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

<p>  </p> <p><strong>Background</strong></p> <p>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. </p> <p><strong>Purpose</strong></p> <p>To systematically review available evidence to identify presentation characteristics and risk factors for early or severe presentations of adult patients with CIADM. </p> <p><strong>Data sources</strong></p> <p>Medline and PubMed databases were reviewed. </p> <p><strong>Study selection</strong></p> <p>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. </p> <p><strong>Data extraction</strong></p> <p>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.</p> <p><strong>Data synthesis</strong></p> <p>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).</p> <p><strong>Limitations</strong></p> <p>Reporting of follow up data, lipase and HLA haplotyping was limited.</p> <p><strong>Conclusions</strong></p> <p>CIADM commonly presents in DKA. While T1D autoantibodies are only positive in 40.4%, they associate with earlier, more severe presentations. </p>