Aims/hypothesis  

Insulin autoantibodies (IAA) precede and predict the onset of type 1 diabetes, but not all children with IAA develop the disease. In affected families, IAA affinity can identify IAA-positive children who are more likely to progress to diabetes. The purpose of this study was to determine whether affinity is a useful marker to stratify type 1 diabetes risk in IAA-positive children from the general population.

Methods  

IAA affinity was determined by competitive binding to ¹²⁵I-insulin with increasing concentrations of cold insulin and with cold proinsulin in sera from 46 IAA-positive children identified in the Karlsburg Type 1 Diabetes Risk Study of a Normal Schoolchild Population in north-eastern Germany.

Results  

IAA affinity ranged between 5×10⁶ and 1.2×10¹¹ l/mol. IAA affinity was higher in 24 children who developed multiple islet autoantibodies or diabetes (median 3.5×10⁹ l/mol; interquartile range [IQR] 2.1×10⁹ to 2.1×10¹⁰ l/mol) than in 22 children who did not develop multiple islet autoantibodies or diabetes (median 1.3×10⁸ l/mol; IQR 3.8×10⁷ to 7.2×10⁸ l/mol; p<0.0001). Using a threshold of 10⁹ l/mol, 22 of the 24 children who developed multiple islet autoantibodies or diabetes were correctly identified by high-affinity IAA and 18 of 22 who did not develop multiple islet autoantibodies or diabetes were correctly identified by low-affinity IAA. IAA affinity was significantly higher in samples with proinsulin reactive IAA (p<0.0001).

Conclusions/interpretation  

IAA affinity measurement provides robust identification of IAA associated with high diabetes risk.