Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives

Bingley, P. J. and Christie, M. R. and Bonifacio, E. and Bonfanti, R. and Shattock, M. and Fonte, M.-T. and Bottazzo, G.-F. and Gale, E. A. M. (1994) Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes, 43 (11). pp. 1304-1310. ISSN 0012-1797

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Item Type:Article
Item Status:Live Archive

Abstract

Prediction of insulin-dependent diabetes mellitus (IDDM) is still largely based on islet cell antibodies (ICAs), but it may be improved by combined analysis with other humoral markers. We examined autoantibodies to insulin (IAAs), glutamic acid decarboxylase (GAD), and M(r) 37,000 and M(r) 40,000 fragments of islet antigens (37 and 40 kDa) together with ICA subtypes in 101 family members with ICAs �10 Juvenile Diabetes Foundation units (JDF U) followed for up to 14 years, of whom 18 have developed IDDM. Life-table analysis showed a 43 risk of IDDM within 10 years for those with ICAs �10 JDF U, rising to 53 for those with ICAs �20 JDF U. The risk for ICAs �10 JDF U was 62 in the family members in the youngest age quartile (<13.2 years) and fell with increasing age to 4 in those >40.7 years of age (P = 0.03). ICAs �10 JDF U combined with IAAs gave a risk of 84 (P = 0.03 compared with IAA-), and ICAs �10 JDF U combined with GAD antibodies gave a risk of 61 (P = 0.018). The risk for ICAs �10 JDF U with antibodies to 37- kDa antigen was 76 (P < 0.0001). Risk increased with the number of autoantibodies, from 8 for ICAs alone to 88 with �3 autoantibodies (14 cases detected) (P < 0.0001). The increased risk associated with multiple antibodies was observed independent of age. The median time to diagnosis in those with antibodies to 37- and/or 40-kDa antigen was 1.5 years, compared with 7.2 years in those with IAAs and GAD antibodies in the absence of antibodies to 37/40 kDa. The intensity and range of the autoantibody response offers better overall prediction of diabetes than any single autoantibody specificity, although antibodies to 37-/40-kDa antigens may prove to be useful markers of early clinical onset. We found that 78 of future cases of IDDM in ICA+ relatives came from the 27 with multiple autoantibodies and estimate that 88 of individuals within this category will need insulin treatment within 10 years. We propose a simple predictive strategy based on these observations.

Keywords:autoantibody, glutamate decarboxylase, insulin antibody, pancreas islet cell antibody, adolescent, adult, algorithm, antibody detection, antibody response, antibody specificity, antibody titer, article, child, clinical trial, controlled clinical trial, controlled study, family study, female, follow up, human, insulin dependent diabetes mellitus, life table, major clinical study, male, priority journal, prognosis, prospective study, risk, screening, Adolescent, Autoantibodies, Child, Preschool, Decision Trees, Diabetes Mellitus, Type 1, Follow-Up Studies, Humans, Islets of Langerhans, Life Tables, Middle Aged, Predictive Value of Tests, Sensitivity and Specificity
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18157
Deposited On:31 Jul 2015 13:54

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