Prevalence of autoantibody-negative diabetes is not rare at all ages and increases with older age and obesity

J Clin Endocrinol Metab. 2007 Jan;92(1):88-92. doi: 10.1210/jc.2006-1494. Epub 2006 Oct 24.


Objective: A significant percentage of nonautoimmune forms of diabetes presents among children in all age groups, with a remarkable increase with age.

Design: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Age Factors
  • Autoantibodies / blood*
  • Body Mass Index
  • Child
  • Child, Preschool
  • Diabetes Mellitus / immunology*
  • Female
  • Glutamate Decarboxylase / immunology
  • Glycated Hemoglobin A / analysis
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics
  • Humans
  • Infant
  • Male
  • Obesity / immunology*


  • Autoantibodies
  • Glycated Hemoglobin A
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • islet cell antibody
  • Glutamate Decarboxylase