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.

The Role of Autoimmunity at Diagnosis of Type 1 Diabetes in the Development of Thyroid and Celiac Disease and Microvascular Complications

“…Measurement of diabetes-associated autoantibodies, such as ICAs, GADAs, and IAAs at presentation with type 1 diabetes is useful for confirming the autoimmune origin of disease (41,42). There is conflicting evidence as to whether diabetes-associated autoantibodies may also be related to long-term development of microvascular complications.…”

“…There is conflicting evidence as to whether diabetes-associated autoantibodies may also be related to long-term development of microvascular complications. Crosssectional studies have mostly found that diabetes-associated autoantibodies are not related to the presence of complications (41)(42)(43)(44). However, higher GADA levels were shown to be more common in patients with peripheral neuropathy and long-standing diabetes (45) and less likely in patients with severe retinopathy and type 1 diabetes (46).…”

“…However, higher GADA levels were shown to be more common in patients with peripheral neuropathy and long-standing diabetes (45) and less likely in patients with severe retinopathy and type 1 diabetes (46). Because the prevalence of positivity for GADAs and IAAs declines with diabetes duration (41,43), their measurement at diagnosis of type 1 diabetes may be more relevant to the development of complications than later testing. To date, no study has investigated whether the presence of autoantibodies at diagnosis predicts the later development of microvascular complications.…”

Relationship between the prevalence of anti-glutamic acid decarboxylase autoantibodies and duration of type 1 diabetes mellitus in Brazilian patients

“…One factor that might have contributed to our results was the high mean age at diagnosis of T1D. It has been previously suggested that GADA could be more persistent in patients with T1D diagnosed after 15 years of age (30). Finally, there are still controversial issues regarding GADA prevalence and titers along disease progression, as well as the factors that contribute to its persistence in serum.…”

Antik�rper gegen Glutamatdecarboxylase und Tyrosinphosphatase-�hnliches Protein IA-2 in der Klassifikation von unselektionierten Diabetespatienten

“…Anders als in der Literatur beschrieben [8] fanden sich aber auch nach einer Diabetesdauer von 25-30 Jahren -in einem Einzelfall sogar nach > 50 Jahren, ähnlich wie bei Hermitte et al [7] -noch positive IA-2-Ak. Die Sensitivität des IA-2-Ak-Assays lag bei 95,3% und erlaubte somit eine klare Identifizierung eines Typ-1-Diabetes bei den IA-2-Ak-positiven Patienten.…”