Diabetes-associated autoantibodies in relation to clinical characteristicsand natural course in children with newly diagnosed type 1 diabetes

We analyzed 747 children, younger than 15 yr of age, with newly diagnosed d iabetes, for antibodies to glutamic acid decarboxylase (GADA). the IA-2 pro tein (IA-2A), insulin (IAA), and islet cells, to evaluate the influence of positivity for GADA, IA-SA, IAA, or multiple (greater than or equal to 3) a utoantibodies at diagnosis, on the clinical presentation and natural course of the disease over the first 2 yr and to characterize autoantibody-negati ve patients. At diagnosis, 73.2% of the children tested positive for GADA, 85.7% for IA-SA, 54.2% for IAA, and 72.6% for multiple autoantibodies. Only 17 subjects (2.3%) had no detectable autoantibodies. The patients testing positive for multiple autoantibodies were younger than the remaining childr en (P < 0.001). A similar age difference was seen when comparing IAA-positi ve and -negative patients (P < 0.001). There was no significant difference between the GADA-positive and -negative subjects in the degree of metabolic decompensation at diagnosis, whereas those testing positive for IA-2A had reduced serum C-peptide concentrations (P = 0.003), and those positive for IAA had lower glycated hemoglobin values. The patients with no detectable a utoantibodies had higher serum C-peptide levels (P = 0.007) at diagnosis th an did the other subjects. The children initially positive for IA-2A had de creased serum C-peptide concentrations at 24 months (P = 0.045), and their daily insulin dose was higher at 18 (P = 0.005) and 24 months (P < 0.001). The patients who tested positive for multiple autoantibodies at diagnosis h ad decreased serum C-peptide levels (P < 0.001) and higher insulin doses (P = 0.005) at 12, 18, and 24 months. A lower proportion of them were also in clinical remission at 12 and 18 months (P = 0.01). Autoantibody-negative s ubjects needed less exogenous insulin at 6 and 18 (P = 0.01) and at 24 mont hs (P < 0.001) than the other subjects, and a higher proportion of them wer e in clinical remission at 18 months (P < 0.001). We conclude that positivi ty for multiple diabetes-related autoantibodies is associated with accelera ted beta-cell destruction and an increased requirement for exogenous insuli n over the second year of clinical disease, indicating that multiple autoan tibodies reflect an aggressive progression to total beta-cell destruction. Patients testing negative for diabetes-associated autoantibodies at diagnos is seem to have a milder degree of beta-cell destruction, but their metabol ic decompensation is similar to that seen in other affected children, sugge sting that they do represent classical type 1 diabetes.