title: GAD65 and IA-2 autoantibodies are common in a subset of siblings of Sardinian Type 2 diabetes families.
abstract: Type 1 diabetes in Sardinia is very common in children, and we hypothesized that Latent Autoimmune Diabetes of Adult (LADA) might constitute a significant proportion of diabetes in adult Sardinian subjects. Since Type 2 diabetes is a familial disorder, we tested this hypothesis by investigating the prevalence of GAD65 and IA-2 autoantibodies (Ab) in Type 2 diabetes multiplex families of Sardinian ancestry enrolled in the Study Group for the Genetics of Diabetes in Sardinia.
  
  
  METHODS
  A total of 684 individuals were ascertained from 252 Sardinian Type 2 diabetes multiplex families with 2.4 affected siblings per family comprising 190 families with two affected, 37 with three, 15 with four, 7 with five, and 3 with six, in addition to 80 unaffected siblings. Controls were household contacts representing 204 healthy spouses of affected siblings. Diagnosis was at 35-69 years of age and insulin was not given in the first 4 years after diagnosis. GAD65Ab and IA-2Ab were determined in standard radioligand binding assays.
  
  
  RESULTS
  Among affected siblings GAD65Ab were positive in 8.8% of insulin-treated (n = 137; P = 0.0006), in 2.5% of non-insulin-treated (n = 467), and in 1.2% of non-diabetic siblings (n = 80) compared with 0.5% of controls (n = 204). IA-2Ab was positive in 6.6% insulin-treated (P = 0.04), 2.1% non-insulin-treated, and 2.5% non-diabetic siblings compared with 1.5% of controls.
  
  
  CONCLUSIONS
  A high frequency of GAD65Ab and IA-2Ab as markers of Type 1 diabetes was found among Type 2 diabetes siblings from Sardinian multiplex families despite excluding those who had been treated with insulin during the first 4 years of disease. Our data support the hypothesis that LADA may be common in Sardinian Type 2 diabetes and stress the importance of investigating markers of Type 1 diabetes in studies of Type 2 diabetes.
authors.affiliation: Cattedra Malattie Metabolismo, Istituto di Clinica Medica, Viale S. Pietro 8, 07100, Sassari, Italy. marimaio@ssmain.uniss.it
authors.forename: Mario
authors.initials: M
authors.lastname: Maioli
authors.forename: G
authors.initials: G
authors.lastname: Tonolo
authors.forename: L
authors.initials: L
authors.lastname: Bekris
authors.forename: R
authors.initials: R
authors.lastname: Cirillo
authors.forename: D
authors.initials: D
authors.lastname: Schranz
authors.forename: E
authors.initials: E
authors.lastname: Cossu
authors.forename: M
authors.initials: M
authors.lastname: Ciccarese
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015992:Body Mass Index; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D011869:Radioligand Assay
chemical_list: D001323:Autoantibodies; C096322:ICA512 autoantibody; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2