• Achenbach, P.
• Gale, Eam
• Ziegler, Ag
• Williams, Alistair
• Endit, Group
• Bingley, Pj
• Bonifacio, E.

Abstract

Aims/hypothesisThe aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2β (IA2βA) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial. MethodsAutoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2βA. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. ResultsOf 212 ICA/IA2A-positive participants (median age 12.1 years; 57% male), 113 developed diabetes (5 year cumulative risk 56%), and 148 were also GADA-positive and IAA-positive (4Ab-positive). IA2βA were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2βA-positive 65 vs 39% in IA2βA-negative, p = 0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p  = 0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2βA, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal FPIR, p 

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