Update on the genetics and pathophysiology of type I diabetes mellitus.
Type I diabetes mellitus results from the genetically predetermined autoimmune destruction of pancreatic beta-cells, resulting in gradual, but complete, loss of insulin secretion. There are strong associations with specific HLA haplotypes, but environmental triggers are also required to initiate beta-cell autoimmunity. These could possibly include enteroviral infection, early weaning from breastfeeding, early exposure to cow's milk antigens, and free radical damage. Once initiated, beta-cell autoimmunity does not always lead to clinical diabetes, suggesting that immunomodulators may be important in the control of beta-cell destruction. Current interventions designed to prevent type I diabetes mellitus are based on attempts to alter this immune response and to preserve beta-cell function. It is important for the pediatrician to understand the background of these trials and to be able to answer parents' questions regarding study participation.
Rennert
O M
OM
Center for Research for Mothers and Children, National Institutes of Health, Bethesda, Maryland, USA.
Francis
G L
GL
D000367:Age Factors; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans