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. 2019 Feb 13;7(1):e000591.
doi: 10.1136/bmjdrc-2018-000591. eCollection 2019.

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

Anupam Kotwal  1 , Candace Haddox  2 , Matthew Block  3 , Yogish C Kudva  1
Affiliations

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

Anupam Kotwal et al. BMJ Open Diabetes Res Care. .

Abstract

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/m2, 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.

Keywords: adult diabetes; cancer; immune pathogenesis type 1 diabetes; insulin deficiency; islet autoimmunity.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
PET scan performed at diagnosis of new-onset insulin-dependent diabetes demonstrating diffusely increased FDG uptake in the pancreas of patient 10. FDG, fluorodeoxyglucose; PET, positron emission tomography.
See this image and copyright information in PMC

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