Full Title: Risk factors and characteristics of checkpoint inhibitor associated autoimmune diabetes (CIADM): a systematic review and delineation from type 1 diabetes

  

Background

Checkpoint inhibitor associated autoimmune diabetes (CIADM) is a distinct form of autoimmune diabetes that is a rare complication of immune checkpoint inhibitor therapy. Data regarding CIADM is 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 using a pre-defined search strategy. Patients meeting diagnostic criteria for CIADM with evidence of hyperglycaemia (blood glucose level >11mmol/L or HbA1c >= 6.5%) and insulin deficiency (C-peptide <0.4nmol/l and/or diabetic ketoacidosis) were included for analysis. 

Data extraction

The search strategy identified 1206 papers. From 146 papers 278 patients were labelled with “CIADM”, with 192 patients meeting our diagnostic criteria and included in analysis.

Data synthesis

Mean age was 63.4years (±12.4). All but one patient (99.5%) had prior exposure to either anti-PD1 or anti-PDL1 therapy. Of the 91 patients tested (47.3%), 59.3% had susceptibility haplotypes for type 1 diabetes. Median time to CIADM onset was 12 weeks (IQR 6-24). Diabetic ketoacidosis (DKA) occurred in 69.7%, and initial C-peptide was low in 91.6%. Type 1 diabetes autoantibodies were present in 40.4% (73/179) 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.