Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study
Open accessAbstract
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.
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Detectable GADA are present in individuals without diabetes mellitus.
“GADA positivity does not confirm the presence of LADA or adult-onset T1DM; detectable GADA are present in individuals without diabetes mellitus89.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [89]
GADA positivity does not confirm the presence of LADA or adult-onset T1DM.
“GADA positivity does not confirm the presence of LADA or adult-onset T1DM; detectable GADA are present in individuals without diabetes mellitus89.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [89]
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Riddle, M. C., Philipson, L. H., Rich, S. S., Carlsson, A., Franks, P. W., Greeley, S. A. W., Nolan, J. J., Pearson, E. R., Zeitler, P. S., & Hattersley, A. T. (2020) · Diabetes Care · doi:10.2337/dci20-0065 · Cited by 117 · see citing works
The epidemiology of type 1 diabetes mellitus in older adults
Tomic, D., Harding, J. L., Jenkins, A. J., Shaw, J. E., & Magliano, D. J. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01046-z · Cited by 58 · see citing works
“GADA positivity does not confirm the presence of LADA or adult-onset T1DM; detectable GADA are present in individuals without diabetes mellitus 89 .”
- Authors
- Sørgjerd, E. P., Thorsby, P. M., Torjesen, P. A., Skorpen, F., Kvaløy, K., & Grill, V.
- Affiliations
- Norwegian University of Science and Technology (NO)
- Oslo University Hospital (NO)
- Corresponding author
- Sørgjerd, Elin Pettersen
- Venue
- BMJ Open Diabetes Research & Care
- Publisher
- BMJ
- Published
- 2015-06
- Volume
- 3
- Issue
- 1
- Pages
- e000076
- ISSN
- 2052-4897 (ISSN-L)
- PMC
- PMC4486684
- OpenAlex
- W2115641328
- Cited by
- 71
- References
- 0
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 14 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 3
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open Diabetes Research & Care (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- BIBSYS Brage (BIBSYS (Norway)) (acceptedVersion, other-oa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc)
- Funders
- Norges Teknisk-Naturvitenskapelige Universitet
- Helse Midt-Norge
- St. Olavs Hospital Universitetssykehuset i Trondheim
- Norwegian Institute of Public Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glutamic acid decarboxylase antibodies, glutamic acid decarboxylase, autoimmune diabetes, type 2 diabetes, thyroid autoimmunity, thyroid peroxidase antibodies, glucose tolerance, prediabetes, HUNT study, non-diabetic adults
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