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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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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. |
format | Online Article Text |
id | pubmed-3636605 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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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