Progression To Insulin Dependence Post-Treatment With Immune Checkpoint Inhibitors In Pre-Existing Type 2 Diabetes

ABSTRACT Objective: To present 2 cases in which patients previously diagnosed with type 2 diabetes (T2D) rapidly progressed to insulin dependence following cancer treatment with immune checkpoint inhibitors (ICH). Both patients were subsequently found to be positive for glutamic acid decarboxylase 65 antibodies (+GAD), indicative of type 1.5 diabetes (T1.5D). Methods: Patient history, laboratory results, and treatment course, in addition to review of the relevant literature, are presented. Results: The first case involved a 78-year-old man with lung cancer and a 30-year history of T2D (controlled with oral medications [OM]) who developed polydipsia, polyuria, and nocturia 5 weeks post-treatment with nivolumab. Basal bolus insulin was required, and frequent insulin increments were necessary to achieve metabolic control. The patient had no personal or family history of autoimmunity. The second case involved a 55-year-old man with metastatic melanoma and a 4-year history of T2D who required transition from OM to basal bolus insulin following treatment with ipilimumab. Hypophysitis prompted discontinuation of ipilimumab and initiation of pembrolizumab, which was followed by the need for an intensive escalation of insulin dosage for glucose control. C-peptide was undetectable. He had a history of autoimmune hypothyroidism. Both patients were nonobese and were +GAD post-ICH. Conclusion: Fulminant β-cell destruction may be enhanced upon treatment with ICH in patients with unrecognized T1.5D. Obtaining GAD before the initiation of treatment in T2D should be considered to identify those at higher risk, and to alert providers on the need for close observation and prompt insulin initiation to prevent metabolic decompensation. Abbreviations: A1C = hemoglobin A1C; BMI = body mass index; CTLA-4 = cytotoxic T-cell-associated antigen; FDA = Food and Drug Administration; GAD = glutamic acid decarboxylase 65 antibodies; ICH = immune checkpoint inhibitors; LADA = latent autoimmune diabetes of the adult; PD1 = programmed death 1; PD1A = anti-PD1 monoclonal antibody; PD-L1 = programmed death-ligand 1; T1D = type 1 diabetes mellitus; T1.5D = type 1.5 diabetes mellitus; T2D = type 2 diabetes mellitus