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

Design: From October of 1992 to October of 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 weeks of disease onset for analysis of anti-islet autoantibodies to GAD65, IA-2, insulin, and ICA. The relationship of autoantibody positivity with HLA class II, BMI, HA1c, age, and ethnicity were analyzed.

Results: Overall 19% (159/859) 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 had significantly increased autoantibody negativity among older children with higher BMI than White. The patients with highest risk HLA genotype, DR3-DQ2/DR4-DQ8, were significantly less autoantibody negative (P = 0.001), while 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 anti-islet autoantibodies with a marked increase in obesity associated autoantibody negative diabetes after age 10, suggesting diabetes heterogeneity at all ages.