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

Authors

• Divya Samat, Department of Internal Medicine, Reading Hospital - Tower Health, PA, USAFollow
• Osadebamwen Osaghae, Department of Internal Medicine, Reading Hospital - Tower Health, PA, USAFollow
• Shivam Singh, Department of Internal Medicine, Reading Hospital - Tower Health, PA, USAFollow
• Mohammad Abu Tineh, Department of Internal Medicine, Reading Hospital - Tower Health, PA, USAFollow
• Anthony Donato, Department of Internal Medicine, Reading Hospital - Tower Health, PA, USAFollow

Author ORCID Identifier

Divya Samat: https://orcid.org/0009-0008-5365-7299

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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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Recommended Citation

Samat D, Osaghae O, Singh S, Abu Tineh M, Donato A. Checkpoint Inhibitor–Associated Autoimmune Diabetes Following PD-1 Blockade: Severe Diabetic Ketoacidosis After Pembrolizumab. Advances in Clinical Medical Research and Healthcare Delivery. 2026; 6(2):40-44. doi: 10.53785/2769-2779.1377.