High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age

OBJECTIVE - To study the presence and levels of GAD65 antibodies (GADA). IA-2 antibodies (IA-2-A), and islet cell antibodies (ICA) during the first years after clinical onset of type 1 diabetes in relation to age at diagnosis. RESEARCH DESIGN AND METHODS - Type 1 diabetic patients (n = 194) <40 years of age were consecutively recruited at the rime of diagnosis by the Belgian Diabetes Registry and followed during the first 4 years of insulin treatment. ICA were determined by indirect immunofluorescence assay and IA-2-A. GADA, and insulin autoantibodies by a radioligand assay. RESULTS - Overall, 94% of initially antibody-positive patients (n = 180) remained positive for at least 1 antibody type 4 years after diagnosis In the case of diagnosis after <7 years of age, GADA. IA-2-A, and ICA persisted in 91, 88, and 71%, respectively, of the initially antibody-positive patients. Antibody persistence was lower in those diagnosed at <7 years of age, amounting to 60% for GADA: 71% for IA-2-A, and 39% for ICA. In 57% of the initially antibody-positive patients, at least 1 type of autoantibody reached peak values after diagnosis. This occurred more frequently for clinical onset after <7 years of age and more often for GADA (49%) than for IA-2-A ( 29%) or ICA (19%). Of the patients, 24% that were negative for GADA at onset became GADA-positive during die following 4 years. Among the 7% initially antibody negative patients, 2 of 14 subjects developed antibodies after clinical onset. CONCLUSIONS- In particular for diagnosis after 7 years of age, islet cell-specific autoantibodies generally persist for many years after diagnosis. There is also a high frequency of increasing antibody levels and of conversion to antibody positivity in the first 4 years after diagnosis and start of insulin treatment. Thus, determination of antibodies at diagnosis can underestimate the number of cases with autoimmune type 1 diabetes, in particular with assays of lower sensitivity. The divergent temporal patterns of ICA, GADA. and IA-2-A suggest that the ICA test recognizes other antibody specificities besides GADA and IA-2-A and reflects other autoimmune processes: it also indicates that GADA assays have a higher diagnostic sensitivity in the period after clinical onset.