Contribution of the medical laboratory in case of suspected insulin overdose

Insulins (human insulin and insulin analogues), widely used as hypoglycemic agents in the treatment of diabetes, can cause unexplained glycemic disorder. The medical laboratory then has a major role in determining and quantifying insulins. However, this is challenging, since pre-analytic and analytic aspects are specific, and appropriate interpretation is complex. This paper covers the various steps, and their pitfalls, for measuring insulins in blood samples. It provides a practical tool to apply in medical laboratories in case of suspected insulin overdose. Analytic strategy is presented, comparing immunoassays and chromatographic methods coupled to mass spectrometry. Tables summarize the appropriate standardized pre-analytic steps, from sampling to storage, to guarantee reliable measurement, a list of commercial immunoassays that measure insulins (with detailed cross-reactivity and sensitivity), and key parameters for interpretation of results in various unexplained glycemic events. Insulins degradation, adsorption, technical analytic limitations and variability in insulins kinetics are some of the pitfalls in insulins measurement. To avoid misinterpretation of results, a good mastery of the total testing process is required. The role of the medical laboratory is therefore central to provide the essential information to avoid the many pre-analytic and analytic pitfalls associated with the quantification of insulin and its analogues in blood. Finally, the article shows the importance of clinical-biological dialogue in interpreting results.