Sydow Konrad, Kueting Theresa, Musshoff Frank, Madea Burkhard, Hess Cornelius
Institute of Forensic Medicine, University of Bonn, Stiftsplatz 12, D-53111 Bonn, Germany.
Forensic Toxicological Center, Bayerstraße 53, 80335 Munich, Germany.
Forensic Sci Int. 2018 Aug;289:397-407. doi: 10.1016/j.forsciint.2018.06.021. Epub 2018 Jun 23.
Since there are no characteristic morphological findings post mortem diagnosis of diabetes mellitus and identification of diabetic coma need to be confirmed by suitable biomarkers. The postmortem identification of preexisting hyperglycemia or diabetic coma can be difficult if the matrices for the determination of the established biomarkers are not available or the obtained results are close to the established cut-off values. 1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of glucose, competes with glucose for renal reabsorption. Therefore low serum concentrations of 1,5-AG, reflect hyperglycemic excursions over the prior 1-2 weeks in diabetic patients. To evaluate postmortem 1,5-AG concentrations in vitreous humor (VH) and cerebrospinal fluid (CSF), a liquid chromatographic mass spectrometric method for the quantification of 1,5-AG in VH and CSF was developed and validated according to international guidelines. In order to establish a cut-off for the identification of an ante mortem existing diabetes and the diagnosis of a diabetic coma in deceased the relationships between 1,5-AG concentrations in VH and CSF to other diabetes associated biochemical parameters of 47 non-diabetic, 86 diabetic and 9 cases of diabetic coma were examined. In 83 of these cases, both matrices could be obtained and analyzed. Comparisons of the respective HbA1c, Glucose in VH or Sum-formula of Traub to 1,5-AG concentrations in VH and CSF resulted in correlation coefficients R≤0.2. For the application of 1,5-AG concentrations in VH against CSF, a linear regression gave a correlation coefficient of R=0.955. Comparable linear correlations of 1,5-AG concentrations could be observed between VH and femoral venous blood (FVB) (R=0.839) as well as between CSF and FVB (R=0.756). Due to overlapping concentration ranges, the determination of a reliable cut-off for the differentiation of diabetic disease to diabetic coma cases was not possible. However, the 1,5-AG concentrations in VH and CSF in cases of deceased diabetics were significantly lower (p<0.05) than in non-diabetic deceased and therefore indicate a pre-existing diabetes or even a diabetic coma as the cause of death.
由于糖尿病患者死后没有特征性的形态学表现，糖尿病昏迷的诊断需要通过合适的生物标志物来确认。如果无法获得用于测定既定生物标志物的样本基质，或者所获得的结果接近既定的临界值，那么生前存在高血糖或糖尿病昏迷的死后鉴定可能会很困难。1,5-脱水葡萄糖醇（1,5-AG）是葡萄糖的1-脱氧形式，它与葡萄糖竞争肾脏重吸收。因此，糖尿病患者血清中低浓度的1,5-AG反映了过去1-2周内的血糖波动。为了评估玻璃体液（VH）和脑脊液（CSF）中死后1,5-AG的浓度，根据国际指南开发并验证了一种用于定量VH和CSF中1,5-AG的液相色谱质谱法。为了确定用于识别生前存在的糖尿病和诊断死者糖尿病昏迷的临界值，研究了47例非糖尿病患者、86例糖尿病患者和9例糖尿病昏迷患者的VH和CSF中1,5-AG浓度与其他糖尿病相关生化参数之间的关系。在这些病例中，有83例可以获得并分析两种样本基质。将各自的糖化血红蛋白（HbA1c）、VH中的葡萄糖或特劳伯总和公式与VH和CSF中的1,5-AG浓度进行比较，相关系数R≤0.2。对于将VH中的1,5-AG浓度与CSF中的浓度进行比较，线性回归得出相关系数R=0.955。在VH和股静脉血（FVB）之间（R=0.839）以及CSF和FVB之间（R=0.756）可以观察到1,5-AG浓度具有类似的线性相关性。由于浓度范围重叠，无法确定区分糖尿病和糖尿病昏迷病例的可靠临界值。然而，糖尿病死者病例中VH和CSF中的1,5-AG浓度显著低于非糖尿病死者（p<0.05），因此表明生前存在糖尿病甚至糖尿病昏迷是死亡原因。
