Immunotherapy-Induced Type 1 Diabetes Mellitus Causing Diabetic Ketoacidosis: A Case Report and Review of Current Guidelines

Our plain-English summary of Immunotherapy-Induced Type 1 Diabetes Mellitus Causing Diabetic Ketoacidosis: A Case Report and Review of Current Guidelines, by P. Disterhaft, C. Kerr, D. Barnett, et al (Cancer Reports, 2024).

The study

• Authors: P. Disterhaft, C. Kerr, D. Barnett, M. Salloum
• Journal: Cancer Reports
• Published: 2024;7(11):e70058
• Type of article: Case report, Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Immune checkpoint inhibitors (ICIs) are becoming more frequently used in the treatment of many types of malignant cancers by disinhibiting T-cell activation, which promotes the destruction of cancer cells. This disinhibition can also result in autoimmune conditions, like endocrinopathies.

Case: We report a case of a 78-year-old male patient with malignant mesothelioma treated with combination ICI therapy who presented with diabetic ketoacidosis (DKA) with no history of diabetes mellitus or hyperglycemia. The patient was admitted to the intensive care unit and treated with intravenous (IV) fluid repletion and IV insulin for DKA. The patient was diagnosed with new-onset type 1 diabetes mellitus (T1DM) induced by ICI therapy.

Discussion: Approximately 75% of patients diagnosed with ICI-induced T1DM initially present with DKA. This, along with the rapid onset of hyperglycemia in this patient, suggests current guidelines for monitoring blood glucose are inadequate. Current guidelines recommend monitoring blood glucose at the following times: baseline, at the initiation of each cycle for 12 weeks, and then every 3-6 weeks thereafter. We propose the following schedule for monitoring blood glucose in patients receiving ICI therapy: baseline, twice weekly for the first six cycles, and then once weekly thereafter. This proposed update is supported by our patient's rapid onset of hyperglycemia and other case reports and reviews showing that most patients with this diagnosis have an initial presentation of DKA. Detecting hyperglycemia and starting treatment early is important in the prevention of acute complications from uncontrolled T1DM, like DKA.

Conclusion: This case adds to the existing body of literature and provides support for more frequent monitoring of blood glucose in patients receiving ICI therapy. Blood glucose monitoring is a simple, reliable, low risk, and inexpensive laboratory test that should be used in patients receiving ICI therapy to ensure prompt diagnosis and treatment of T1DM.

© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.

In plain English

This was a case report of one patient, with a discussion of guidelines. A 78-year-old man with unresectable malignant mesothelioma was receiving two immunotherapy drugs, nivolumab and ipilimumab. The article does not say where in the body the mesothelioma arose and does not discuss asbestos. In January 2024, 16 days after his fourth treatment cycle, he came to an emergency department in Phoenix, Arizona, with two weeks of thirst, frequent urination and fatigue. His blood glucose was 757 mg/dL, with ketones and acidosis, consistent with diabetic ketoacidosis. He had no history of diabetes. His last fasting glucose, 37 days earlier, was 104 mg/dL. After intensive care treatment with fluids and insulin, he was diagnosed with type 1 diabetes caused by the immunotherapy. Diabetes antibody tests were negative and C-peptide was low. He went home on insulin. The authors cited earlier reviews in which 71% to 76% of such cases first appeared as ketoacidosis. They proposed checking blood glucose at baseline, twice weekly for the first six cycles, then weekly.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report of a single patient, with a discussion of current blood glucose monitoring guidelines
• Who was studied: One 78-year-old male patient with unresectable malignant mesothelioma (site not stated), hypertension, hyperlipidemia, atrial fibrillation and benign prostatic hyperplasia, seen at an emergency department in Phoenix, Arizona, in January 2024
• Exposure: Combination immune checkpoint inhibitor therapy, started in October 2023: nivolumab (a PD-1 inhibitor) every 3 weeks and ipilimumab (a CTLA-4 inhibitor) every 6 weeks. Four cycles were completed before admission. Asbestos exposure is not discussed.
• Main results:
  • The patient presented 16 days after completing his fourth cycle of immunotherapy, with a 2-week history of polydipsia, polyuria and fatigue
  • Admission tests in this patient showed blood glucose 757 mg/dL, serum ketones 6.31 mmol/L and urine ketones 20 mg/dL, consistent with diabetic ketoacidosis
  • The patient had no prior diabetes. His most recent fasting blood glucose, 37 days before hospitalization, was 104 mg/dL.
  • The patient's HbA1C during admission was 10.1%
  • Glutamic acid decarboxylase antibodies and islet cell antibodies were negative in this patient, and C-peptide was low (0.67 ng/mL; reference 0.8 to 3.85)
  • After ICU treatment with IV fluids and IV insulin, the patient was moved to subcutaneous insulin on day two, after the ketoacidosis resolved
  • The patient received his fifth cycle of immunotherapy 23 days after hospitalization
  • At 65 days after discharge, the patient's HbA1C was 7.9%
  • Not a finding of this case: the authors cited two earlier systematic reviews (by de Filette and colleagues and Lin and colleagues) reporting that 71% to 76% of patients with immunotherapy-induced type 1 diabetes first present with diabetic ketoacidosis
• The authors' conclusion: The authors considered current American Society of Clinical Oncology monitoring inadequate. Those guidelines call for checks at baseline, at the start of each cycle for 12 weeks, then every 3 to 6 weeks. The authors proposed checking blood glucose at baseline, twice weekly for the first six cycles, and once weekly thereafter for patients on immune checkpoint inhibitor therapy.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, checkpoint inhibitors, Mesothelioma.

Related studies

• Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1/JAK2 inhibitor — T. Ge, A.L. Phung, et al. (2022)
• New-Onset Diabetes with Ketoacidosis Precipitated by COVID-19 in Children: A Report of Two Cases — N. Chekhlabi, A. Haoudar, et al. (2021)
• Checkpoint inhibitor immunotherapy induced inflammatory arthritis secondary to Nivolumab and Ipilimumab: a pediatric first — J.A. Storwick, H. Tam, et al. (2024)
• Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma — K. Hotta, N. Fujimoto (2020)
• Monitoring immunE DysregulAtion foLLowing Immune checkpOint-inhibitioN (MEDALLION): protocol for an observational cancer immunotherapy cohort study — A. Gault, L. Hogarth, et al. (2024)
• Permanent diabetes insipidus in a patient with mesothelioma treated with immunotherapy — L. Brilli, L. Calabrò, et al. (2020)

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