A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal.

2.50
Hdl Handle:
http://hdl.handle.net/10541/79973
Title:
A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal.
Authors:
Parkinson, Craig; Drake, William M; Roberts, Margaret E; Meeran, K; Besser, G M; Trainer, Peter J
Abstract:
Standard medical therapy for patients with acromegaly includes somatostatin analogs. Owing to the widespread expression of somatostatin receptors, these may be associated with unwanted effects, such as altered glucose tolerance and impaired gut hormone release. Pegvisomant is a novel pegylated GH analog that competes with wild-type GH for GH-receptor binding sites but contains a position 120, amino acid substitution that prevents functional GH receptor dimerization, a known prerequisite for GH signal transduction and generation of IGF-I. We have studied the short-term effects of these two therapies (pegvisomant 20 mg/d for 7 d and octreotide 50 microg thrice daily for 7 d) on glucose tolerance and stimulated gut hormone release in six healthy male volunteers in an open-label, random-order, cross-over study. Subjects were assessed at baseline (oral glucose tolerance test and standard mixed meal) and on d 6 and 7 of each therapy with a minimum washout of 2 wk between treatments. Area under the curve and peak responses were analyzed using one-way repeated-measures ANOVA (on ranks where appropriate). Pegvisomant had no effect on glucose tolerance or stimulated gut hormone response during an oral glucose tolerance test and a standard meal. In contrast, octreotide significantly increased fasting plasma glucose, lowered fasting plasma insulin, and led to deterioration in glucose tolerance; three subjects developed impaired glucose tolerance and one diabetes mellitus by World Health Organization criteria. Octreotide significantly impaired stimulated release of cholecystokinin, gastrin, insulin, and pancreatic polypeptide. In conclusion, pegvisomant, unlike octreotide, is not associated with deterioration in glucose tolerance and impairment of stimulated gut hormone release in normal males.
Affiliation:
Department of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom.
Citation:
A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal. 2002, 87 (4):1797-804 J. Clin. Endocrinol. Metab.
Journal:
The Journal of Clinical Endocrinology and Metabolism
Issue Date:
Apr-2002
URI:
http://hdl.handle.net/10541/79973
DOI:
10.1210/jc.87.4.1797
PubMed ID:
11932320
Type:
Article
Language:
en
ISSN:
0021-972X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorParkinson, Craig-
dc.contributor.authorDrake, William M-
dc.contributor.authorRoberts, Margaret E-
dc.contributor.authorMeeran, K-
dc.contributor.authorBesser, G M-
dc.contributor.authorTrainer, Peter J-
dc.date.accessioned2009-09-07T10:12:13Z-
dc.date.available2009-09-07T10:12:13Z-
dc.date.issued2002-04-
dc.identifier.citationA comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal. 2002, 87 (4):1797-804 J. Clin. Endocrinol. Metab.en
dc.identifier.issn0021-972X-
dc.identifier.pmid11932320-
dc.identifier.doi10.1210/jc.87.4.1797-
dc.identifier.urihttp://hdl.handle.net/10541/79973-
dc.description.abstractStandard medical therapy for patients with acromegaly includes somatostatin analogs. Owing to the widespread expression of somatostatin receptors, these may be associated with unwanted effects, such as altered glucose tolerance and impaired gut hormone release. Pegvisomant is a novel pegylated GH analog that competes with wild-type GH for GH-receptor binding sites but contains a position 120, amino acid substitution that prevents functional GH receptor dimerization, a known prerequisite for GH signal transduction and generation of IGF-I. We have studied the short-term effects of these two therapies (pegvisomant 20 mg/d for 7 d and octreotide 50 microg thrice daily for 7 d) on glucose tolerance and stimulated gut hormone release in six healthy male volunteers in an open-label, random-order, cross-over study. Subjects were assessed at baseline (oral glucose tolerance test and standard mixed meal) and on d 6 and 7 of each therapy with a minimum washout of 2 wk between treatments. Area under the curve and peak responses were analyzed using one-way repeated-measures ANOVA (on ranks where appropriate). Pegvisomant had no effect on glucose tolerance or stimulated gut hormone response during an oral glucose tolerance test and a standard meal. In contrast, octreotide significantly increased fasting plasma glucose, lowered fasting plasma insulin, and led to deterioration in glucose tolerance; three subjects developed impaired glucose tolerance and one diabetes mellitus by World Health Organization criteria. Octreotide significantly impaired stimulated release of cholecystokinin, gastrin, insulin, and pancreatic polypeptide. In conclusion, pegvisomant, unlike octreotide, is not associated with deterioration in glucose tolerance and impairment of stimulated gut hormone release in normal males.en
dc.language.isoenen
dc.subject.meshAdministration, Oral-
dc.subject.meshAdult-
dc.subject.meshBlood Glucose-
dc.subject.meshCholecystokinin-
dc.subject.meshCross-Over Studies-
dc.subject.meshEating-
dc.subject.meshFood-
dc.subject.meshGlucose-
dc.subject.meshGlucose Tolerance Test-
dc.subject.meshHormones-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshInsulin-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshOctreotide-
dc.subject.meshPancreatic Polypeptide-
dc.subject.meshReceptors, Somatotropin-
dc.subject.meshReference Values-
dc.titleA comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom.en
dc.identifier.journalThe Journal of Clinical Endocrinology and Metabolismen

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