Vol.159 (4), p.381-388
Hauptverfasser: De Waele, Kathleen, Ishkanian, Stacey L, Bogarin, Roberto, Miranda, Charmaine A, Ghatei, Mohammad A, Bloom, Stephen R, Pacaud, Danièle, Chanoine, Jean-Pierre
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container_end_page 388
container_issue 4
container_start_page 381
container_title European journal of endocrinology
container_volume 159
creator De Waele, Kathleen
Ishkanian, Stacey L
Bogarin, Roberto
Miranda, Charmaine A
Ghatei, Mohammad A
Bloom, Stephen R
Pacaud, Danièle
Chanoine, Jean-Pierre
description ObjectiveGhrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not 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) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.DesignA 56-week prospective, randomized, cross-over trial.MethodsNine subjects with PWS (age 14.6 (10.8–18.9) years, body mass index (BMI) Z-score +1.9 (0.6–3.0)) 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.ResultsEight subjects completed the study. Oct caused a decrease in both acylated (−53%) and desacyl (−54%) fasting ghrelin concentrations (P
doi_str_mv 10.1530/EJE-08-0462
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Acylated (but not 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) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.DesignA 56-week prospective, randomized, cross-over trial.MethodsNine subjects with PWS (age 14.6 (10.8–18.9) years, body mass index (BMI) Z-score +1.9 (0.6–3.0)) 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.ResultsEight subjects completed the study. Oct caused a decrease in both acylated (−53%) and desacyl (−54%) fasting ghrelin concentrations (P&lt;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-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones.ConclusionsOct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future 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.</description><identifier>ISSN: 0804-4643</identifier><identifier>EISSN: 1479-683X</identifier><identifier>DOI: 10.1530/EJE-08-0462</identifier><identifier>PMID: 18603572</identifier><language>eng</language><publisher>Colchester: BioScientifica</publisher><subject>Adolescent ; Appetite - drug effects ; Biological and medical sciences ; Blood Glucose - metabolism ; Body Composition - drug effects ; Body Height - drug effects ; Body Mass Index ; Body Weight - drug effects ; Child ; Clinical Study ; Cross-Over Studies ; Endocrinopathies ; Feeding Behavior - drug effects ; Female ; Fundamental and applied biological sciences. Psychology ; Gallbladder Diseases - diagnostic imaging ; Gastrointestinal Agents - administration &amp; dosage ; Ghrelin - blood ; Homeostasis - drug effects ; Humans ; Insulin-Like Growth Factor I - metabolism ; Male ; Medical sciences ; Metabolic diseases ; Obesity ; Octreotide - administration &amp; dosage ; Peptide YY - blood ; Prader-Willi Syndrome - drug therapy ; Prader-Willi Syndrome - metabolism ; Ultrasonography ; Vertebrates: endocrinology</subject><ispartof>European journal of endocrinology, 2008-10, Vol.159 (4), p.381-388</ispartof><rights>2008 European Society of Endocrinology</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b425t-afa54725e240fe81e0ee23ae3b32d46e61c84e57c7f4db65672ddd2b08af998e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20759992$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18603572$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Waele, Kathleen</creatorcontrib><creatorcontrib>Ishkanian, Stacey L</creatorcontrib><creatorcontrib>Bogarin, Roberto</creatorcontrib><creatorcontrib>Miranda, Charmaine A</creatorcontrib><creatorcontrib>Ghatei, Mohammad A</creatorcontrib><creatorcontrib>Bloom, Stephen R</creatorcontrib><creatorcontrib>Pacaud, Danièle</creatorcontrib><creatorcontrib>Chanoine, Jean-Pierre</creatorcontrib><title>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</title><title>European journal of endocrinology</title><addtitle>Eur J Endocrinol</addtitle><description>ObjectiveGhrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not 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) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.DesignA 56-week prospective, randomized, cross-over trial.MethodsNine subjects with PWS (age 14.6 (10.8–18.9) years, body mass index (BMI) Z-score +1.9 (0.6–3.0)) 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.ResultsEight subjects completed the study. Oct caused a decrease in both acylated (−53%) and desacyl (−54%) fasting ghrelin concentrations (P&lt;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-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones.ConclusionsOct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future 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.</description><subject>Adolescent</subject><subject>Appetite - drug effects</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Body Composition - drug effects</subject><subject>Body Height - drug effects</subject><subject>Body Mass Index</subject><subject>Body Weight - drug effects</subject><subject>Child</subject><subject>Clinical Study</subject><subject>Cross-Over Studies</subject><subject>Endocrinopathies</subject><subject>Feeding Behavior - drug effects</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gallbladder Diseases - diagnostic imaging</subject><subject>Gastrointestinal Agents - administration &amp; dosage</subject><subject>Ghrelin - blood</subject><subject>Homeostasis - drug effects</subject><subject>Humans</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Obesity</subject><subject>Octreotide - administration &amp; dosage</subject><subject>Peptide YY - blood</subject><subject>Prader-Willi Syndrome - drug therapy</subject><subject>Prader-Willi Syndrome - metabolism</subject><subject>Ultrasonography</subject><subject>Vertebrates: endocrinology</subject><issn>0804-4643</issn><issn>1479-683X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90b-O1DAQBnALgbi9g4oeuYHmCDiOkzglOi3_tBIUIOiiiT3Z9SmxF4_D6TregTfhkXgSvOwKOqoZyT9_lvwx9qgUz8u6Ei_W79aF0IVQjbzDVqVqu6LR1Ze7bCW0UIVqVHXGzomuhSjzLu6zs1I3oqpbuWI_N8FvCzDJ-S0PJkUMyVnkeYE0o0_cwEJIHDgtlMB5tNyiyceE3Hm-3UWc8jTBm8wjJBc88WFJ3IZ8z4fEYRzRJH6DbrtLz_iAO_jmwhI5eMthv8fk0p8wWobrLInfuLTjHyJYjL--__jspslxuvU2hhkfsHsjTIQPT_OCfXq1_nj1pti8f_326uWmGJSsUwEj1KqVNUolRtQlCkRZAVZDJa1qsCmNVli3ph2VHZq6aaW1Vg5Cw9h1GqsL9vSYu4_h64KU-tmRwWkCj2GhvulqrbWsMrw8QhMDUcSx30c3Q7ztS9EfKupzRb3Q_aGirB-fYpdhRvvPnjrJ4MkJABmYxgjeOPrrpGjrrusOrjy6wQUyLn--G52B_z7-GxpUr08</recordid><startdate>20081001</startdate><enddate>20081001</enddate><creator>De Waele, Kathleen</creator><creator>Ishkanian, Stacey L</creator><creator>Bogarin, Roberto</creator><creator>Miranda, Charmaine A</creator><creator>Ghatei, Mohammad A</creator><creator>Bloom, Stephen R</creator><creator>Pacaud, Danièle</creator><creator>Chanoine, Jean-Pierre</creator><general>BioScientifica</general><general>Portland Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20081001</creationdate><title>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</title><author>De Waele, Kathleen ; Ishkanian, Stacey L ; Bogarin, Roberto ; Miranda, Charmaine A ; Ghatei, Mohammad A ; Bloom, Stephen R ; Pacaud, Danièle ; Chanoine, Jean-Pierre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b425t-afa54725e240fe81e0ee23ae3b32d46e61c84e57c7f4db65672ddd2b08af998e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adolescent</topic><topic>Appetite - drug effects</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Body Composition - drug effects</topic><topic>Body Height - drug effects</topic><topic>Body Mass Index</topic><topic>Body Weight - drug effects</topic><topic>Child</topic><topic>Clinical Study</topic><topic>Cross-Over Studies</topic><topic>Endocrinopathies</topic><topic>Feeding Behavior - drug effects</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gallbladder Diseases - diagnostic imaging</topic><topic>Gastrointestinal Agents - administration &amp; dosage</topic><topic>Ghrelin - blood</topic><topic>Homeostasis - drug effects</topic><topic>Humans</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Obesity</topic><topic>Octreotide - administration &amp; dosage</topic><topic>Peptide YY - blood</topic><topic>Prader-Willi Syndrome - drug therapy</topic><topic>Prader-Willi Syndrome - metabolism</topic><topic>Ultrasonography</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Waele, Kathleen</creatorcontrib><creatorcontrib>Ishkanian, Stacey L</creatorcontrib><creatorcontrib>Bogarin, Roberto</creatorcontrib><creatorcontrib>Miranda, Charmaine A</creatorcontrib><creatorcontrib>Ghatei, Mohammad A</creatorcontrib><creatorcontrib>Bloom, Stephen R</creatorcontrib><creatorcontrib>Pacaud, Danièle</creatorcontrib><creatorcontrib>Chanoine, Jean-Pierre</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Waele, Kathleen</au><au>Ishkanian, Stacey L</au><au>Bogarin, Roberto</au><au>Miranda, Charmaine A</au><au>Ghatei, Mohammad A</au><au>Bloom, Stephen R</au><au>Pacaud, Danièle</au><au>Chanoine, Jean-Pierre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>European journal of endocrinology</jtitle><addtitle>Eur J Endocrinol</addtitle><date>2008-10-01</date><risdate>2008</risdate><volume>159</volume><issue>4</issue><spage>381</spage><epage>388</epage><pages>381-388</pages><issn>0804-4643</issn><eissn>1479-683X</eissn><abstract>ObjectiveGhrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not 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) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.DesignA 56-week prospective, randomized, cross-over trial.MethodsNine subjects with PWS (age 14.6 (10.8–18.9) years, body mass index (BMI) Z-score +1.9 (0.6–3.0)) 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.ResultsEight subjects completed the study. Oct caused a decrease in both acylated (−53%) and desacyl (−54%) fasting ghrelin concentrations (P&lt;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-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones.ConclusionsOct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future 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.</abstract><cop>Colchester</cop><pub>BioScientifica</pub><pmid>18603572</pmid><doi>10.1530/EJE-08-0462</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE
subjects Adolescent
Appetite - drug effects
Biological and medical sciences
Blood Glucose - metabolism
Body Composition - drug effects
Body Height - drug effects
Body Mass Index
Body Weight - drug effects
Child
Clinical Study
Cross-Over Studies
Endocrinopathies
Feeding Behavior - drug effects
Female
Fundamental and applied biological sciences. Psychology
Gallbladder Diseases - diagnostic imaging
Gastrointestinal Agents - administration & dosage
Ghrelin - blood
Homeostasis - drug effects
Humans
Insulin-Like Growth Factor I - metabolism
Male
Medical sciences
Metabolic diseases
Obesity
Octreotide - administration & dosage
Peptide YY - blood
Prader-Willi Syndrome - drug therapy
Prader-Willi Syndrome - metabolism
Ultrasonography
Vertebrates: endocrinology
title 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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