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Licensed Unlicensed Requires Authentication Published by De Gruyter October 23, 2013

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

Béatrice Heurtault, Nathalie Reix, Nicolas Meyer, Françoise Gasser, Marie-Josée Wendling, Charline Ratomponirina, Nathalie Jeandidier, Rémy Sapin and Arnaud Agin

Abstract

Background: Over the last few decades, new synthetic insulin analogues have been developed. Their measurement is of prime importance in the investigation of hypoglycaemia, but their quantification is hampered by variable cross-reactivity with many insulin assays. For clinical analysis, it has now become essential to know the potential cross-reactivity of analogues of interest.

Methods: In this work, we performed an extensive study of insulin analogue cross-reactivity using numerous human insulin immunoassays. We investigated the cross-reactivity of five analogues (lispro, aspart, glulisine, glargine, detemir) and two glargine metabolites (M1 and M2) with 16 commercial human insulin immunoassays as a function of concentration.

Results: The cross-reactivity values for insulin analogues or glargine metabolites ranged from 0% to 264%. Four assays were more specific to human insulin, resulting in negligible cross-reactivity with the analogues. However, none of the 16 assays was completely free of cross-reactivity with analogues or metabolites. The results show that analogue cross-reactivity, which varies to a large degree, is far from negligible, and should not be overlooked in clinical investigations.

Conclusions: 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.


Corresponding author: Arnaud Agin, Laboratoire d’Hormonologie, Hôpitaux Universitaires de Strasbourg, 1 place de l’Hôpital, 67091 Strasbourg Cedex, France, Fax: +33 369551885, E-mail: ; and ICube UMR7357 Université de Strasbourg/CNRS, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France

The authors thank G. Coumaros and all the hormonology laboratory technicians for their technical assistance on this project as well as Klump and Guth laboratories (Strasbourg, France). We also specifically acknowledge Nathalie Heider for carefully reviewing the manuscript including English revision.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2013-06-06
Accepted: 2013-09-04
Published Online: 2013-10-23
Published in Print: 2014-03-01

©2014 by Walter de Gruyter Berlin Boston

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