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. 2015 Jun 25;3(1):e000076.
doi: 10.1136/bmjdrc-2014-000076. eCollection 2015.

Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study

Elin Pettersen Sørgjerd  1 , Per M Thorsby  2 , Peter A Torjesen  2 , Frank Skorpen  3 , Kirsti Kvaløy  1 , Valdemar Grill  4
Affiliations

Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study

Elin Pettersen Sørgjerd et al. BMJ Open Diabetes Res Care. .

Abstract

Background: It is well known that anti-GAD (glutamic acid decarboxylase) serves as a marker for development of autoimmune diabetes in adults. On the other hand, the clinical implications of anti-GAD positivity in persistently non-diabetic (PND) adults are poorly elucidated. Our aim was to establish the frequency of anti-GAD in PNDs in an all-population-based cohort from the Nord-Trøndelag health study (HUNT) and to prospectively test for associations with glucose tolerance and thyroid autoimmunity.

Methods: We formed a primary study population (4496 individuals), selected randomly from the age group 20-90 years (50% men/women), who were non-diabetic both at HUNT2 (1995-1997) and HUNT3 (2006-2008). Anti-GAD-positive individuals at HUNT2, together with anti-GAD-negative individuals aged 20-29 years, were retested for anti-GAD positivity at HUNT3. A secondary study population consisted of individuals with type 2 diabetes (T2D, n=349) at HUNT3 who developed diabetes between HUNT2 and HUNT3.

Results: The frequency of anti-GAD positivity in PND was 1.7% (n=76) at HUNT2. Positivity did not associate with gender, family history of diabetes, or glucose levels, but was associated with thyroid-associated autoimmunity (increased frequency of positivity for anti-TPO (thyroid peroxidase), p<0.002). HLA-DQA1/DQB1, a risk haplotype for autoimmunity, was also associated with anti-GAD positivity in PND. The incidence of anti-GAD positivity was low (0.4%) in the subsample of individuals who were anti-GAD negative in HUNT2. Anti-GAD positivity in PNDs was frequently evanescent, with 54% losing, usually low-grade, positivity between HUNT2 and HUNT3. An evanescent state of autoimmunity as assessed by anti-GAD positivity during "pre-diabetes" in individuals later diagnosed with T2D could, however, not be affirmed.

Conclusions: Anti-GAD positivity in PND is associated with HLA risk haplotypes and thyroid autoimmunity but not with clinical parameters of diabetes. Fleeting anti-GAD positivity is common; however, results do not support the notion of a history of autoimmunity in T2D in the present cohort.

Keywords: Adult Diabetes; Autoantibodies; Autoimmunity.

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Figures

Figure 1
Figure 1
Flow sheet over the primary study population as well as comparative individuals of “pre-diabetic” individuals followed from HUNT2 to HUNT3 (GAD, glutamic acid decarboxylase; neg, negative; pos, positive).
Figure 2
Figure 2
Frequency of anti-GAD (glutamic acid decarboxylase) positivity in the adult population of the HUNT2 survey distributed across different age categories.
See this image and copyright information in PMC

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