High titre of antiglutamic acid decarboxylase autoantibody is a strong predictor of the development of thyroid autoimmunity in patients with type 1 diabetes and latent autoimmune diabetes in adults

Abstract

Type 1 diabetes mellitus (T1DM) is frequently associated with autoimmune thyroid diseases (AITD), but little is known about the risk of AITD in latent autoimmune diabetes in adults (LADA). We evaluated the genetic and immunological factors involved in the development of thyroid autoimmunity in patients with LADA and T1DM. One hundred and ninety T1DM and 135 LADA patients were recruited in the study. Thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), glutamic acid decarboxylase antibody (GADA) and thyroid function were measured. The cytotoxic-lymphocyte-associated antigen-4 (CTLA-4) +49A/G and CT60 polymorphisms and the human leucocyte antigen (HLA)-DQA1-DQB1 genotype were determined. The prevalence of thyroid antibodies (TGAb and/or TPOAb) and thyroid dysfunction was 27·4% and 9·5% in patients with T1DM, and 21·5% and 11·1% in patients with LADA. Thyroid-antibody-positive T1DM patients had higher frequencies of GADA and HLA-DQA1*03-DQB1*0401 haplotypes than thyroid-antibody negatives (P < 0·05). Thyroid-antibody-positive LADA patients had higher GADA titre, lower C-peptide levels and higher frequencies of HLA-DQA1*03-DQB1*0401 haplotypes (P < 0·05). The CTLA-4 +49A/G and CT60 polymorphism was associated with T1DM complicated with thyroid autoimmunity (OR = 2·33 and 2·54). Logistic regression revealed that only high-titre GADA was associated with development of thyroid autoimmunity in patients with T1DM and LADA (OR = 3·50 and 3·10, respectively), and the presence of thyroid antibody predicted high risk for thyroid dysfunction in patients with T1DM and LADA (OR = 9·25 and 10·70, respectively). Regular screening of thyroid antibody and function are recommended, especially in patients with T1DM and LADA with high GADA titre.