Work

Prevalence and Regional Distribution of Autoantibodies Against GAD65Ab in a European Population Without Diabetes: The EPIC-InterAct Study

Year: 2015

Type: article

Abstract: Geographical differences in type 1 diabetes (T1D) prevalence in Europe have been well documented, but little is known about the geographical distribution of autoantibodies specific to GAD65 (GAD65Ab) in the general population without diabetes, which is reported to range between 0.4 and 3%. However, these studies used different methods to define GAD65Ab positivity with cutoff values based on the 97–99th centile or at +3 SD above the mean among healthy individuals without T1D or type 2 diabetes (T2D). In doing so, the prevalence of GAD65Ab among the study cohorts was, by definition, 1–3%. The application of different cutoff levels greatly impairs the direct comparison of prevalence data between studies. Our aims were to 1) explore the prevalence of GAD65Ab positivity using a cutoff defined by specific competition of antibody binding to radiolabeled GAD65 with added autoantigen across eight European countries and 2) compare characteristics of age, sex, and BMI in relation to GAD65Ab positivity. A center-stratified random subcohort of 16,835 (4.9%) individuals was selected from the original European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study (1). After exclusion of individuals with known diabetes, GAD65Ab were analyzed in 15,802 (men/women 5,927/9,875, mean age 52.4 ± 9.2 years) samples. The cutoff for GAD65Ab positivity was determined through a competition assay at ≥65 WHO units/mL, and all samples were analyzed at a single laboratory using a radioligand binding assay (2). In all, 316/15,802 (2.0%) samples were GAD65Ab positive. Sweden, Denmark, U.K., and Spain had the highest and France had the lowest prevalence of GAD65Ab positivity (Table 1); however, these differences were not statistically significant (P = 0.80). We did not detect any association between GAD65Ab positivity and age, sex, or BMI.

Source: Diabetes Care

DOI: 10.2337/dc15-0305