Presentation of new onset type 1 diabetes with diabetic ketoacidosis and hyperosmolar hyperglycaemia after a single dose of nivolumab and ipilimumab.

Summary: A Caucasian man in his 60s with recent diagnosis of metastatic renal cell carcinoma presented to the emergency department with a 5-day history of severe polyuria, polydipsia and fatigue and 1-day history of confusion, abdominal pain, nausea and vomiting. Investigations revealed an overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS). He had received the first dose of immunotherapy with nivolumab and ipilimumab 3 weeks prior to this attendance. New-onset type 1 diabetes (T1DM) was confirmed based on the clinical features at presentation, seropositivity for glutamic acid decarboxylase antibodies and significant insulin deficiency. He is currently on a multiple daily injections of insulin and uses intermittent-scanned glucose monitoring. Given the irreversible impact on beta-cell function and clinical response with insulin resulting in improved diabetes control, immunotherapy was resumed for his metastatic cancer with good radiological response. Although rare, new-onset T1DM can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes. Learning points: Although rare, new onset of T1DM after immunotherapy can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes and normal glycaemic parameters. Due to the irreversible destruction of beta-cells, treatment with steroids is not indicated in contrast to other settings such as immunotherapy-induced hypophysitis. Presence of low c-peptide levels post-acute presentation is indicative of an irreversible impact on beta-cell function and supports resuming immunotherapy given the significant benefits on cancer prognosis. Clinicians must maintain a high index of suspicion in regards to diagnosis and management of new-onset type 1 diabetes and advice patients on reporting symptoms suggestive of diabetes and/or diabetes-related hyperglycaemic emergencies.