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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.
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
html.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.


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