Diabetol Int. 2025 Feb 10;16(2):427-431. doi: 10.1007/s13340-025-00795-0. eCollection 2025 Apr.
ABSTRACT
Immune checkpoint inhibitor (ICI)-related type 1 diabetes mellitus (T1DM) is a severe immune-related adverse event (irAE), occurring in < 1% of cases. ICI-related T1DM typically progresses more rapidly than conventional acute-onset T1DM, but is slower than conventional fulminant T1DM, suggesting different processes of onset and progression. Positivity rates for glutamic acid decarboxylase (GAD) antibodies differ, with ICI-related T1DM showing a lower positivity rate than conventional acute-onset T1DM. However, no detailed follow-up studies have examined the GAD antibody levels before and after the onset of ICI-related T1DM. We report the case of a 58-year-old Japanese man with type 2 diabetes mellitus diagnosed with renal carcinoma and multiple lung metastases. Chemotherapy with pembrolizumab (an anti-programmed death-1 antibody) was initiated. On the first day of treatment, the patient's insulin secretion capacity was preserved, and GAD antibodies were negative. Thirty-four days after chemotherapy initiation, the patient developed diabetic ketoacidosis and was diagnosed with ICI-related T1DM. Interestingly, GAD antibodies became positive (17.7 U/mL) approximately one month after the initial ICI administration. Subsequently, GAD antibody levels declined rapidly, with negative conversion occurring in only 205 days (approximately 6.5 months). To the best of our knowledge, this is the first reported case of closely monitoring GAD antibody dynamics before and after the onset of ICI-related T1DM. Here, the dynamics of the GAD antibodies were clearly distinct from those in conventional acute-onset T1DM. This case report may provide valuable insights into the differences between the autoimmune responses of ICI-related and conventional T1DM in their disease onset and progression.
PMID:40166447 | PMC:PMC11954774 | DOI:10.1007/s13340-025-00795-0