Type 1 diabetes mellitus during immune checkpoint inhibitor therapy in cancer patients

Abstract

The development of immune checkpoint inhibitors (ICIs) has led to significant changes in the treatment strategies for malignant tumors. Results from numerous randomized trials of this class of drugs, alongside their widespread adoption in clinical practice, have demonstrated superior therapeutic efficacy in patients with both locally advanced and disseminated disease. However, the use of ICIs is associated with a range of adverse effects resulting from the strong induction of the patient’s immune response. Unlike other forms of anticancer drug therapy (such as chemotherapy or targeted therapy), the side effects associated with immune checkpoint therapy (ICT) are unpredictable and manifest across various organs and body systems as signs of immune-mediated tissue inflammation. Currently, there are no known predictive factors for the timing, type, or severity of immune-related adverse events associated with ICT. The use of immune checkpoint therapy (ICT) in cancer patients can lead to various disorders, including those affecting the endocrine system. The most common of these are thyroiditis, hypopituitarism, and adrenal insufficiency. However, the literature indicates that type 1 diabetes is also an immune-related complication of ICT. The progression of insulin deficiency in ICT-associated type 1 diabetes occurs more rapidly than in conventional type 1 diabetes. The incidence of type 1 diabetes associated with the use of immune checkpoint inhibitors (ICIs) in cancer patients ranges from 0.3% to 3.5% (1). Immune-related diabetes (irDM) presents with diabetic ketoacidosis or ketosis, typically developing within two weeks of the onset of clinical symptoms of hyperglycemia, such as dry mouth, polydipsia, and polyuria. These symptoms necessitate urgent diagnosis and timely insulin therapy, as endogenous insulin secretion declines within 2–3 weeks of the initial clinical manifestations of diabetes.Furthermore, it has been shown that the level of positive autoantibodies associated with pancreatic islet activity ranges from 5 to 50 MU, while the level of exocrine pancreatic enzymes is only slightly elevated. In this review, we describe the clinical features of type 1 diabetes associated with ICT and present a case from our clinical practice.