Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives

P Achenbach; E Bonifacio; AJK Williams; AG Ziegler; EAM Gale; PJ Bingley; Group ENDIT

doi:10.1007/s00125-007-0912-9

Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives

P Achenbach, E Bonifacio, AJK Williams, AG Ziegler, EAM Gale, PJ Bingley, Group ENDIT

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Abstract

Aims/hypothesis The aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2ÃŽÂ² (IA2ÃŽÂ²A) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial. Methods Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2ÃŽÂ²A. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. Results Of 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). IA2ÃŽÂ²A were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2ÃŽÂ²A-positive 65 vs 39% in IA2ÃŽÂ²A-negative, pÃ¢Â€Â‰=Ã¢Â€Â‰0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p Ã¢Â€Â‰=Ã¢Â€Â‰0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2ÃŽÂ²A, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal FPIR, pÃ¢Â€Â‰

Translated title of the contribution	Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives
Original language	English
Pages (from-to)	488 - 492
Number of pages	5
Journal	Diabetologia
Volume	51
Issue number	3
DOIs	https://doi.org/10.1007/s00125-007-0912-9
Publication status	Published - Mar 2008

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@article{cf67f9825af24c46931b591346b36558,

title = "Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives",

abstract = "Aims/hypothesis The aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2{\~A}{\v Z}{\^A}² (IA2{\~A}{\v Z}{\^A}²A) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial. Methods Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2{\~A}{\v Z}{\^A}²A. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. Results Of 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). IA2{\~A}{\v Z}{\^A}²A were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2{\~A}{\v Z}{\^A}²A-positive 65 vs 39% in IA2{\~A}{\v Z}{\^A}²A-negative, p{\~A}¢{\^A}€{\^A}‰={\~A}¢{\^A}€{\^A}‰0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p {\~A}¢{\^A}€{\^A}‰={\~A}¢{\^A}€{\^A}‰0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2{\~A}{\v Z}{\^A}²A, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal FPIR, p{\~A}¢{\^A}€{\^A}‰",

author = "P Achenbach and E Bonifacio and AJK Williams and AG Ziegler and EAM Gale and PJ Bingley and Group ENDIT",

year = "2008",

month = mar,

doi = "10.1007/s00125-007-0912-9",

language = "English",

volume = "51",

pages = "488 -- 492",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Berlin Heidelberg",

number = "3",

}

TY - JOUR

T1 - Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives

AU - Achenbach, P

AU - Bonifacio, E

AU - Williams, AJK

AU - Ziegler, AG

AU - Gale, EAM

AU - Bingley, PJ

AU - ENDIT, Group

PY - 2008/3

Y1 - 2008/3

N2 - Aims/hypothesis The aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2ÃŽÂ² (IA2ÃŽÂ²A) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial. Methods Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2ÃŽÂ²A. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. Results Of 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). IA2ÃŽÂ²A were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2ÃŽÂ²A-positive 65 vs 39% in IA2ÃŽÂ²A-negative, pÃ¢Â€Â‰=Ã¢Â€Â‰0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p Ã¢Â€Â‰=Ã¢Â€Â‰0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2ÃŽÂ²A, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal FPIR, pÃ¢Â€Â‰

AB - Aims/hypothesis The aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2ÃŽÂ² (IA2ÃŽÂ²A) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial. Methods Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2ÃŽÂ²A. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. Results Of 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). IA2ÃŽÂ²A were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2ÃŽÂ²A-positive 65 vs 39% in IA2ÃŽÂ²A-negative, pÃ¢Â€Â‰=Ã¢Â€Â‰0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p Ã¢Â€Â‰=Ã¢Â€Â‰0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2ÃŽÂ²A, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal FPIR, pÃ¢Â€Â‰

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-39049158164&partnerID=8YFLogxK

U2 - 10.1007/s00125-007-0912-9

DO - 10.1007/s00125-007-0912-9

M3 - Article (Academic Journal)

C2 - 18193190

SN - 0012-186X

VL - 51

SP - 488

EP - 492

JO - Diabetologia

JF - Diabetologia

IS - 3

ER -

Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives

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