title: Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial.
abstract: This study evaluated the possible role of enterovirus infections in the pathogenesis of type I (insulin-dependent) diabetes in a prospective dietary intervention trial. Children participated in the second pilot of the Trial to Reduce IDDM in Genetically at Risk (TRIGR) project. They were randomized into two groups receiving either a casein hydrolysed formula (Nutramigen) or a regular formula, whenever breast milk was not available over the first 6-8 months of life. Altogether 19 children who turned positive for autoantibodies associated with type I diabetes by 2 years of age and 84 matched control children were analysed for enterovirus antibodies and enterovirus RNA in serum. Enterovirus infections were common during the first 2 years of life and more frequent among boys than girls (P = 0.02). Autoantibody-positive children had more enterovirus infections than autoantibody-negative children before the appearance of autoantibodies (0.83 versus 0.29 infection per child, P = 0.01). The average levels of IgG antibodies to echovirus antigen were also higher in autoantibody-positive than in autoantibody-negative children (P = 0.0009). No difference was found in the frequency of enterovirus infections between children receiving the casein hydrolysed formula or regular formula. These results suggest that enterovirus infections are associated with the induction of beta-cell autoimmunity in young children with increased genetic susceptibility to type I diabetes.
authors.affiliation: JDRF Center for Prevention of Type 1 Diabetes in Finland, Department of Virology, University of Tampere Medical School and Tampere University Hospital, Tampere, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Sadeharju
authors.forename: A-M
authors.initials: AM
authors.lastname: Hämäläinen
authors.forename: M
authors.initials: M
authors.lastname: Knip
authors.forename: M
authors.initials: M
authors.lastname: Lönnrot
authors.forename: P
authors.initials: P
authors.lastname: Koskela
authors.forename: S M
authors.initials: SM
authors.lastname: Virtanen
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
authors.forename: H K
authors.initials: HK
authors.lastname: Akerblom
authors.forename: H
authors.initials: H
authors.lastname: Hyöty
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D019540:Area Under Curve; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002364:Caseins; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D004769:Enterovirus Infections / Q000150:complications*; D005260:Female; D005312:Fetal Blood / Q000821:virology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007225:Infant Food; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D011446:Prospective Studies; D011492:Protein Hydrolysates; D012367:RNA, Viral / Q000032:analysis; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000914:Antibodies, Viral; D002364:Caseins; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007074:Immunoglobulin G; D011492:Protein Hydrolysates; D012367:RNA, Viral; C026375:trypticase-soy broth