Prediction and diagnosis of type 1 diabetes using beta-cell autoantibodies.

The clinical manifestation of type 1 diabetes is the endpoint of a long-lasting immune-mediated destruction process of the B-cells. Autoantibodies originating from this process can be applied in the diagnosis and clinical discrimination of autoimmune diabetes as well as in the prediction of this disease. At clinical diagnosis between 80-90% of patients with type 1 diabetes are positive for antibodies to B-cell antigens, such as ICA and antibodies to glutamic acid decarboxylase or IA2. These antibodies can also be detected in the presymptomatic period before onset of the disease, and can thus be used to predict type 1 diabetes. Using a combination of antibodies, diabetes can be predicted in 70-80% of future cases of diabetes, with a positive predictive value between 30-80%, depending on the type of antibody tested for and the population studied. Between 5 and 30% of patients initially diagnosed with type 2 diabetes will show progression to insulin dependency and turn out to have type 1 within three years of diagnosis. It is clinically relevant to identify these patients early in the course of disease, as deterioration of metabolic control results in an increased risk for macro- and micro-vascular complications. Autoantibodies to glutamic acid decarboxylase or ICA are of high diagnostic sensitivity in these cases and are better predictors for future insulin dependency than biochemical or clinical parameters. Increasing knowledge on the applicability of antibodies for diabetes prediction and diagnosis and the development of commercial assays for antibodies to glutamic acid decarboxylase and IA2 antibodies has enabled the implementation of B-cell autoantibodies in routine diagnostic settings.

Absence of a PDX-1 mutation and normal gastroduodenal immunohistology in a child with pancreatic agenesis.

Pancreatic agenesis is a rare condition, of which only a limited number of cases have been described. One recent paper reported a homozygous mutation in the pancreatic duodenal homeobox gene 1 (PDX-1) in a child with pancreatic agenesis. We report a 6-year-old boy with pancreatic agenesis, treated medically, without abnormalities in the PDX-1 gene coding sequence and with normal gastroduodenal endocrine cell distribution. Genes other than PDX-1 also appear to be involved in human pancreatic agenesis.

Antibody screening in a population of children.

The first large-scale (secondary) intervention trials have been initiated in first-degree family members of patients with insulin-dependent diabetes mellitus (IDDM). Within a few years, data from these studies may suggest that intervention is possible, thereby opening similar approaches in the general population. However, before large-scale intervention studies can be initiated, several problems need to be solved. One of these problems is the lack of knowledge on the natural course of beta-cell autoimmunity. This review analyses this and other issues related to population-based prediction for IDDM. At present, no long-term follow-up studies are available in large-sized populations, but data show that prediction in the general population is both technically feasible and likely to have sufficient power to be useful in prevention trials. More data need to be generated, not only to determine which markers are most likely to give good prediction but also to obtain knowledge on the natural course, psychosocial impact and cost-effectiveness of screening.