title: Environmental triggers of type 1 diabetes.
abstract: High risk HLA class II alleles account for 40% of the genetic susceptibility to type 1 diabetes in Caucasians, but the majority of the genetically predisposed do not develop the disease. This supports some environmental modification of the autoimmune destruction of beta cells that precedes type 1 diabetes. Identical twin studies and geographical variation in incidence also argue for a critical role of environmental factors. Attention has been directed to the possible harmful effect of cow's milk protein (or protective effect of breast-feeding) and enteric infections in early life. Natural history studies that follow children at increased risk of type 1 diabetes provide the best opportunity to study environmental triggers. The Australian Baby Diab Study has followed approximately 500 babies from birth who have a first-degree relative with type 1 diabetes. No prospective association between duration of breast-feeding or introduction of cow's milk and the development of islet autoimmunity was found. The same Australian cohort demonstrated a relationship between rotavirus infection and the first appearance or increase in islet antibodies. Enteroviral infection is seen more frequently in prediabetic children and prior to the onset of islet autoimmunity in Finnish cohorts. Environmental factors may interact. Breast milk protects against enteric infections; enteric infections in turn could increase immunity to dietary antigens by increasing intestinal permeability. It is also possible that an alteration in gut mucosal immune function in genetically susceptible individuals underlies any effect of dietary or viral proteins on the development of islet autoimmunity in early life.
authors.affiliation: Department of Endocrinology, Women and Children's Hospital, North Adelaide, SA 5006, Australia. jcouper@medicine.adelaide.edu.au
authors.forename: J J
authors.initials: JJ
authors.lastname: Couper
mesh_terms: D000818:Animals; D001942:Breast Feeding; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000821:virology*; D004769:Enterovirus Infections / Q000821:virology; D004781:Environmental Exposure / Q000009:adverse effects*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008892:Milk / Q000276:immunology; D012400:Rotavirus Infections / Q000821:virology; D014764:Viral Proteins / Q000276:immunology
chemical_list: D006680:HLA Antigens; D014764:Viral Proteins