FRI645 A Case Of Diabetic Ketoacidosis After Initiation Of Decitabine And Venetoclax Chemotherapy

Disclosure: R. Maini: None. J. Milosavljevic: None. S. Aleksic: None. Background: Decitabine, a pyrimidine nucleotide analogue, and venetoclax, a Bcl-2 inhibitor (ABT-199), are chemotherapy agents used for the treatment of myelodysplastic syndromes. Clinical trials have shown hyperglycemia as an adverse reaction for both of these medications, but DKA has not been reported. Clinical Case: A 71-year-old woman with a history of T2D and myelodysplastic syndrome (MDS) presented with nausea, vomiting, and diarrhea for five days. Initial tests revealed blood glucose 839 mg/dL, an anion gap of 19 mEq/L (n 7-16), serum bicarbonate 14 mmol/L (n 20-30), venous pH of 7.24, and hydroxybutyrate >4 mmol/L (n< 0.3), consistent with diabetic ketoacidosis. Her anti-glutamic acid decarboxylase autoantibodies were negative. Chest CT showed bibasilar pulmonary opacities, concerning for multifocal pneumonia. She was placed on an insulin drip and fluids according to the institution's protocol and her anion gap closed within a day. She was transitioned to subcutaneous insulin. The patient had well-controlled T2D, with an HbA1c of 5.6% two weeks before her presentation and an admission fructosamine level of 377 umol/L (n 200-285). Her BMI was 25. Her only T2D medication was semaglutide 0.25 mg weekly but had not taken a dose in three weeks due to the national shortage. Five weeks prior to this presentation, she began weekly chemotherapy infusions of decitabine and oral venetoclax as part of a clinical trial (2021-13466) for MDS treatment, with her last infusion one week before her presentation. Conclusion: This is the first case to demonstrate DKA precipitated by decitabine and venetoclax treatment. While both agents have been linked to severe hyperglycemia in safety clinical trials, DKA has not been previously reported. Data from animal studies have shown that prolonged exposure of mouse islets to Bcl-2 antagonists increase levels of reactive oxygen species and induce pancreatic β cell apoptosis (1). Further research is needed to assess the benefits and risks of this chemotherapy regimen in patients with diabetes. References: 1.) Aharoni-Simon M, et al. Bcl-2 Regulates Reactive Oxygen Species Signaling and a Redox-Sensitive Mitochondrial Proton Leak in Mouse Pancreatic β-Cells. Endocrinology. 2016 Jun. Presentation: Friday, June 16, 2023