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

Immune checkpoint inhibitor‑associated diabetes mellitus in patients with HCC: Report of three cases and literature review

“…In case 1 of the present study, the patient presented with nausea, vomiting, fever and lethargy as symptoms of DKA, while the other two patients were diagnosed ICI-DM after laboratory tests during routine follow-up examinations. According to a previous study, 44.8% of ICI-DM cases had damage to other endocrine glands in addition to diabetes, including hypophysitis (5.2%) and thyroiditis (30.8%) ( 4 ). In case 1 of the present study, the pathology was accompanied by DKA and thyroiditis.…”

“…ICI-induced type 1 diabetes mellitus (T1DM) is an irAE with an incidence of 0.2-1.0% ( 3 ). A systematic review study demonstrated that in 172 ICI-induced DM (ICI-DM) cases, tumor types included melanoma (43.6%; 75/172), lung cancer (30.2%; 52/172), renal cell carcinoma (5.8%; 10/172), breast cancer (3.5%; 6/172), gastrointestinal cancers (3.5%; 6/172), lymphomas (2.9%; 5/172) and hepatocellular carcinoma (1.2%; 2/172) ( 4 ). Current research also suggests that the primary mechanism of ICI-induced T1DM is T-cell stimulation due to the loss of interaction between PD-1 and PD-L1 in pancreatic islets ( 5 ).…”

Immune checkpoint inhibitor-induced diabetes mellitus with nivolumab

“…There have been wide discrepancies in the time from ICI initiation to diabetes onset, with a systematic review by Liu et al reporting a median onset time of 12 weeks (range 0–122) 4 11. Another systematic review by Akturk et al reported a median of 10.5 weeks (range 0.71–64) for nivolumab 8.…”

“…Significant hyperglycaemia is suggested to occur rapidly and the majority of reported cases of ICI-DM have been in patients presenting in DKA 4 11 12. HbA1c is generally lower than 10% at time of diagnosis and C-peptide levels are either undetectable or inappropriately low for the degree of hyperglycaemia 2 4 13.…”

“…ICI-DM has been reported with both positive and negative T1DM-associated autoantibodies, with at least one autoantibody being present in 40%–50% of cases 4 12 13. Of these, GAD antibody positivity is the most common and has additionally been correlated with a shorter time to onset of ICI-DM 8 11 18. Similarly, the relevance of T1DM-associated human leucocyte antigen (HLA) loci to ICI-DM requires further clarification 4 13.…”