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. 2010 Feb;59(2):416-22.
doi: 10.2337/db09-0747. Epub 2009 Oct 28.

GAD antibody positivity predicts type 2 diabetes in an adult population

Virve M Lundgren  1 , Bo Isomaa, Valeriya Lyssenko, Esa Laurila, Pasi Korhonen, Leif C Groop, Tiinamaija Tuomi; Botnia Study Group
Affiliations

GAD antibody positivity predicts type 2 diabetes in an adult population

Virve M Lundgren et al. Diabetes. 2010 Feb.

Abstract

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.

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 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.

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Figures

FIG. 1.
FIG. 1.
Flowchart showing the number of relatives and control subjects at baseline and during the follow-up according to GADA positivity and progression to diabetes (DM).
FIG. 2.
FIG. 2.
The proportion of nondiabetic subjects having any GADA+ relatives (■), GADA+ nondiabetic relatives (▤), GADA+ type 2 diabetic relatives (LADA, □), or type 1 diabetic relatives (formula image) according to strength of GADA positivity. P < 0.0001, GADA+high versus GADA− regarding subjects having any GADA+ relatives or type 1 diabetic relatives; P = 0.002, GADA+high versus GADA− regarding subjects having GADA+ type 2 diabetic relatives; P = 0.01, GADA+high versus GADA− regarding subjects having nondiabetic GADA+ relatives.
FIG. 3.
FIG. 3.
Development of diabetes according to strength of GADA positivity: GADAs in the highest quartile (GADA+high) or three lower quartiles of positivity (GADA+low/med) or no GADA (GADA−). The data are adjusted for age, sex, and BMI. The y-axis shows the cumulative proportion of subjects without diabetes; the x-axis shows the follow-up time in years (P < 0.00001, Cox proportional hazards model).
See this image and copyright information in PMC

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