Immunotherapy-induced DKA: Are sugars on the rise?

Abstract

e14602 Background: Type 1 Diabetes Mellitus (T1DM) is a serious side effect of Immune Checkpoint Inhibitors (ICIs), which typically presents as Diabetic Ketoacidosis (DKA) in 70% of cases. The majority of cases of ICI-Induced DKA are in older patients, with a high morbidity and mortality. Recent data shows that the incidence of ICI-induced DKA is rising, and as a unique clinical entity, it is still not yet fully understood. The purpose of this study is to gain further understanding about the typical onset of ICI-Induced DKA, the association with HbA1c, C-peptide, and Islet autoantibodies, and the challenges of identifying DKA and complications associated with treating DKA in the older patient. Methods: This study is a multi-centre case series of patients with a diagnosis of solid tumours who received ICIs, and subsequently presented with Diabetic Ketoacidosis. Results: Twelve patients were identified at centres across the United Kingdom. The median age was 68 years (range 45-86), and seven of the patients were female. No patients had a background of diabetes. Eight patients were treated with pembrolizumab, and four patients were treated with a combination of Ipilimumab and Nivolumab. The median time to onset of DKA from starting ICIs was 21 weeks (range 3-117). The mean pH level at presentation of DKA was 7.01, mean glucose level was 33mmol/L and mean HbA1c was 80mmol/mol. Seven of the patients required ICU admission, with complications including acute kidney injury (AKI) and fluid overload. C-peptide level was only tested in six patients; three of the six patients had an undetectable C-peptide level at presentation. One patient had positive T1DM-associated autoantibodies, and interestingly had the shortest onset to DKA at 3 weeks after ICI initiation. For nine of the twelve patients, this was their only presentation of ICI toxicity to date. All patients were subsequently diagnosed with insulin-dependent diabetes after their DKA presentation. Conclusions: This demonstrates the rapid and often unpredictable onset of DKA presenting as a new phenomenon in older patients , with a sharp rise in glucose levels and fall in C-peptide level. The presentation of DKA in this older population was found to be associated with likely requirement for ICU admission, resistant blood sugars requiring higher insulin doses, high risk of fluid overload, and acute kidney injury. This study helps to enlighten clinicians regarding this unique clinical presentation of DKA following ICI treatment, and the importance of patient education and recommended diagnostic tests and management for best clinical practice.