Keywords
latent autoimmune diabetes of adults
diabetes mellitus type 1.5
diabetes mellitus type 1
diabetes mellitus type 2
diabetes complications
How to Cite
Abstract
Context: Latent autoimmune diabetes in adults (LADA) is a form of diabetes with clinical, immunological, and pathophysiological features that overlap with type 1 and type 2 diabetes. Its diagnosis is often delayed or misclassified as type 2 diabetes, which can negatively affect patient outcomes.
Objective: To describe the diagnostic criteria, clinical phenotypes, associated complications, and current therapeutic options in patients with LADA.
Methodology: A narrative review was conducted based on a non-systematic collection of the available scientific literature. Databases such as PubMed and Scopus were consulted, selecting relevant observational studies, clinical trials, reviews, and expert consensus documents. Articles in English and Spanish were included, without applying additional formal inclusion criteria or methodological assessment.
Results: The review highlights the proposed diagnostic criteria, clinical phenotypes based on autoantibody titers, and their associations with metabolic and autoimmune characteristics. Microvascular and macrovascular complications are discussed, along with current therapeutic strategies aimed at preserving beta-cell function.
Conclusions: LADA is an underdiagnosed condition that requires clinical suspicion and autoantibody testing in adults with recent-onset diabetes. Early identification can prevent inappropriate treatments and enable interventions that may preserve pancreatic function and improve long-term outcomes.
References
Buzzetti R, Zampetti S, Maddaloni E. Adult-onset autoimmune diabetes: Current knowledge and implications for management. Nat Rev Endocrinol. 2017;13:674–686. https://doi.org/10.1038/nrendo.2017.99
Buzzetti R, Tuomi T, Mauricio D, Pietropaolo M, Zhou Z, Pozzilli P, et al. Management of latent autoimmune diabetes in adults: A consensus statement from an international expert panel. Diabetes. 2020;69(10):2037–2047. https://doi.org/10.2337/dbi20-0017
Cabrera Rode E, Licea Puig ME. Nueva definición, prevalencia, caracterización y tratamiento de la diabetes autoinmune latente del adulto. Rev Cuba Endocrinol. 2008;19(1).
Pozzilli P, Pieralice S. Latent autoimmune diabetes in adults: Current status and new horizons. Endocrinol Metab (Seoul). 2018;33(2):147–159. https://doi.org/10.3803/EnM.2018.33.2.147
Ramu D, Ramaswamy S, Rao S, Paul SFD. The worldwide prevalence of latent autoimmune diabetes of adults among adult-onset diabetic individuals: A systematic review and meta-analysis. Endocrine. 2023;82:28–41. https://doi.org/10.1007/s12020-023-03424-5
Pollak CF, Vásquez AT. Diabetes autoinmune (latente) del adulto. Rev Med Chile. 2012;140(11):1476–1481. https://doi.org/10.4067/S0034-98872012001100015
Ravikumar V, Ahmed A, Anjankar A. A review on latent autoimmune diabetes in adults. Cureus. 2023;15(10):e47915. https://doi.org/10.7759/cureus.47915
Deutsch AJ, Ahlqvist E, Udler MS. Phenotypic and genetic classification of diabetes. Diabetologia. 2022;65:1758–1769. https://doi.org/10.1007/s00125-022-05769-4
Sørgjerd EP, Skorpen F, Kvaløy K, Midthjell K, Grill V. Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: The HUNT study, Norway. Diabetologia. 2012;55(2012):1310–1318. https://doi.org/10.1007/s00125-012-2463-y
Huang G, Yin M, Xiang Y, Li X, Shen W, Luo S, et al. Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: A prospective study with 3-year follow-up. Diabetes Metab Res Rev. 2016;32(6):615–622. https://doi.org/10.1002/dmrr.2779
Hernandez M, Mollo A, Marsal JR, Esquerda A, Capel I, Puig-Domingo M, et al. Insulin secretion in patients with latent autoimmune diabetes (LADA): Half way between type 1 and type 2 diabetes: Action LADA 9. BMC Endo Dis. 2015;15(1):1. https://doi.org/10.1186/1472-6823-15-1
American Diabetes Association Professional Practice Committee for Diabetes. 2. Diagnosis and classification of diabetes: Standards of care in diabetes—2026. Diabetes Care. 2026;49(S1):S27–49. https://doi.org/10.2337/dc26-S002
Pieralice S, Pozzilli P. Latent autoimmune diabetes in adults: A review on clinical implications and management. Diabetes Metab J. 2018;42(6):451–464. https://doi.org/10.4093/dmj.2018.0190
Fourlanos S, Perry C, Stein MS, Stankovich J, Harrison LC, Colman PG. A clinical screening tool identifies autoimmune diabetes in adults. Diabetes Care. 2006;29(5):970–975. https://doi.org/10.2337/diacare.295970
Monge L, Bruno G, Pinach S, Grassi G, Maghenzani G, Dani F, et al. A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic-based cohort of patients with diabetes onset over 50 years. Diabet Med. 2004;21(5):456–459. https://doi.org/10.1111/j.1464-5491.2004.01177.x
Davies H, Brophy S, Fielding A, Bingley P, Chandler M, Hilldrup I, et al. Latent autoimmune diabetes in adults (LADA) in South Wales: Incidence and characterization. Diabet Med. 2008;25(11):1354–1357. https://doi.org/10.1111/j.1464-5491.2008.02580.x
Szepietowska B, G??bocka A, Puch U, Gorska M, Szelachowska M. Latent autoimmune diabetes in adults in a population-based cohort of Polish patients with newly diagnosed diabetes mellitus. Arch Med Sci. 2012;8(3):491–495. https://doi.org/10.5114/aoms.2012.29405
Hjort R, Ahlqvist E, Carlsson PO, Grill V, Groop L, Martinell M, et al. Overweight, obesity and the risk of LADA: Results from a Swedish case-control study and the Norwegian HUNT Study. Diabetologia. 2018;61:1333–1343. https://doi.org/10.1007/s00125-018-4596-0
Krokstad S, Langhammer A, Hveem K, Holmen TL, Midthjell K, Stene TR, et al. Cohort profile: the HUNT study, Norway. Int J Epidemiol. 2013;42(4):968–977. https://doi.org/10.1093/ije/dys095
Schloot NC, Pham MN, Hawa MI, Pozzilli P, Scherbaum WA, Schott M, et al. Inverse relationship between organ-specific autoantibodies and systemic immune mediators in type 1 diabetes and type 2 diabetes: Action LADA 11. Diabetes Care. 2016;39(11):1932–1939. https://doi.org/10.2337/dc16-0293
Lundholm MD, Zhou K. Latent autoimmune diabetes in adults: Not type 1, not type 2, a little of both. Cleve Clin J Med. 2025;92(12):757–763. https://doi.org/10.3949/ccjm.92a.25069
Myhill P, Davis WA, Bruce DG, Mackay IR, Zimmet P, Davis TME. Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: The Fremantle Diabetes Study. Diabet Med. 2008;25(10):1245–1250. https://doi.org/10.1111/j.1464-5491.2008.02562.x
Lu J, Hou X, Zhang L, Hu C, Zhou J, Pang C, et al. Associations between clinical characteristics and chronic complications in latent autoimmune diabetes in adults and type 2 diabetes. Diabet Metab Res Rev. 2015;31(4):411–420. https://doi.org/10.1002/dmrr.2626
Isomaa B, Almgren P, Henricsson M, Taskinen MR, Tuomi T, Groop L, et al. Chronic complications in patients with slowly progressing autoimmune type 1 diabetes (LADA). Diabetes Care. 1999;22(8):1347–1353. https://doi.org/10.2337/diacare.22.8.1347
Wang C, Lu J, Lu W, Yu H, Jiang L, Li M, et al. Evaluating peripheral nerve function in asymptomatic patients with type 2 diabetes or latent autoimmune diabetes of adults (LADA): Results from nerve conduction studies. J Diabetes Complicat. 2015;29(2):265–269. https://doi.org/10.1016/j.jdiacomp.2014.11.001
Hawa MI, Kolb H, Schloot N, Beyan H, Paschou SA, Buzzetti R, et al. Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: Action LADA 7. Diabetes Care. 2013;36(4):908–913. https://doi.org/10.2337/dc12-0931
Maddaloni E, Coleman RL, Agbaje O, Buzzetti R, Holman RR. Time-varying risk of microvascular complications in latent autoimmune diabetes of adulthood compared with type 2 diabetes in adults: A post-hoc analysis of the UK Prospective Diabetes Study 30-year follow-up data (UKPDS 86). Lancet Diabet Endocrinol. 2020;8(3):06–15. https://doi.org/10.1016/S2213-8587(20)30003-6
Tuomi T, Carlsson A, Li H, Isomaa B, Miettinen A, Nilsson A, et al. Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. Diabetes. 1999;48(1):150–157. https://doi.org/10.2337/diabetes.48.1.150
Rasouli B, Andersson T, Carlsson P-O, Grill V, Groop L, Martinelli M, et al. Smoking and the risk of LADA: results from a swedish population-based case-control study. Diabetes Care. 2016;39(5):794–800. https://doi.org/10.2337/dc15-2348
Yin W, Luo S, Xiao Z, Zhang Z, Liu B, Zhou Z. Latent autoimmune diabetes in adults: A focus on ?-cell protection and therapy. Front Endocrinol. 2022;13. https://doi.org/10.3389/fendo.2022.959011
Thunander M, Thorgeirsson H, Törn C, Petersson C, Landin-Olsson M. ?-cell function and metabolic control in latent autoimmune diabetes in adults with early insulin versus conventional treatment: A 3-year follow-up. Eur J Endocrinol. 2011;164(2):239–245. https://doi.org/10.1530/EJE-10-0901
Zhou Z, Li X, Huang G, Peng J, Yang L, Yan X, et al. Rosiglitazone combined with insulin preserves islet beta cell function in adult-onset latent autoimmune diabetes (LADA). Diabetes Metab Res Rev. 2005;21(2):203–208. https://doi.org/10.1002/dmrr.503
Maruyama T, Tanaka S, Shimada A, Funae O, Kasuga A, Kanatsuka A, et al. Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus. J Clin Endocrinol Metab. 2008;93(6):2115–2121. https://doi.org/10.1210/jc.2007-2267
Zhao Y, Yang L, Xiang Y, Liu L, Huang G, Long Z, et al. Dipeptidyl peptidase 4 inhibitor sitagliptin maintains ?-cell function in patients with recent-onset latent autoimmune diabetes in adults: One year prospective study. J Clin Endocrinol Metab. 2014;99(5):E876-880. https://doi.org/10.1210/jc.2013-3633
Johansen OE, Boehm BO, Grill V, Trrjesen PA, Bhattacharya S, Patel S, et al. C-peptide levels in latent autoimmune diabetes in adults treated with linagliptin versus glimepiride: Exploratory results from a 2-year double-blind, randomized, controlled study. Diabetes Care. 2014;37(1):e11-12. https://doi.org/10.2337/dc13-1523
Pozzilli P, Leslie RD, Peters AL, Buzzetti R, Shankar SS, Milicevic Z, et al. Dulaglutide treatment results in effective glycaemic control in latent autoimmune diabetes in adults (LADA): A post-hoc analysis of the AWARD-2, -4 and -5 Trials. Diabetes Obes Metab. 2018;20(6):1490–1498. https://doi.org/10.1111/dom.13237
Da Porto A, Varisco E, Antonello M, Casarsa V, Sechi LA. Semaglutide treatment in adult-onset autoimmune diabetes: A case study with long-term follow-up and periodic evaluation of beta-cell function. Cureus. 2024;16:e55771. https://doi.org/10.7759/cureus.55771
Hu J, Zhang R, Zou H, Xie L, Zhou Z, Xiao Y. Latent autoimmune diabetes in adults (LADA): From immunopathogenesis to immunotherapy. Front Endocrinol (Lausanne). 2022;13:917169. https://doi.org/10.3389/fendo.2022.917169
Sun Q, Yang M, Jing Y, Meng L, Zhang C, Ruan J, et al. Latent autoimmune diabetes in youth. Front Immunol. 2025;16:1691377. https://doi.org/10.3389/fimmu.2025.1691377
Mourelatou NG, Kounatidis D, Jude EB, Rebelos E. Vitamin D supplementation as a therapeutic strategy in autoimmune diabetes: Insights and implications for LADA management. Nutrients. 2024;16(23):4072. https://doi.org/10.3390/nu16234072
Björklund A, Hals IK, Grill V, Ludvigsson J. Latent autoimmune diabetes in adults: Background, safety and feasibility of an ongoing pilot study with intra-lymphatic injections of GAD-alum and oral vitamin D. Front Endocrinol (Lausanne). 2022;13:926021. https://doi.org/10.3389/fendo.2022.926021
Ramos EL, Dayan CM, Chatenoud L, Sumnik Z, Simmons KM, Szypowska A, et al. Teplizumab and ?-cell function in newly diagnosed type 1 diabetes. N Engl J Med. 2023;389(23):2151–2161. https://doi.org/10.1056/NEJMoa2308743
Kreiner FF, von Scholten BJ, Coppieters K, von Herrath M. Current state of antigen-specific immunotherapy for type 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2021;28(4):411–418. https://doi.org/10.1097/MED.0000000000000647
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