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Checkpoint Inhibitor–Associated Autoimmune Diabetes Following PD-1 Blockade: Severe Diabetic Ketoacidosis After Pembrolizumab
Journal article   Open access

Checkpoint Inhibitor–Associated Autoimmune Diabetes Following PD-1 Blockade: Severe Diabetic Ketoacidosis After Pembrolizumab

Divya Samat, Osadebamwen Osaghae, Shivam Singh, Mohammad Abu Tineh and Anthony Donato
Advances in Clinical Medical Research and Healthcare Delivery, v 6(2), pp 40-44
17 May 2026
DOI: https://doi.org/10.53785/2769-2779.1377
Featured in Collection :   Drexel's Newest Publications
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https://doi.org/10.53785/2769-2779.1377View
Published, Version of Record (VoR) Open CC BY-NC V4.0

Abstract

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by enhancing antitumor T-cell activity through blockade of inhibitory pathways including programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Loss of immune tolerance can lead to immune-related adverse events (irAEs), including endocrine toxicities. Checkpoint inhibitor–associated autoimmune diabetes (CIADM) is rare but clinically significant because it often presents abruptly with diabetic ketoacidosis (DKA) and profound insulin deficiency. We describe an 81-year-old male with stage III clear-cell renal cell carcinoma who developed abrupt-onset autoimmune diabetes 8 weeks after initiating adjuvant pembrolizumab. The patient presented with severe hyperglycemia and high anion-gap metabolic acidosis consistent with DKA. HbA1c had increased from 5.7% three months earlier to 9.0% at presentation, supporting recent onset sustained hyperglycemia. C-peptide levels were 0.61 ng/mL (laboratory reference 0.80–3.85 ng/mL), and autoimmune markers were negative (glutamic acid decarboxylase antibody <5 IU/mL; insulinoma-associated antigen-2 antibody <5.4 U/mL). He received intravenous fluids and insulin infusion with resolution of DKA, was transitioned to subcutaneous insulin, and remained insulin-dependent at discharge. Pembrolizumab was continued with endocrinology co-management. He completed 1 year of adjuvant pembrolizumab therapy without recurrence of DKA. CIADM typically presents abruptly with diabetic ketoacidosis and lack of significant A1c elevation due to rapid β -cell failure over a short period of time, often without traditional islet autoantibodies. Endocrine immune-related adverse events are usually irreversible and therefore most patients require lifelong insulin therapy. Routine glucose monitoring, and a low threshold for metabolic evaluation in symptomatic patients are essential to timely diagnosis and management.

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