Aspects of the etiology, prediction, and prevention of insulin-dependent diabetes mellitus in childhood.
This article focuses on recent developments that have defined the autoimmune nature of this entity and its genetic basis, especially the crucial roles of aspartic acid at position 57 of the DQ beta chain and arginine at position 52 of the DQ alpha chain of the HLA complex on chromosome 6 in conferring susceptibility; other genetic markers on other genes are mentioned. These genetic markers help to explain the worldwide differences in prevalence and incidence of type 1 diabetes. Because the autoimmune process may be gradual, markers of beta pancreatic cell damage, such as islet cell antibodies, glutamic acid decarboxylase antibodies, and insulin autoantibodies, coupled with evidence of progressive failure of insulin secretion may be used to predict the future onset of disease. In turn, accurate prediction may permit preventive intervention. Two intervention trials are mentioned: (1) Diabetes Prevention 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 first steps reflect the remarkable progress and understanding of this major problem of childhood and the hopes for its future prevention.
Sperling
M A
MA
Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania, USA.
D001327:Autoimmune Diseases / Q000209:etiology* / Q000517:prevention & control*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000517:prevention & control*; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D018716:Molecular Mimicry; D011237:Predictive Value of Tests; D012307:Risk Factors
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen