The role of the Armanni-Ebstein lesion, hepatic steatosis, biochemical analysis and second generation anti-psychotic drugs in fatal diabetic ketoacidosis

Kodikara, Sarathchandra; Paranitharan, P.; Pollanen, Michael S.

doi:10.1016/j.jflm.2012.05.003

Cited by 23 publications

(23 citation statements)

References 12 publications

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“…4a). Diffuse fatty changes in the renal tubules and scattered mild fatty changes were also observed in the liver cells [2,14,15]. In the present case, no signs of viral or bacterial pneumonia were observed in the lung tissue.…”

Section: Histopathological Findingssupporting

confidence: 53%

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

et al. 2016

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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.

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Section: Histopathological Findingssupporting

confidence: 53%

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

et al. 2016

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“…In the current study, basal vacuolizations were seen at a β‐hydroxybutyrate level of 1.16 mmol/L with the highest level being 29.35 mmol/L, representing a wider range than previously reported. Three prior studies reported on vitreous acetone levels which ranged from 0.5 to 12.8 mmol/L in decedents with basal vacuolization who died of starvation and diabetic ketoacidosis . At Forensic Science SA, acetone can be detected in the blood on toxicological screening, but it does not appear as a quantitative measurement.…”

Section: Discussionmentioning

confidence: 99%

“…Intravacuolar lipids have been demonstrated on Oil Red O staining and electron microscopy . Recently, this pattern of vacuolization has been referred to as the “Armanni–Ebstein phenomenon” , possibly after a report on autopsy cases of diabetics with Armanni–Ebstein lesions by Ritchie and Waugh who mentioned fine basal fat droplets in the cytoplasm of proximal tubules not affected by the Armanni–Ebstein lesion in two of their five cases . However, a recent review of the literature showed that the originally reported Armanni–Ebstein lesion instead represented a clear‐cell change with intracytoplasmic glycogen accumulation in hyperglycemic states, therefore suggesting that basal vacuolizations should be recognized as a distinct entity from the Armanni–Ebstein lesion on the basis of different morphology, constituents, and etiology .…”

mentioning

confidence: 98%

Basal Vacuolization in Renal Tubular Epithelial Cells at Autopsy and Their Relation to Ketoacidosis

Zhou

Yool

Byard

2017

Journal of Forensic Sciences

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Basal vacuolization of renal tubular epithelial cells is a useful postmortem marker for ketoacidosis. To investigate its incidence and relationship to the severity of ketoacidosis, 158 autopsy cases with elevated β-hydroxybutyrate (>1 mmol/L) over a 7-year-period were retrospectively reviewed. Sixty-eight cases (43%) exhibited basal vacuolizations (vitreous β-hydroxybutyrate: 1.16-29.35 mmol/L, mean 10.28 mmol/L), and 90 cases (57%) did not (vitreous β-hydroxybutyrate: 1.03-13.7 mmol/L, mean 2.84 mmol/L). Quantitative analysis revealed on average a fourfold elevation in β-hydroxybutyrate in cases with basal vacuolizations compared to those without; 10.3% of cases with β-hydroxybutyrate concentrations between 1.01 and 2.00 mmol/L had basal vacuolizations, and this incidence increased to 33.3% with concentrations between 4.01 and 6.00 mmol/L. A marked increase in incidence to >70% was observed with concentrations >6.00 mmol/L, and basal vacuoles were invariably present (100%) with concentrations >14.01 mmol/L. This study demonstrates that basal vacuolizations are a sensitive marker for significant ketoacidosis and reaffirms its use as an indicator for likely cases of fatal ketoacidosis at autopsy.

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“…Limited autopsy studies demonstrated that tubular vacuolation of the kidneys -so called Armanni-Ebstein lesions -strongly indicate death in diabetic coma [17]. As Armanni-Ebstein lesions point to poorly controlled diabetes further biochemical analysis of body fluids is indispensable in order to prove diabetic coma as specific cause of death [18,19].…”

Section: Postmortem Biochemistry In Blood and Autoptic Findings Of Lementioning

confidence: 99%

Postmortem Analysis of Vitreous Humor For Detection of Antemortem Disorders in Glucose Metabolism. An Old Method Revisited

Holstein¹,

Titze

Heß

2018

Exp Clin Endocrinol Diabetes

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It has been estimated that 15% up to one third of cases of deaths due to diabetic ketoacidosis occur in individuals with so far unknown diabetes. Moreover, cardiac arrhythmias that occur during nocturnal hypoglycaemia include bradycardia and ectopics that may provoke lethal arrhythmias. As postmortem capillary glucose concentrations have no diagnostic value, the postmortem forensic proof of hyperglycaemia or hypoglycaemia remains a challenge. The established but rarely applied method of postmortem determination of glucose and lactate in vitreous humor with or without calculation of the sum formula of Traub could provide reliable exclusion or proof of severe antemortem disorders in glucose metabolism. To date, diagnostic puncture of vitreous humor is more established for the postmortem detection of diabetic ketoacidosis than for the exclusion or proof of lethal hypoglycaemia. Vitreous humor is protected from postmortem degradation and contamination due to its isolated localization. The autolytic process in vitreous humor is considerably delayed compared to blood or liquor. In vitreous humor also the triggering agent of hypoglycaemia (insulin, insulin analogues) is easier to be detected than in blood since insulins are very unstable in postmortem blood. Furthermore, parameters of long term glycaemic control such as 1,5-anhydroglucitol, HbA1c and fructosamine can be determined in vitreous humor. However, limitations and interference factors of this method should be carefully considered. So far, clinical diabetology has taken no broad notice of this useful forensic procedure.

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The role of the Armanni-Ebstein lesion, hepatic steatosis, biochemical analysis and second generation anti-psychotic drugs in fatal diabetic ketoacidosis

Cited by 23 publications

References 12 publications

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

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

Basal Vacuolization in Renal Tubular Epithelial Cells at Autopsy and Their Relation to Ketoacidosis

Postmortem Analysis of Vitreous Humor For Detection of Antemortem Disorders in Glucose Metabolism. An Old Method Revisited

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