ASPECTS OF THE ETIOLOGY, PREDICTION, AND PREVENTION OF INSULIN-DEPENDENT DIABETES-MELLITUS IN CHILDHOOD

This article focuses on recent developments that have defined the auto immune nature of this entity and its genetic basis, especially the cru cial roles of aspartic acid at position 57 of the DQ beta chain and ar ginine at position 52 of the DQ alpha chain of the HLA complex on chro mosome 6 in conferring susceptibility; other genetic markers on other genes are mentioned. These genetic markers help to explain the worldwi de differences in prevalence and incidence of type 1 diabetes. Because the autoimmune process may be gradual, markers of beta pancreatic cel l damage, such as islet cell antibodies, glutamic acid decarboxylase a ntibodies, and insulin autoantibodies, coupled with evidence of progre ssive failure of insulin secretion may be used to predict the future o nset of disease. In turn, accurate prediction may permit preventive in tervention. Two intervention trials are mentioned: (1) Diabetes Preven tion Trial for Type 1, a multicenter trial in the United States using insulin; and (2) European Nicotinamide Diabetes Intervention Trial in Europe using nicotinamide as the preventive or delaying agent. These f irst steps reflect the remarkable progress and understanding of this m ajor problem of childhood and the hopes for its future prevention.