K. Decochez et al., High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age, DIABET CARE, 23(6), 2000, pp. 838-844
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 ye
ars 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 treatme
nt. ICA were determined by indirect immunofluorescence assay and IA-2-A. GA
DA, and insulin autoantibodies by a radioligand assay.
RESULTS - Overall, 94% of initially antibody-positive patients (n = 180) re
mained 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 i
n 91, 88, and 71%, respectively, of the initially antibody-positive patient
s. Antibody persistence was lower in those diagnosed at <7 years of age, am
ounting to 60% for GADA: 71% for IA-2-A, and 39% for ICA. In 57% of the ini
tially antibody-positive patients, at least 1 type of autoantibody reached
peak values after diagnosis. This occurred more frequently for clinical ons
et 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 a
ntibody negative patients, 2 of 14 subjects developed antibodies after clin
ical onset.
CONCLUSIONS- In particular for diagnosis after 7 years of age, islet cell-s
pecific autoantibodies generally persist for many years after diagnosis. Th
ere is also a high frequency of increasing antibody levels and of conversio
n to antibody positivity in the first 4 years after diagnosis and start of
insulin treatment. Thus, determination of antibodies at diagnosis can under
estimate 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 specif
icities besides GADA and IA-2-A and reflects other autoimmune processes: it
also indicates that GADA assays have a higher diagnostic sensitivity in th
e period after clinical onset.