Postmortem diagnosis of diabetes mellitus and its complications.

FORENSIC SCIENCE 181 Croat Med J. 2015;56:181-93 doi: 10.3325/cmj.2015.56.181 Postmortem diagnosis of diabetes mellitus and its complications Cristian Palmiere CURML, Centre Universitaire Romand De Medecine Legale, Lausanne University Hospital, Lausanne, Switzerland Diabetes mellitus has become a major cause of death worldwide and diabetic ketoacidosis is the most common cause of death in children and adolescents with type 1 diabetes. Acute complications of diabetes mellitus as causes of death may be difficult to diagnose due to missing characteristic macroscopic and microscopic findings. Biochemical analyses, including vitreous glucose, blood (or alternative specimen) beta-hydroxybutyrate, and blood glycated hemoglobin determination, may complement postmortem investigations and provide useful information for determining the cause of death even in corpses with advanced decompositional changes. In this article, we performed a review of the literature pertaining to the diagnostic performance of classical and novel biochemical parameters that may be used in the forensic casework to identify disorders in glucose metabolism. We also present a review focusing on the usefulness of traditional and alternative specimens that can be sampled and subsequently analyzed to diagnose acute complications of diabetes mellitus as causes of death. Received: March 2, 2015 Accepted: May 11, 2015 Correspondence to: Cristian Palmiere CURML, Centre Universitaire Romand De Medecine Legale Chemin de la Vulliette 4 1000 Lausanne 25, Switzerland www.cmj.hr 182 FORENSIC SCIENCE Diabetes mellitus has become a major cause of death worldwide in people younger than 60 years. Over the past three decades, the number of people with diabetes mellitus has more than doubled globally, making it one of the most important public health challenges to all nations (1). Worldwide, 382 million adults (8.3%) are living with diabetes, and the estimate is projected to rise to more than 592 million by 2035. At least US $147 billion was spent on diabetes health care in Europe in 2013, whereas North America and the Caribbean spent $263 billion (2). Currently, in Australia, approximately 4.0% of people aged 15 years and over has been diagnosed with diabetes. Some estimates suggest that this figure will rise to as much as 2 million by 2025 as a result of increasing obesity and aging as well as changes in the ethnic composition of the Australian population (2,3). Type 1 diabetes is characterized by cellular-mediated autoimmune destruction of pancreatic beta-cells resulting in insulin deficiency and, thus, hyperglycemia (4,5). In the United States, Canada, and Europe, type 1 diabetes accounts for 5 to 10% of all cases of diabetes. A second and more prevalent category, type 2 diabetes, is characterized by a combination of insulin resistance and inadequate compensatory insulin secretory response (5,6). Prevalence and morbidity data in cases of already diagnosed diabetes underestimate the actual burden of the disease since it is usually not diagnosed until it has become clinically apparent and complications occur. A number of local and national surveys have reported both diagnosed and undiagnosed diabetes rates based on population health surveys, though the relative prevalence of diagnosed and undiagnosed cases varies widely. The NorthWest Adelaide Health Survey, for example, found a ratio of 5–6:1 for diagnosed vs undiagnosed diabetes, consistent with the latest Australian Bureau of Statistics National Health Survey data showing a ratio of 5:1, whereas a previous Australian Diabetes, Obesity and Lifestyle Study estimated one undiagnosed case for every diagnosed case in Australia (3,7). Analogously, a high proportion of the estimated 26 million Americans with diabetes remains undiagnosed and unaware of their disease, and more than 90% of the estimated 79 million adults with pre-diabetes remains undetected (8,9). Diabetic ketoacidosis (DKA) is a life-threatening condition that can occur when there is a complete lack of insulin, as in type 1 diabetes, or inadequate insulin levels associated with stress or severe illness in either type 1 or type 2 diabetes (10). It has been estimated that nearly a third www.cmj.hr Croat Med J. 2015;56:181-93 of all deaths from DKA occurs in individuals with no known history of diabetes (6,11). DKA is the most common cause of death in children and adolescents with type 1 diabetes and accounts for half of all deaths in diabetic patients younger than 24 years of age (12). Depending on the reports, DKA at the clinical diagnosis of type 1 diabetes in the pediatric population may range from 15% to more than 77% of cases (13). In the realm of forensic pathology, acute complications of diabetes mellitus as causes of death may be difficult to diagnose due to missing characteristic macroscopic and microscopic findings. Nevertheless, when biochemical investigations complement autopsy and histology, fatal DKA can be easily diagnosed despite unknown disease history and even in corpses with advanced decompositional changes (6,14,15). The aim of this article is to perform a review of the literature pertaining to the diagnostic performance of classical and novel biomarkers that may be used in forensic pathology routine to identify disorders in glucose metabolism. Moreover, we wish to present a review of the literature focusing on the usefulness of traditional and alternative specimens that can be sampled at autopsy and subsequently analyzed to diagnose acute complications of diabetes mellitus as causes of death. Vitreous glucose In clinical practice, the most important biochemical markers to identify disorders in glucose metabolism are blood glucose concentration and glycated hemoglobin levels. In the realm of forensic pathology, postmortem blood glucose concentration is unreliable and of no diagnostic value in estimating antemortem blood glucose levels due to substantial fluctuations in glucose concentrations after death. After the cessation of cardiac and respiratory functions, surviving cells continue to metabolize blood glucose for some time and glycolysis continues spontaneously, causing a rapid decrease in blood glucose levels. Furthermore, death may be preceded by agonal processes and/or cardiopulmonary resuscitation, often associated with catecholamine release or administration. This results in subsequent mobilization of liver glycogen and increases in blood glucose concentrations as a counterbalancing phenomenon. Another possible pitfall in estimating antemortem blood glucose values using postmortem blood glucose concentrations is the variation of glucose 183 Palmiere: Postmortem diagnosis of diabetes mellitus and its complications levels depending on the sampling site. The highest blood glucose concentrations have been found in hepatic vein blood, followed by inferior vena cava, superior vena cava, and cardiac right ventricle blood, likely following glycogen breakdown in the liver. Co (...truncated)