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.