Cargando…

Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes

OBJECTIVE: Insulin-dependent diabetes can occur with immune checkpoint inhibitor (ICI) therapy. We aimed to characterize the frequency, natural history and potential predictors of ICI-induced diabetes. RESEARCH DESIGN AND METHODS: We reviewed 1444 patients treated with ICIs over 6 years at our cance...

Descripción completa

Detalles Bibliográficos
Autores principales: Kotwal, Anupam, Haddox, Candace, Block, Matthew, Kudva, Yogish C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398813/
https://www.ncbi.nlm.nih.gov/pubmed/30899528
http://dx.doi.org/10.1136/bmjdrc-2018-000591
_version_ 1783399646080532480
author Kotwal, Anupam
Haddox, Candace
Block, Matthew
Kudva, Yogish C
author_facet Kotwal, Anupam
Haddox, Candace
Block, Matthew
Kudva, Yogish C
author_sort Kotwal, Anupam
collection PubMed
description OBJECTIVE: Insulin-dependent diabetes can occur with immune checkpoint inhibitor (ICI) therapy. We aimed to characterize the frequency, natural history and potential predictors of ICI-induced diabetes. RESEARCH DESIGN AND METHODS: We reviewed 1444 patients treated with ICIs over 6 years at our cancer center, and from the 1163 patients who received programmed cell death protein 1 (PD-1) inhibitors, we identified 21 such cases, 12 of which developed new-onset insulin-dependent diabetes and 9 experienced worsening of pre-existing type 2 diabetes. RESULTS: ICI-induced diabetes occurred most frequently with pembrolizumab (2.2%) compared with nivolumab (1%) and ipilimumab (0%). The median age was 61 years, and body mass index was 31 kg/m(2), which are both higher than expected for spontaneous type 1 diabetes. Other immune-related adverse events occurred in 62%, the most common being immune mediated thyroid disease. New-onset insulin-dependent diabetes developed after a median of four cycles or 5 months; 67% presented with diabetic ketoacidosis and 83% with low or undetectable C-peptide. Autoantibodies were elevated in 5/7 (71%) at the time of new-onset diabetes. Diabetes did not resolve during a median follow-up of 1 year. CONCLUSIONS: PD-1 inhibitors can lead to insulin deficiency presenting as new-onset diabetes or worsening of pre-existing type 2 diabetes, with a frequency of 1.8 %. The underlying mechanism appears similar to spontaneous type 1 diabetes but there is a faster progression to severe insulin deficiency. Better characterization of ICI-induced diabetes will improve patient care and enhance our understanding of immune-mediated diabetes.
format Online
Article
Text
id pubmed-6398813
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-63988132019-03-21 Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes Kotwal, Anupam Haddox, Candace Block, Matthew Kudva, Yogish C BMJ Open Diabetes Res Care Clinical Care/Education/Nutrition OBJECTIVE: Insulin-dependent diabetes can occur with immune checkpoint inhibitor (ICI) therapy. We aimed to characterize the frequency, natural history and potential predictors of ICI-induced diabetes. RESEARCH DESIGN AND METHODS: We reviewed 1444 patients treated with ICIs over 6 years at our cancer center, and from the 1163 patients who received programmed cell death protein 1 (PD-1) inhibitors, we identified 21 such cases, 12 of which developed new-onset insulin-dependent diabetes and 9 experienced worsening of pre-existing type 2 diabetes. RESULTS: ICI-induced diabetes occurred most frequently with pembrolizumab (2.2%) compared with nivolumab (1%) and ipilimumab (0%). The median age was 61 years, and body mass index was 31 kg/m(2), which are both higher than expected for spontaneous type 1 diabetes. Other immune-related adverse events occurred in 62%, the most common being immune mediated thyroid disease. New-onset insulin-dependent diabetes developed after a median of four cycles or 5 months; 67% presented with diabetic ketoacidosis and 83% with low or undetectable C-peptide. Autoantibodies were elevated in 5/7 (71%) at the time of new-onset diabetes. Diabetes did not resolve during a median follow-up of 1 year. CONCLUSIONS: PD-1 inhibitors can lead to insulin deficiency presenting as new-onset diabetes or worsening of pre-existing type 2 diabetes, with a frequency of 1.8 %. The underlying mechanism appears similar to spontaneous type 1 diabetes but there is a faster progression to severe insulin deficiency. Better characterization of ICI-induced diabetes will improve patient care and enhance our understanding of immune-mediated diabetes. BMJ Publishing Group 2019-02-13 /pmc/articles/PMC6398813/ /pubmed/30899528 http://dx.doi.org/10.1136/bmjdrc-2018-000591 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0
spellingShingle Clinical Care/Education/Nutrition
Kotwal, Anupam
Haddox, Candace
Block, Matthew
Kudva, Yogish C
Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
title Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
title_full Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
title_fullStr Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
title_full_unstemmed Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
title_short Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
title_sort immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
topic Clinical Care/Education/Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398813/
https://www.ncbi.nlm.nih.gov/pubmed/30899528
http://dx.doi.org/10.1136/bmjdrc-2018-000591
work_keys_str_mv AT kotwalanupam immunecheckpointinhibitorsanemergingcauseofinsulindependentdiabetes
AT haddoxcandace immunecheckpointinhibitorsanemergingcauseofinsulindependentdiabetes
AT blockmatthew immunecheckpointinhibitorsanemergingcauseofinsulindependentdiabetes
AT kudvayogishc immunecheckpointinhibitorsanemergingcauseofinsulindependentdiabetes