| Beta cell function during rapamycin monotherapy in long-term type 1 diabetes. | |
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MedLine Citation:
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PMID: 21046356 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: Type 1 diabetes is considered non-reversible at end-stage disease when there is no measurable insulin production. However, there are indications that insulin-producing beta cells could be present or return if autoimmunity could be controlled. We therefore sought to determine whether immunosuppression therapy can reinstate beta cell function in patients with long-term type 1 diabetes. METHODS: We examined pancreatic beta cell function in 22 patients with long-term type 1 diabetes (median disease duration 27 years), who had been receiving rapamycin monotherapy (0.1 mg/kg; target trough levels 8-10 ng/ml; 26-314 days) as pre-conditioning for islet transplantation. As control, beta cell function was measured in 14 patients (median disease duration 17 years) who were waiting for an islet transplant without rapamycin pre-conditioning. RESULTS: Fasting C-peptide increased from <0.03 nmol/l (0.0066 nmol/l, interquartile range [IQR] 0.0003-0.023) at baseline to 0.039 nmol/l (IQR 0.0066-0.096) at end of rapamycin monotherapy (p < 0.005). In 12 patients, fasting C-peptide increased to >0.076 nmol/l (C-peptide responders). Exogenous insulin requirement decreased from 0.64 U/kg daily (IQR 0.56-0.72) to 0.57 U/kg (IQR 0.45-0.70; p = 0.01), but this reduction was significant only in the 12C-peptide-responsive patients. Rapamycin monotherapy was also associated with a decrease in insulin antibody titre (median decrease 110 to 35.9 U/ml; p < 0.001) and fasting serum proinsulin (median decrease 0.51 to 0.28 pmol/l; p = 0.001). All variables remained unchanged in the 14 control patients. CONCLUSIONS/INTERPRETATION: Therapies to reinstate beta cell function may be applicable to patients with long-term C-peptide-negative type 1 diabetes. TRIAL REGISTRATION: ClinicalTrial.gov NCT01060605. |
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Authors:
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L Piemonti; P Maffi; L Monti; V Lampasona; G Perseghin; P Magistretti; A Secchi; E Bonifacio |
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Publication Detail:
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Type: Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
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Title: Diabetologia Volume: 54 ISSN: 1432-0428 ISO Abbreviation: Diabetologia Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-07 Completed Date: 2011-05-02 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
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Languages: eng Pagination: 433-9 Citation Subset: IM |
Affiliation:
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Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. piemonti.lorenzo@hsr.it |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT01060605 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Diabetes Mellitus, Type 1 / blood, drug therapy*, physiopathology* Female Humans Immunosuppressive Agents / therapeutic use* Insulin-Secreting Cells / physiology* Male Middle Aged Proinsulin / blood Sirolimus / therapeutic use* |
| Grant Support | |
ID/Acronym/Agency:
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JT01Y01//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Immunosuppressive Agents; 53123-88-9/Sirolimus; 9035-68-1/Proinsulin |
| Comments/Corrections | |
Comment In:
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Nat Rev Endocrinol. 2011 Feb;7(2):62
[PMID:
21332092
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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