GAD65 and IA-2 autoantibodies are common in a subset of siblings of Sardinian Type 2 diabetes families

Diabetes Res Clin Pract. 2002 Apr;56(1):41-7. doi: 10.1016/s0168-8227(01)00348-5.


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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Body Mass Index
  • Child
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / immunology*
  • Female
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Isoenzymes / immunology*
  • Male
  • Middle Aged
  • Nuclear Family
  • Radioligand Assay


  • Autoantibodies
  • ICA512 autoantibody
  • Isoenzymes
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2