High Titer of Autoantibodies to GAD Identifies a Specific Phenotype of Adult-Onset Autoimmune Diabetes
Open accessAbstract
OBJECTIVE—The aim of the present study was to define heterogeneity of adult-onset autoimmune diabetes based on characterization of GAD antibodies (GADAs). RESEARCH DESIGN AND METHODS—Patients enrolled in a nationwide survey, the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study, have been screened for GADAs and IA-2 antibodies (IA-2As) and further characterized for GADA titer, antibodies to thyroid peroxidase (TPO), and HLA DRB1-DQB1 polymorphisms. RESULTS—Of 4,250 consecutive type 2 diabetic patients, 4.5% had either GADAs and/or IA-2As. Patients with autoimmune diabetes showed a clinical phenotype significantly different from that of type 2 diabetes, including higher fasting glucose and A1C, lower BMI and uric acid, lower prevalence of metabolic syndrome and its components, and higher frequency of TPO antibodies. More interestingly, analysis of GADA titers showed a bimodal distribution that identified two subgroups of patients with high (>32 GADA arbitrary units) and low (≤32 GADA arbitrary units) GADA titers. Compared with those with low GADA titers, patients with high GADA titers had more prominent traits of insulin deficiency and a profile of more severe autoimmunity resulting in higher A1C, lower BMI, a lower prevalence of metabolic syndrome and its components (P < 0.02 for all), a higher prevalence of IA-2As, TPO antibodies (P < 0.003 for both), and DRB1*03-DQB1*0201 (50 vs. 26.8%, P = 0.001), and a decreasing frequency of DQB1*0602 and DRB1*0403 (from type 2 to low and to high GADA titer autoimmune diabetes; P < 0.001 for trend for both comparisons). CONCLUSIONS—GADA titers identify two subgroups of patients with adult-onset autoimmune diabetes having distinct clinical, autoimmune, and genetic features.
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?
Compared with people who have T2DM, those with LADA tend to be younger at diagnosis.
“Compared with people who have T2DM, those with LADA tend to be younger at diagnosis, leaner, have faster decline in β-cell function and fewer components of the metabolic syndrome80,81.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [80]
Compared with people who have T2DM, those with LADA tend to have fewer components of the metabolic syndrome.
“Compared with people who have T2DM, those with LADA tend to be younger at diagnosis, leaner, have faster decline in β-cell function and fewer components of the metabolic syndrome80,81.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [80]
Compared with people who have T2DM, those with LADA tend to be leaner.
“Compared with people who have T2DM, those with LADA tend to be younger at diagnosis, leaner, have faster decline in β-cell function and fewer components of the metabolic syndrome80,81.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [80]
Compared with people who have T2DM, those with LADA tend to have faster decline in β-cell function.
“Compared with people who have T2DM, those with LADA tend to be younger at diagnosis, leaner, have faster decline in β-cell function and fewer components of the metabolic syndrome80,81.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [80]
The clinical-association section reports more prominent insulin deficiency in patients with high GADA titers, but that is not a measure of how quickly β-cell function declines. Table 1 compares clinical characteristics of autoimmune and type 2 diabetes; neither it nor the passages found by searching for progression and insulin secretion report comparative rates of β-cell decline. Page numbers were not available in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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
Diagnosis and Classification of Diabetes Mellitus
American Diabetes Association (2006) · Diabetes Care · doi:10.2337/diacare.29.s1.06.s43 · Cited by 924 · see citing works
Diabetes Antibody Standardization Program: first assay proficiency evaluation
Bingley, P. J., Bonifacio, E., Mueller, P. W., & Laboratories, P. (2003) · Diabetes · doi:10.2337/diabetes.52.5.1128 · Cited by 362 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Verge CF, Stenger D, Bonifacio E, Colman PG, Pilcher C, Bingley PJ, Eisenbarth GS: Combined use of autoantibodies (IA-2 autoantibody, GAD autoantibody, insulin autoantibody, cytoplasmic islet cell anti- bodies) in type 1 diabetes: Combinatorial Islet Autoantibody Workshop. Diabetes 47:1857-1866, 1998
Cited by
Sorted by citations
Vigneri, P., Frasca, F., Sciacca, L., Pandini, G., & Vigneri, R. (2009) · Endocrine Related Cancer · doi:10.1677/erc-09-0087 · Cited by 1,009 · see citing works
Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype
Hawa, M. I., Kolb, H., Schloot, N., Beyan, H., Paschou, S. A., Buzzetti, R., Mauricio, D., De Leiva, A., Yderstraede, K., Beck-Neilsen, H., et al. (2013) · Diabetes Care · doi:10.2337/dc12-0931 · Cited by 339 · see citing works
Self-citationAdult-onset autoimmune diabetes: current knowledge and implications for management
Buzzetti, R., Zampetti, S., & Maddaloni, E. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.99 · Cited by 271 · see citing works
Self-citationJones, A. G., McDonald, T. J., Shields, B. M., Hagopian, W., & Hattersley, A. T. (2021) · Diabetes Care · doi:10.2337/dc20-2834 · Cited by 122 · see citing works
Maddaloni, E., Lessan, N., Al Tikriti, A., Buzzetti, R., Pozzilli, P., & Barakat, M. T. (2015) · PLOS ONE · doi:10.1371/journal.pone.0131837 · Cited by 93 · see citing works
Self-citationZampetti, S., Capizzi, M., Spoletini, M., Campagna, G., Leto, G., Cipolloni, L., Tiberti, C., Bosi, E., Falorni, A., Buzzetti, R., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2037 · Cited by 82 · see citing works
Self-citationThe 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
Past, present and future of latent autoimmune diabetes in adults
Liu, B., Xiang, Y., Liu, Z., & Zhou, Z. (2020) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3205 · Cited by 50 · see citing works
Zhu, Y., Qian, L., Liu, Q., Zou, J., Zhou, Y., Yang, T., Huang, G., Zhou, Z., & Liu, Y. (2020) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2019.0007 · Cited by 26 · see citing works
- Authors
- Buzzetti, R., Di Pietro, S., Giaccari, A., Petrone, A., Locatelli, M., Suraci, C., Capizzi, M., Arpi, M. L., Bazzigaluppi, E., Dotta, F., Bosi, E., & for the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study Group
- Affiliations
- Agostino Gemelli University Polyclinic (IT)
- Diabetes Unit Instituto Nazionale Riposo e Cura Anziani (INRCA), Rome, Italy
- Università Cattolica del Sacro Cuore (IT)
- Sapienza University of Rome (IT)
- Bambino Gesù Children's Hospital (IT)
- Ospedale Sandro Pertini (IT)
- University of Catania (IT)
- Vita-Salute San Raffaele University (IT)
- University of Siena (IT)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2007-04-01
- Volume
- 30
- Issue
- 4
- Pages
- 932-938
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2098739800
- Cited by
- 242
- References
- 2
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 12 · 2023: 10 · 2022: 20 · 2021: 14 · 2020: 14 · 2019: 18 · 2018: 22 · 2017: 7 · 2016: 10 · 2015: 11 · 2014: 14 · 2013: 11 · 2012: 16
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Funders
- Novo Nordisk
- 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 › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- glutamic acid decarboxylase antibodies, IA-2 autoantibodies, thyroid peroxidase antibodies, metabolic syndrome, insulin deficiency, type 2 diabetes, disease heterogeneity
- MeSH terms
- Adult, Autoantibodies, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Glutamate Decarboxylase, Humans, Insulin, Italy, Phenotype
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
