| Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptin. | |
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MedLine Citation:
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PMID: 20920044 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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AIM: Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned that short-term IIT could enable evaluation of the beta-cell protective capacity of OADs, free from confounding hyperglycaemia. We applied this strategy to assess the effect of sitagliptin on beta-cell function. METHODS: In this pilot study, 37 patients with T2DM of 6.0 + 6.4 years duration and A1c 7.0 + 0.8% on 0-2 OADs were switched to 4-8 weeks of IIT consisting of basal detemir and premeal insulin aspart. Subjects achieving fasting glucose <7.0 mmol/l 1 day after completing IIT (n = 21) were then randomized to metformin with either sitagliptin (n = 10) or placebo (n = 11). Subjects were followed for 48 weeks, with serial assessment of beta-cell function [ratio of AUC(Cpep) to AUC(gluc) over Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (AUC(Cpep/gluc) /HOMA-IR)] on 4-h meal tests. RESULTS: During the study, fasting glucagon-like-peptide-1 was higher (p = 0.003) and A1c lower in the sitagliptin arm (p = 0.016). Nevertheless, although beta-cell function improved during the IIT phase, it declined similarly in both arms over time (p = 0.61). By study end, AUC(Cpep/gluc) /HOMA-IR was not significantly different between the placebo and sitagliptin arms (median 71.2 vs 80.4; p = 0.36). CONCLUSIONS: Pretreatment IIT can provide a useful strategy for evaluating the beta-cell protective capacity of diabetes interventions. In this pilot study, improved A1c with sitagliptin could not be attributed to a significant effect on preservation of beta-cell function. |
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Authors:
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R Retnakaran; Y Qi; C Opsteen; E Vivero; B Zinman |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Diabetes, obesity & metabolism Volume: 12 ISSN: 1463-1326 ISO Abbreviation: Diabetes Obes Metab Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-05 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100883645 Medline TA: Diabetes Obes Metab Country: England |
Other Details:
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Languages: eng Pagination: 909-15 Citation Subset: IM |
Copyright Information:
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© 2010 Blackwell Publishing Ltd. |
Affiliation:
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Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada. rretnakaran@mtsinai.on.ca |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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