Pegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly.

2.50
Hdl Handle:
http://hdl.handle.net/10541/81993
Title:
Pegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly.
Authors:
Higham, Claire E; Rowles, Susannah V; Russell-Jones, D; Umpleby, A M; Trainer, Peter J
Abstract:
INTRODUCTION: Acromegaly is complicated by an increased incidence of diabetes mellitus caused by impaired insulin sensitivity and reduced beta-cell function. Pegvisomant blocks activity at GH receptors, normalizing IGF-I in over 90% of patients and improving insulin sensitivity. The mechanisms for this increase in insulin sensitivity are not fully determined. We used stable isotope techniques to investigate the effects of pegvisomant on glucose and lipid metabolism in acromegaly. METHODS: Five patients (age, 43 yr +/- sd) with active acromegaly were studied on two occasions: before pegvisomant and after 4 wk of pegvisomant (20 mg daily sc). (2)H(5)-glycerol was infused overnight to measure overnight and early morning (basal) glycerol production rate (Ra). The next morning (2)H(2)-glucose was infused for 2 h before and throughout a hyperinsulinemic euglycemic (1.5 mU/kg x min insulin) clamp to measure basal glucose Ra and insulin-stimulated peripheral glucose disposal (Rd). RESULTS: Mean IGF-I was significantly reduced after pegvisomant treatment (mean, 539 +/- 176 vs. 198 +/- 168 microg/ml; P = 0.001). The insulin sensitivity of endogenous glucose production was significantly increased after pegvisomant [mean glucose Ra *insulin, 118.5 +/- 28 vs. 69.2 +/- 22 micromol/kg x min *(mU/liter); P = 0.04]. No differences in glucose Rd were seen after pegvisomant. All patients showed a reduction in glycerol Ra adjusted for insulin [mean, 18.12 +/- 1.75 vs. 14.4 +/- 4.75 micromol/kg x min *(mU/liter); P = 0.08] and overnight FFA concentrations (mean area under the curve, 278 +/- 84 vs. 203 +/- 71; P < 0.05) after pegvisomant. CONCLUSION: Short-term administration of pegvisomant leads to a reduction in overnight endogenous glucose production, and this may be related to reduced levels of FFA.
Affiliation:
Department of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom.
Citation:
Pegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly. 2009, 94 (7):2459-63 J. Clin. Endocrinol. Metab.
Journal:
The Journal of Clinical Endocrinology and Metabolism
Issue Date:
Jul-2009
URI:
http://hdl.handle.net/10541/81993
DOI:
10.1210/jc.2008-2086
PubMed ID:
19366854
Type:
Article
Language:
en
ISSN:
1945-7197
Appears in Collections:
All Christie Publications ; Endocrinology

Full metadata record

DC FieldValue Language
dc.contributor.authorHigham, Claire E-
dc.contributor.authorRowles, Susannah V-
dc.contributor.authorRussell-Jones, D-
dc.contributor.authorUmpleby, A M-
dc.contributor.authorTrainer, Peter J-
dc.date.accessioned2009-09-22T09:25:04Z-
dc.date.available2009-09-22T09:25:04Z-
dc.date.issued2009-07-
dc.identifier.citationPegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly. 2009, 94 (7):2459-63 J. Clin. Endocrinol. Metab.en
dc.identifier.issn1945-7197-
dc.identifier.pmid19366854-
dc.identifier.doi10.1210/jc.2008-2086-
dc.identifier.urihttp://hdl.handle.net/10541/81993-
dc.description.abstractINTRODUCTION: Acromegaly is complicated by an increased incidence of diabetes mellitus caused by impaired insulin sensitivity and reduced beta-cell function. Pegvisomant blocks activity at GH receptors, normalizing IGF-I in over 90% of patients and improving insulin sensitivity. The mechanisms for this increase in insulin sensitivity are not fully determined. We used stable isotope techniques to investigate the effects of pegvisomant on glucose and lipid metabolism in acromegaly. METHODS: Five patients (age, 43 yr +/- sd) with active acromegaly were studied on two occasions: before pegvisomant and after 4 wk of pegvisomant (20 mg daily sc). (2)H(5)-glycerol was infused overnight to measure overnight and early morning (basal) glycerol production rate (Ra). The next morning (2)H(2)-glucose was infused for 2 h before and throughout a hyperinsulinemic euglycemic (1.5 mU/kg x min insulin) clamp to measure basal glucose Ra and insulin-stimulated peripheral glucose disposal (Rd). RESULTS: Mean IGF-I was significantly reduced after pegvisomant treatment (mean, 539 +/- 176 vs. 198 +/- 168 microg/ml; P = 0.001). The insulin sensitivity of endogenous glucose production was significantly increased after pegvisomant [mean glucose Ra *insulin, 118.5 +/- 28 vs. 69.2 +/- 22 micromol/kg x min *(mU/liter); P = 0.04]. No differences in glucose Rd were seen after pegvisomant. All patients showed a reduction in glycerol Ra adjusted for insulin [mean, 18.12 +/- 1.75 vs. 14.4 +/- 4.75 micromol/kg x min *(mU/liter); P = 0.08] and overnight FFA concentrations (mean area under the curve, 278 +/- 84 vs. 203 +/- 71; P < 0.05) after pegvisomant. CONCLUSION: Short-term administration of pegvisomant leads to a reduction in overnight endogenous glucose production, and this may be related to reduced levels of FFA.en
dc.language.isoenen
dc.subject.meshAcromegaly-
dc.subject.meshAdult-
dc.subject.meshCircadian Rhythm-
dc.subject.meshFatty Acids, Nonesterified-
dc.subject.meshFemale-
dc.subject.meshGlucose-
dc.subject.meshHormone Antagonists-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshInsulin Resistance-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshLipid Metabolism-
dc.subject.meshLongitudinal Studies-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshOsmolar Concentration-
dc.titlePegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly.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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