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GAD Antibody Positivity Predicts Type 2 Diabetes in an Adult Population

Author

  • Virve M. Lundgren
  • Bo Isomaa
  • Valeriya Lyssenko
  • Esa Laurila
  • Pasi Korhonen
  • Leif Groop
  • Tiinamaija Tuomi

Summary, in English

OBJECTIVE-To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FHT1) or type 2 diabetes (FHT2) in nondiabetic subjects. RESEARCH DESIGN AND METHODS-GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA(+)-a total of 253 GADA(+) and 2,511 GADA(-) subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis. RESULTS-Subjects within the highest quartile of GADA(+) (GADA(high)(+)) had more often first-degree FHT1 (29.2 vs. 7.9%, P < 0.00001) and GADA(+) type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA(-) subjects. During the follow-up, the GADA(+) subjects developed diabetes significantly more often than the GADA(-) subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA(high)(+) conferred a 4.9-fold increased risk of diabetes (95% CI 2.8-8.5) compared with GADA(-)-seroconversion to positive during the follow-up was associated with 6.5-fold (2.8-15.2) and first-degree FHT1 with 2.2-fold (1.2-4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non-insulin-dependent phenotype 1 year after diagnosis. GADA(+) and GADA(-) subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes. CONCLUSIONS-GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.

Publishing year

2010

Language

English

Pages

416-422

Publication/Series

Diabetes

Volume

59

Issue

2

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X