The role of autoimmunity at diagnosis of type 1 diabetes in the development of thyroid and celiac disease and microvascular complications.
OBJECTIVE
The purpose of this study was to explore whether the presence of thyroid and endomysial autoantibodies at diagnosis of type 1 diabetes in children predicts development of thyroid and celiac disease, respectively, and whether diabetes-associated autoantibodies at diagnosis predict development of microvascular complications up to 13 years later.


METHODS
Autoantibodies were measured at diagnosis of type 1 diabetes in 173 children aged 0-15 years and included thyroperoxidase antibody (TPOA), endomysial antibody (EMA), islet cell autoantibody, GAD antibody (GADA), and insulin autoantibody. Thyroid disease was defined as thyroid stimulating hormone level > or = 5 microU/ml. Celiac disease was confirmed by small-bowel biopsy. Assessment of microvascular complications included stereoscopic fundal photography, pupillometry, thermal threshold, and albumin excretion rate (AER).


RESULTS
The incidence rates for thyroid and celiac disease were 0.9 and 0.7 per 100 patient-years, respectively. Within 13 years, 6 of 13 children with positive TPOA tests at diagnosis developed thyroid disease compared with 5 of 139 children with negative TPOA tests (P < 0.001). All four patients with positive EMA titers at diagnosis had biopsy-proven celiac disease. Five of 11 patients who developed thyroid disease and 4 of 8 who developed celiac disease had negative TPOA and EMA tests at diagnosis, respectively. Retinopathy was detected in 39% and elevated AER in 36%. The presence of diabetes-associated autoantibodies at diagnosis did not predict microvascular complications though GADA titer levels predicted pupillary abnormality.


CONCLUSIONS
Elevated TPOA and EMA levels at diagnosis of type 1 diabetes predict the development of thyroid and celiac disease, respectively. In children with negative antibody titers at diagnosis, screening at 2-year intervals is recommended.
Glastras
Sarah J
SJ
Institute of Endocrinology and Diabetes, Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia. swatzlaf@gmp.usyd.edu.au
Craig
Maria E
ME
Verge
Charles F
CF
Chan
Albert K
AK
Cusumano
Janine M
JM
Donaghue
Kim C
KC
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D002446:Celiac Disease / Q000276:immunology* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000175:diagnosis* / Q000276:immunology* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000276:immunology* / Q000401:mortality; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007453:Iodide Peroxidase / Q000276:immunology*; D016019:Survival Analysis; D013959:Thyroid Diseases / Q000276:immunology* / Q000401:mortality
D001323:Autoantibodies; D007453:Iodide Peroxidase