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Pitfalls in Diagnosing Hypoglycemia Due to Exogenous Insulin

Validation and Utility of an Insulin Analog Assay
Published:October 07, 2022DOI:https://doi.org/10.1016/j.mayocp.2022.07.021

      Abstract

      Objective

      To overcome the limitations of commercially available insulin immunoassays which have variable detection of analog insulin and can lead to clinically discordant results and misdiagnosis in the workup of factitious hypoglycemia.

      Patients and Methods

      We performed analytical validation of a liquid chromatography high resolution accurate mass (LC-HRAM) immunoassay to detect insulin analogs. We completed clinical assessment using a large cohort of human serum samples from 78 unique individuals, and subsequently used the assay in the evaluation of eight individuals with high diagnostic suspicion for factitious hypoglycemia.

      Results

      The performance characteristics show that the LC-HRAM immunoassay can be applied to detect five commonly used synthetic insulin analogs (lispro, glulisine, aspart, glargine metabolite, and detemir) in human serum. Our clinical cases show that this assay could be used in the diagnosis of factitious hypoglycemia by identifying the analog insulin(s) in question.

      Conclusion

      The LC-HRAM immunoassay reported here overcomes a gap in our diagnostic pathway for hypoglycemia. The results obtained from our studies suggest that this method is appropriate for use in clinical laboratories when factitious hypoglycemia is considered as a differential diagnosis.

      Abbreviations and Acronyms:

      CMSL (Clinical Mass Spectrometry Laboratory), LC-HRAM (liquid chromatography high resolution accurate mass), MS (mass spectrometry)
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      Linked Article

      • Explaining Unexplained Hypoglycemia Due To Insulin Analogs
        Mayo Clinic ProceedingsVol. 97Issue 11
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          Hypoglycemia is a potentially life-threatening condition that requires urgent medical attention. Most hypoglycemia in patients with diabetes is related to medication use, and recent studies have indicated the contributions of insulin analogs in cases of hypoglycemia.1,2 Even in patients without diabetes, it is important to exclude insulin administration as a cause of hypoglycemia, yet detection of insulin analogs is not straightforward. The small structural changes that result in favorable pharmacokinetics of insulin analogs also affect the detection of analog insulin by immunoassays, culminating in varying results from different commercially available assays.
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