A Concerted Vision to Advance the Knowledge of Diabetes Mellitus Related to Immune Checkpoint Inhibitors

Abstract

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.

Immune checkpoint inhibitor‑associated diabetes mellitus in patients with HCC: Report of three cases and literature review

“…de Filette et al ( 44 ) reported that at least one of the islet autoantibodies was positive in 53% of patients with TIDM and 15% of them had at least two positive autoantibodies. However, the association between islet autoantibodies and diagnosis of ICI-DM remains unclear ( 45 ). In the case series reported in the present study, ICA in case 1 was positive for DKA, while GADA was positive in case 2 and the patient from case 3 was negative for autoantibodies.…”