Comparison of two insulin assays for first-phase insulin release in type 1 diabetes prediction and prevention studies.

Background: Detection of below-threshold first-phase insulin release or FPIR (1+3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace the less practical but current standard of a radioimmunoassay (RIA) for FPIR.

Methods: One hundred thirty-three islet autoantibody positive relatives of persons with type 1 diabetes underwent 161 IVGTTs. Insulin concentrations were measured by both assays in 1056 paired samples. A rule classifying FPIR (below-threshold, above-threshold, uncertain) by the IEMA was derived and validated against FPIR by the RIA.

Results: The insulin IEMA-based rule accurately classified below- and above-threshold FPIRs by the RIA in 110/161 (68%) IVGTTs, but was uncertain in 51/161 (32%) tests for which FPIR by RIA is needed. An uncertain FPIR by the IEMA was more likely among below-threshold vs above-threshold FPIRs by the RIA (64% [30/47] vs. 18% [21/114], respectively; p<0.05).

Conclusions: An insulin IEMA for FPIR in subjects at risk for type 1 diabetes accurately determined below- and above-threshold FPIRs in 2/3 of tests relative to the current standard of the insulin RIA, but could not reliably classify the remaining FPIRs. TrialNet is limiting the insulin RIA for FPIR to the latter given the practical advantages of the more specific IEMA.