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Cited by 339Diabetes and associated disordersDiabetes Management and ResearchAdrenal Hormones and Disorders

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Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype

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Hawa, Mohammed I., Kolb, Hubert, Schloot, Nanette, Beyan, Huriya, Paschou, Stavroula A., Buzzetti, Raffaella, Mauricio, Didac, De Leiva, Alberto, Yderstraede, Knud, Beck-Neilsen, Henning, Tuomilehto, Jaakko, Sarti, Cinzia, Thivolet, Charles, Hadden, David, Hunter, Steven, Schernthaner, Guntram, Scherbaum, Werner A., Williams, Rhys, Brophy, Sinead, Pozzilli, Paolo, Leslie, Richard David, on behalf of the Action LADA consortium·2013·Diabetes Care
DOI 10.2337/dc12-0931PMC PMC3609504
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Abstract

OBJECTIVE: Specific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non–insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes. RESEARCH DESIGN AND METHODS: We consecutively studied 6,156 European diabetic patients attending clinics within 5 years of diagnosis (age range, 30–70 years) examined cross-sectionally clinically and for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 (IA-2A) and zinc-transporter 8 (ZnT8A). RESULTS: Of 6,156 patients, 541 (8.8%) had GADA and only 57 (0.9%) IA-2A or ZnT8A alone. More autoantibody-positive than autoantibody-negative patients were younger, leaner, on insulin (49.5 vs. 13.2%), and female (P < 0.0001 for each), though LADA patients (9.7% of total) did not show categorically distinct clinical features from autoantibody-negative type 2 diabetes. Similarly, more GADA patients with high (>200 World Health Organization IU) (n = 403) compared with low (n = 138) titer were female, lean, and insulin treated (54.6 vs. 39.7%) (P < 0.02 for each). Autoantibody-positive patients usually had GADA (541 of 598; 90.5%) and had LADA more often than type 1 autoimmune diabetes (odds ratio 3.3). CONCLUSIONS: Adult-onset autoimmune diabetes emerges as a prevalent form of autoimmune diabetes. Our results indicate that adult-onset autoimmune diabetes in Europe encompasses type 1 diabetes and LADA in the same broad clinical and autoantibody-positive spectrum. At diagnosis, patients with adult-onset autoimmune diabetes are usually non–insulin requiring and clinically indistinguishable from patients with type 2 diabetes, though they tend to be younger and leaner. Only with screening for autoantibodies, especially GADA, can they be identified with certainty.

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Figure 1 Venn diagram of numbers of patients with GADA, IA-2A, or ZnT8A; n = 598 of 6,156 (9.8%). Of the autoantibody-positive samples, GADA was identified in 90% of the samples when an autoantibody was detected, with IA-2A and ZnT8A accounting for the remaining 10% of the autoantibodies detected. GADA, n = 541 (8.8%); IA-2A, n = 144 (2.3%); and ZnT8A, n = 110 (1.8%).
Figure 1 Venn diagram of numbers of patients with GADA, IA-2A, or ZnT8A; n = 598 of 6,156 (9.8%). Of the autoantibody-positive samples, GADA was identified in 90% of the samples when an autoantibody was detected, with IA-2A and ZnT8A accounting for the remaining 10% of the autoantibodies detected. GADA, n = 541 (8.8%); IA-2A, n = 144 (2.3%); and ZnT8A, n = 110 (1.8%).CC BY-NC-ND · PubMed Central

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Metadata

Authors
Hawa, M. I., Kolb, H., Schloot, N., Beyan, H., Paschou, S. A., Buzzetti, R., Mauricio, D., De Leiva, A., Yderstraede, K., Beck-Neilsen, H., Tuomilehto, J., Sarti, C., Thivolet, C., Hadden, D., Hunter, S., Schernthaner, G., Scherbaum, W. A., Williams, R., Brophy, S., Pozzilli, P., Leslie, R. D., & on behalf of the Action LADA consortium
Affiliations
  • Queen Mary University of London (GB)
  • Heinrich Heine University Düsseldorf (DE)
  • Blizard Institute, Queen Mary University of London, London, U.K.
  • Sapienza University of Rome (IT)
  • Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)
  • Hospital de Sant Pau (ES)
  • Odense University Hospital, Odense, Denmark
  • Odense University Hospital (DK)
  • Finnish Institute for Health and Welfare (FI)
  • Hôpital Edouard Herriot (FR)
  • Royal Victoria Hospital (GB)
  • Krankenanstalt Rudolfstiftung der Stadt Wien (AT)
  • Swansea University (GB)
  • Università Campus Bio-Medico (IT)
Corresponding author
Leslie, Richard David
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2013-03-14
Volume
36
Issue
4
Pages
908-913
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc12-0931
PMC
PMC3609504
OpenAlex
W1969080742
Cited by
339
References
24
Citations by year
2026: 25 · 2025: 22 · 2024: 19 · 2023: 15 · 2022: 33 · 2021: 22 · 2020: 23 · 2019: 29 · 2018: 31 · 2017: 30 · 2016: 23 · 2015: 25 · 2014: 25 · 2013: 16
FWCI
12.87
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
Diabetes Care (publishedVersion, cc-by-nc-nd)
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
latent autoimmune diabetes in adults, type 1 diabetes, glutamic acid decarboxylase antibodies, IA-2 autoantibodies, autoantibody detection, clinical phenotype, type 2 diabetes misdiagnosis, insulin requirement, antibody titers

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