Diverging evolution of anti-GAD and anti-IA-2 antibodies in long-standing diabetes mellitus as a function of age at onset: no association with complications

Abstract

Glutamic acid decarboxylase autoantibodies (GAD-A) and tyrosine phosphatase IA-2 autoantibodies (IA2-A) were measured in sera of 50 recently diagnosed (<6 wk, 33% younger than 15 yr), 19 short-term (1 to 9 yr, 35% with onset age below 15 yr) and 89 long-standing diabetic patients (>10 yr, 57% with onset age below 15 yr). Complications were assessed by clinical examination, retinal angiographs and microalbuminuria measurement. Both prevalences and levels of GAD-A and IA2-A decreased with increasing duration of diabetes. However even in those with long duration diabetes, 15 to 63% of the sera were still positive for one or two antibodies. In the group with onset after the age of 15 yr, significantly higher prevalences and levels of GAD-A (but not IA2-A) was observed in comparison with the group with earlier onset. No association was found with any microvascular complications in any group. We conclude that GAD-A and IA2-A persist in some diabetic patients, despite a long duration. Persistence of GAD-A was greatest in those with postpubertal disease onset. We speculate that persistence of some beta-cells or specific environmental factors can sustain one autoimmune reaction especially in some postpubertal-onset diabetic patients.