GAD antibody positivity predicts type 2 diabetes in an adult population.
OBJECTIVE
To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FH(T1)) or type 2 diabetes (FH(T2)) in nondiabetic subjects.


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 FH(T1) (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 FH(T1) 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.
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Virve M
VM
Lundgren
Bo
B
Isomaa
Valeriya
V
Lyssenko
Esa
E
Laurila
Pasi
P
Korhonen
Leif C
LC
Groop
Tiinamaija
T
Tuomi
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology*; D005387:Finland; D005968:Glutamate Decarboxylase / Q000097:blood / Q000276:immunology*; D006801:Humans; D012016:Reference Values
D001323:Autoantibodies; D005968:Glutamate Decarboxylase