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
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Antibodies may disappear over time.
“Furthermore, antibodies may disappear over time (26).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 16
- [1]Wenzlau JM Juhl K Yu L The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci USA 2007; 104: 17040– 17045 17942684 PMC2040407
- [2]Zanone MM Catalfamo E Pietropaolo SL Glutamic acid decarboxylase and ICA512/IA-2 autoantibodies as disease markers and relationship to residual beta-cell function and glycemic control in young type 1 diabetic patients. Metabolism 2003; 52: 25– 29 12524658
- [3]Notkins AL Lernmark A Autoimmune type 1 diabetes: resolved and unresolved issues. J Clin Invest 2001; 108: 1247– 1252 11696564 PMC209446
- [4]Hermitte L Atlan-Gepner C Mattei C Diverging evolution of anti-GAD and anti-IA-2 antibodies in long-standing diabetes mellitus as a function of age at onset: no association with complications. Diabet Med 1998; 15: 586– 591 9686699
- [5]Graham J Hagopian WA Kockum I Diabetes Incidence in Sweden Study Group Swedish Childhood Diabetes Study Group Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes. Diabetes 2002; 51: 1346– 1355 11978629
- [6]Falorni A Grubin CE Takei I Radioimmunoassay detects the frequent occurrence of autoantibodies to the Mr 65,000 isoform of glutamic acid decarboxylase in Japanese insulin-dependent diabetes. Autoimmunity 1994; 19: 113– 125 7772701
- [7]Genovese S Bonfanti R Bazzigaluppi E Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM. Diabetologia 1996; 39: 1223– 1226 8897011
- [8]Knip M Kukko M Kulmala P Humoral beta-cell autoimmunity in relation to HLA-defined disease susceptibility in preclinical and clinical type 1 diabetes. Am J Med Genet 2002; 115: 48– 54 12116176
- [9]Savola K Bonifacio E Sabbah E Childhood Diabetes in Finland Study Group IA-2 antibodies—a sensitive marker of IDDM with clinical onset in childhood and adolescence. Diabetologia 1998; 41: 424– 429 9562346
- [10]Qu HQ Polychronakos C The effect of the MHC locus on autoantibodies in type 1 diabetes. J Med Genet 2009; 46: 469– 471 19429597 PMC3270821
- [11]Rich SS Concannon P Erlich H The Type 1 Diabetes Genetics Consortium. Ann N Y Acad Sci 2006; 1079: 1– 8 17130525
- [12]Yu L Rewers M Gianani R Antiislet autoantibodies usually develop sequentially rather than simultaneously. J Clin Endocrinol Metab 1996; 81: 4264– 4267 8954025
- [15]Kawasaki E Takino H Yano M Autoantibodies to glutamic acid decarboxylase in patients with IDDM and autoimmune thyroid disease. Diabetes 1994; 43: 80– 86 8262321
- [16]Hagopian WA Sanjeevi CB Kockum I Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children. J Clin Invest 1995; 95: 1505– 1511 7706455 PMC295633
- [17]Palmer JP C-peptide in the natural history of type 1 diabetes. Diabetes Metab Res Rev 2009; 25: 325– 328 19267337 PMC2895504
- [19]Ellard S Bellanné-Chantelot C Hattersley AT European Molecular Genetics Quality Network (EMQN) MODY group Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008; 51: 546– 553 18297260 PMC2270360
Cited by
Sorted by citations
Holt, R. I. G., DeVries, J. H., Hess-Fischl, A., Hirsch, I. B., Kirkman, M. S., Klupa, T., Ludwig, B., Nørgaard, K., Pettus, J., Renard, E., et al. (2021) · Diabetes Care · doi:10.2337/dci21-0043 · Cited by 699 · see citing works
Lynam, A., McDonald, T., Hill, A., Dennis, J., Oram, R., Pearson, E., Weedon, M., Hattersley, A., Owen, K., Shields, B., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-031586 · Cited by 72 · 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
Gill, M., Chhabra, H., Shah, M., Zhu, C., & Grunberger, G. (2018) · Endocrine Practice · doi:10.4158/ep-2017-0220 · Cited by 8 · see citing works
- Authors
- Tridgell, D. M., Spiekerman, C., Wang, R. S., & Greenbaum, C. J.
- Affiliations
- University of Washington (US)
- Benaroya Research Institute (US)
- Corresponding author
- Spiekerman, Charles
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2011-03-21
- Volume
- 34
- Issue
- 4
- Pages
- 988-993
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC3064062
- OpenAlex
- W2012251106
- Cited by
- 49
- References
- 0
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 8 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 2 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 3
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Juvenile Diabetes Research Foundation International
- University of Washington
- National Human Genome Research Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK062418)
- National Institute of Child Health and Human Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- type 1 diabetes, glutamic acid decarboxylase antibodies, IA-2 autoantibodies, age at diagnosis, disease duration, autoantibody prevalence, antibody persistence, autoantibody detection
- MeSH terms
- Adolescent, Adult, Autoantibodies, Child, Child, Preschool, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, Glutamate Decarboxylase, Humans, Male, Middle Aged, Time Factors, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
