Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
Forensic Medicine Laboratory, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
Sci Rep. 2024 Aug 16;14(1):18972. doi: 10.1038/s41598-024-68973-9.
Postmortem metabolomics holds promise for identifying crucial biological markers relevant to death investigations and clinical scenarios. We aimed to assess its applicability in diagnosing hypothermia, a condition lacking definitive biomarkers. Our retrospective analysis involved 1095 postmortem femoral blood samples, including 150 hypothermia cases, 278 matched controls, and 667 randomly selected test cases, analyzed using UHPLC-QTOF mass spectrometry. The model demonstrated robustness with an R2 and Q2 value of 0.73 and 0.68, achieving 94% classification accuracy, 92% sensitivity, and 96% specificity. Discriminative metabolite patterns, including acylcarnitines, stress hormones, and NAD metabolites, along with identified pathways, suggest that metabolomics analysis can be helpful to diagnose fatal hypothermia. Exposure to cold seems to trigger a stress response in the body, increasing cortisol production to maintain core temperature, possibly explaining the observed upregulation of cortisol levels and alterations in metabolic markers related to renal function. In addition, thermogenesis seems to increase metabolism in brown adipose tissue, contributing to changes in nicotinamide metabolism and elevated levels of ketone bodies and acylcarnitines, these findings highlight the effectiveness of UHPLC-QTOF mass spectrometry, multivariate analysis, and pathway identification of postmortem samples in identifying metabolite markers with forensic and clinical significance. The discovered patterns may offer valuable clinical insights and diagnostic markers, emphasizing the broader potential of postmortem metabolomics in understanding critical states or diseases.
死后代谢组学有望鉴定与死亡调查和临床情况相关的关键生物标志物。我们旨在评估其在诊断体温过低（缺乏明确生物标志物的病症）中的适用性。我们的回顾性分析涉及 1095 例死后股动脉血样本，包括 150 例体温过低病例、278 例匹配对照和 667 例随机选择的测试病例，使用 UHPLC-QTOF 质谱法进行分析。该模型具有稳健性，R2 和 Q2 值分别为 0.73 和 0.68，达到 94%的分类准确性、92%的灵敏度和 96%的特异性。鉴定出的具有区分性的代谢物模式，包括酰基辅酶 A、应激激素和 NAD 代谢物以及相关途径，表明代谢组学分析有助于诊断致命性体温过低。暴露于寒冷似乎会引发体内应激反应，增加皮质醇的产生以维持核心体温，这可能解释了观察到的皮质醇水平上调以及与肾功能相关的代谢标志物的改变。此外，产热似乎会增加棕色脂肪组织的代谢，导致烟酰胺代谢的改变和酮体和酰基辅酶 A 水平的升高，这些发现突出了 UHPLC-QTOF 质谱法、死后样本的多变量分析和途径鉴定在鉴定具有法医学和临床意义的代谢物标志物方面的有效性。所发现的模式可能提供有价值的临床见解和诊断标志物，强调死后代谢组学在理解关键状态或疾病方面的更广泛潜力。
