GADA Titer-Related Risk for Organ-Specific Autoimmunity in LADA Subjects Subdivided according to Gender (NIRAD Study 6)
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CONTEXT: Latent autoimmune diabetes in adults (LADA) includes a heterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. OBJECTIVE: The aim of the present study was to evaluate GADA titer-related risk for β-cell and other organ-specific autoimmunity in LADA subjects. METHODS: Adult-onset autoimmune diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. RESULTS: High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P≤0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for trend≤0.001). TPO was the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P=0.0004 and P=0.0006, respectively), where the presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P<0.0001). CONCLUSIONS: In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender.
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The prevalence of several autoantibodies associated with type 1 diabetes mellitus tends to decrease with increasing age at diagnosis, but glutamic acid decarboxylase antibody remains the dominant autoantibody in adult-onset type 1 diabetes mellitus regardless of ethnicity.
“Although the prevalence of several autoantibodies associated with T1DM tends to decrease with increasing age at diagnosis61, GADA remains the dominant autoantibody in adult-onset T1DM regardless of ethnicity62–64.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [62]
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- Authors
- Zampetti, S., Capizzi, M., Spoletini, M., Campagna, G., Leto, G., Cipolloni, L., Tiberti, C., Bosi, E., Falorni, A., Buzzetti, R., & for the NIRAD Study Group
- Affiliations
- Sapienza University of Rome (IT)
- Vita-Salute San Raffaele University (IT)
- University of Perugia (IT)
- Corresponding author
- Buzzetti, Raffaella
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-10-01
- Volume
- 97
- Issue
- 10
- Pages
- 3759-3765
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2001072123
- Cited by
- 82
- References
- 33
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 18 · 2019: 6 · 2018: 11 · 2017: 2 · 2016: 8 · 2015: 4 · 2014: 4 · 2013: 8
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- Novo Nordisk
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- latent autoimmune diabetes in adults, organ-specific autoimmunity, thyroid peroxidase antibodies, thyroid autoimmunity, IA-2 autoantibodies, zinc transporter 8 antibodies, anti-tissue transglutaminase antibodies, type 2 diabetes, sex differences, autoantibody profile
- MeSH terms
- Adult, Autoantibodies, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Glutamate Decarboxylase, Humans, Male, Middle Aged, Risk Factors, Thyroid Gland, Autoimmunity, Seroepidemiologic Studies, Age of Onset, Sex Distribution, Insulin-Secreting Cells
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