title: Prevalence of autoantibody-negative diabetes is not rare at all ages and increases with older age and obesity.
abstract: OBJECTIVE
  A significant percentage of nonautoimmune forms of diabetes presents among children in all age groups, with a remarkable increase with age.
  
  
  METHODS
  From October 1992 to October 2004, a total of 859 children less than 18 yr of age were newly diagnosed with diabetes at the Barbara Davis Center for Childhood Diabetes and had blood samples obtained within 2 wk of disease onset for analysis of antiislet autoantibodies to glutamic acid decarboxylase-65, insulinoma-associated antigen-2, insulin, and islet cell autoantibodies. The relationship of autoantibody positivity with human leukocyte antigen (HLA) class II, body mass index (BMI), glycosylated hemoglobin, age, and ethnicity was analyzed.
  
  
  RESULTS
  Overall 19% (159 of 859) of these children with newly diagnosed diabetes were negative for all autoantibodies, and autoantibody negativity was significantly increased with age (P < 0.01). The Hispanic and Black subjects had significantly increased autoantibody negativity among older children with higher BMI than White subjects. The patients with the highest risk HLA genotype, DR3-DQ2/DR4-DQ8, were significantly less autoantibody negative (P = 0.001), whereas the HLA-protective allele, DQB1*0602, was significantly increased among the autoantibody-negative patients (P < 0.0001). Insulin autoantibodies were dramatically age dependent and were inversely correlated with age in both prevalence (P < 0.0001) and levels (P < 0.0001). Autoantibody positivity was inversely correlated with both BMI and age using multivariate analysis (P < 0.0001 and P = 0.0078, respectively).
  
  
  CONCLUSIONS
  A significant percentage of children newly diagnosed with diabetes are negative for all antiislet autoantibodies with a marked increase in obesity-associated autoantibody-negative diabetes after age 10, suggesting diabetes heterogeneity at all ages.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, PO Box 6511, Mail Stop B140, Aurora, Colorado 80045-6511, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: Sunanda
authors.initials: S
authors.lastname: Babu
authors.forename: Jeesuk
authors.initials: J
authors.lastname: Yu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barker
authors.forename: Georgeanna
authors.initials: G
authors.lastname: Klingensmith
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001323:Autoantibodies / Q000097:blood*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009765:Obesity / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens; C069051:HLA-DQB1 antigen; C024211:islet cell antibody