Postmortem Metabolomics of Insulin Intoxications and the Potential Application to Find Hypoglycemia-Related Deaths

Postmortem metabolomics can assist death investigations by characterizing metabolic fingerprints differentiating causes of death. Hypoglycemia-related deaths, including insulin intoxications, are difficult to identify and, thus, presumably underdiagnosed. This investigation aims to differentiate insulin intoxication deaths by metabolomics, and identify a metabolic fingerprint to screen for unknown hypoglycemia-related deaths. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry data were obtained from 19 insulin intoxications (hypo), 19 diabetic comas (hyper), and 38 hangings (control). Screening for potentially unknown hypoglycemia-related deaths was performed using 776 random postmortem cases. Data were processed using XCMS and SIMCA. Multivariate modeling revealed group separations between hypo, hyper, and control groups. A metabolic fingerprint for the hypo group was identified, and analyses revealed significant decreases in 12 acylcarnitines, including nine hydroxylated-acylcarnitines. Screening of random postmortem cases identified 46 cases (5.9%) as potentially hypoglycemia-related, including six with unknown causes of death. Autopsy report review revealed plausible hypoglycemia-cause for five unknown cases. Additionally, two diabetic cases were found, with a metformin intoxication and a suspicious but unverified insulin intoxication, respectively. Further studies are required to expand on the potential of postmortem metabolomics as a tool in hypoglycemia-related death investigations, and the future application of screening for potential insulin intoxications.

Automated summary

Postmortem metabolomics can be used to differentiate causes of death, particularly those related to hypoglycemia. This study focused on identifying a metabolic fingerprint for insulin intoxication deaths and screening for unknown hypoglycemia-related deaths. The results showed distinct metabolic differences between insulin intoxication deaths and other groups.