Endocrine Abstracts

Preparations of recombinant insulin and insulin analogues are used in the treatment of insulin-dependent diabetes. Recombinant insulin that corresponds to the human sequence might be expected to cross-react extensively with insulin assays. Insulin analogues contain modifications that alter their action profiles and may therefore interact unpredictably with detection antibodies. In the differential diagnosis of hypoglycaemia it is important to be aware of the extent of the cross-reactivity of different insulin preparations with the insulin assay in use.

Ten commercial insulin preparations were investigated: Actrapid, NovoRapid, Levemir and Insulatard (Novo Nordisk); Humulin S, Humalog, Humulin M3 and Humulin I (Lilly); Apidra and Lantus (Sanofi-Aventis). A measure of cross-reactivity in the Architect Insulin immunoassay (Abbott) was obtained by means of an experiment designed to measure recovery in pooled human serum. The insulin preparations were sequentially diluted in insulin-depleted human serum to attain a stock material that was used to spike a pooled human serum (post-prandial) to final nominal concentrations of 20 and 100 mU/l. The Architect Insulin immunoassay is standardised against the WHO International Reference Preparation material 66/304.

All insulin preparations cross-reacted with the Architect insulin assay, but to varying degrees. The human sequence insulin preparations (Actrapid, Humulin S, Insulatard, Humulin I and Humulin M3) demonstrated similar levels of recovery (between 81 and 89%), indicating extensive cross-reactivity in the insulin assay. The insulin analogues (NovoRapid, Apidra, Humalog, Levemir and Lantus) demonstrated variable degrees of recovery. Apidra, a rapid-acting insulin, showed the lowest recovery at 12 and 14%, while Lantus, an ultra-long acting insulin, over-recovered at 127 and 140%, demonstrating significant cross-reactivity with the assay.

Commercially available insulin preparations cross-react with the Architect Insulin immunoassay. Interpretation of insulin levels in hypoglycaemia in the context of exogenous insulin administration requires knowledge of the cross-reactivity of such insulin preparations with the assay.