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Immune Therapy and β-Cell Death in Type 1 Diabetes

Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing β-cells. The killing of β-cells is not currently measurable; β-cell functional studies routinely used are affected by environmental factors such as glucose and cannot distinguish death from dysfunction. Moreover, it...

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Autores principales: Lebastchi, Jasmin, Deng, Songyan, Lebastchi, Amir H., Beshar, Isabel, Gitelman, Stephen, Willi, Steven, Gottlieb, Peter, Akirav, Eitan M., Bluestone, Jeffrey A., Herold, Kevan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636605/
https://www.ncbi.nlm.nih.gov/pubmed/23423576
http://dx.doi.org/10.2337/db12-1207
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author Lebastchi, Jasmin
Deng, Songyan
Lebastchi, Amir H.
Beshar, Isabel
Gitelman, Stephen
Willi, Steven
Gottlieb, Peter
Akirav, Eitan M.
Bluestone, Jeffrey A.
Herold, Kevan C.
author_facet Lebastchi, Jasmin
Deng, Songyan
Lebastchi, Amir H.
Beshar, Isabel
Gitelman, Stephen
Willi, Steven
Gottlieb, Peter
Akirav, Eitan M.
Bluestone, Jeffrey A.
Herold, Kevan C.
author_sort Lebastchi, Jasmin
collection PubMed
description Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing β-cells. The killing of β-cells is not currently measurable; β-cell functional studies routinely used are affected by environmental factors such as glucose and cannot distinguish death from dysfunction. Moreover, it is not known whether immune therapies affect killing. We developed an assay to identify β-cell death by measuring relative levels of unmethylated INS DNA in serum and used it to measure β-cell death in a clinical trial of teplizumab. We studied 43 patients with recent-onset T1D, 13 nondiabetic subjects, and 37 patients with T1D treated with FcR nonbinding anti-CD3 monoclonal antibody (teplizumab) or placebo. Patients with recent-onset T1D had higher rates of β-cell death versus nondiabetic control subjects, but patients with long-standing T1D had lower levels. When patients with recent-onset T1D were treated with teplizumab, β-cell function was preserved (P < 0.05) and the rates of β-cell were reduced significantly (P < 0.05). We conclude that there are higher rates of β-cell death in patients with recent-onset T1D compared with nondiabetic subjects. Improvement in C-peptide responses with immune intervention is associated with decreased β-cell death.
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spelling pubmed-36366052014-05-01 Immune Therapy and β-Cell Death in Type 1 Diabetes Lebastchi, Jasmin Deng, Songyan Lebastchi, Amir H. Beshar, Isabel Gitelman, Stephen Willi, Steven Gottlieb, Peter Akirav, Eitan M. Bluestone, Jeffrey A. Herold, Kevan C. Diabetes Brief Report Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing β-cells. The killing of β-cells is not currently measurable; β-cell functional studies routinely used are affected by environmental factors such as glucose and cannot distinguish death from dysfunction. Moreover, it is not known whether immune therapies affect killing. We developed an assay to identify β-cell death by measuring relative levels of unmethylated INS DNA in serum and used it to measure β-cell death in a clinical trial of teplizumab. We studied 43 patients with recent-onset T1D, 13 nondiabetic subjects, and 37 patients with T1D treated with FcR nonbinding anti-CD3 monoclonal antibody (teplizumab) or placebo. Patients with recent-onset T1D had higher rates of β-cell death versus nondiabetic control subjects, but patients with long-standing T1D had lower levels. When patients with recent-onset T1D were treated with teplizumab, β-cell function was preserved (P < 0.05) and the rates of β-cell were reduced significantly (P < 0.05). We conclude that there are higher rates of β-cell death in patients with recent-onset T1D compared with nondiabetic subjects. Improvement in C-peptide responses with immune intervention is associated with decreased β-cell death. American Diabetes Association 2013-05 2013-04-16 /pmc/articles/PMC3636605/ /pubmed/23423576 http://dx.doi.org/10.2337/db12-1207 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Brief Report
Lebastchi, Jasmin
Deng, Songyan
Lebastchi, Amir H.
Beshar, Isabel
Gitelman, Stephen
Willi, Steven
Gottlieb, Peter
Akirav, Eitan M.
Bluestone, Jeffrey A.
Herold, Kevan C.
Immune Therapy and β-Cell Death in Type 1 Diabetes
title Immune Therapy and β-Cell Death in Type 1 Diabetes
title_full Immune Therapy and β-Cell Death in Type 1 Diabetes
title_fullStr Immune Therapy and β-Cell Death in Type 1 Diabetes
title_full_unstemmed Immune Therapy and β-Cell Death in Type 1 Diabetes
title_short Immune Therapy and β-Cell Death in Type 1 Diabetes
title_sort immune therapy and β-cell death in type 1 diabetes
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636605/
https://www.ncbi.nlm.nih.gov/pubmed/23423576
http://dx.doi.org/10.2337/db12-1207
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