A Severe Case of Diabetic Ketoacidosis and New-Onset Type 1 Diabetes Mellitus Associated with Anti-Glutamic Acid Decarboxylase Antibodies Following Immunotherapy with Pembrolizumab

Specialty: Endocrinology and Metabolic Objective: Unusual or unexpected effect of treatment Background: Immune checkpoint inhibitors (ICIs) are a novel class of antibodies, which have been increasingly utilized in cancer immunotherapies. Pembrolizumab is a humanized IgG4 monoclonal antibody, which acts against programmed cell death (PD)-1 receptors to help restore the body's T-cell and immune response. Case Report: In this case, we present a 51-year-old woman with a past medical history of lung adenocarcinoma and triple-positive breast cancer who was actively receiving therapy with pembrolizumab. Following her second chemotherapy cycle, she developed a severe case of diabetic ketoacidosis (DKA), with concern for new-onset autoimmune type 1 diabetes mellitus (T1DM), secondary to her recent ICI therapy. The patient was initiated on a high-dose insulin infusion for rapid glycemic control and was successfully transitioned to a subcutaneous regimen approximately 24 h after presentation. She additionally developed other autoimmune-related complications, including hepatoxicity, duodenitis, and a maculopapular rash, which all resolved upon discontinuation of the ICI treatment. Her laboratory test results were consistent with positive anti-glutamic acid decarboxylase (anti-GAD) antibodies and undetectable c-peptides, illustrating the uniqueness of an ICI potentially precipitating an autoimmune T1DM. Conclusions: Immune-related adverse events from ICI therapy warrant further investigation to acknowledge the risk of potentially life-threatening adverse reactions, such as the development of DKA. Patients receiving ICI therapy should be educated on signs and symptoms of hyperglycemia, and routine measurements of blood glucose levels should be completed during each chemotherapy cycle. Future research in assessing potential biomarkers of beta cell dysfunction, such as anti-GAD antibodies and c-peptides, is of interest, particularly for patients receiving ICI therapies.

Automated summary

This case report highlights a female patient receiving pembrolizumab therapy who developed severe autoimmune adverse reactions, including diabetic ketoacidosis, and discusses the unique scenario of ICI therapy potentially precipitating autoimmune T1DM. Further investigation into immune-related adverse events from ICI therapy is warranted, with a focus on educating patients on hyperglycemia symptoms and conducting routine blood glucose level measurements. Research on potential biomarkers of beta cell dysfunction in patients receiving ICI therapies is of interest for future studies.