학술논문
Checkpoint Inhibitor--Associated Autoimmune Diabetes Is Distinct From Type 1 Diabetes
CASE REPORT
CASE REPORT
Document Type
Academic Journal
Author
Source
Journal of Clinical Endocrinology & Metabolism. November 2019, Vol. 104 Issue 11, p5499, 8 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Immune checkpoint inhibitors (ICIs) improve survival of patients with advanced cancers, including melanoma, non--small cell lung cancer, renal cell carcinoma, bladder cancer, head and neck squamous cell carcinoma, and Hodgkin [...]
Context: Checkpoint inhibitor--associated autoimmune diabetes mellitus (CIADM) is a rare illness, and little is known about its incidence, clinical features, or pathogenesis. Case Series Description: Consecutive patients from a single quaternary melanoma center who developed new-onset insulin-requiring diabetes after commencing anti--programmed cell death-1 (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 toMarch 2018 developed CIADM. Nine patients hadno history of diabetes, and one had pre-existing type 2 diabetes mellitus. Median time from immunotherapy start to CIADM diagnosis was 25 weeks [interquartile range (IQR), 17.5 to 34.5 weeks]. All patients had normal serum C-peptide shortly before CIADM onset and an inappropriately low level when measured soon after. At CIADM diagnosis, median hemoglobin A1c was 7.6% (IQR, 7.15% to 9.75%), median glucose level was 32.5 [micro]mol/L (IQR, 21.6 to 36.7 [micro]mol/L), and median C-peptide concentration was 0.35 nmol/L (IQR, 0.10 to 0.49 [micro]mol/L). Type 1 diabetes (T1D)-associated autoantibodies (DAAs) were present in two patients (both of whom had anti--glutamic acid decarboxylase antibody); all were negative for insulin-associated protein 2, insulin, and ZnT8. Three patients were heterozygous for an HLA class II T1D-risk haplotype; two additional patients also carried protective haplotypes for T1D. 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 lacks DAA or T1D-associated HLA-risk haplotypes, and is associated with difficult glycemic control from the onset. As such, CIADM represents a new model of auto-inflammatory [beta]-cell failure. (J Clin Endocrinol Metab 104: 5499-5506, 2019)
Context: Checkpoint inhibitor--associated autoimmune diabetes mellitus (CIADM) is a rare illness, and little is known about its incidence, clinical features, or pathogenesis. Case Series Description: Consecutive patients from a single quaternary melanoma center who developed new-onset insulin-requiring diabetes after commencing anti--programmed cell death-1 (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 toMarch 2018 developed CIADM. Nine patients hadno history of diabetes, and one had pre-existing type 2 diabetes mellitus. Median time from immunotherapy start to CIADM diagnosis was 25 weeks [interquartile range (IQR), 17.5 to 34.5 weeks]. All patients had normal serum C-peptide shortly before CIADM onset and an inappropriately low level when measured soon after. At CIADM diagnosis, median hemoglobin A1c was 7.6% (IQR, 7.15% to 9.75%), median glucose level was 32.5 [micro]mol/L (IQR, 21.6 to 36.7 [micro]mol/L), and median C-peptide concentration was 0.35 nmol/L (IQR, 0.10 to 0.49 [micro]mol/L). Type 1 diabetes (T1D)-associated autoantibodies (DAAs) were present in two patients (both of whom had anti--glutamic acid decarboxylase antibody); all were negative for insulin-associated protein 2, insulin, and ZnT8. Three patients were heterozygous for an HLA class II T1D-risk haplotype; two additional patients also carried protective haplotypes for T1D. 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 lacks DAA or T1D-associated HLA-risk haplotypes, and is associated with difficult glycemic control from the onset. As such, CIADM represents a new model of auto-inflammatory [beta]-cell failure. (J Clin Endocrinol Metab 104: 5499-5506, 2019)