Advertisement

Frontiers of Medicine

, Volume 6, Issue 3, pp 243–247 | Cite as

Diagnostic criteria of latent autoimmune diabetes in adults (LADA): a review and reflection

  • Yu Liao
  • Yufei Xiang
  • Zhiguang ZhouEmail author
Review

Abstract

Diabetes has become a major public health problem in China nowadays. There are almost 97 million diabetic patients nationwide. Latent autoimmune diabetes in adults (LADA) is a subtype of autoimmune diabetes. Although it has been reported for about 20 years, the diagnostic criteria of this disease remain controversial. The discussion mainly focused on serum autoantibodies, period of insulin need and age of diagnosis. Besides, β cell function, metabolic parameters, genetic factors and cell immunity may also contribute to the formulation of the criteria. Here, we aim to review and discuss the diagnostic criteria of latent autoimmune diabetes in adults.

Keywords

LADA diagnostic criteria autoantibodies insulin independence age of diagnosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    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(5): 1654–1659PubMedCrossRefGoogle Scholar
  2. 2.
    Rolandsson O, Palmer JP. Latent autoimmune diabetes in adults (LADA) is dead: long live autoimmune diabetes! Diabetologia 2010; 53(7): 1250–1253PubMedCrossRefGoogle Scholar
  3. 3.
    Teng J, Leslie RD. Type 1 diabetes and latent autoimmune diabetes in adults. J Cent S Univ (Med Sci) (Zhong Nan Da Xue Xue Bao Yi Xue Ban) 2006; 31(6): 809–813 (in Chinese)Google Scholar
  4. 4.
    Fourlanos S, Dotta F, Greenbaum CJ, Palmer JP, Rolandsson O, Colman PG, Harrison LC. Latent autoimmune diabetes in adults (LADA) should be less latent. Diabetologia 2005; 48(11): 2206–2212PubMedCrossRefGoogle Scholar
  5. 5.
    Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J; China National Diabetes and Metabolic Disorders Study Group. Prevalence of diabetes among men and women in China. N Engl J Med 2010; 362(12): 1090–1101PubMedCrossRefGoogle Scholar
  6. 6.
    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(7): 511–519PubMedCrossRefGoogle Scholar
  7. 7.
    Naik RG, Brooks-Worrell BM, Palmer JP. Latent autoimmune diabetes in adults. J Clin Endocrinol Metab 2009; 94(12): 4635–4644PubMedCrossRefGoogle Scholar
  8. 8.
    Groop L, Tuomi T, Rowley M, Zimmet P, Mackay IR. Latent autoimmune diabetes in adults (LADA)—more than a name. Diabetologia 2006; 49(9): 1996–1998PubMedCrossRefGoogle Scholar
  9. 9.
    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): 1245–1250PubMedCrossRefGoogle Scholar
  10. 10.
    Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes 1993; 42(2): 359–362PubMedCrossRefGoogle Scholar
  11. 11.
    Zimmet PZ, Tuomi T, Mackay IR, Rowley MJ, Knowles W, Cohen M, Lang DA. Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med 1994; 11(3): 299–303PubMedCrossRefGoogle Scholar
  12. 12.
    Scherbaum WA. Type 1, type 2 diabetes, MODY and LADA. Making a differential diagnosis. MMW Fortschr Med 2001; 143(37): 45–48 (in German)PubMedGoogle Scholar
  13. 13.
    Silva ME. Do we need to diagnosis Latent Autoimmune Diabetes in Adults (LADA)? Arq Bras Endocrinol Metabol 2007; 51(1): 8–10 (in Portuguese)PubMedCrossRefGoogle Scholar
  14. 14.
    Pan X, Yang W, Xiao J, Chen S. Clinical characteristic and main diagnostic points of latent autoimmune diabetes in adults. Chin J Integr Med (Zhonghua Nei Ke Za Zhi) 1997; 36(3): 159–164 (in Chinese)Google Scholar
  15. 15.
    Zhou Z. Where is the forward road of LADA study? Chin J Endocrinol Metab (Zhonghua Nei Fen Mi Dai Xie Za Zhi) 2005; 21(4): 301–303 (in Chinese)Google Scholar
  16. 16.
    Zhou Z, Wu H. Diagnosis and treatments of latent autoimmune diabetes in adults. Chin J Endocrinol Metab (Zhonghua Nei Fen Mi Dai Xie Za Zhi) 1998; 14(1): 1–2 (in Chinese)Google Scholar
  17. 17.
    Chi L, Liu X, Li X, Nie B, Li X. The diagnostic criteria of latent autoimmune diabetes of adults. J Chin Physicians (Zhongguo Yi Shi Za Zhi) 2006; 8(5): 610–613 (in Chinese)Google Scholar
  18. 18.
    Li X, Huang G, Yan X, Yang L, Zhou ZG. Relation between insulin resistance and glutamic acid decarboxylase antibody titers in latent autoimmune diabetes in adults. J South Med Univ (Nan Fang Yi Ke Da Xue Xue Bao) 2010; 30(6): 1247–1249 (in Chinese)Google Scholar
  19. 19.
    Huang G, Wang X, Li Z, Li H, Li X, Zhou Z. Insulin autoantibody could help to screen latent autoimmune diabetes in adults in phenotypic type 2 diabetes mellitus in Chinese. Acta Diabetol 2010 May 16. [Epub ahead of print] DOI: 10.1007/s00592-010-0196-2Google Scholar
  20. 20.
    Bottazzo GF, Bosi E, Cull CA, Bonifacio E, Locatelli M, Zimmet P, Mackay IR, Holman RR. IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71). Diabetologia 2005; 48(4): 703–708PubMedCrossRefGoogle Scholar
  21. 21.
    Dang M, Rockell J, Wagner R, Wenzlau JM, Yu L, Hutton JC, Gottlieb PA, Davidson HW. Human type 1 diabetes is associated with T cell autoimmunity to zinc transporter 8. J Immunol 2011; 186(10): 6056–6063PubMedCrossRefGoogle Scholar
  22. 22.
    Li X, Zhou ZG, Huang G, Yan X, Yang L, Chen XY, Wang JP. Optimal cutoff point of glutamate decarboxylase antibody titers in differentiating two subtypes of adult-onset latent autoimmune diabetes. Ann N Y Acad Sci 2004; 1037(1): 122–126PubMedCrossRefGoogle Scholar
  23. 23.
    van Deutekom AW, Heine RJ, Simsek S. The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus. Diabet Med 2008; 25(2):117–125PubMedCrossRefGoogle Scholar
  24. 24.
    Weber P, Ambrosova P, Canov P, Weberova D, Kuklinek P, Meluzinova H, Matejovska-Kubesova H, Cejkova P, Bielakova K, Cerna M. GAD antibodies in T1D and LADA-relations to age, BMI, c-peptide, IA-2 and HLA-DRB1*03 and DRB1*04 alleles. Adv Gerontol 2011; 24(2): 312–318PubMedGoogle Scholar
  25. 25.
    Lampasona V, Petrone A, Tiberti C, Capizzi M, Spoletini M, di Pietro S, Songini M, Bonicchio S, Giorgino F, Bonifacio E, Bosi E, Buzzetti R. Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: non insulin requiring autoimmune diabetes (NIRAD) 4.2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: non insulin requiring autoimmune diabetes (NIRAD) 4. Diabetes Care 2010; 33(1): 104–108PubMedCrossRefGoogle Scholar
  26. 26.
    Yan X, Zhou Z, Huang G, Wang J, Yang L. Optimization of radioligand assays for islet autoantibodies. J Chin Physicians (Zhongguo Yi Shi Za Zhi) 2004; 6(6): 731–734 (in Chinese)Google Scholar
  27. 27.
    Brophy S, Yderstraede K, Mauricio D, Hunter S, Hawa M, Pozzilli P, Schernthaner G, Schloot N, Buzzetti R, Davies H, Leslie D, Williams R. Time to insulin initiation cannot be used in defining latent autoimmune diabetes in adults. Diabetes Care 2008; 31(3): 439–441PubMedCrossRefGoogle Scholar
  28. 28.
    Zhou J, Ma XJ, Bao YQ, Pan XP, Lu W, Hu C, Xiang KS, Jia WP. Study on prevalence of latent autoimmune diabetes in adults and its relationship with metabolic syndrome. Natl Med J China (Zhonghua Yi Xue Za Zhi) 2009; 89(18): 1250–1254 (in Chinese)Google Scholar
  29. 29.
    Horton V, Stratton I, Bottazzo GF, Shattock M, Mackay I, Zimmet P, Manley S, Holman R, Turner R. Genetic heterogeneity of autoimmune diabetes: age of presentation in adults is influenced by HLA DRB1 and DQB1 genotypes (UKPDS 43). Diabetologia 1999; 42(5): 608–616PubMedCrossRefGoogle Scholar
  30. 30.
    Weber P, Meluzínová H, Kubesová H, Ambrosová P, Polcarová V, Cejkova P, Cerna M. Type 1 diabetes and LADA—occurrence of HLA-DRB1*03 and DRB1*04 alleles in two age different groups of diabetics. Adv Gerontol 2009; 23(2): 243–248Google Scholar
  31. 31.
    Yang Z, Wang K, Li T, Sun W, Li Y, Chang YF, Dorman JS, LaPorte RE. Childhood diabetes in China. Enormous variation by place and ethnic group. Diabetes Care 1998; 21(4): 525–529PubMedCrossRefGoogle Scholar
  32. 32.
    Davies H, Brophy S, Fielding A, Bingley P, Chandler M, Hilldrup I, Brooks C, Williams R. Latent autoimmune diabetes in adults (LADA) in South Wales: incidence and characterization. Diabet Med 2008; 25(11): 1354–1357PubMedGoogle Scholar
  33. 33.
    Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Quality-of-life measures in children and adults with type 1 diabetes. Diabetes Care 2010; 33(10): 2175–2177CrossRefGoogle Scholar
  34. 34.
    Yang L, Zhou ZG, Huang G, Yan X. Islet β cell function in latent autoimmune diabetes in adults with islet cell antibodies. J Cent S Univ (Med Sci) (Zhong Nan Da Xue Xue Bao Yi Xue Ban) 2004; 29(3): 309–314 (in Chinese)Google Scholar
  35. 35.
    Yang L, Zhou ZG, Huang G, Ouyang LL, Li X, Yan X. Six-year follow-up of pancreatic beta cell function in adults with latent autoimmune diabetes. World J Gastroenterol 2005; 11(19): 2900–2905PubMedGoogle Scholar
  36. 36.
    Li X, Zhou Z, Huang G, Su H, Yan X, Yang L. Metabolic syndrome in adult-onset latent autoimmune diabetes. Metab Syndr Relat Disord 2005; 3(2): 174–180PubMedCrossRefGoogle Scholar
  37. 37.
    Hawa MI, Thivolet C, Mauricio D, Alemanno I, Cipponeri E, Collier D, Hunter S, Buzzetti R, de Leiva A, Pozzilli P, Leslie RD. Metabolic syndrome and autoimmune diabetes: action LADA 3. Diabetes Care 2009; 32(1): 160–164PubMedCrossRefGoogle Scholar
  38. 38.
    Baum P, Hermann W, Verlohren HJ, Wagner A, Lohmann T, Grahmann F. Diabetic neuropathy in patients with “latent autoimmune diabetes of the adults” (LADA) compared with patients with type 1 and type 2 diabetes. J Neurol 2003; 250(6): 682–687PubMedCrossRefGoogle Scholar
  39. 39.
    Arikan E, Sabuncu T, Ozer EM, Hatemi H. The clinical characteristics of latent autoimmune diabetes in adults and its relation with chronic complications in metabolically poor controlled Turkish patients with type 2 diabetes mellitus. J Diabetes Complications 2005; 19(5): 254–258PubMedCrossRefGoogle Scholar
  40. 40.
    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(9): 2062–2064PubMedCrossRefGoogle Scholar
  41. 41.
    Bakhtadze E, Cervin C, Lindholm E, Borg H, Nilsson P, Arnqvist HJ, Bolinder J, Eriksson JW, Gudbjörnsdottir S, Nyström L, Agardh CD, Landin-Olsson M, Sundkvist G, Groop LC. Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients. Diabetologia 2008; 51(12): 2224–2232PubMedCrossRefGoogle Scholar
  42. 42.
    Meierhoff G, Ott PA, Lehmann PV, Schloot NC. Cytokine detection by ELISPOT: relevance for immunological studies in type 1 diabetes. Diabetes Metab Res Rev 2002; 18(5): 367–380PubMedCrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of EducationCentral South UniversityChangshaChina

Personalised recommendations