University of Twente 2015 - Dissertation
Given its vast medical, financial and social implications, diabetes mellitus is a huge burden on
society (1). With a worldwide prevalence of 382 million people (2), it is one of the most common
chronic diseases. And the prevalence of diabetes is still increasing each year (3). In 2013, the
global health expenditure on this disease is estimated to be at least 581 billion International
The American Diabetes Association (ADA) classifies diabetes according to both clinical
stages and etiologic types (Figure 1). All patients can be classified according to clinical stage.
Considering etiology, three main types can be distinguished: type 1, type 2, and gestational
diabetes (4). Type 1 diabetes accounts for only 5-10% of those with diabetes (4). Although
the etiology is not completely understood, the general pathological finding is the destruction
of pancreatic β-cells, usually in the presence of islet cell autoantibodies, autoantibodies to
insulin, autoantibodies to glutamic acid decarboxylase, and/or autoantibodies to the tyrosine
phosphatase IA-2 and IA-3β. Type 1 diabetes has multiple genetic predispositions (5), but the
observation that the concordance rate in monozygotic twins is not 100% indicates that beside
genetic factors, environmental factors are also involved in the development of the disease (6).
This type of diabetes usually affects children or young adults, but it can occur at any age.
Some forms of type 1 diabetes do not have known etiologies and these fall under the category
idiopathic diabetes. Patients with this type of diabetes usually do not show evidence of islet
autoimmunity, but they are prone to episodes of ketoacidosis and show varying degrees of
insulin deficiency. Idiopathic diabetes is strongly inherited and there seems to be an ethnic
preference since most patients are of African or Asian ancestry (4).