DOI: https://doi.org/10.22141/2224-0721.15.3.2019.172116

Latent autoimmune diabetes in adults: a modern look at the problem

N.V. Pashkovska

Abstract


The lecture provides modern information on latent autoimmune diabetes in adults. Data of literature on the epidemiology, factors and mechanisms of development, clinical features of this disease are presented. The possible variants of latent autoimmune diabetes in adults course are identified and characterized. The questions of diagnostic features, differential diagnosis and the prospects of treatment are outlined.

Keywords


latent autoimmune diabetes in adults; diabetes mellitus

References


Ahlqvist E, Storm P, Käräjämäki A, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. LancetDiabetes Endocrinol. 2018;6(5):361-369. DOI: 10.1016/S2213-8587(18)30051-2.

Groop LC, Bottazzo GF, Doniach D. Islet cell antibodies identify latent type I diabetes in patients aged 35-75 years at diagnosis. Diabetes. 1986 Feb;35(2):237-41. doi: 10.2337/diab.35.2.237.

Irvine WJ, McCallum CJ, Gray RS, Duncan LJ. Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents. Lancet. 1977 May 14;1(8020):1025-7. doi: 10.1016/s0140-6736(77)91258-2.

Juneja R, Palmer JP. Type 1 1/2 diabetes: myth or reality? Autoimmunity. 1999;29(1):65-83.

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 Feb;42(2):359-62. doi: 10.2337/diab.42.2.359.

Zimmet PZ, Tuomi T, Mackay IR, et al. 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 Apr;11(3):299-303.

Turner R, Stratton I, Horton V, et al. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. Lancet. 1997 Nov 1;350(9087):1288-93. doi: 10.1016/s0140-6736(97)03062-6.

Groop L, Lundgren V, Lyssenko V, et al. Gada positivity in relatives of type 2 diabetes or LADA. Diabetes. 2005;54(Suppl 2):160.

Punthakee Z, Goldenberg R, Katz P. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Can J Diabetes. 2018 Apr;42 Suppl 1:S10-S15. doi: 10.1016/j.jcjd.2017.10.003.

Koufakis T, Karras SN, Zebekakis P, Kotsa K. Results of the First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults further highlight the need for a novel diabetes classification system. Ann Transl Med. 2018 Dec;6(Suppl 2):S102. doi: 10.21037/atm.2018.11.40.

Appel SJ, Wadas TM, Rosenthal RS, Ovalle F. Latent autoimmune diabetes of adulthood (LADA): an often misdiagnosed type of diabetes mellitus. J Am Acad Nurse Pract. 2009 Mar;21(3):156-9. doi: 10.1111/j.1745-7599.2009.00399.x.

Yasui J, Kawasaki E, Tanaka S, et al. Clinical and Genetic Characteristics of Non-Insulin-Requiring Glutamic Acid Decarboxylase (GAD) Autoantibody-Positive Diabetes: A Nationwide Survey in Japan. PLoS One. 2016 May 13;11(5):e0155643. doi: 10.1371/journal.pone.0155643.

Pozzilli P, Pieralice S. Latent Autoimmune Diabetes in Adults: Current Status and New Horizons. Endocrinol Metab (Seoul). 2018 Jun;33(2):147-159. doi: 10.3803/EnM.2018.33.2.147.

Stenström G, Gottsäter A, Bakhtadze E, Berger B, Sundkvist G. Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function, and treatment. Diabetes. 2005 Dec;54 Suppl 2:S68-72. doi: 10.2337/diabetes.54.suppl_2.s68.

Bruno G, Runzo C, Cavallo-Perin P, et al. Incidence of type 1 and type 2 diabetes in adults aged 30-49 years: the population-based registry in the province of Turin, Italy. Diabetes Care. 2005 Nov;28(11):2613-9. doi: 10.2337/diacare.28.11.2613.

Radtke MA, Midthjell K, Nilsen TI, Grill V. Heterogeneity of patients with latent autoimmune diabetes in adults: linkage to autoimmunity is apparent only in those with perceived need for insulin treatment: results from the Nord-Trøndelag Health (HUNT) study. Diabetes Care. 2009 Feb;32(2):245-50. doi: 10.2337/dc08-1468.

Buzzetti R, Di Pietro S, Giaccari A, et al. High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. Diabetes Care. 2007 Apr;30(4):932-8. doi: 10.2337/dc06-1696.

Roh MO, Jung CH, Kim BY, Mok JO, Kim CH. The prevalence and characteristics of latent autoimmune diabetes in adults (LADA) and its relation with chronic complications in a clinical department of a university hospital in Korea. Acta Diabetol. 2013 Apr;50(2):129-34. doi: 10.1007/s00592-010-0228-y.

Yang Z, Wang K, Li T, et al. Childhood diabetes in China: Enormous variation by place and ethnic group. Diabetes Care. 1998 Apr;21(4):525-9. doi: 10.2337/diacare.21.4.525.

Barinas-Mitchell E, Pietropaolo S, Zhang YJ, et al. Islet cell autoimmunity in a triethnic adult population of the Third National Health and Nutrition Examination Survey. Diabetes. 2004 May;53(5):1293-302. doi: 10.2337/diabetes.53.5.1293.

Maddaloni E, Lessan N, Al Tikriti A, Buzzetti R, Pozzilli P, Barakat MT. Latent Autoimmune Diabetes in Adults in the United Arab Emirates: Clinical Features and Factors Related to Insulin-Requirement. PLoS One. 2015 Aug 7;10(8):e0131837. doi: 10.1371/journal.pone.0131837.

Cervin C, Lyssenko V, Bakhtadze E, et al. Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes. Diabetes. 2008 May;57(5):1433-7. doi: 10.2337/db07-0299.

Tikhonova TM. Substantiation for Approaches to Treatment of Latent Autoimmune Diabetes in Adults. Mìžnarodnij endokrinologìčnij žurnal. 2014;(63):28-32. (in Ukrainian).

Andersen MK, Lundgren V, Turunen JA, et al. Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years. Diabetes Care. 2010 Sep;33(9):2062-4. doi: 10.2337/dc09-2188.

Haller K, Kisand K, Pisarev H, et al. Insulin gene VNTR, CTLA-4 +49A/G and HLA-DQB1 alleles distinguish latent autoimmune diabetes in adults from type 1 diabetes and from type 2 diabetes group. Tissue Antigens. 2007 Feb;69(2):121-7. doi: 10.1111/j.1399-0039.2006.00745.x.

Cosentino A, Gambelunghe G, Tortoioli C, Falorni A. CTLA-4 gene polymorphism contributes to the genetic risk for latent autoimmune diabetes in adults. Ann N Y Acad Sci. 2002 Apr;958:337-40. doi: 10.1111/j.1749-6632.2002.tb03000.x.

Vatay A, Rajczy K, Pozsonyi E, et al. Differences in the genetic background of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus. Immunol Lett. 2002 Nov 1;84(2):109-115.

S'emschikov VS, Hamnueva LYu, Byikova NM. Latent autoimmune diabetes in adults. Sibirskiy meditsinskiy zhurnal. 2014;2:16-20. (in Russian).

Hjort R, Ahlqvist E, Carlsson PO, et al. Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study. Diabetologia. 2018 Jun;61(6):1333-1343. doi: 10.1007/s00125-018-4596-0.

Buzzetti R, Zampetti S, Maddaloni E. Adult-onset autoimmune diabetes: current knowledge and implications for management. Nat Rev Endocrinol. 2017 Nov;13(11):674-686. doi: 10.1038/nrendo.2017.99.

Hernandez M, Mollo A, Marsal JR, et al. Insulin secretion in patients with latent autoimmune diabetes (LADA): half way between type 1 and type 2 diabetes: action LADA 9. BMC Endocr Disord. 2015 Jan 9;15:1. doi: 10.1186/1472-6823-15-1.

Hawa MI, Kolb H, Schloot N, et al. Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: Action LADA 7. Diabetes Care. 2013 Apr;36(4):908-13. doi: 10.2337/dc12-0931.

Maddaloni E, Pozzilli P. Getting it right for people with LADA. Diabetes Voice. 2014;59:31-32.

Fourlanos S, Dotta F, Greenbaum CJ, et al. Latent autoimmune diabetes in adults (LADA) should be less latent. Diabetologia. 2005 Nov;48(11):2206-12. doi: 10.1007/s00125-005-1960-7.

Leslie RD, Palmer J, Schloot NC, Lernmark A. Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment. Diabetologia. 2016 Jan;59(1):13-20. doi: 10.1007/s00125-015-3789-z.

Fourlanos S, Perry C, Stein MS, Stankovich J, Harrison LC, Colman PG. A clinical screening tool identifies autoimmune diabetes in adults. Diabetes Care. 2006 May;29(5):970-5. doi: 10.2337/diacare.295970.

Pilla SJ, Balasubramanyam A, Knowler WC, et al. Islet autoantibody positivity in overweight and obese adults with type 2 diabetes. Autoimmunity. 2018 Dec;51(8):408-416. doi: 10.1080/08916934.2018.1547711.

Tuomi T, Carlsson A, Li H, et al. Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. Diabetes. 1999 Jan;48(1):150-7. doi: 10.2337/diabetes.48.1.150.

Mollo A, Hernandez M, Marsal JR, et al. Latent autoimmune diabetes in adults is perched between type 1 and type 2: evidence from adults in one region of Spain. Diabetes Metab Res Rev. 2013 Sep;29(6):446-51. doi: 10.1002/dmrr.2411.

Genovese S, Bazzigaluppi E, Goncalves D, et al. Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes. Eur J Endocrinol. 2006 Mar;154(3):441-7. doi: 10.1530/eje.1.02115.

Petrone A, Suraci C, Capizzi M, et al. The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with high GAD antibody titer in Latent autoimmune diabetes in adults: Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study 3. Diabetes Care. 2008 Mar;31(3):534-8. doi: 10.2337/dc07-1457.

Zampetti S, Spoletini M, Petrone A, et al. Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5). Diabet Med. 2010 Jun;27(6):701-4. doi: 10.1111/j.1464-5491.2010.02997.x.

Zampetti S, Capizzi M, Spoletini M, et al. GADA titer-related risk for organ-specific autoimmunity in LADA subjects subdivided according to gender (NIRAD study 6). J Clin Endocrinol Metab. 2012 Oct;97(10):3759-65. doi: 10.1210/jc.2012-2037.

Myhill P, Davis WA, Bruce DG, Mackay IR, Zimmet P, Davis TM. Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study. Diabet Med. 2008 Oct;25(10):1245-50. doi: 10.1111/j.1464-5491.2008.02562.x.

Lu J, Hou X, Zhang L, et al. Associations between clinical characteristics and chronic complications in latent autoimmune diabetes in adults and type 2 diabetes. Diabetes Metab Res Rev. 2015 May;31(4):411-20. doi: 10.1002/dmrr.2626.

Alam U, Jeziorska M, Petropoulos IN, et al. Latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy. Diabet Med. 2018 Dec 21. doi: 10.1111/dme.13888.

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 Sep-Oct;19(5):254-8. doi: 10.1016/j.jdiacomp.2005.02.004.

Myhill P, Davis WA, Bruce DG, Mackay IR, Zimmet P, Davis TM. Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study. Diabet Med. 2008 Oct;25(10):1245-50. doi: 10.1111/j.1464-5491.2008.02562.x.

Olsson L, Grill V, Midthjell K, Ahlbom A, Andersson T, Carlsson S. Mortality in adult-onset autoimmune diabetes is associated with poor glycemic control: results from the HUNT Study. Diabetes Care. 2013 Dec;36(12):3971-8. doi: 10.2337/dc13-0564.

Napoli N, Chandran M, Pierroz DD, et al. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2017 Apr;13(4):208-219. doi: 10.1038/nrendo.2016.153.

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.

Kobayashi T, Nakanishi K, Murase T, Kosaka K. Small doses of subcutaneous insulin as a strategy for preventing slowly progressive beta-cell failure in islet cell antibody-positive patients with clinical features of NIDDM. Diabetes. 1996 May;45(5):622-6. doi: 10.2337/diab.45.5.622.

Maruyama T, Tanaka S, Shimada A, et al. Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus. J Clin Endocrinol Metab. 2008 Jun;93(6):2115-21. doi: 10.1210/jc.2007-2267.

Davis TM, Wright AD, Mehta ZM, et al. Islet autoantibodies in clinically diagnosed type 2 diabetes: Prevalence and relationship with metabolic control (UKPDS 70). Diabetologia. 2005 Apr;48(4):695-702. doi: 10.1007/s00125-005-1690-x.

Cernea S, Buzzetti R, Pozzilli P. Beta-cell protection and therapy for latent autoimmune diabetes in adults. Diabetes Care. 2009 Nov;32 Suppl 2:S246-52. doi: 10.2337/dc09-S317.

Jansen A, Rosmalen JG, Homo-Delarche F, Dardenne M, Drexhage HA. Effect of prophylactic insulin treatment on the number of ER-MP23+ macrophages in the pancreas of NOD mice. Is the prevention of diabetes based on beta-cell rest? J Autoimmun. 1996 Jun;9(3):341-8. doi: 10.1006/jaut.1996.0046.

Ellis SL, Moser EG, Snell-Bergeon JK, Rodionova AS, Hazenfield RM, Garg SK. Effect of sitagliptin on glucose control in adult patients with type 1 diabetes: a pilot, double-blind, randomized, crossover trial. Diabet Med. 2011 Oct;28(10):1176-81. doi: 10.1111/j.1464-5491.2011.03331.x.

Johansen OE, Boehm B, Grill V, 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):e11-2. doi: 10.2337/dc13-1523.

Buzzetti R, Pozzilli P, Frederich R, Iqbal N4, Hirshberg B5. Saxagliptin improves glycaemic control and C-peptide secretion in latent autoimmune diabetes in adults (LADA). Diabetes Metab Res Rev. 2016 Mar;32(3):289-96. doi: 10.1002/dmrr.2717.

Pozzilli P, Leslie RD, Peters AL, 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 Jun;20(6):1490-1498. doi: 10.1111/dom.13237.

Silko YV, Nikonova TV, Shestakova MV. Incretins role in Latent autoimmune diabetes of adults pathogenesis, the possibility of therapy with combination of glucagon-like peptide-1 agonist (GLP-1) and insulin. Obesity and metabolism. 2016;13(2):3-6. doi: 10.14341/OMET201623-6.

Pozzilli P, Guglielmi C. Immunomodulation for the prevention of SPIDDM and LADA. Ann N Y Acad Sci. 2006 Oct;1079:90-8. doi: 10.1196/annals.1375.012.

Chatenoud L, Bluestone J. CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol. 2007 Aug;7(8):622-32. doi: 10.1038/nri2134.

Redondo MJ. LADA: time for a new definition. Diabetes. 2013 Feb;62(2):339-40. doi: 10.2337/db12-1171.






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