Risk Factors and Characteristics of Checkpoint Inhibitor-Associated Autoimmune Diabetes Mellitus (CIADM): A Systematic Review and Delineation From Type 1 Diabetes

Abstract

Background: Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) is a distinct form of autoimmune diabetes that is a rare complication of immune checkpoint inhibitor therapy. Data regarding CIADM are limited.

Purpose: To systematically review available evidence to identify presentation characteristics and risk factors for early or severe presentations of adult patients with CIADM.

Data sources: MEDLINE and PubMed databases were reviewed.

Study selection: English full text articles from 2014 to April 2022 were identified with a predefined search strategy. Patients meeting diagnostic criteria for CIADM with evidence of hyperglycemia (blood glucose level >11 mmol/L or HbA1c ≥6.5%) and insulin deficiency (C-peptide <0.4 nmol/L and/or diabetic ketoacidosis [DKA]) were included for analysis.

Data extraction: With the search strategy we identified 1,206 articles. From 146 articles, 278 patients were labeled with "CIADM," with 192 patients meeting our diagnostic criteria and included in analysis.

Data synthesis: Mean ± SD age was 63.4 ± 12.4 years. All but one patient (99.5%) had prior exposure to either anti-PD1 or anti-PD-L1 therapy. Of the 91 patients tested (47.3%), 59.3% had susceptibility haplotypes for type 1 diabetes (T1D). Median time to CIADM onset was 12 weeks (interquartile range 6-24). DKA occurred in 69.7%, and initial C-peptide was low in 91.6%. T1D autoantibodies were present in 40.4% (73 of 179) and were significantly associated with DKA (P = 0.0009) and earlier time to CIADM onset (P = 0.02).

Limitations: Reporting of follow-up data, lipase, and HLA haplotyping was limited.

Conclusions: CIADM commonly presents in DKA. While T1D autoantibodies are only positive in 40.4%, they associate with earlier, more severe presentations.