Associated immune disorders
People with type 1 diabetes and their close relatives are more likely to carry circulating autoantibodies associated with a range of autoimmune disorders, including Addison's disease, coeliac disease and autoimmune thyroid disease, or (more rarely) to develop these disorders. Type 1 diabetes forms part of the autoimmune polyendocrine syndromes I and II, and with IPEX, the immunodysregulation polyendocrinopathy enteropathy X linked syndrome. This page provides a brief introduction to the autoimmune disorders which overlap with type 1 diabetes.
Circulating autoantibodies to a number of immune disorders occur more frequently in type 1 diabetes, particularly when this presents in childhood or adolescence.
These include antibodies to the thyroid antigens thyroid peroxidase (TPO) and thyroglobulin (TG),[a] endomysial antibodies (EMA) and tissue transglutaminase (TTG) antibodies found in coeliac disease, and 21-hydroxylase (21-OH) antibodies associated with Addison’s disease.
These antibodies also predict progression to the respective clinical disorders (although such progression is far from inevitable), and autoantibody screening is recommended at diagnosis of type 1 diabetes and thereafter in those who test positive or when there is clinical suspicion of a problem.
It has been estimated that about 8% of children with type 1 diabetes will also develop thyroid dysfunction, and that 6% will develop coeliac disease. Autoimmune Addison's disease affects 1/10,000 of the non-diabetic population, and between 0.1% and 0.5% of those with type 1 diabetes.
The highest risk HLA genotype for type 1 diabetes is DR3-DQ2, DR4-DQ8. About 5% of those carrying this genotype in the general population will develop type 1 diabetes in childhood. DR3-DQ2 is associated with coeliac disease, and about 3% of those in the general population with this haplotype will develop biopsy-proven coeliac disease or persistent tissue transglutaminase (TTG) antibodies by the age of 5 years. Autoimmune thyroid disease has also been associated with DR3-DQ2. Addison’s is associated with a rare subtype of DR3-DQ2, DR4-DQ8 in which the DR4 subtype is DRB1*0404, which is found in 1% of the general population and 30% of those with Addison’s disease.
^ Barker JM. Type 1 diabetes-associated natural history, genetic associations and screening. J Clin Endocrinol Metab 2006;91:1210–17
^ Thyroid autoantibodies are also common in type 2 diabetes, but this is because older people frequently develop these antibodies, and is unrelated to the diabetes itself.