title: Neonatal levels of adiponectin, interleukin-10 and interleukin-12 are associated with the risk of developing type 1 diabetes in childhood and adolescence: A nationwide Danish case-control study.
abstract: An in-depth understanding of the early phase of type 1 diabetes (T1D) pathogenesis is important for targeting primary prevention. We examined if 14 preselected mediators of immune responses differed in neonates that later developed T1D compared to control neonates.
  
  
  
  The study is a case-control study with a 1:2 matching. The individuals were born between 1981 through 2002. Cases were validated using the National Patient Register and the Danish Childhood Diabetes Register. Interleukin(IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, interferon gamma, tumor necrosis factor alpha, transforming growth factor beta 1 (active form), leptin, adiponectin, c-reactive protein, mannose-binding lectin and soluble triggering receptor expressed on myeloid cells-1 were measured by using a flowmetric Luminex xMAP® technology. We tested two models both including a number of possible confounders. In the first model (model 1) we also adjusted for HLA-DQB1 genotype. A total of 1930 groups of assay-matched cases and controls (4746 individuals) were included in the statistical analyses.
  
  
  
  Adiponectin was negatively associated with later risk of T1D in both models (relative change (RC), model 1: 0.95, P=0.046 and model 2: 0.95, P=0.006). IL-10 and IL-12 were both positively associated with T1D risk in the model 2 (RC, 1.19, P=0.006 and 1.07, P=0.02, respectively)-these results were borderline significant in model 1, but showed the same direction as the results from model 2.
  
  
  
  Our results indicate that specific immunological signatures are already present at time of birth in children developing T1D before the age of 18years.
authors.affiliation: Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Paediatrics, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev. Denmark. Electronic address: steffen.ullitz.thorsen.01@regionh.dk.
authors.forename: Steffen U
authors.initials: SU
authors.lastname: Thorsen
authors.affiliation: Department of Public Health, Section of Biostatistics, University of Copenhagen, Oester Farimagsgade 5, 1710 Copenhagen K, Denmark.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Pipper
authors.affiliation: Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Paediatrics, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev. Denmark.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Eising
authors.affiliation: Department of Congenital Disorders, Center for Neonatal Screening, Statens Serum Institut Artillerivej 5, 2300 Copenhagen S, Denmark.
authors.forename: Kristin
authors.initials: K
authors.lastname: Skogstrand
authors.affiliation: Department of Congenital Disorders, Center for Neonatal Screening, Statens Serum Institut Artillerivej 5, 2300 Copenhagen S, Denmark.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Paediatrics, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev. Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Jannet
authors.initials: J
authors.lastname: Svensson
authors.affiliation: Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Paediatrics, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev. Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood*; D008297:Male; D008954:Models, Biological; D012306:Risk
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C508609:IL10 protein, human; D016753:Interleukin-10; D018664:Interleukin-12
keywords: C-reactive protein; Cytokines/immunology; Diabetes Mellitus, Type 1; Mannose-binding lectin; TREM1, human