Analysis of pathogenesis of juvenile new-onset diabetes

Measurement of anti-islet autoantibodies at the time of disease onset contributes greatly to the differentiation of Type 1A diabetes with HLA Class II subtyping also contributing.

Blood samples were obtained from 900 patients with age from 1 month to 25 years (median age 11.1 years) within 2 weeks of diabetes onset to test anti-islet autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma antigen (IA-2AA), the zinc transporter-8 (ZnT8AA), and islet-cell antibodies (ICA). Polymorphisms of the HLA Class II gene were typed in 547 randomly selected patients.

Of the 900 subjects analyzed, 145 (16.1%) were negative for all five anti-islet autoantibodies, and autoantibody negativity significantly increased with age: 10.2% (38/372) among children <10 years of age, 14.2% (46/325) in those 10-14 years of age, and 30.1% (61/203) in those >14 years of age (P < 0.001). The prevalence of IA-2AA was the highest among young children. The prevalence of GADA increased with age while the prevalence of IAA was inversely correlated with age. At diagnosis, the subjects with negative antibodies had a higher body mass index (P < 0.001) and less high risk HLA genotype DR3-DQ2/DR4-DQ8 (P < 0.01).

A large percentage of children and youths negative for all anti-islet autoantibodies at the onset of diabetes are likely to have the non-immune form, especially those without DR3/DR4 and obese patients. Among autoantibody-positive Type 1A patients, IAA and GADA showed a reciprocal prevalence, suggesting differential disease pathogenesis.