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

Abstract

Patient: Female, 51-year-old Final Diagnosis: Diabetic ketoacidosis Symptoms: Abdominal pain • diarrhea Medication: Pembrolizumab Clinical Procedure: — 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 chemo-therapy cycle, she developed a severe case of diabetic ketoacidosis (DKA), with concern for new-onset auto-immune 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.

Anti‑PD‑1 immune checkpoint inhibitor inducing endocrine toxicity in a patient with advanced lung cancer: A case report and literature review

“…Due to the rapid onset of DM, patients with ICI-DM may test positive for diabetes autoantibodies. Of note, this differs from conventional T1DM (51).…”

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

“…Baseline characteristics are presented in Table 2 . In addition to our patients, 171 cases were identified [ 7 , 8 , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [...…”

Reaching the Diagnosis of Checkpoint Inhibitor-Induced Diabetes Mellitus in Different Clinical Scenarios: A Real-World Application of Updated Diagnostic Criteria

“…Lo Preiato et al [22] agreed that a total of 43.0% of patients had positive anti-GAD antibodies in their database, in contrast with the much higher prevalence of type 1 DM, with no comparison with a control group. Many reports have identified CPI-DM cases with both positive and negative specific autoantibodies but without strong conclusions [23][24][25][26]. A case report and literature review study showed that islet autoantibodies may be present before CPI treatment in non-diabetic patients and, when exposed to CPI therapy, may precipitate the onset of DM [27].…”

“…A case report and literature review study showed that islet autoantibodies may be present before CPI treatment in non-diabetic patients and, when exposed to CPI therapy, may precipitate the onset of DM [27]. Positive autoantibodies were associated with earlier and more severe presentations of CPI-DM [23][24][25][26]. In our series, positive islet autoantibodies were detected in three of four cases (one with anti-IA2, one with anti-GAD positivity, and one with anti-IA2, anti-GAD, and anti-ZnT8 positivity).…”