Elsevier

Legal Medicine

Volume 22, September 2016, Pages 23-29
Legal Medicine

Case Report
Usefulness of postmortem biochemistry in identification of ketosis: Diagnosis of ketoacidosis at the onset of autoimmune type 1 diabetes in an autopsy case with cold exposure and malnutrition

https://doi.org/10.1016/j.legalmed.2016.07.006Get rights and content

Highlights

Abstract

A severely malnourished, Japanese female in her twenties was found dead in her apartment. On autopsy, most of the findings from the internal examination were suggestive of hypothermia. Postmortem biochemistry, however, showed severely increased levels of glycated hemoglobin (HbA1c) and blood and urine glucose levels. Levels of acetone, 3-hydroxybutyric acid, and acetoacetate in various body fluids were also highly increased, indicating ketosis. The serum insulin and c-peptide levels were severely low, and subsequent testing was positive for anti-GAD antibodies. Immunohistochemical examination of the pancreatic islet cells revealed few insulin-positive cells but many glucagon-positive cells on staining. Furthermore, slight invasion of CD8-positive lymphocytes in the pancreatic islets of Langerhans was observed. Results of immunostaining of the pancreatic and bronchial epithelial tissues were partly positive for the Influenza A virus. We concluded that severe ketoacidosis associated with rapid-onset hyperglycemia due to autoimmune type 1 diabetes (AT1D) had occurred shortly before death. However, the ketosis was accompanied by hypothermia and malnutrition as well as diabetic ketoacidosis (DKA). Therefore, we retrospectively collected biochemical data on cases of hypothermia and malnutrition and compared them with the present case. Serum glucose, acetone, 3-hydroxybutyric acid, and acetoacetic acid can be used for screening and diagnosis to distinguish DKA from ketosis due to hypothermia and malnutrition. Therefore, in the present case, we diagnosed that the natural cause of death was due to AT1D. In conclusion, screening investigations for relevant biochemical markers can provide essential information for the diagnosis of metabolic disturbances, which fail to demonstrate characteristic autopsy findings.

Introduction

Diabetes mellitus (DM) may cause severe metabolic disturbances, which that can be fatal. These can be difficult to diagnose based on macroscopic and histological findings alone at autopsy [1], [2], [3]. In such cases, postmortem biochemical markers can provide supporting information [1]. When investigating on metabolic and endocrin disorders, a number of postmortem biochemical laboratory procedures have been reported to be useful for autopsy diagnoses [1], [4], [5]. Particularly in the postmortem diagnosis of DM, a common metabolic disease, the main evidence for the diagnosis can be derived from postmortem biochemical parameters [3], [6], [7].

Diabetic ketoacidosis (DKA) at the onset of autoimmune type 1 diabetes (AT1D) is a complication of DM characterized by extreme and rapid progression of hyperglycemia and ketoacidosis due to the destruction of the pancreatic β cells [8], [9]. The clinical diagnosis of DKA at the onset of AT1D can be made when the following biochemical parameters are found: (1) elevation of urinary and/or serum ketone bodies; (2) high plasma and urinary glucose levels (>250 mg/dL and >100 mg/dL, respectively); (3) an anion gap of >12 mEq/L and arterial blood pH of <7.3; and (4) elevation of plasma blood urea nitrogen (BUN) and creatinine levels [8]. Patients diagnosed with DKA at the onset of AT1D are likely to die within 24 h of the onset of hyperglycemia unless they receive immediate treatment for DKA [8]. In forensics, DKA at the onset of AT1D has become more widely recognized as a cause of sudden death [2], [10]. However, methods for the postmortem diagnosis of DKA at the onset of AT1D have not yet been fully established because there are no characteristic anatomical findings.

Here, we report on a postmortem biochemical diagnosis of DKA at the onset of AT1D, which was made in spite of considerable autopsy findings that were suggestive of hypothermia as being the cause of death. We compared these findings to postmortem cases of other ketotic conditions, namely hypothermia and malnutrition. We also considered whether it was possible to use the postmortem biochemical profile for DKA diagnosis and compare it to other ketotic conditions, such as hypothermia and malnutrition.

Section snippets

Case history

A Japanese female in her twenties was found dead in her apartment bathroom by her boyfriend at 7:30 a.m. in early February morning.

Five days earlier, she had had a bicycle accident and received a blow to the right inguinal region, after which she experienced nausea and general malaise. She was absent from work for the following 3 days. On the 4th day, she was found dead in her apartment bathroom. She was nude from the waist down and had fallen while taking a cold-water shower. A gas safety

Discussion

In the present case, most of the macropathological findings on internal examination suggested possible hypothermia (cold exposure) as the cause of death. However, according to the postmortem biochemistry, postmortem HbA1c levels were markedly increased and the glucose levels in the blood of the right heart and urine glucose levels were extremely elevated. HbA1c levels have been reported to stabilize within 72 h postmortem [28], while blood glucose concentrations have been reported to decrease

Conflict of interest statement

The authors declare that they have no proprietary, financial, professional, or other personal interest of any kind in any product, service, and/or company that could be construed as influencing this current manuscript entitled “Usefulness of postmortem biochemistry in forensic autopsy: diagnosis of ketoacidosis at the onset of autoimmune type 1 diabetes in an autopsy case with cold exposure and malnutrition.”

References (45)

  • B.L. Zhu et al.

    Postmortem serum uric acid and creatinine levels in relation to the causes of death

    Forensic Sci. Int.

    (2002)
  • T. Ishikawa et al.

    Comparative evaluation of postmortem serum concentrations of neopterin and C-reactive protein

    Forensic Sci. Int.

    (2008)
  • M. Fukuda et al.

    Mitochondrial DNA mutations are associated with both decreased insulin secretion and advanced microvascular complications in Japanese diabetic subjects

    J. Diabetes Complications

    (1999)
  • M. Tominaga et al.

    Evaluation of postmortem drug concentrations in cerebrospinal fluid compared with blood and pericardial fluid

    Forensic Sci. Int.

    (2015)
  • K. Uemura et al.

    Biochemical blood markers and sampling sites in forensic autopsy

    J. Forensic Leg. Med.

    (2008)
  • J. Hockenhull et al.

    Investigation of markers to indicate and distinguish death sue to alcoholic ketoacidosis, diabetic ketoacidosis and hyperosmolar hyperglycemic state using post-mortem samples

    Forensic Sci. Int.

    (2012)
  • C. Palmiere et al.

    Postmortem diagnosis of unsuspected diabetes mellitus

    Forensic Sci. Int.

    (2013)
  • T. Keltanen et al.

    Measuring postmortem glycated hemoglobin – a comparison of three methods

    Leg. Med. (Tokyo)

    (2013)
  • Keltanen et al.

    Measuring postmortem glycated hemoglobin – a comparison if three methods

    Leg. Med. (Tokyo)

    (2013)
  • B.L. Zhu et al.

    Postmortem serum uric acid and creatinine levels in relation to the causes of death

    Forensic Sci. Int.

    (2002)
  • J. Kanetake et al.

    The relationship of a high level of serum beta-hydroxybutyrate to cause of death

    Leg. Med. (Tokyo)

    (2005)
  • E. Osuna et al.

    Postmortem vitreous humor beta-hydroxybutyrate: its utility for the postmortem interpretation of diabetes mellitus

    Forensic Sci. Int.

    (2005)
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