Pathophysiology, diagnosis, and management of immune checkpoint inhibitor-induced diabetes mellitus.

Abstract

Immune Checkpoint Inhibitors (ICIs) have revolutionized cancer treatment, offering hope for patients with various malignancies. However, along with their remarkable anticancer effects, ICIs can also trigger immune-related adverse events (irAEs). One such noteworthy complication is the development of Diabetes Mellitus (DM), which particularly resembles Type 1 Diabetes Mellitus (T1DM). The aim of this review is to provide insights into the epidemiology, pathophysiology, diagnostic issues, and treatment considerations of ICI-induced DM (ICI-DM), emphasizing the importance of early recognition and management to mitigate adverse outcomes. Although still rare, the incidence has increased with the widespread use of ICIs, especially PD-1/PD-L1 blockers (from 0.2% to 1.9%). Factors affecting the development of ICI-DM, such as specific ICIs, patient demographics, and genetic predispositions, are discussed. The complex interplay between immune dysregulation and pancreatic β-cell destruction contributes to diagnostic challenges, with presentations varying from asymptomatic hyperglycemia to diabetic ketoacidosis (DKA). Management strategies prioritize meticulous glycemic and electrolyte regulation along with tailored intravenous insulin therapy in cases of DKA. DM remission is rare, therefore treatment with both long-acting insulin at bedtime and short-acting insulin before meals is needed in longterm. Total daily insulin requirements can be estimated at 0.3-0.4 units/kg/day for most patients as a starting dose.