title: Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: Action LADA 7.
abstract: OBJECTIVE
  Specific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non-insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes.
  
  
  METHODS
  We consecutively studied 6,156 European diabetic patients attending clinics within 5 years of diagnosis (age range, 30-70 years) examined cross-sectionally clinically and for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 (IA-2A) and zinc-transporter 8 (ZnT8A).
  
  
  RESULTS
  Of 6,156 patients, 541 (8.8%) had GADA and only 57 (0.9%) IA-2A or ZnT8A alone. More autoantibody-positive than autoantibody-negative patients were younger, leaner, on insulin (49.5 vs. 13.2%), and female (P < 0.0001 for each), though LADA patients (9.7% of total) did not show categorically distinct clinical features from autoantibody-negative type 2 diabetes. Similarly, more GADA patients with high (>200 World Health Organization IU) (n = 403) compared with low (n = 138) titer were female, lean, and insulin treated (54.6 vs. 39.7%) (P < 0.02 for each). Autoantibody-positive patients usually had GADA (541 of 598; 90.5%) and had LADA more often than type 1 autoimmune diabetes (odds ratio 3.3).
  
  
  CONCLUSIONS
  Adult-onset autoimmune diabetes emerges as a prevalent form of autoimmune diabetes. Our results indicate that adult-onset autoimmune diabetes in Europe encompasses type 1 diabetes and LADA in the same broad clinical and autoantibody-positive spectrum. At diagnosis, patients with adult-onset autoimmune diabetes are usually non-insulin requiring and clinically indistinguishable from patients with type 2 diabetes, though they tend to be younger and leaner. Only with screening for autoantibodies, especially GADA, can they be identified with certainty.
authors.affiliation: Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Hawa
authors.forename: Hubert
authors.initials: H
authors.lastname: Kolb
authors.forename: Nanette
authors.initials: N
authors.lastname: Schloot
authors.forename: Huriya
authors.initials: H
authors.lastname: Beyan
authors.forename: Stavroula A
authors.initials: SA
authors.lastname: Paschou
authors.forename: Raffaella
authors.initials: R
authors.lastname: Buzzetti
authors.forename: Didac
authors.initials: D
authors.lastname: Mauricio
authors.forename: Alberto
authors.initials: A
authors.lastname: De Leiva
authors.forename: Knud
authors.initials: K
authors.lastname: Yderstraede
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Neilsen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sarti
authors.forename: Charles
authors.initials: C
authors.lastname: Thivolet
authors.forename: David
authors.initials: D
authors.lastname: Hadden
authors.forename: Steven
authors.initials: S
authors.lastname: Hunter
authors.forename: Guntram
authors.initials: G
authors.lastname: Schernthaner
authors.forename: Werner A
authors.initials: WA
authors.lastname: Scherbaum
authors.forename: Rhys
authors.initials: R
authors.lastname: Williams
authors.forename: Sinead
authors.initials: S
authors.lastname: Brophy
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.forename: Richard David
authors.initials: RD
authors.lastname: Leslie
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D027682:Cation Transport Proteins / Q000276:immunology; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000276:immunology; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; C096322:ICA512 autoantibody; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8