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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.
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“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]
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“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]
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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
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