Heterogeneity between insulin and proinsulin in the potency for insulin autoantibodies (IAA) in newly diagnosed type 1 diabetes children

INTRODUCTION: Autoantibodies against insulin (IAA) are early appearing markers of autoimmunity against the pancreatic islet beta cells and predict progression to type 1 diabetes if additional islet autoantibodies also develop. It is still controversial if proinsulin rather than insulin is the primary autoantibody. METHODS: The aim of the present study was to compare the half-maximal concentration (IC50) between insulin and proinsulin to displace the binding of insulin to insulin autoantibodies (IAA) in the Antibody Detection by Agglutination PCR (ADAP) assay. RESULTS: IC50 as a measure of potency to displace insulin binding to IAA was determined in 36 newly diagnosed type 1 diabetes children. The ability of either insulin or proinsulin to displace IAA was heterogenous. Proinsulin curves were consistently right-shifted relative to insulin as median IC50 was 21.0 nM (IQR 14.9-25.1) for insulin and 26.1 nM (IQR 12.3-37.5) for proinsulin. A significant age × sex interaction was observed (F (1,31) = 14.3, p < 0.001), indicating that IC50 for both insulin and proinsulin increased with age in boys but decreased in girls. It may reflect whether autoantibodies to insulin or proinsulin was first appearing or of variable maturation from the time of initiation through progression to clinical onset. CONCLUSION: It was concluded that the IC50 of insulin and proinsulin for IAA was comparable in children with newly diagnosed type 1 diabetes. The ADAP IAA assay should prove useful to determine whether insulin or proinsulin is the primary target at the time of seroconversion to IAA.