Cross-reactivity of 12 recombinant insulin preparations in the Beckman Unicel DxI 800 insulin assay

Abstract

Background: Insulin analogues used in the treatment of insulin-dependent diabetes may result in hypoglycaemia; however, these preparations show variable cross-reactivity in many insulin assays. In order to investigate a suspected insulin overdose, it is therefore essential to characterize the cross-reactivity of these preparations in insulin assays. Methods: The cross-reactivity of 12 commercial insulin preparations was assessed on the Beckman DxI analyser, by comparison with the insulin calibration curve corresponding to the midpoint of the dose-response curve. This was achieved by manually plotting the relative light units generated by the analyser for each preparation. Results: All 12 insulin preparations examined showed significant cross-reactivity with the Beckman DxI insulin assay, with 11 of the insulin preparations demonstrating cross-reactivity of 83% or greater. The lowest cross-reactivity was observed with detemir with a value of 47.6%. Conclusion: When investigating hypoglycaemia it is important to be aware of the cross-reactivity of the recombinant insulin analogues in insulin assays. This study has established the cross-reactivity of 12 preparations in the Beckman DxI insulin assay.

Commercial insulin immunoassays fail to detect commonly prescribed insulin analogues

“…Previous studies have demonstrated that for several analogues, including insulins lispro and aspart, some commercial immumoassays do not detect the presence of analogues in spiked serum (8)(9)(10)(11)(12). In many cases, this information is not provided to clinical laboratories as part of the manufacturer's instructions and there has been no systematic assessment of crossreactivity of the many commercial analogues available with the insulin assays used in clinical laboratories.…”

Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification

“…Lack of control of crossreactivity of insulin analogues leads to misdiagnosis with clearly established clinical impact. As a consequence, different studies focused on the determina tion of the crossreactivity of various analogues using one particular insulin assay [14,[17][18][19][20][21][22]. Those works showed, for example, that the Architect insulin assay (Abbott Labo ratories) had a low crossreactivity to the insulin analogue aspart, whereas it detected lispro and glargine, in con centrations as high as the theoretical concentrations [12].…”

Clinical Utility and Cross-Reactivity of Insulin and C-Peptide Assays by the Lumipulse G1200 System

“…Previous studies showed variable cross-reactivity of insulin analogues; some assays showed high cross-reactivity with almost all analogues, while some showed cross-reactivity with almost none [ 10 11 12 13 24 25 29 30 31 32 33 34 ]. Parfitt et al [ 25 ] reported that a single amino acid change could produce significant cross-reactivity in some insulin assays, and cross-reactivity of analogues with up to three amino acid substitutions relative to human insulin, such as insulin glargine, was highly variable across assay platforms.…”