THEROSCLEROSIS IS THOUGHTto begin in childhood and to develop silently for decades before clinical events such as myocardial infarction or stroke occur. Autopsy studies in children and adolescents have confirmed the presence of preclinical atherosclerotic lesions and shown their associations with antemortem vascular risk factors. [1][2][3] Studies using ultrasound imaging have demonstrated atherosclerotic wall thickening in the arteries of children with risk factors. [4][5][6] Longitudinal studies have shown that risk factor levels measured in childhood are predictive of risk factor levels in adulthood. [7][8][9] Moreover, levels of serum cholesterol measured in young adult men have been associated with cardiovascular disease in midlife. 10,11 Al-
Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing -cells in the pancreatic islets in genetically susceptible subjects. A series of evidence supports a critical role of exogenous factors in the development of type 1 diabetes, such as 1) the fact that <10% of individuals with HLA-conferred diabetes susceptibility do progress to clinical disease, 2) a pairwise concordance of type 1 diabetes of <40% among monozygotic twins, 3) a more than 10-fold difference in the disease incidence among Caucasians living in Europe, 4) a severalfold increase in the incidence over the last 50 years, and 5) migration studies indicating that the disease incidence has increased in population groups who have moved from a low-incidence to a high-incidence region. This article discusses the trigger-booster hypothesis claiming that the diabetic disease process is triggered by an exogenous factor with definite seasonal variation and driven by one or several other environmental determinants. In addition, there are a series of modifying factors affecting the fate and pace of the process. Accordingly, progression to clinical type 1 diabetes typically requires the unfortunate combination of genetic disease susceptibility, a diabetogenic trigger, and a high exposure to a driving antigen. Diabetes 54 (Suppl. 2):S125-S136, 2005
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