Document Detail


Treatment with recombinant human insulin-like growth factor (rhIGF)-I/rhIGF binding protein-3 complex improves metabolic control in subjects with severe insulin resistance.
MedLine Citation:
PMID:  20233784     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Diabetes in the context of severe insulin resistance (SIR) presents a major therapeutic challenge because conventional therapies including insulin and insulin sensitizers often fail to achieve adequate metabolic control. Adjunctive therapy with recombinant human IGF-I (rhIGF-I)/recombinant human IGF binding protein-3 (rhIGFBP-3) has been shown to improve insulin sensitivity in both type 1 and type 2 diabetes and may have a role in the treatment of SIR. We report clinical and physiological outcomes after adjunctive therapy with rhIGF-I/rhIGFBP-3 in five subjects with SIR. RESEARCH DESIGN AND METHODS: Five females (median age, 17 yr; range, 5-37) with SIR (two with pathogenic insulin receptor mutations) were treated with 0.5-2.0 mg/kg rhIGF-I/rhIGFBP-3 using a 16-wk dose escalation protocol. Glycosylated hemoglobin was recorded monthly. At baseline and end of treatment all patients were evaluated using continuous glucose monitoring sensing and admitted for overnight GH profiling and insulin-modified stable-label iv glucose tolerance test. Changes in body composition were assessed using dual-energy x-ray absorptiometry and magnetic resonance imaging. RESULTS: Treatment with rhIGF-I/rhIGFBP-3 was well tolerated, and all subjects reported clinical improvements with reduction in acanthosis nigricans. Glycosylated hemoglobin was reduced (8.5% pretreatment to 7.1%; P < 0.03) with a trend toward reduction in mean continuous glucose monitoring sensing glucose (10.7 vs. 8.5 mmol/liter; P = 0.08). Effects of treatment on other biochemical measures were variable, but there was a trend toward improved C-peptide responses during the iv glucose tolerance test. CONCLUSIONS: rhIGF-I/rhIGFBP-3 is well tolerated and clinically effective in subjects with SIR.
Authors:
Fiona M Regan; Rachel M Williams; Anna McDonald; A Margot Umpleby; Carlo L Acerini; Stephen O'Rahilly; Roman Hovorka; Robert K Semple; David B Dunger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-16
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-06     Completed Date:  2010-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2113-22     Citation Subset:  AIM; IM    
Affiliation:
University of Cambridge, Department of Pediatrics, Cambridge, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Acanthosis Nigricans / drug therapy*
Adolescent
Adult
Body Mass Index
Breast / anatomy & histology
Child, Preschool
Female
Hemoglobin A, Glycosylated / drug effects,  metabolism
Humans
Insulin Resistance / genetics*
Insulin-Like Growth Factor Binding Protein 3 / therapeutic use*
Insulin-Like Growth Factor I / metabolism,  therapeutic use*
Mutation
Puberty
Receptor, Insulin / genetics*
Recombinant Proteins / therapeutic use
Grant Support
ID/Acronym/Agency:
080952/Z/06/Z//Wellcome Trust
Chemical
Reg. No./Substance:
0/Hemoglobin A, Glycosylated; 0/Insulin-Like Growth Factor Binding Protein 3; 0/Recombinant Proteins; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.10.1/Receptor, Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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