Short CommunicationCommercial insulin immunoassays fail to detect commonly prescribed insulin analogues
Section snippets
Insulin analogues
Fifteen different insulin analogues were supplied by the Pharmacy at the Royal Devon and Exeter Hospital, UK. Details of the analogues assessed are provided in Table 1 and the amino acid sequences and structure modifications for each analogue are provided in the online methods.
Results
This cross-reactivity of commercial insulin assays to insulin analogues are shown in Table 1.
Discussion
We have shown that commercially available insulin assays fail to detect many insulin analogues commonly prescribed in the United Kingdom. This is the first study to comprehensively assess all combinations of available exogenous insulins and assays in the UK.
As the complexity of modification to the native human insulin molecule increases, the ability of assays to detect them decreased. Four of the insulins tested (Actrapid®, Humulin® S, Humulin® I and Insulatard®) have identical sequence and
Author contributions
CP, DC, AA, LC, CE, GW, and TM researched the data. CP and TM wrote the manuscript and researched the data.
DC, AA, LC, CE, and GW reviewed/edited the manuscript.
Acknowledgements
TM is funded by National Institute of Health Research CSO Fellowship, this paper's guarantor. DC is funded by the Diabetes Research & Wellness Foundation (RGAG/217). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Technical support was provided by Nicholas Porter (Royal Surrey County Hospital), David Halsall (Addenbrooke's Hospital), Keith Burling (NIHR Cambridge Biomedical Research Centre, Core Biochemical Assay
References (16)
- et al.
Forensic aspects of insulin
Diabetes Res. Clin. Pract.
(2013) - et al.
Insulin immunoassays in the detection of insulin analogues in factitious hypoglycemia
Endocr. Pract.
(2008) - et al.
Emergency management of diabetes and hypoglycaemia
Emerg. Med. J.
(2006) - et al.
Investigation of hypoglycaemia
Clin. Endocrinol.
(1996) - et al.
The biochemical investigation of cases of hypoglycaemia: an assessment of the clinical effectiveness of analytical services
J. Clin. Pathol.
(2002) - et al.
Detection of surreptitious administration of analog insulin to an 8-week-old infant
Pediatrics
(2010) - et al.
Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin
BMJ Open
(2011) - et al.
Cross-reactivity of three recombinant insulin analogs with five commercial insulin immunoassays
Clin. Chem.
(2004)
Cited by (53)
Insulin: Know what your immunoassay detects. Evaluation of two new immunoassays
2023, Clinica Chimica ActaFactitious hypoglycemia in insulin-treated diabetic patients
2023, Annales d'EndocrinologieExplaining Unexplained Hypoglycemia Due To Insulin Analogs
2022, Mayo Clinic ProceedingsPitfalls in Diagnosing Hypoglycemia Due to Exogenous Insulin: Validation and Utility of an Insulin Analog Assay
2022, Mayo Clinic ProceedingsCitation Excerpt :Bovine insulin internal standard (50 μL from 1nmol/L working internal standard solution) was added to each well. Immunoaffinity extraction of insulin from samples was performed using mass spectrometer immunoassay (MSIA) tips derivatized with the insulin antibody that recognize a conserved region within the insulin beta chain found in the therapeutic insulin analogs, endogenous human insulin and in nonhuman animal insulin.9-12 Briefly, ThermoFisher Scientific MSIA-tips are programmed on a Versette Automated Liquid Handling System (ThermoFisher Scientific) to perform aspirate/dispense cycles.
Explaining unexplained hypoglycemia: How LC-MS/MS can help
2022, Practical Laboratory MedicinePattern of C-peptide response to oral glucose tolerance test: Interest and cut-off values
2022, Annales d'EndocrinologieCitation Excerpt :The first one is the evaluation of beta cell function particularly in the context of recently diagnosed type 1 diabetes. C-peptide measurement is there preferred to insulin measurement which is often subject to cross-reactions with the therapeutic insulin analogs used to treat diabetic patients, whatever the immunoassay kit used [13]. In this indication, C-peptide can be measured either in basal fasting conditions and/or after a stimulation such as a mixed meal tolerance test.