Disease-Associated Autoantibodies as Surrogate Markers of Type 1 Diabetes in Young Children at Increased Genetic Risk1
To evaluate the emergence of diabetes-associated autoantibodies in young children and to assess whether such antibodies can be used as surrogate markers of type 1 diabetes in young subjects at increased genetic risk, we studied 180 initially unaffected siblings (92 boys and 88 girls) of children wit...
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Published in | The journal of clinical endocrinology and metabolism Vol. 85; no. 3; pp. 1126 - 1132 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.03.2000
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Online Access | Get full text |
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Summary: | To evaluate the emergence of diabetes-associated autoantibodies
in young children and to assess whether such antibodies can be used as
surrogate markers of type 1 diabetes in young subjects at increased
genetic risk, we studied 180 initially unaffected siblings (92 boys and
88 girls) of children with newly diagnosed type 1 diabetes. All
siblings were younger than 6 yr of age at the initial sampling, and
they were monitored for the emergence of islet cell antibodies (ICA),
insulin autoantibodies (IAA), glutamate decarboxylase antibodies
(GADA), and IA-2 antibodies (IA-2A) up to the age of 6 yr and for
progression to clinical type 1 diabetes up to the age of 10 yr. All 160
siblings with DNA samples available were typed for susceptible (DQB1*02
and *0302) and protective (DQB1*0301 and *0602–03) HLA DQB1 alleles.
Twenty-two siblings (12.2%) tested positive for ICA in their first
antibody-positive sample before the age of 6 yr, 13 (7.2%) tested
positive for IAA, 15 (8.3%) tested positive for GADA, and 14 (7.8%)
tested positive for IA-2A. There were 16 siblings (8.9%) who had 1
detectable autoantibody, 5 (2.8%) had 2, and 12 (6.7%) had 3 or more.
In the group of 82 siblings with increased human leukocyte
antigen-defined genetic susceptibility [DQB1*02/*0302, *0302/x (x=
other than *02 or a protective allele), *02/y (y = other than*
0302 or a protective allele)], 18 (22.0%) tested positive for ICA in
their first antibody-positive sample, 10 (12.2%) tested positive for
IAA, 14 (17.1%) tested positive for GADA, and 12 (14.6%) tested
positive for IA-2A. One antibody was detectable in 6 siblings (7.3%),
2 were detectable in 5 (6.1%), and 3 or more were detectable in 12
(14.6%). Fifteen siblings (18.3%) presented with clinical type 1
diabetes before the age of 10 yr. All of the progressors showed
increased human leukocyte antigen-defined genetic susceptibility.
Thirteen of those 15 siblings, who presented with clinical type 1
diabetes before the age of 10 yr, had at least 2 antibodies detectable
before the age of 6 yr (disease sensitivity, 87%; 95% confidence
interval, 60–98%). Thirteen of the 17 siblings who tested positive
for 2 or more autoantibodies before the age of 6 yr developed type 1
diabetes before the age of 10 yr (positive predictive value, 76%; 95%
confidence interval, 50–93%). These observations suggest that
disease-associated autoantibodies can well be used as surrogate markers
of clinical type 1 diabetes in primary prevention trials targeting
young subjects with increased genetic disease susceptibility. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.85.3.6466 |