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GAD Antibody Positivity Predicts Type 2 Diabetes in an Adult Population

Lundgren, Virve M. ; Isomaa, Bo ; Lyssenko, Valeriya LU ; Laurila, Esa LU ; Korhonen, Pasi ; Groop, Leif LU and Tuomi, Tiinamaija (2010) In Diabetes 59(2). p.416-422
Abstract
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 =... (More)
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. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
59
issue
2
pages
416 - 422
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000274435900012
  • scopus:77449143964
  • pmid:19864397
ISSN
1939-327X
DOI
10.2337/db09-0747
language
English
LU publication?
yes
id
f669a30e-a8b2-419d-88ec-e40993438e13 (old id 1568953)
date added to LUP
2016-04-01 13:23:49
date last changed
2022-02-11 20:57:45
@article{f669a30e-a8b2-419d-88ec-e40993438e13,
  abstract     = {{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 &lt; 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 &lt; 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.}},
  author       = {{Lundgren, Virve M. and Isomaa, Bo and Lyssenko, Valeriya and Laurila, Esa and Korhonen, Pasi and Groop, Leif and Tuomi, Tiinamaija}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{416--422}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{GAD Antibody Positivity Predicts Type 2 Diabetes in an Adult Population}},
  url          = {{http://dx.doi.org/10.2337/db09-0747}},
  doi          = {{10.2337/db09-0747}},
  volume       = {{59}},
  year         = {{2010}},
}