Diabetes mellitus geïnduceerd door immuuntherapie: een casus

Abstract

Immunotherapy-induced diabetes mellitus: a case-report A 73-year-old man presented with diabetic ketoacidosis (DKA) after the recent initiation of immunochemotherapy to treat a lung adenocarcinoma. Pembrolizumab is an IgG4 monoclonal antibody targeting an immune checkpoint protein called ‘programmed cell death protein 1’ (PD-1), which results in antitumoral immunity. Immune checkpoint inhibitors (ICI), such as pembrolizumab, are known for their ability to cause immune-related adverse events (irAEs). Immunotherapy-induced diabetes mellitus (DM) occurs predominantly with the inhibition of PD-1 or its ligand (‘programmed cell death protein 1 ligand’ (PD-L1)). The onset is typically acute with a rapidly progressive deficiency of the endogenous insulin production, resulting in hyperglycaemia and a low or absent serum level of C-peptide with a relatively low to normal HbA1c in the acute phase. The significant loss of endogenous insulin production makes DKA a frequent first presentation. This rapid pathophysiological evolution was present in the discussed patient, who developed DM in less than 6 weeks and needed insulin therapy to establish an adequate glycaemic control. Given the increasingly widespread use of ICI in the treatment of various tumours, caution has to be taken to identify these potentially life-threatening irAEs. Awareness and alertness to glycemia on blood sampling, as well as patient education regarding red flags are fundamental, in addition to adequate recognition and treatment of (potential) ketoacidosis.