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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Umpleby, A. M. Higham, C. E. Russell-Jones, D. Rowles, S. Trainer, P. J.
Description	Country affiliation: United kingdom Author Affiliation: Higham CE ( Department of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom.)
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.
ISSN	0021972X
e-ISSN	19457197
Journal	The Journal of Clinical Endocrinology & Metabolism
Issue Number	7
Volume Number	94
Language	English
Publisher	Oxford University Press
Publisher Date	2009-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Acromegaly Blood Drug Therapy Fatty Acids, Nonesterified Human Growth Hormone Analogs & Derivatives Insulin Resistance Metabolism Circadian Rhythm Drug Effects Glucose Hormone Antagonists Pharmacology Therapeutic Use Insulin-like Growth Factor I Lipid Metabolism Longitudinal Studies Osmolar Concentration Clinical Trial Research Support, Non-u.s. Gov't Discipline Endocrinology Discipline Metabolism
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology

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