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

• Published in: Metabolites 2023-01, Vol.13 (1), p.5
• Main Authors: Ward, Liam J, Engvall, Gustav, Green, Henrik, Kugelberg, Fredrik C, Söderberg, Carl, Elmsjö, Albert
• Format: Article
• Language: English
• Subjects: acylcarnitines; Autopsies; Autopsy; biomarkers; Coma; Death; death investigation; Diabetes mellitus; Drug use; forensic science; Glucose; High-performance liquid chromatography; hyperglycemia; Hypoglycemia; Insulin; Insulin resistance; Intoxication; Investigations; Males; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolomics; Metformin; Poisoning; Scientific imaging
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo13010005

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.