Emerging Perspectives on Latent Autoimmune Diabetes in Adults: A Distinct Diabetes Mellitus Variant
Abstract
Latent Autoimmune Diabetes in Adults (LADA) is an autoimmune disease in which the immune system slowly attacks and destroys insulin-producing beta cells in the pancreas. It is different from Type 1 diabetes, which is generally due to the autoimmune destruction of insulin-producing cells, pancreatic beta cells, LADA variant in diabetes progresses more gradually and often intensify later in life. This slower onset mimics Type 2 diabetes mellitus, differentiating it from other diabetes mellitus forms. LADA comprises features of both Type 1 and Type 2 diabetes, which apparently leads to misdiagnosis as Type 2 in its early phases. As the disease progresses, pancreatic insulin production declines consistently, emphasize the value of accurate diagnosis and personalized management to prevent various serious complications. Research shows that about 10% of individuals initially diagnosed with Type 2 diabetes actually have LADA, it is traceable by circulating islet autoantibodies. These patients poorly respond to oral medications like sulfonylureas- Glimepiride, Glipizide. LADA identification is pivotal for improving effective treatment, though it remains challenging due to limited directions for antibody screening in adult-onset cases. Greater knowledgeon LADA enhances its clinical handling and increases awareness on the broader spectrum of autoimmune diabetes and about it’s different variants like- Type 1 diabetes, Type 2 diabetes mellitus, Gestational diabetes, Type 5 diabetes, MODY- Maturity onset diabetes in young.
Keywords:
Latent auto-immune diabetes in adults (LADA), Pancreatic beta cells, Diabetes mellitus, Emphasize, Sulfonylureas
References
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17. Lee SH, Kwon HS, Yoo SJ, Ahn YB, Yoon KH, Cha BY, Lee KW, Son HY. Identifying latent autoimmune diabetes in adults in Korea: the role of C-peptide and metabolic syndrome. Diabetes Res Clin Pract. 2009;83:e62–e65. doi: 10.1016/j.diabres.2008.11.031.
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19. Sachan A, Zaidi G, Sahu RP, Agrawal S, Colman PG, Bhatia E. Low prevalence of latent autoimmune diabetes in adults in northern India. Diabet Med. 2015;32:810–813. doi: 10.1111/dme.12644
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21. Qu HQ, Grant SF, Bradfield JP, Kim C, Frackelton E, Hakonarson H, Polychronakos C. Association analysis of type 2 diabetes Loci in type 1 diabetes. Diabetes. 2008;57:1983–1986. doi: 10.2337/db08-0270
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24. Barinas-Mitchell E, Pietropaolo S, Zhang YJ, Henderson T, Trucco M, Kuller LH, Pietropaolo M. Islet cell autoimmunity in a triethnic adult population of the Third National Health and Nutrition Examination Survey. Diabetes. 2004;53:1293–1302. doi: 10.2337/diabetes.53.5.1293.
25. Buzzetti R, Spoletini M, Zampetti S, Campagna G, Marandola L, Panimolle F, Dotta F, Tiberti C NIRAD Study Group (NIRAD 8) Tyrosine phosphatase-related islet antigen 2(256-760) autoantibodies, the only marker of islet autoimmunity that increases by increasing the degree of BMI in obese subjects with type 2 diabetes. Diabetes Care. 2015;38:513–520. doi: 10.2337/dc14-1638.
26. Hjort R, Ahlqvist E, Carlsson PO, Grill V, Groop L, Martinell M, Rasouli B, Rosengren A, Tuomi T, Asvold BO, Carlsson S. Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study. Diabetologia. 2018;61:1333–1343. doi: 10.1007/s00125-018-4596-0.
27. 48.Leslie RD, Kolb H, Schloot NC, Buzzetti R, Mauricio D, De Leiva A, Yderstraede K, Sarti C, Thivolet C, Hadden D, Hunter S, Schernthaner G, Scherbaum W, Williams R, Pozzilli P. Diabetes classification: grey zones, sound and smoke: Action LADA 1. Diabetes Metab Res Rev. 2008;24:511–519. doi: 10.1002/dmrr.877.
28. Genovese S, Bazzigaluppi E, Goncalves D, Ciucci A, Cavallo MG, Purrello F, Anello M, Rotella CM, Bardini G, Vaccaro O, Riccardi G, Travaglini P, Morenghi E, Bosi E, Pozzilli P. Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes. Eur J Endocrinol. 2006;154:441–447. doi: 10.1530/eje.1.02115.
29. Desai M, Cull CA, Horton VA, Christie MR, Bonifacio E, Lampasona V, Bingley PJ, Levy JC, Mackay IR, Zimmet P, Holman RR, Clark A. GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77. Diabetologia. 2007;50:2052–2060. doi: 10.1007/s00125-007-0745-6.
30. Fourlanos S, Perry C, Stein MS, Stankovich J, Harrison LC, Colman PG. A clinical screening tool identifies autoimmune diabetes in adults. Diabetes Care. 2006;29:970–975. doi: 10.2337/diacare.295970.
31. Monge L, Bruno G, Pinach S, Grassi G, Maghenzani G, Dani F, Pagano G. 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;21:456–459. doi: 10.1111/j.1464-5491.2004.01177.x.
32. Davis AK, DuBose SN, Haller MJ, Miller KM, DiMeglio LA, Bethin KE, Goland RS, Greenberg EM, Liljenquist DR, Ahmann AJ, Marcovina SM, Peters AL, Beck RW, Greenbaum CJ T1D Exchange Clinic Network. Prevalence of detectable C-Peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care. 2015;38:476–481. doi: 10.2337/dc14-1952.
33. Pipi E, Marketou M, Tsirogianni A. Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus. World J Diabetes. 2014;5:505–510. doi: 10.4239/wjd.v5.i4.505
34. George P, McCrimmon RJ. Potential role of non-insulin adjunct therapy in type 1 diabetes. Diabet Med. 2013;30:179–188. doi: 10.1111/j.1464-5491.2012.03744.x.
35. Zhou Z, Li X, Huang G, Peng J, Yang L, Yan X, Wang J. Rosiglitazone combined with insulin preserves islet beta cell function in adult-onset latent autoimmune diabetes (LADA) Diabetes Metab Res Rev. 2005;21:203–208. doi: 10.1002/dmrr.503.
2. Mayo Clinic Staff. “Diabetic Ketoacidosis: Symptoms and Causes”. Mayo Clinic. Last modified March 16, 2023. https://www.mayoclinic.org/diseases-conditions/diabetic-ketoacidosis/symptoms-causes/syc-20371551
3. Pieralice S, Pozzilli P. Latent Autoimmune Diabetes in Adults: A Review on Clinical Implications and Management. Diabetes Metab J. 2018 Dec;42(6):451-464. doi: 10.4093/dmj.2018.0190. PMID: 30565440; PMCID: PMC6300440.
4. Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010;464:1293–1300. doi: 10.1038/nature08933. [DOI] [PMC free article] [PubMed] [Google Scholar]
5. 2.Mishra R, Hodge KM, Cousminer DL, Leslie RD, Grant SFA. A global perspective of latent autoimmune diabetes in adults. Trends Endocrinol Metab. 2018;29:638–650. doi: 10.1016/j.tem.2018.07.001. [DOI] [PubMed] [Google Scholar]
6. Pozzilli P, Di Mario U. Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention. Diabetes Care. 2001;24:1460–1467. doi: 10.2337/diacare.24.8.1460. [DOI] [PubMed] [Google Scholar]
7. 7.American Diabetes Association. (2) Classification and diagnosis of diabetes. Diabetes Care. 2015;38(Suppl):S8–S16. doi: 10.2337/dc15-S005. [DOI] [PubMed] [Google Scholar]
8. 8.Leslie RD, Williams R, Pozzilli P. Clinical review: type 1 diabetes and latent autoimmune diabetes in adults: one end of the rainbow. J Clin Endocrinol Metab. 2006;91:1654–1659. doi: 10.1210/jc.2005-1623.
9. Sabbah E, Savola K, Ebeling T, Kulmala P, Vahasalo P, Ilonen J, Salmela PI, Knip M. Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes. Diabetes Care. 2000;23:1326–1332. doi: 10.2337/diacare.23.9.1326. [DOI] [PubMed] [Google Scholar]
10. 12.Howson JM, Rosinger S, Smyth DJ, Boehm BO ADBW-END Study Group. Todd JA. Genetic analysis of adult-onset autoimmune diabetes. Diabetes. 2011;60:2645–2653. doi: 10.2337/db11-0364
11. Park Y, Wintergerst KA, Zhou Z. Clinical heterogeneity of type 1 diabetes (T1D) found in Asia. Diabetes Metab Res Rev. 2017;33:e2907. doi: 10.1002/dmrr.2907.
12. Buzzetti R, Zampetti S, Maddaloni E. Adult-onset autoimmune diabetes: current knowledge and implications for management. Nat Rev Endocrinol. 2017;13:674–686. doi: 10.1038/nrendo.2017.99
13. Naik RG, Brooks-Worrell BM, Palmer JP. Latent autoimmune diabetes in adults. J Clin Endocrinol Metab. 2009;94:4635–4644. doi: 10.1210/jc.2009-1120.
14. Rawshani A, Landin-Olsson M, Svensson AM, Nystrom L, Arnqvist HJ, Bolinder J, Gudbjornsdottir S. The incidence of diabetes among 0–34 year olds in Sweden: new data and better methods. Diabetologia. 2014;57:1375–1381. doi: 10.1007/s00125-014-3225-9
15. Zinman B, Kahn SE, Haffner SM, O'Neill MC, Heise MA, Freed MI ADOPT Study Group. Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe. Diabetes. 2004;53:3193–3200. doi: 10.2337/diabetes.53.12.3193.
16. Qi X, Sun J, Wang J, Wang PP, Xu Z, Murphy M, Jia J, Wang J, Xie Y, Xu W. Prevalence and correlates of latent autoimmune diabetes in adults in Tianjin, China: a population-based cross-sectional study. Diabetes Care. 2011;34:66–70. doi: 10.2337/dc10-0488
17. Lee SH, Kwon HS, Yoo SJ, Ahn YB, Yoon KH, Cha BY, Lee KW, Son HY. Identifying latent autoimmune diabetes in adults in Korea: the role of C-peptide and metabolic syndrome. Diabetes Res Clin Pract. 2009;83:e62–e65. doi: 10.1016/j.diabres.2008.11.031.
18. Britten AC, Jones K, Torn C, Hillman M, Ekholm B, Kumar S, Barnett AH, Kelly MA. Latent autoimmune diabetes in adults in a South Asian population of the U.K. Diabetes Care. 2007;30:3088–3090. doi: 10.2337/dc07-0896.
19. Sachan A, Zaidi G, Sahu RP, Agrawal S, Colman PG, Bhatia E. Low prevalence of latent autoimmune diabetes in adults in northern India. Diabet Med. 2015;32:810–813. doi: 10.1111/dme.12644
20. Field SF, Howson JM, Smyth DJ, Walker NM, Dunger DB, Todd JA. Analysis of the type 2 diabetes gene, TCF7L2, in 13,795 type 1 diabetes cases and control subjects. Diabetologia. 2007;50:212–213. doi: 10.1007/s00125-006-0506-y
21. Qu HQ, Grant SF, Bradfield JP, Kim C, Frackelton E, Hakonarson H, Polychronakos C. Association analysis of type 2 diabetes Loci in type 1 diabetes. Diabetes. 2008;57:1983–1986. doi: 10.2337/db08-0270
22. Desai M, Zeggini E, Horton VA, Owen KR, Hattersley AT, Levy JC, Walker M, Gillespie KM, Bingley PJ, Hitman GA, Holman RR, McCarthy MI, Clark A. An association analysis of the HLA gene region in latent autoimmune diabetes in adults. Diabetologia. 2007;50:68–73. doi: 10.1007/s00125-006-0513-z.
23. Andersen MK, Lundgren V, Turunen JA, Forsblom C, Isomaa B, Groop PH, Groop L, Tuomi T. Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years. Diabetes Care. 2010;33:2062–2064. doi: 10.2337/dc09-2188.
24. Barinas-Mitchell E, Pietropaolo S, Zhang YJ, Henderson T, Trucco M, Kuller LH, Pietropaolo M. Islet cell autoimmunity in a triethnic adult population of the Third National Health and Nutrition Examination Survey. Diabetes. 2004;53:1293–1302. doi: 10.2337/diabetes.53.5.1293.
25. Buzzetti R, Spoletini M, Zampetti S, Campagna G, Marandola L, Panimolle F, Dotta F, Tiberti C NIRAD Study Group (NIRAD 8) Tyrosine phosphatase-related islet antigen 2(256-760) autoantibodies, the only marker of islet autoimmunity that increases by increasing the degree of BMI in obese subjects with type 2 diabetes. Diabetes Care. 2015;38:513–520. doi: 10.2337/dc14-1638.
26. Hjort R, Ahlqvist E, Carlsson PO, Grill V, Groop L, Martinell M, Rasouli B, Rosengren A, Tuomi T, Asvold BO, Carlsson S. Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study. Diabetologia. 2018;61:1333–1343. doi: 10.1007/s00125-018-4596-0.
27. 48.Leslie RD, Kolb H, Schloot NC, Buzzetti R, Mauricio D, De Leiva A, Yderstraede K, Sarti C, Thivolet C, Hadden D, Hunter S, Schernthaner G, Scherbaum W, Williams R, Pozzilli P. Diabetes classification: grey zones, sound and smoke: Action LADA 1. Diabetes Metab Res Rev. 2008;24:511–519. doi: 10.1002/dmrr.877.
28. Genovese S, Bazzigaluppi E, Goncalves D, Ciucci A, Cavallo MG, Purrello F, Anello M, Rotella CM, Bardini G, Vaccaro O, Riccardi G, Travaglini P, Morenghi E, Bosi E, Pozzilli P. Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes. Eur J Endocrinol. 2006;154:441–447. doi: 10.1530/eje.1.02115.
29. Desai M, Cull CA, Horton VA, Christie MR, Bonifacio E, Lampasona V, Bingley PJ, Levy JC, Mackay IR, Zimmet P, Holman RR, Clark A. GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77. Diabetologia. 2007;50:2052–2060. doi: 10.1007/s00125-007-0745-6.
30. Fourlanos S, Perry C, Stein MS, Stankovich J, Harrison LC, Colman PG. A clinical screening tool identifies autoimmune diabetes in adults. Diabetes Care. 2006;29:970–975. doi: 10.2337/diacare.295970.
31. Monge L, Bruno G, Pinach S, Grassi G, Maghenzani G, Dani F, Pagano G. 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;21:456–459. doi: 10.1111/j.1464-5491.2004.01177.x.
32. Davis AK, DuBose SN, Haller MJ, Miller KM, DiMeglio LA, Bethin KE, Goland RS, Greenberg EM, Liljenquist DR, Ahmann AJ, Marcovina SM, Peters AL, Beck RW, Greenbaum CJ T1D Exchange Clinic Network. Prevalence of detectable C-Peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care. 2015;38:476–481. doi: 10.2337/dc14-1952.
33. Pipi E, Marketou M, Tsirogianni A. Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus. World J Diabetes. 2014;5:505–510. doi: 10.4239/wjd.v5.i4.505
34. George P, McCrimmon RJ. Potential role of non-insulin adjunct therapy in type 1 diabetes. Diabet Med. 2013;30:179–188. doi: 10.1111/j.1464-5491.2012.03744.x.
35. Zhou Z, Li X, Huang G, Peng J, Yang L, Yan X, Wang J. Rosiglitazone combined with insulin preserves islet beta cell function in adult-onset latent autoimmune diabetes (LADA) Diabetes Metab Res Rev. 2005;21:203–208. doi: 10.1002/dmrr.503.
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P, M., K, L. V., P, H., Ch, S., Uppala, P. K., & Maddi, R. (2026). Emerging Perspectives on Latent Autoimmune Diabetes in Adults: A Distinct Diabetes Mellitus Variant. Journal of Integral Sciences, 9(1), 21-33. https://doi.org/10.37022/jis.v9i1.138
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