Endocrine Abstracts

JOINT476

Background: Atezolizumab, a PD-L1 inhibitor, has significantly improved outcomes in advanced bladder cancer. However, immune checkpoint inhibitors (ICIs) can cause immune-related adverse events, including autoimmune diabetes mellitus (ADM). Although immune-related T1DM is a rare complication, it has been increasingly reported with ICIs, including nivolumab, pembrolizumab, and atezolizumab. The estimated incidence of ICI-induced diabetes ranges from 0.2% to 1.4%, with most cases occurring within 1–6 months after initiation of therapy.

Case Presentation: A 46-year-old military officer with stage IV bladder cancer (pT4pN0M0, G3) was hospitalized on **March 6, 2024**, due to progressive fatigue, polyuria, polydipsia, and severe hyperglycemia (29.8 mmol/l). He had previously undergone multiple transurethral resections (TURs), radical cystectomy with Bricker urinary diversion (July 2023), and four cycles of gemcitabine-cisplatin chemotherapy (July–October 2023). In January–February 2024, he received two cycles of atezolizumab (T-centrix). Within weeks, he developed worsening hyperglycemia. Laboratory tests confirmed new-onset T1DM: glucose 26.65 mmol/l, ketonuria 3.9 mmol/l, and positive autoimmune markers—glutamic acid decarboxylase antibodies (GADA: 85.1 U/mL) and islet cell antibodies (ICA: 43.7 U/mL). The C-peptide level was markedly reduced (0.33 ng/mL), indicating β-cell destruction. No prior history of diabetes or autoimmune diseases was noted. The patient was started on basal-bolus insulin therapy and intravenous hydration. Over the hospitalization period, glycemic control improved, with glucose levels stabilizing (7.5–15 mmol/l). He was discharged after treatment with recommendations for endocrinology and oncology follow-up, regular HbA1c monitoring, and continued glycemic management. Atezolizumab-induced diabetes has been documented in several case reports. A systematic review of ICI-related diabetes cases found that median onset occurs within 6–12 weeks of therapy initiation, often presenting with diabetic ketoacidosis (DKA). Atezolizumab-related cases remain less frequent than those linked to PD-1 inhibitors, but the mechanism is believed to involve T-cell–mediated β-cell destruction, similar to classic autoimmune diabetes.

Conclusion: This case highlights atezolizumab’s potential to induce autoimmune diabetes, likely via immune-mediated β-cell destruction. The onset of hyperglycemia within weeks of ICI therapy underscores the importance of regular glucose monitoring in patients receiving immune checkpoint inhibitors. Early detection and timely intervention can prevent life-threatening complications.