Etiology

Type 1 diabetes is due to autoimmune destruction of insulin-secreting pancreatic ft cells of islets of Langerhans. T1D typically occurs in young individuals with an age of onset of less than 40 years. The autoimmune reaction is likely to be triggered by an environmental agent in utero or in very early life (Figure 1). The earliest markers of ft cell destruction are the appearance of autoantibodies to glutamic acid decarboxyla-se(GAD), islet cells, and insulin. Autoantibodies have been detected 10-15 years before the onset of disease and, furthermore, have been known to disappear without T1D occurring in a few individuals. One to two years before onset of the disease, evidence of ft cell impairment can be detected, initially evidenced by a reduction in the first phase of insulin response to intravenous glucose and in the later stages by an abnormal oral glucose tolerance. In contrast to the slow ft cell destruction, the onset of T1D is acute and is usually measured in weeks. At this stage in the etiological process, it is likely that 70% of ft cells have been destroyed and those remaining are inhibited by the action of cytokines.

There is a subgroup of patients who develop diabetes in adult life and do not require insulin during the first few years after diagnosis; they have an autoimmune component to their disease with positive GAD and islet cell antibodies. This condition is named latent autoimmune diabetes (LADA). There are several common features between T1D and LADA, including T cell insulitis, islet antibody posi-tivity, and high rates of HLA DR3 and DR4. The prevalence of LADA in newly diagnosed diabetics

Environmental

Environmental

Figure 1 The etiology of type 1 diabetes mellitus. DM, diabetes mellitus; LADA, latent autoimmune diabetes.

has been shown to range from 2.8% to 22.3% in different studies depending on the markers used and characteristics of the patients. Although these patients present with type 2 diabetes, they have been shown to progress to insulin dependency especially if the diabetes is diagnosed at a younger age and the patient is not overweight. Therefore, there may be a role for measuring GAD antibody in newly diagnosed patients with type 2 diabetes to identify the LADA subgroup especially in the younger age groups. This group of patients is now classified as type 1 diabetes by the new WHO classification.

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