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

Abstract

This study has established the cross-reactivity of five insulin analogues and two glargine metabolites using 16 immunoassays to facilitate the choice of the immunoassay(s) and to provide sensitive and specific analyses in clinical routine or investigation.

Cross-reactivity of insulin analogues with three insulin assays

“…Owen and Roberts perform their study in FBS and not in human serum, which probably does not possess the same activity as the human carboxypeptidase and therefore our results (performed in human serum) match Agin et al's. 3,10 Recently, Heurtault et al 20 have conducted an extensive study with similar results.…”

“…The simultaneous presence of the primary ligand (human insulin) and of the cross-reactant may have miscellaneous effects depending on the assay and on the analogue assessed. 20 The aim of this study was to determine the interference caused by the new analogues (lispro, aspart, detemir, glargine, and glulisine) in three different automated analysers.…”

Peripheral IV Insulin Infusion Infiltration Presenting as “Insulin Resistance”

“…At our institution, serum insulin is processed weekly with same day results, although with laboratory approval, immediate processing is available. In addition, if the patient had previously received exogenous insulin, then endogenous insulin antibodies may interfere with the insulin assay (7). …”

Fatal Insulin Overdoses: Case Report and Update on Testing Methodology

“…Two different platforms were used to verify the insulin results. The Roche e411 assay is known to have a 2% cross‐reactivity with most insulin analogs , whereas the Siemens Centaur assay has moderate‐to‐good reactivity with most commercially available analogs except glulisine , explaining the low and very high levels detected, respectively. Different insulin immunoassays have variable cross‐reactivities with synthetic insulin, ranging from 0% to 264% ; this highlights the importance of understanding the specificity of the insulin assay being used and which analogs it is able to detect.…”

“…The Roche e411 assay is known to have a 2% cross‐reactivity with most insulin analogs , whereas the Siemens Centaur assay has moderate‐to‐good reactivity with most commercially available analogs except glulisine , explaining the low and very high levels detected, respectively. Different insulin immunoassays have variable cross‐reactivities with synthetic insulin, ranging from 0% to 264% ; this highlights the importance of understanding the specificity of the insulin assay being used and which analogs it is able to detect. Other possible limitations with immunoassays, in general, include interference with anti‐insulin antibodies, lack of an international standardized methodology, and inability to identify the specific kind of insulin .…”