The rubric of immune-related (ir) diabetes mellitus (DM) (irDM) encompasses various hyperglycemic disorders related to immune checkpoint inhibitors (ICPis). Beyond sharing similarities with conventional DM, irDM is a distinct, yet important, entity. The present narrative review provides a comprehensive overview of the literature regarding irDM published in major databases from January 2018 until January 2023. Initially considered rare, irDM is increasingly being reported. To advance the knowledge of irDM, the present review suggests a concerted vision comprising two intertwined aspects: a scientific-centered and a patient-centered view. The scientific-centered aspect addresses the pathophysiology of irDM, integrating: (i) ICPi-induced pancreatic islet autoimmunity in genetically predisposed patients; (ii) altered gut microbiome; (iii) involvement of exocrine pancreas; (iv) immune-related acquired generalized lipodystrophy. The patient-centered aspect is both nurtured by and nurturing the four pillars of the scientific-centered aspect: awareness, diagnosis, treatment, and monitoring of irDM. The path forward is a multidisciplinary initiative towards: (i) improved characterization of the epidemiological, clinical, and immunological profile of irDM; (ii) standardization of reporting, management, and surveillance protocols for irDM leveraging global registries; (iii) patient stratification according to personalized risk for irDM; (iv) new treatments for irDM; and (v) uncoupling ICPi efficacy from immunotoxicity.
Keywords: anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibodies; anti-programmed cell death (anti-PD-1) antibodies; anti-programmed cell death ligand 1 (anti-PD-L1) antibodies; autoimmunity; diabetic ketoacidosis; immune checkpoint inhibitors; immune-related adverse events; immune-related diabetes mellitus; immunotoxicity; pancreatic islet autoantibodies.