Detection of diabetic metabolism disorders post-mortem--forensic case reports on cause of death hyperglycaemia.

Diabetic coma is the most severe form of hyperglycaemic metabolic disorders. The post-mortem diagnosis of this disorder of glucose metabolism can be difficult and vague due to a lack of characteristic morphological findings. Six death cases caused by diabetic coma are described with special focus on biochemical (and histological) findings. The possible glycaemia markers glucose, lactate, HbA1c, fructosamine, anhydroglucitol, and ketone bodies were measured and the usefulness of these parameters is evaluated and discussed. Estimations of glucose concentrations in vitreous humour or cerebrospinal fluid and of ketone bodies in blood or other matrices are obligatory while measurements of HbA1c, fructosamine, or anhydroglucitol can only provide additional information on the long-term adjustment of diabetes in the deceased. Lactate concentrations (addition of glucose and lactate levels to form the sum formula of Traub) do not give more information than the glucose concentration itself and can be therefore omitted.

[Post-mortem diagnosis of diabetic crisis in the presence of suspicious findings at the scene]. / Postmortale Diagnose diabetischer Stoffwechselentgleisungen bei verdächtigen Auffindungssituationen.

In Germany, approximately 8 million people suffer from diabetes mellitus, of which over 90% have type 2 diabetes. Worldwide, there are around 246 million people with diabetes mellitus. As diabetes is often symptomless for a long time, around 2.5% of the population have diabetes without knowing it. Diabetic coma is a life-threatening complication, which affects up to 1.2% of all diabetics annually and is associated with a mortality rate of 20-25%. Since in 25% of patients the diabetic coma is the first manifestation of the disease, a valid post-mortem biochemical method for the diagnosis of the metabolic crisis is very important. The article presents cases from the authors' own autopsy material showing that the analysis of the vitreous humour is indispensable for the reconstruction of the events leading to death even in cases in which the cause of death is seemingly clear.

Residual dysphasia after severe hypoglycemia in a patient with immune-mediated primary adrenal insufficiency and type 1 diabetes mellitus: case report and systematic review of the literature.

OBJECTIVE: To describe a 24-year-old patient with immune-mediated primary adrenal insufficiency and type 1 diabetes mellitus (T1DM) receiving intensive diabetes management who was comatose at presentation attributable to severe hypoglycemia and had residual dysphasia after recovery and to summarize the related literature. METHODS: We present a case report and the findings on systematic review of the pertinent literature to identify the cumulative incidence of severe hypoglycemia with use of intensive insulin therapy in patients with primary adrenal insufficiency and T1DM and to determine the incidence of dysphasia after severe hypoglycemia. RESULTS: After 5 days of mechanical ventilation, our patient was revived. He had severe dysphasia after recovery of consciousness. Magnetic resonance imaging of the brain revealed encephalomalacia in the left temporal, frontal, and parietal lobes. After 6 years of follow-up, he continues to have residual deficits of expressive dysphasia and difficult-to-control seizures but no other neurologic disorders. Systematic review of the literature revealed that studies from the 1950s reported mortality due to hypoglycemia in such a cohort, but no recent studies have described the cumulative incidence of severe hypoglycemia in a cohort of patients with primary adrenal insufficiency and T1DM. To the best of our knowledge, we report the first findings on magnetic resonance imaging of the head in such a patient. CONCLUSION: Fortunately, residual dysphasia is an infrequent outcome after severe hypoglycemia.

Diffusion-weighted MR imaging in early diagnosis and prognosis of hypoglycemia.

SUMMARY: We describe 2 cases of diffusion-weighted (DW) MR imaging in hypoglycemic coma. One patient, with diffuse cortical lesions, had a poor outcome, but the other, with transient white matter abnormalities, made a complete recovery. The distinctive patterns of DW MR imaging abnormalities in hypoglycemic patients should be recognized and may be a predictor of clinical outcome.

[Biochemical analysis of the vitreous body of the eye in post-mortem diagnosis of diabetic coma].

The biochemical test of the vitreous body (VB) may be used in post-mortem diagnosis of diabetes mellitus and diabetic coma. Concentrations of glucose, lactate, keton bodies in the VB of the eye do not depend on duration of post-mortem period. Methods of diagnosis of hyperglycemic, hypoglycemic and ketoacidotic comas in the postmortem period are proposed. VB glucose over 17 mmol/l is a specific marker indicating death due to diabetic coma with hyperglycemia. Blood lactate under 16 mmol/l and glucose absence in the VB specifically mark death of hypoglycemic coma. In death of diabetic coma with ketoacidosis, a sharp rise in the level of VB ketonic bodies was observed.

Glycolysis and oxidtion enzyme activity in rat brain during insulin-induced hypoglycemia against the background of alloxan-induced diabetes mellitus.

Insulin-induced hypoglycemic coma in animals with alloxan diabetes was observed at a higher basal glucose level in the blood compared to healthy animals. It was associated with inhibition of glycolysis and glycogenolysis and decreased activities of succinate dehydrogenase and glutamate dehydrogenase in the cerebral hemispheres and brainstem.

[Diffusion-weighted magnetic resonance imaging in hypoglycemic coma]. / Intérêt de l'IRM de diffusion dans le coma hypoglycémique.

Hypoglycemia is a classic cause of coma and can result in irreversible neuronal loss. Until now, the main prognostic factors were depth of hypoglycemia and duration of coma. We report the case of a 55-Year-old woman who suffered severe hypoglycemic coma with abnormal cortico- subcortical diffusion weighted MR images. These MRI abnormalities preceded severe atrophy of these cerebral areas. This findings suggests that diffusion abnormalities in hypoglycemic coma may be related to neuronal loss and may thus have prognostic value.

Accumulation of triglycerides in the proximal tubule of the kidney in diabetic coma.

AIMS: The present study was initiated by a very recent histochemical observation of lipid accumulation in the renal cortex of a woman who died in a diabetic coma. Two older reports of lipid accumulation in the kidneys of patients who died, most likely in a state of non-regulated diabetes, supported this observation. We have examined whether lipid accumulation in the renal cortex is characteristic of diabetic coma and, if so, which type of lipid accumulates. METHODS: Three groups were studied. Ten subjects who died in a diabetic coma, eight diabetics who died of known causes unrelated to diabetes, and seven normal control subjects without any diagnosed diabetes who died of known causes. All were subjected to histological examination for lipid accumulation in the renal cortex. Detailed analysis of cortex lipids was performed for two of the subjects who died in a diabetic coma and all diabetic controls as well as non-diabetic control subjects. RESULTS: All subjects who died in a diabetic coma showed vacuolar lesions staining strongly for lipid in the proximal tubules. Neither normal controls nor non-coma diabetics showed these lesions. Compared with normal controls, renal cortex lipid was about tripled in the two analysed diabetic coma subjects due to 60-100-fold increases of triglycerides. The non-coma diabetics did not differ from the other controls with respect to triglycerides or other types of lipid, except that cholesteryl esters were elevated, though still a quantitatively minor component. CONCLUSION: Our findings strongly indicate that vacuolar lesions in the proximal tubules are characteristic of diabetic coma and that they are caused by accumulated triglycerides. Therefore, histological examination of renal cortex using a lipid stain may be a useful forensic tool in establishing diabetic coma as the cause of death.

Lipids in the proximal tubules of the kidney in diabetic coma.

Vacuolization of the renal tubular epithelial cells (the Armanni-Ebstein lesion) associated with diabetic hyperglycemia is usually regarded as an accumulation of glycogen. In a case of death of diabetic coma, the vacuoles were stained strongly for lipids. This observation may have both clinical and therapeutic consequences, and may increase our knowledge of the metabolism in diabetes.

Armanni-Ebstein lesions of the kidney: diagnostic of death in diabetic coma?

In the period from January 1986 through April 1993, 47 cases with diabetes mellitus were autopsied at the Institute of Forensic Medicine, Odense University. In 26 cases, the diabetes had been treated with insulin, in 21 cases with oral medication or diet only. In eight insulin-dependent cases, tubular vacuolation was found in the kidneys, the so-called Armanni-Ebstein lesions. The circumstances of death and postmortem analyses of blood, urine and/or vitreous humor supported a presumed diabetic coma as the cause of death in these eight cases. Of the remaining 39 cases, six were too putrefied for histologic examination. In the remaining 33 cases and in a series of 20 non-diabetics, the cause of death was ascertained as illness (other than diabetes), traffic accidents, drowning or intoxication. In none of these cases was a diabetic coma suspected, and none of these cases showed tubular vacuolation in the kidneys. The authors conclude that tubular vacuolation of the kidneys strongly indicates death in diabetic coma.

Hyperosmolar non-ketotic diabetic coma and rhabdomyolysis.

Rhabdomyolysis is a rare but potentially fatal complication of hyperosmolar states. We report a case of severe hyperosmolar non-ketotic diabetic coma causing rhabdomyolysis in a young man. Despite very high levels of creatine kinase there was no detectable myoglobinuria. Creatine kinase estimation should be a standard investigation in all patients presenting with a hyperosmolar state.

Initiation of protein synthesis and heat-shock protein-72 expression in the rat brain following severe insulin-induced hypoglycemia.

Following stress such as heat shock or transient cerebral ischemia, global brain protein synthesis initiation is depressed through modulation of eucaryotic initiation factor (eIF) activities, and modification of ribosomal subunits. Concomitantly, expression of a certain class of mRNA, heat-shock protein (HSP) mRNA, is induced. Here we report that the activity of eucaryotic initiation factor-2 (eIF-2), a protein that participates in the regulation of a rate-limiting initiation step of protein synthesis, transiently decreases following insulin-induced severe hypoglycemia in the rat brain neocortex. Expression of HSP 72, a 72-kDa HSP, in surviving neurons was seen at 1-7 days of recovery following 30 min of hypoglycemic coma, but not at 1 h and 6 h of recovery. In the neocortex, HSP 72 was first seen in layer IV, and later also in surviving neurons in layer II. In the CA1 region and in the crest of dentate gyrus, HSP 72 expression was evident in cells adjacent to irreversibly damaged neurons. In the CA3 region and the hilus of dentate gyrus, HSP 72 was expressed in a few scattered neurons. In septal nucleus, HSP 72 was expressed in a lateral to medial fashion over a period of 1-3 days of recovery. We conclude that severe insulin-induced hypoglycemia induces a stress response in neurons in the recovery phase, including inhibition of protein synthesis initiation, depression of eIF-2 activity, and a delayed and prolonged expression of HSP 72 in surviving neurons. The HSP 72 expression may be a protective response to injurious stress.

[Fatality in diabetic coma during foreign travel]. / Todesfall im Coma diabeticum bei Auslandsaufenthalt.

The case history and the autopsy findings of a 44-year-old women who died shortly after her flight to Khartoum (Sudan) in a hospital is presented. The clinical diagnosis in Africa was "shock caused by gastroenteritis". The body was embalmed thoroughly and brought back to Germany. The autopsy was performed just prior to the cremation (according to "section 3 Abs. 2 Nr. 2 Feuerbestattungsgesetz"). Morphological findings (nodular glomerulosclerosis and glycogen nephrosis with Armanni-Ebstein-cells) and postmortem biochemical analyses of vitreous humour led to the diagnosis of a hyperglycaemic coma. The fatal course might have been prevented by sufficient health information to the patient (who suffered from type 1 diabetes); the diagnostic errors in the hospital could have easily been avoided by careful anamnesis and diagnostic procedures.

Neuropathologic findings in three cases of profound hypoglycemia.

Three clinical cases of profound hypoglycemia are described with survival periods ranging from 2 1/2 months to 6 years. Although prolonged clinical coma was present in all cases, only subtle evidence of neuronal loss was found. The value of immunohistochemical examination of the grey and white matter of the telencephalon in detecting evidence of neuronal loss in such cases is demonstrated. Infarcts were uniformly absent, as would be expected from the lack of cerebral acidosis in hypoglycemia. In addition to the usual absence of infarction, the pathologic findings in hypoglycemia distinguish themselves from hypoxic/ischemic encephalopathy in that the cerebellum is regularly spared, and that there is sometimes a characteristic involvement of the dentate gyrus, a structure relatively resistant to hypoxic/ischemic damage.