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      KCI등재 SCOPUS SCIE

      Latent Autoimmune Diabetes in Adults: Current Status and New Horizons

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      https://www.riss.kr/link?id=A105908470

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      다국어 초록 (Multilingual Abstract)

      Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes i...

      Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.

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      참고문헌 (Reference)

      1 Lampasona V, "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" 33 : 104-108, 2010

      2 Grant SF, "Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes" 38 : 320-323, 2006

      3 Turner R, "UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group" 350 : 1288-1293, 1997

      4 Buzzetti R, "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" 38 : 513-520, 2015

      5 D'Alessio DA, "Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes" 94 : 81-88, 2009

      6 Petrone A, "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" 31 : 534-538, 2008

      7 Roh MO, "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" 50 : 129-134, 2013

      8 Tuomi T, "The many faces of diabetes: a disease with increasing heterogeneity" 383 : 1084-1094, 2014

      9 Rawshani A, "The incidence of diabetes among 0-34 year olds in Sweden: new data and better methods" 57 : 1375-1381, 2014

      10 Arikan E, "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" 19 : 254-258, 2005

      1 Lampasona V, "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" 33 : 104-108, 2010

      2 Grant SF, "Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes" 38 : 320-323, 2006

      3 Turner R, "UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group" 350 : 1288-1293, 1997

      4 Buzzetti R, "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" 38 : 513-520, 2015

      5 D'Alessio DA, "Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes" 94 : 81-88, 2009

      6 Petrone A, "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" 31 : 534-538, 2008

      7 Roh MO, "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" 50 : 129-134, 2013

      8 Tuomi T, "The many faces of diabetes: a disease with increasing heterogeneity" 383 : 1084-1094, 2014

      9 Rawshani A, "The incidence of diabetes among 0-34 year olds in Sweden: new data and better methods" 57 : 1375-1381, 2014

      10 Arikan E, "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" 19 : 254-258, 2005

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      14 Buzzetti R, "Saxagliptin improves glycaemic control and C-peptide secretion in latent autoimmune diabetes in adults (LADA)" 32 : 289-296, 2016

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      16 Tian L, "Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor" 151 : 3049-3060, 2010

      17 Balme M, "Retinopathy in latent autoimmune diabetes of adults: the Fremantle Diabetes Study" 19 : 602-605, 2002

      18 Qi X, "Prevalence and correlates of latent autoimmune diabetes in adults in Tianjin, China: a population-based cross-sectional study" 34 : 66-70, 2011

      19 Zinman B, "Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe" 53 : 3193-3200, 2004

      20 Hjort R, "Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study" 61 : 1333-1343, 2018

      21 Maioli M, "Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults" 163 : 541-549, 2010

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      36 Hernandez M, "Insulin secretion in patients with latent autoimmune diabetes (LADA): half way between type 1 and type 2 diabetes. Action LADA 9" 15 : 1-, 2015

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      38 Haller K, "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" 69 : 121-127, 2007

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      41 Pozzilli P, "Immunomodulation for the prevention of SPIDDM and LADA" 1079 : 90-98, 2006

      42 Lee SH, "Identifying latent autoimmune diabetes in adults in Korea: the role of C-peptide and metabolic syndrome" 83 : e62-e65, 2009

      43 Brooks-Worrell BM, "Identification of autoantibody-negative autoimmune type 2 diabetic patients" 34 : 168-173, 2011

      44 Bottazzo GF, "IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71)" 48 : 703-708, 2005

      45 Buzzetti R, "High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes" 30 : 932-938, 2007

      46 Zampetti S, "High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7)" 171 : 697-704, 2014

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      48 Maddaloni E, "Getting it right for people with LADA" 59 : 31-32, 2014

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      51 Cervin C, "Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes" 57 : 1433-1437, 2008

      52 Howson JM, "Genetic analysis of adult-onset autoimmune diabetes" 60 : 2645-2653, 2011

      53 Zampetti S, "GADA titer-related risk for organ-specific autoimmunity in LADA subjects subdivided according to gender (NIRAD study 6)" 97 : 3759-3765, 2012

      54 Agardh CD, "GAD65 vaccination: 5 years of follow-up in a randomised dose-escalating study in adult-onset autoimmune diabetes" 52 : 1363-1368, 2009

      55 Desai M, "GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77" 50 : 2052-2060, 2007

      56 Zhou Z, "Frequency, immunogenetics, and clinical characteristics of latent autoimmune diabetes in China (LADA China study): a nationwide, multicenter, clinic-based cross-sectional study" 62 : 543-550, 2013

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      58 Wang C, "Evaluating peripheral nerve function in asymptomatic patients with type 2 diabetes or latent autoimmune diabetes of adults (LADA): results from nerve conduction studies" 29 : 265-269, 2015

      59 Ellis SL, "Effect of sitagliptin on glucose control in adult patients with type 1 diabetes: a pilot, double-blind, randomized, crossover trial" 28 : 1176-1181, 2011

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      61 Pozzilli P, "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" 20 : 1490-1498, 2018

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      65 Leslie RD, "Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment" 59 : 13-20, 2016

      66 Signore A, "Detection of insulitis by pancreatic scintigraphy with 99mTc-labeled IL-2 and MRI in patients with LADA (Action LADA 10)" 38 : 652-658, 2015

      67 Takeda H, "Clinical, autoimmune, and genetic characteristics of adult-onset diabetic patients with GAD autoantibodies in Japan (Ehime Study)" 25 : 995-1001, 2002

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      72 Isomaa B, "Chronic complications in patients with slowly progressing autoimmune type 1 diabetes (LADA)" 22 : 1347-1353, 1999

      73 Myhill P, "Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study" 25 : 1245-1250, 2008

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      75 Van der Auwera BJ, "CTLA-4 gene polymorphism confers susceptibility to insulin-dependent diabetes mellitus (IDDM) independently from age and from other genetic or immune disease markers. The Belgian Diabetes Registry" 110 : 98-103, 1997

      76 Johansen OE, "Beta-cell function in latent autoimmune diabetes in adults treated with linagliptin vs glimepiride: exploratory results from a 2-year double-blind randomized controlled study" 33 (33): 2012

      77 Steffes MW, "Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial" 26 : 832-836, 2003

      78 Foley JE, "Beta cell function following 1 year vildagliptin or placebo treatment and after 12 week washout in drug-naive patients with type 2 diabetes and mild hyperglycaemia: a randomised controlled trial" 54 : 1985-1991, 2011

      79 Pozzilli P, "Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention" 24 : 1460-1467, 2001

      80 Achenbach P, "Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12" 61 : 1644-1649, 2018

      81 Lu J, "Associations between clinical characteristics and chronic complications in latent autoimmune diabetes in adults and type 2 diabetes" 31 : 411-420, 2015

      82 Zampetti S, "Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5)" 27 : 701-704, 2010

      83 Tuomi T, "Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease" 42 : 359-362, 1993

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      85 Buzzetti R, "Adult-onset autoimmune diabetes: current knowledge and implications for management" 13 : 674-686, 2017

      86 Hawa MI, "Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: Action LADA 7" 36 : 908-913, 2013

      87 Bottini N, "A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes" 36 : 337-338, 2004

      88 Frayling TM, "A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity" 316 : 889-894, 2007

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