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. 2011 Apr;34(4):988-93.
doi: 10.2337/dc10-1903. Epub 2011 Feb 17.

Interaction of onset and duration of diabetes on the percent of GAD and IA-2 antibody-positive subjects in the type 1 diabetes genetics consortium database

David M Tridgell  1 , Charles Spiekerman, Richard S Wang, Carla J Greenbaum
Affiliations

Interaction of onset and duration of diabetes on the percent of GAD and IA-2 antibody-positive subjects in the type 1 diabetes genetics consortium database

David M Tridgell et al. Diabetes Care. 2011 Apr.

Abstract

Objective: GAD antibodies (GADA) are more common in type 1 diabetic subjects diagnosed at an older age, whereas insulinoma-antigen 2 antibodies (IA-2A) are more common in subjects with younger onset. The prevalence of both antibodies decreases with longer duration of type 1 diabetes. We evaluated the interaction between age of diagnosis (onset) and duration of diabetes on the percentage of GADA- and IA-2A-positive subjects.

Research design and methods: Data were used from 5,020 individuals with type 1 diabetes obtained from the Type 1 Diabetes Genetics Consortium dataset. The percentages of GADA- and IA-2A-positive subjects were modeled with duration as the continuous independent variable using a modified spline.

Results: Within the first 5 years from diagnosis, 19.4% of individuals (median age 13 years) had neither GADA nor IA-2A, and by 6 to 13 years after diagnosis (median age 18 years), 31.7% were antibody-negative. There was no significant interaction between onset of disease and duration of diabetes for IA-2A (P = 0.30). The interaction was significant for GADA (P = 0.0002), resulting from differences in subjects diagnosed at or older than age 14. For these individuals, there was no apparent effect of duration of disease on the percentage of GADA-positive subjects within the first 5 years of diagnosis.

Conclusions: Onset and duration of diabetes both have an important effect on antibody status. The interaction of onset and duration on GADA positivity, but not on IA-2A, suggests differences in biology. These data provide a context for clinicians to interpret results of autoantibody testing in clinical practice.

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Figures

Figure 1
Figure 1
The percentage of antibody-positive subjects is affected by the onset and duration of type 1 diabetes for GADA (A and C, respectively) and IA-2A (B and D, respectively). Onset was limited to age ≥2 years for panels C and D, as described in the text. Given an increase in the scatter (due to lower numbers of subjects), the x-axis is truncated at both an onset and duration of 30 years. n, number of subjects.
Figure 2
Figure 2
A smoothing function was used to plot the percentage of antibody-positive subjects within each tertile of onset, with duration as a continuous variable for GADA (A), IA-2A (B), and Aby+ (C). Aby+, GADA- and/or IA-2A–positive.
Figure 3
Figure 3
Spline plots modeling onset and duration on the percentage of antibody-positive subjects. The interaction of onset and duration was significant for GADA (A) but not for IA-2A (B) or Aby+ (C). P values for the interaction of onset and duration are shown at the top of each plot. The vertical lines at 5.5 years and 13.5 years indicate breakpoints in the spline, which is the division between the tertiles of duration. Aby+, GADA- and/or IA-2A–positive.
See this image and copyright information in PMC

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