RT Journal Article
SR Electronic
T1 Successful Prospective Prediction of Type 1 Diabetes in Schoolchildren Through Multiple Defined Autoantibodies
JF Diabetes Care
JO Diabetes Care
FD American Diabetes Association
SP 505
OP 511
DO 10.2337/diacare.25.3.505
VO 25
IS 3
A1 LaGasse, James M.
A1 Brantley, Michael S.
A1 Leech, Nicola J.
A1 Rowe, Rachel E.
A1 Monks, Stephanie
A1 Palmer, Jerry P.
A1 Nepom, Gerald T.
A1 McCulloch, David K.
A1 Hagopian, William A.
YR 2002
UL http://care.diabetesjournals.org/content/25/3/505.abstract
AB OBJECTIVE—Almost 90% of type 1 diabetes appears in individuals without a close family history. We sought to evaluate the best current predictive strategy, multiple defined autoantibodies, in a long-term prospective study in the general population. RESEARCH DESIGN AND METHODS—Autoantibodies to pancreatic islets (islet cell antibodies [ICAs]) and defined autoantibodies (d-aab) to human GAD, IA2/ICA512, and insulin were tested in 4,505 Washington schoolchildren. Eight years later, 3,000 (67%) subjects were recontacted, including 97% of subjects with any test >99th percentile. RESULTS—Six subjects developed diabetes (median interval 2.8 years), all from among the 12 individuals with multiple d-aab, representing 50% positive predictive value (95% CI 25–75%) and 100% sensitivity (58–100%). Among the others, diabetes occurred in 0 of 6 with one d-aab plus ICA, 0 of 26 with ICA only, 0 of 7 with one d-aab equaling the 99th percentile and another d-aab equaling the 97.5th percentile, 0 of 86 with one d-aab, and 0 of 2,863 with no d-aab or ICA. Adjusted for verification bias, multiple d-aab were 99.9% specific (99.86–99.93%). At this age, new d-aab seldom appeared. Once present, d-aab usually persisted regardless of disease progression, although less so for insulin autoantibodies. Insulin secretion by sequential glucose tolerance testing remained normal in four multiple d-aab subjects not developing diabetes. Of children developing diabetes, five of six (83%) would be included if HLA-DQ genotyping preceded antibody testing, but HLA-DQ did not explain outcomes among high-risk subjects, even when considered along with other genetic markers. CONCLUSIONS—Multiple d-aab were established by age 14 years and prospectively identified all schoolchildren who developed type 1 diabetes within 8 years.