ESPE Abstracts

Objective: to determine risk factors of co-existing thyroid autoimmunity in children with type 1 diabetes mellitus (T1DМ).

Material and Methods: 48 children with combined autoimmune pathology (45 – with T1DМ and autoimmune thyroiditis and 3 – with T1DМ and Grave’s disease) – main group, age 12.51±3.57 years) and 99 patients with only T1DM (comparison group, age 11.76±3.05 years) were recruited. Groups were comparable in age (P=0.19) and T1DM duration (P=0.66). We assessed CTLA4 gene for rs231775 (+49 A/G) variant, PTPN22 gene for rs2476601 (+1858C/T) variant and microsatellite repeat in exon 5 of MICA class I gene. Evaluation of anthropometric parameters; biochemical blood parameters; glycosylated hemoglobin (HbA1c), vitamin D, thyroid hormones, antibodies to thyroid peroxidase (anti-TPO), glutamate decarboxylase (GAD) and zinc transporter8 (ZnT8) levels was carried out. Results were processed using Statistica 10 and Excel 10.

Results: Statistically significant difference in the frequency of CTLA4 genotypes +49A>G was found between patients with combined autoimmune pathology and isolated T1DМ: AG and GG genotypes increased three-fold the risk of autoimmune thyroid diseases (OR=2.94, 95% CI: 1.13-7.68). Patients of the main group had higher prevalence of combinations of A5.1/A5.1 genotype of the MICA gene with certain genotypes at loci +49A/G of the CTLA4 gene and +1858C/T of the PTPN22 gene. In particular, autoimmune thyroid pathology was more likely in patients with combination of CTLA-4 +49 A/G GG genotype and MICA gene A5.1/A5.1 genotype (OR=19.40, 95% CI: 2.35-160.22); combination of PTPN22 +1858C/T CT and TT genotypes and A5.1/A9 of the MICA gene (OR = 4.01, 95% CI: 1.11-14.46). Children with polyglandular autoimmune pathology showed higher prevalence of severe vitamin D deficiency (level <10 ng/ml) (OR = 4.26, 95% CI: 1.53-11.82). Among the factors, associated with co-existing autoimmune thyroid diseases we also detected female gender (OR=3.08, CI 1.48-6.36), high levels of GAD antibodies (>50 U/ml) (OR = 2.66, CI: 1.27-5.56) and ZnT8 antibodies (>1500 U/ml) (OR=4.57, CI: 1.43-14.62).

Conclusions: 1. Co-existing autoimmune thyroid diseases in children with T1DМ were associated with severe vitamin D deficiency, female gender, high levels of GAD ant ZnT8 antibodies. 2. We have demonstrated that a distinct association exists between polyglandular autoimmune pathology and carrying of G allele of CTLA-4 at loci +49 A/G; combinations of genotype A5.1/A5.1 of the MICA gene with GG genotypes at loci +49A/G CTLA4 or CT and TT genotypes at loci +1858C/T of the PTPN22 gene.