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.

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