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Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors

Insulin-dependent diabetes may occur in patients with cancers who are treated with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year period at two academic institutions and identified 27 patients in whom this developed, or an incidence of 0.9%. The patients had a variety of sol...

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Autores principales: Stamatouli, Angeliki M., Quandt, Zoe, Perdigoto, Ana Luisa, Clark, Pamela L., Kluger, Harriet, Weiss, Sarah A., Gettinger, Scott, Sznol, Mario, Young, Arabella, Rushakoff, Robert, Lee, James, Bluestone, Jeffrey A., Anderson, Mark, Herold, Kevan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054443/
https://www.ncbi.nlm.nih.gov/pubmed/29937434
http://dx.doi.org/10.2337/dbi18-0002
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author Stamatouli, Angeliki M.
Quandt, Zoe
Perdigoto, Ana Luisa
Clark, Pamela L.
Kluger, Harriet
Weiss, Sarah A.
Gettinger, Scott
Sznol, Mario
Young, Arabella
Rushakoff, Robert
Lee, James
Bluestone, Jeffrey A.
Anderson, Mark
Herold, Kevan C.
author_facet Stamatouli, Angeliki M.
Quandt, Zoe
Perdigoto, Ana Luisa
Clark, Pamela L.
Kluger, Harriet
Weiss, Sarah A.
Gettinger, Scott
Sznol, Mario
Young, Arabella
Rushakoff, Robert
Lee, James
Bluestone, Jeffrey A.
Anderson, Mark
Herold, Kevan C.
author_sort Stamatouli, Angeliki M.
collection PubMed
description Insulin-dependent diabetes may occur in patients with cancers who are treated with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year period at two academic institutions and identified 27 patients in whom this developed, or an incidence of 0.9%. The patients had a variety of solid-organ cancers, but all had received either anti–PD-1 or anti–PD-L1 antibodies. Diabetes presented with ketoacidosis in 59%, and 42% had evidence of pancreatitis in the peridiagnosis period. Forty percent had at least one positive autoantibody and 21% had two or more. There was a predominance of HLA-DR4, which was present in 76% of patients. Other immune adverse events were seen in 70%, and endocrine adverse events in 44%. We conclude that autoimmune, insulin-dependent diabetes occurs in close to 1% of patients treated with anti–PD-1 or –PD-L1 CPIs. This syndrome has similarities and differences compared with classic type 1 diabetes. The dominance of HLA-DR4 suggests an opportunity to identify those at highest risk of these complications and to discover insights into the mechanisms of this adverse event.
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spelling pubmed-60544432019-08-01 Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors Stamatouli, Angeliki M. Quandt, Zoe Perdigoto, Ana Luisa Clark, Pamela L. Kluger, Harriet Weiss, Sarah A. Gettinger, Scott Sznol, Mario Young, Arabella Rushakoff, Robert Lee, James Bluestone, Jeffrey A. Anderson, Mark Herold, Kevan C. Diabetes Diabetes Symposium: Emerging Areas of Islet Biology Insulin-dependent diabetes may occur in patients with cancers who are treated with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year period at two academic institutions and identified 27 patients in whom this developed, or an incidence of 0.9%. The patients had a variety of solid-organ cancers, but all had received either anti–PD-1 or anti–PD-L1 antibodies. Diabetes presented with ketoacidosis in 59%, and 42% had evidence of pancreatitis in the peridiagnosis period. Forty percent had at least one positive autoantibody and 21% had two or more. There was a predominance of HLA-DR4, which was present in 76% of patients. Other immune adverse events were seen in 70%, and endocrine adverse events in 44%. We conclude that autoimmune, insulin-dependent diabetes occurs in close to 1% of patients treated with anti–PD-1 or –PD-L1 CPIs. This syndrome has similarities and differences compared with classic type 1 diabetes. The dominance of HLA-DR4 suggests an opportunity to identify those at highest risk of these complications and to discover insights into the mechanisms of this adverse event. American Diabetes Association 2018-08 2018-06-24 /pmc/articles/PMC6054443/ /pubmed/29937434 http://dx.doi.org/10.2337/dbi18-0002 Text en © 2018 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders 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. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Diabetes Symposium: Emerging Areas of Islet Biology
Stamatouli, Angeliki M.
Quandt, Zoe
Perdigoto, Ana Luisa
Clark, Pamela L.
Kluger, Harriet
Weiss, Sarah A.
Gettinger, Scott
Sznol, Mario
Young, Arabella
Rushakoff, Robert
Lee, James
Bluestone, Jeffrey A.
Anderson, Mark
Herold, Kevan C.
Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
title Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
title_full Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
title_fullStr Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
title_full_unstemmed Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
title_short Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
title_sort collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors
topic Diabetes Symposium: Emerging Areas of Islet Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054443/
https://www.ncbi.nlm.nih.gov/pubmed/29937434
http://dx.doi.org/10.2337/dbi18-0002
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