title: Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years.
abstract: OBJECTIVE
  We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years.
  
  
  METHODS
  Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D(>35y); n = 257) or <20 years of age (T1D(<20y); n = 158), and type 2 diabetes.
  
  
  RESULTS
  Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D(>35y) patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA.
  
  
  CONCLUSIONS
  LADA patients differed genetically and phenotypically from both T1D(>35y) and type 2 diabetic patients in a manner dependent on GADA levels.
authors.affiliation: Research Program for Molecular Medicine, Helsinki University, Helsinki, Finland.
authors.forename: Mette K
authors.initials: MK
authors.lastname: Andersen
authors.forename: Virve
authors.initials: V
authors.lastname: Lundgren
authors.forename: Joni A
authors.initials: JA
authors.lastname: Turunen
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Bo
authors.initials: B
authors.lastname: Isomaa
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
mesh_terms: D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007328:Insulin; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
references.citation: Diabetes. 2010 Feb;59(2):416-22
references.pmid: 19864397
references.citation: Diabetes Care. 2003 Feb;26(2):452-7
references.pmid: 12547879
references.citation: Diabetes. 2006 Jun;55(6):1890-4
references.pmid: 16731859
references.citation: Diabetes. 2008 May;57(5):1433-7
references.pmid: 18310307
references.citation: J Clin Invest. 1992 Dec;90(6):2242-50
references.pmid: 1469084
references.citation: Diabetes Care. 2007 Apr;30(4):932-8
references.pmid: 17392553
references.citation: Biotechniques. 1995 May;18(5):870-7
references.pmid: 7619493
references.citation: Diabetes. 1999 Jan;48(1):150-7
references.pmid: 9892237
references.citation: Diabetologia. 2007 Jan;50(1):68-73
references.pmid: 17143607
references.citation: Diabetes Care. 2005 Aug;28(8):2019-24
references.pmid: 16043748
references.citation: Tissue Antigens. 2007 Feb;69(2):121-7
references.pmid: 17257313
references.citation: Lancet. 1997 Nov 1;350(9087):1288-93
references.pmid: 9357409
references.citation: Diabetes Care. 2008 Mar;31(3):534-8
references.pmid: 18056891
references.citation: Diabetes. 2010 Jan;59(1):302-10
references.pmid: 19833889
references.citation: Diabetologia. 2005 Nov;48(11):2195-9
references.pmid: 16193287