Insights into insulin analog cross-reactivity: a comparative study of Siemens Atellica and LC-MS/MS

Abstract Background To address the challenges posed by inconsistent detection of analog insulin in commercially available insulin immunoassays, resulting in potential discrepancies in clinical findings and misdiagnosis during the investigation of factitious hypoglycemia., we aimed to evaluate the ability of the Siemens Atellica automated immunoassay to detect insulin analogs compared with LC-MS/MS. Methods Five insulin analogs were analyzed at 10 ng/mL spiked into serum samples, with recombinant human insulin as positive controls. Insulin and C-peptide assays were performed using Siemens Atellica and LC-MS/MS. Recovery rates were calculated. Results Siemens Atellica immunoassay demonstrated robust cross-reactivity (92–121%) of insulin analogs. In contrast, glargine was detected by LC-MS/MS but other analogs were not observed (<10% recovery). Conclusion Our results indicate that the insulin assay conducted on the Siemens Atellica platform could be used to diagnose factitious hypoglycemia by detecting the specific insulin analogs involved. The findings from our studies indicate the suitability of this method for clinical laboratory use in cases where factitious hypoglycemia is under consideration as a potential diagnosis. Clinicians should take these results into account when interpreting insulin measurements, particularly in instances where insulin analog overdose is suspected.