Checkpoint inhibitor associated autoimmune diabetes (CIADM) is distinct from type 1 diabetes.

updated at 15:16 by Tsang VHM, McGrath RT, Clifton-Bligh RJ, Scolyer RA, Jakrot V, Guminski AD, Long GV, Menzies AM via American Goiter Association

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Checkpoint inhibitor associated autoimmune diabetes (CIADM) is distinct from type 1 diabetes.
J Clin Endocrinol Metab. 2019 Jul 02;:
Authors: Tsang VHM, McGrath RT, Clifton-Bligh RJ, Scolyer RA, Jakrot V, Guminski AD, Long GV, Menzies AM
Abstract
CONTEXT: Checkpoint inhibitor associated autoimmune diabetes mellitus (CIADM) is a rare illness, with little known as to incidence, clinical features or pathogenesis.
CASE SERIES DESCRIPTION: Consecutive patients from a single quaternary melanoma centre who developed new onset insulin-requiring diabetes after commencing anti-PD-1 immunotherapy were studied to describe CIADM characteristics. Ten (1.9%) of 538 patients with metastatic melanoma treated with anti-PD-1 based immunotherapy from March 2015 to March 2018 developed CIADM. Nine patients had no prior history of diabetes, one had pre-existing T2DM. Median time from immunotherapy start to CIADM diagnosis was 25 weeks (IQR 17.5-34.5). All patients had normal serum C-peptide shortly before CIADM onset, and an inappropriately low level when measured soon after. At CIADM diagnosis, median HbA1c was 7.6% (IQR 7.15-9.75), median glucose was 32.5mmol/L (IQR 21.6-36.7), and median C-peptide concentration was 0.35nmol/L (IQR 0.10-0.49). Type 1 diabetes (T1D)-associated autoantibodies (DAA) were present in two patients (both GAD); all were negative for IA-2, insulin and ZnT8. Three patients were heterozygous for a HLA Class II T1D-risk haplotype; two additional patients also carried protective haplotypes for T1DM. All patients continued immunotherapy; eight (80%) had complete or partial oncological response, and all patients required ongoing insulin therapy.
CONCLUSION: CIADM is characterized by sudden permanent beta-cell failure occurring after immunotherapy. It is distinct from T1D, usually without DAA or T1D-associated HLA risk haplotypes, and difficult glycaemic control from the onset. As such, CIADM represents a new model of auto-inflammatory beta-cell failure.
PMID: 31265074 [PubMed - as supplied by publisher]