Unknown

Dataset Information

0

Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12.


ABSTRACT: AIMS/HYPOTHESIS:Adult-onset type 1 diabetes, in which the 65 kDa isoform of GAD (GAD65) is a major autoantigen, has a broad clinical phenotype encompassing variable need for insulin therapy. This study aimed to evaluate whether autoantibodies against N-terminally truncated GAD65 more closely defined a type 1 diabetes phenotype associated with insulin therapy. METHODS:Of 1114 participants with adult-onset diabetes from the Action LADA (latent autoimmune diabetes in adults) study with sufficient sera, we selected those designated type 1 (n?=?511) or type 2 diabetes (n?=?603) and retested the samples in radiobinding assays for human full-length GAD65 autoantibodies (f-GADA) and N-terminally truncated (amino acids 96-585) GAD65 autoantibodies (t-GADA). Individuals' clinical phenotypes were analysed according to antibody binding patterns. RESULTS:Overall, 478 individuals were f-GADA-positive, 431 were t-GADA-positive and 628 were negative in both assays. Risk of insulin treatment was augmented in t-GADA-positive individuals (OR 4.69 [95% CI 3.57, 6.17]) compared with f-GADA-positive individuals (OR 3.86 [95% CI 2.95, 5.06]), irrespective of diabetes duration. Of 55 individuals who were f-GADA-positive but t-GADA-negative, i.e. with antibody binding restricted to the N-terminus of GAD65, the phenotype was similar to type 2 diabetes with low risk of progression to insulin treatment. Compared with these individuals with N-terminal GAD65-restricted GADA, t-GADA-positive individuals were younger at diagnosis (p?=?0.005), leaner (p?

SUBMITTER: Achenbach P 

PROVIDER: S-EPMC6445455 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12.

Achenbach Peter P   Hawa Mohammed I MI   Krause Stephanie S   Lampasona Vito V   Jerram Samuel T ST   Williams Alistair J K AJK   Bonifacio Ezio E   Ziegler Anette G AG   Leslie R David RD  

Diabetologia 20180404 7


<h4>Aims/hypothesis</h4>Adult-onset type 1 diabetes, in which the 65 kDa isoform of GAD (GAD65) is a major autoantigen, has a broad clinical phenotype encompassing variable need for insulin therapy. This study aimed to evaluate whether autoantibodies against N-terminally truncated GAD65 more closely defined a type 1 diabetes phenotype associated with insulin therapy.<h4>Methods</h4>Of 1114 participants with adult-onset diabetes from the Action LADA (latent autoimmune diabetes in adults) study wi  ...[more]

Similar Datasets

| S-EPMC3609504 | biostudies-literature
| S-EPMC2606853 | biostudies-literature
| S-EPMC5584925 | biostudies-literature
| S-EPMC4560857 | biostudies-literature
| S-EPMC9404871 | biostudies-literature
2024-12-19 | PXD058474 | Pride
| S-EPMC9184721 | biostudies-literature
2024-12-19 | PXD059037 | Pride
| S-EPMC2496870 | biostudies-literature
| S-EPMC8096264 | biostudies-literature