The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Latent Autoimmune Diabetes of Adults (LADA) Is Likely to Represent a Mixed Population of Autoimmune (Type 1) and Nonautoimmune (Type 2) Diabetes
Open accessAbstract
Latent autoimmune diabetes of adults (LADA) is typically defined as a new diabetes diagnosis after 35 years of age, presenting with clinical features of type 2 diabetes, in whom a type 1 diabetes–associated islet autoantibody is detected. Identifying autoimmune diabetes is important since the prognosis and optimal therapy differ. However, the existing LADA definition identifies a group with clinical and genetic features intermediate between typical type 1 and type 2 diabetes. It is unclear whether this is due to 1) true autoimmune diabetes with a milder phenotype at older onset ages that initially appears similar to type 2 diabetes but later requires insulin, 2) a disease syndrome where the pathophysiologies of type 1 and type 2 diabetes are both present in each patient, or 3) a heterogeneous group resulting from difficulties in classification. Herein, we suggest that difficulties in classification are a major component resulting from defining LADA using a diagnostic test—islet autoantibody measurement—with imperfect specificity applied in low-prevalence populations. This yields a heterogeneous group of true positives (autoimmune type 1 diabetes) and false positives (nonautoimmune type 2 diabetes). For clinicians, this means that islet autoantibody testing should not be undertaken in patients who do not have clinical features suggestive of autoimmune diabetes: in an adult without clinical features of type 1 diabetes, it is likely that a single positive antibody will represent a false-positive result. This is in contrast to patients with features suggestive of type 1 diabetes, where false-positive results will be rare. For researchers, this means that current definitions of LADA are not appropriate for the study of autoimmune diabetes in later life. Approaches that increase test specificity, or prior likelihood of autoimmune diabetes, are needed to avoid inclusion of participants who have nonautoimmune (type 2) diabetes. Improved classification will allow improved assignment of prognosis and therapy as well as an improved cohort in which to analyze and better understand the detailed pathophysiological components acting at onset and during disease progression in late-onset autoimmune diabetes.
Overview
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
Verification
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?
The cited source doesn’t support the claim as written.
In the citing paper
“It is considered a variant of T1DM that is somewhat enriched for T2DM features and typically progresses more slowly than does classic autoimmune T1DM in children and young adults74.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [74]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Diagnostic accuracy may be improved by using higher-specificity tests, using confirmatory testing for other autoantibodies, and restricting testing to those with clinical features suggestive of autoimmune diabetes (48).”
From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [48]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Baekkeskov, S., Aanstoot, H.-J., Christgai, S., Reetz, A., Solimena, M., Cascalho, M., Folli, F., Richter-Olesen, H., & Camilli, P.-D. (1990) · Nature · doi:10.1038/347151a0 · Cited by 1,964
ISLET-CELL ANTIBODIES IN DIABETES MELLITUS WITH AUTOIMMUNE POLYENDOCRINE DEFICIENCIES
Bottazzo, G., Florin-Christensen, A., & Doniach, D. (1974) · The Lancet · doi:10.1016/s0140-6736(74)90140-8 · Cited by 1,469
Insulin antibodies in insulin-dependent diabetics before insulin treatment
Palmer, J. P., Asplin, C. M., Clemons, P., Lyen, K., Tatpati, O., Raghu, P. K., & Paquette, T. L. (1983) · Science · doi:10.1126/science.6362005 · Cited by 1,078
Turner, R., Stratton, I., Horton, V., Manley, S., Zimmet, P., Mackay, I. R., Shattock, M., Bottazzo, G. F., & Holman, R. (1997) · The Lancet · doi:10.1016/s0140-6736(97)03062-6 · Cited by 779
Interpretation by Physicians of Clinical Laboratory Results
Casscells, W., Schoenberger, A., & Graboys, T. B. (1978) · New England Journal of Medicine · doi:10.1056/nejm197811022991808 · Cited by 765
The clinical utility of C‐peptide measurement in the care of patients with diabetes
Jones, A. G., & Hattersley, A. T. (2013) · Diabetic Medicine · doi:10.1111/dme.12159 · Cited by 666
Self-citationTuomi, T., Groop, L., Zimmet, P., Rowley, M. J., Knowles, W. J., & Mackay, I. R. (1993) · Diabetes · doi:10.2337/diab.42.2.359 · Cited by 578
Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies.
Tuomi, T., Carlsson, A., Li, H., Isomaa, B., Miettinen, A., Nilsson, A.-L., Nissén, M., Ehrnström, B. O., Forsén, B., Snickars, B., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.1.150 · Cited by 504
Mechanisms of Autoantibody-Induced Pathology
Ludwig, R. J., Vanhoorelbeke, K., Leypoldt, F., Kaya, Z., Bieber, K., McLachlan, S. M., Komorowski, L., Luo, J., Cabral-Marques, O., Hammers, C. M., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00603 · Cited by 491
Thomas, N. J., Jones, S. E., Weedon, M. N., Shields, B. M., Oram, R. A., & Hattersley, A. T. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30362-5 · Cited by 417
Self-citationZimmet, P., Tuomi, T., Mackay, I. R., Rowley, M. J., Knowles, W., Cohen, M., & Lang, D. A. (1994) · Diabetic Medicine · doi:10.1111/j.1464-5491.1994.tb00275.x · Cited by 413
Bækkeskov, S., Aanstoot, H., Christgau, S., Reetz, A., Solimena, M., Cascalho, M., Folli, F. B., Richter-Olesen, H., & Camilli, P. V. D. (1990) · Nature · doi:10.1038/347782a0 · Cited by 352
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
Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity
Suurmond, J., & Diamond, B. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78084 · Cited by 335
Buzzetti, R., Tuomi, T., Mauricio, D., Pietropaolo, M., Zhou, Z., Pozzilli, P., & Leslie, R. D. (2020) · Diabetes · doi:10.2337/dbi20-0017 · Cited by 305
Islet Cell Antibodies Identify Latent Type I Diabetes in Patients Aged 35–75 Years at Diagnosis
Groop, L., Bottazzo, G. F., & Doniach, D. (1986) · Diabetes · doi:10.2337/diab.35.2.237 · Cited by 297
Irvine, W. J., McCallum, C. J., Gray, R. S., Campbell, C. J., Duncan, L. J. P., Farquhar, J. W., Vaughan, H., & Morris, P. J. (1977) · Diabetes · doi:10.2337/diab.26.2.138 · Cited by 282
Clinical Applications of Diabetes Antibody Testing
Bingley, P. J. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1365 · Cited by 278
Adult-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
Hagopian, W., SANJEEVI, C. B., Kockum, I. S., Landin‐Olsson, M., Karlsen, A. E., Sundkvist, G., Dahlquist, G. G., Palmer, J. P., & Lernmark, Å. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117822 · Cited by 251
Self-citationZhou, Z., Xiang, Y., Ji, L., Jia, W., Ning, G., Huang, G., Yang, L., Lin, J., Liu, Z., Hagopian, W. A., et al. (2013) · Diabetes · doi:10.2337/db12-0207 · Cited by 251
Self-citationBuzzetti, R., Di Pietro, S., Giaccari, A., Petrone, A., Locatelli, M., Suraci, C., Capizzi, M., Arpi, M. L., Bazzigaluppi, E., Dotta, F., et al. (2007) · Diabetes Care · doi:10.2337/dc06-1696 · Cited by 242
ISLET-CELL ANTIBODIES IN JUVENILE DIABETES MELLITUS OF RECENT ONSET
Lendrum, R., Walker, G., & Gamble, D. R. (1975) · The Lancet · doi:10.1016/s0140-6736(75)91683-9 · Cited by 222
Diagnostic testing and interpretation of tests for autoimmunity
Castro, C., & Gourley, M. F. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.09.041 · Cited by 213
Classification of diabetes mellitus.
Borg, W. P., & Rs, S. (2000) · PubMed · Cited by 206
Zinman, B., Kahn, S. E., Haffner, S. M., O’Neill, M., Heise, M. A., Freed, M. I., & ADOPT Study Group* (2004) · Diabetes · doi:10.2337/diabetes.53.12.3193 · Cited by 198
Hagopian, W., Karlsen, A. E., Gottsäter, A., Landin‐Olsson, M., Grubin, C. E., Sundkvist, G., Petersen, J. S., Boel, E., Dyrberg, T., & Lernmark, Å. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116195 · Cited by 198
Self-citationClassification of Diabetes Mellitus
Irani, A. J. (2015) · Jaypee Brothers Medical Publishers (P) Ltd. eBooks · doi:10.5005/jp/books/12855_84 · Cited by 197
Thomas, N. J., Lynam, A. L., Hill, A. V., Weedon, M. N., Shields, B. M., Oram, R. A., McDonald, T. J., Hattersley, A. T., & Jones, A. G. (2019) · Diabetologia · doi:10.1007/s00125-019-4863-8 · Cited by 183
Self-citationThe Presence of GAD and IA-2 Antibodies in Youth With a Type 2 Diabetes Phenotype
KLINGENSMITH, G. J., Pyle, L., Arslanian, S. A., Copeland, K. C., Cuttler, L., KAUFMAN, F. R., Laffel, L. M., Marcovina, S. M., Tollefsen, S. E., Weinstock, R. S., et al. (2010) · Diabetes Care · doi:10.2337/dc10-0373 · Cited by 170
GAD Antibodies in NIDDM: Ten-year follow-up from the diagnosis
NISKANEN, L. K., Tuomi, T., Karjalainen, J., Groop, L., & Uusitupa, M. I. J. (1995) · Diabetes Care · doi:10.2337/diacare.18.12.1557 · Cited by 163
Lampasona, V., Petrone, A., Tiberti, C., Capizzi, M., Spoletini, M., di Pietro, S., Songini, M., Bonicchio, S., Giorgino, F., Bonifacio, E. E., et al. (2009) · Diabetes Care · doi:10.2337/dc08-2305 · Cited by 159
Cousminer, D. L., Ahlqvist, E., Mishra, R., Andersen, M. K., Chesi, A., Hawa, M. I., Davis, A. K., Hodge, K. M., Bradfield, J. P., Zhou, K., et al. (2018) · Diabetes Care · doi:10.2337/dc18-1032 · Cited by 140
Davis, T. M. E., Zimmet, P., Davis, W. A., Bruce, D. G., Fida, S., & Mackay, I. R. (2000) · Diabetic Medicine · doi:10.1046/j.1464-5491.2000.00359.x · Cited by 130
Radtke, M., Midthjell, K., Nilsen, T. I. L., & Grill, V. (2008) · Diabetes Care · doi:10.2337/dc08-1468 · Cited by 105
Lampasona, V., Pittman, D. L., Williams, A. J., Achenbach, P., Schlosser, M., Akolkar, B., Winter, W. E., Laboratories, P., Watson, K., Weets, I., et al. (2019) · Clinical Chemistry · doi:10.1373/clinchem.2019.304196 · Cited by 103
Self-citationMaddaloni, 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
Hjort, R., Ahlqvist, E., Carlsson, P., Grill, V., Groop, L., Martinell, M., Rasouli, B. S., Rosengren, A. H., Tuomilehto, J., Åsvold, B. O., et al. (2018) · Diabetologia · doi:10.1007/s00125-018-4596-0 · Cited by 93
Study, B. M. D. I. C., Mishra, R., Chesi, A., Cousminer, D. L., Hawa, M. I., Bradfield, J. P., Hodge, K. M., Guy, V. C., Hakonarson, H. H., Mauricio, D., et al. (2017) · BMC Medicine · doi:10.1186/s12916-017-0846-0 · Cited by 89
Maioli, M., Pes, G. M., Delitala, G., Puddu, L., Falorni, A., Tolu, F., Lampis, R., Orrù, V., Secchi, G., Cicalo, A., et al. (2010) · European Journal of Endocrinology · doi:10.1530/eje-10-0427 · Cited by 81
Falorni, A., Gambelunghe, G., Forini, F., Kassi, G., Cosentino, A., Candeloro, P., Bolli, G. B., Brunetti, P., & Calcinaro, F. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.1.6301 · Cited by 80
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
Self-citationIrvine, W. J., Sawers, J. S. A., Feek, C. M., Prescott, R. J., & Duncan, L. J. P. (1979) · PubMed · Cited by 65
Sabbah, E., Kulmala, P., Veijola, R., Vähäsalo, P., Karjalainen, J., Tuomilehto‐Wolf, E., Åkerblom, H. K., & Knip, M. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.7.8675560 · Cited by 60
Clinical phenotype and β-cell autoimmunity in Italian patients with adult-onset diabetes
Genovese, S., Bazzigaluppi, E., Gonçalves, D., Ciucci, A., Cavallo, M. G., Purrello, F., Anello, M., Rotella, C. M., Bardini, G., Vaccaro, O., et al. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02115 · Cited by 59
Falorni, A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.1.309 · Cited by 58
Achenbach, P., Hawa, M. I., Krause, S., Lampasona, V., Jerram, S. T., Williams, A. J. K., Bonifacio, E. E., Ziegler, A. G., & Leslie, R. D. G. (2018) · Diabetologia · doi:10.1007/s00125-018-4605-3 · Cited by 51
Grubb, A. L., McDonald, T. J., Rutters, F., Donnelly, L. A., Hattersley, A. T., Oram, R. A., Palmer, C. N. A., van der Heijden, A. A. W. A., Carr, F., Elders, P. J. M., et al. (2018) · Diabetes Care · doi:10.2337/dc18-0431 · Cited by 51
Self-citationImplications of the impact of prevalence on test thresholds and outcomes: lessons from tuberculosis
Bentley, T. G. K., Catanzaro, A., & Ganiats, T. G. (2012) · BMC Research Notes · doi:10.1186/1756-0500-5-563 · Cited by 49
Williams, A. J. K., Lampasona, V., Schlosser, M., Mueller, P. W., Pittman, D. L., Winter, W. E., Akolkar, B., Wyatt, R., Brigatti, C., Krause, S., et al. (2015) · Diabetes · doi:10.2337/db14-1693 · Cited by 46
Demographic associations for autoantibodies in disease-free individuals of a European population
Haller‐Kikkatalo, K., Alnek, K., Metspalu, A., Mihailov, E., Metsküla, K., Kisand, K., Pisarev, H., Salumets, A., & Uibo, R. (2017) · Scientific Reports · doi:10.1038/srep44846 · Cited by 31
Autoimmunity plays a role in the onset of diabetes after 40 years of age
Rolandsson, O., Hampe, C. S., Sharp, S. J., Ardanáz, E., Boeing, H., Fagherazzi, G., Mancini, F. R., Nilsson, P. M., Overvad, K., Chirlaque, M., et al. (2019) · Diabetologia · doi:10.1007/s00125-019-05016-3 · Cited by 23
Dabelea, D., Ma, Y., Knowler, W. C., Marcovina, S. M., Saudek, C. D., Arakaki, R., White, N. H., Kahn, S. E., Orchard, T. J., Goldberg, R. B., et al. (2014) · Diabetic Medicine · doi:10.1111/dme.12437 · Cited by 18
Batstra, M. R., van Driel, A., Petersen, J. S., van Donselaar, C. A., van Tol, M. J., Bruining, G. J., Grobbee, D. E., Dyrberg, T., & Aanstoot, H. (1999) · Clinical Chemistry · doi:10.1093/clinchem/45.12.2269 · Cited by 18
Genetic Aspects of Latent Autoimmune Diabetes in Adults: A Mini-Review
Andersen, M. K., & Hansen, T. F. (2018) · Current Diabetes Reviews · doi:10.2174/1573399814666180730123226 · Cited by 17
Flagged first, then by citations
Cited by
Sorted by citations
2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024
American Diabetes Association Professional Practice Committee, ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Ekhlaspour, L., Gaglia, J. L., Hilliard, M. E., Johnson, E. L., et al. (2024) · Diabetes Care · doi:10.2337/dc24-s002 · Cited by 2,086
2. Diagnosis and classification of diabetes: standards of care in diabetes-2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Ebekozien, O., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s002 · Cited by 1,393
2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2026
American Diabetes Association Professional Practice Committee for Diabetes*, Bajaj, M., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Briggs Early, K., ChallaSivaKanaka, S., et al. (2026) · Diabetes Care · doi:10.2337/dc26-s002 · Cited by 473
Adult-Onset Type 1 Diabetes: Current Understanding and Challenges
Leslie, R. D., Evans‐Molina, C., Freund-Brown, J., Buzzetti, R., Dabelea, D., Gillespie, K. M., Goland, R., Jones, A. G., Kacher, M. L., Phillips, L. S., et al. (2021) · Diabetes Care · doi:10.2337/dc21-0770 · Cited by 288
Self-citationHeterogeneity and endotypes in type 1 diabetes mellitus
REDONDO, M. J., & Morgan, N. G. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00853-0 · Cited by 182
Metadata
- Authors
- Jones, A. G., McDonald, T. J., Shields, B. M., Hagopian, W., & Hattersley, A. T.
- Affiliations
- University of Exeter (GB)
- Pacific Northwest Research Institute, Seattle, WA
- Corresponding author
- Jones, Angus G.
- Hattersley, Andrew T.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2021-06-01
- Volume
- 44
- Issue
- 6
- Pages
- 1243-1251
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC8247509
- OpenAlex
- W3161458931
- Cited by
- 122
- References
- 55
- Citations by year
- 2026: 28 · 2025: 21 · 2024: 24 · 2023: 20 · 2022: 20 · 2021: 9
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (acceptedVersion)
- Figshare (submittedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion, public-domain)
- Funders
- Wellcome Trust (098395/Z/12/Z)
- National Institute for Health and Care Research (ICA-SCL-2016-02-003, CS-2015-15-018)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK063829)
- 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, type 2 diabetes, islet autoantibodies, diagnostic specificity, false positives, disease classification, disease heterogeneity, diagnostic criteria
- MeSH terms
- Latent Autoimmune Diabetes in Adults, Adult, Autoantibodies, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Insulin
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
