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Extrapancreatic Autoimmune Manifestations in Type 1 Diabetes Patients and Their First-Degree Relatives

A multicenter study

¹ Department of Pediatrics, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
² Division of Pediatric Endocrinology, Haemek Medical Center, Afula, Israel
³ Department of Pediatrics, Assaf Harofeh Medical Center, Zerifin, Israel
⁴ Immunology Laboratory, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
⁵ Endocrine Laboratory, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
⁶ Division of Biostatistics, E. Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
⁷ Dana Children’s Hospital, Tel-Aviv, Israel

OBJECTIVE—To investigate the prevalence of autoimmune diseases in young patients (probands) with type 1 diabetes and their first-degree relatives, and to determine the spectrum of extrapancreatic manifestations in these subjects.

RESEARCH DESIGN AND METHODS—The study population included 109 probands age 13 ± 4.9 years and 412 first-degree relatives age 28.7 ± 16.2 years. The prevalence rates of autoimmune thyroiditis and celiac disease were determined in all probands and in 100 of the 412 first-degree relatives. Control groups included 78 subjects age 14.9 ± 10.4 years for the prevalence of autoimmune thyroiditis and 120,000 youth ages 16–17 years for the prevalence of celiac disease. Thyroiditis and celiac disease were diagnosed by abnormally high thyroid peroxidase (TPO), thyroglobulin (TG), antigliadin, and antiendomysial antibody titers. Celiac was confirmed by biopsy. A questionnaire was used to interview probands and relatives to determine the spectrum of autoimmune manifestations.

RESULTS—The prevalence of autoimmune thyroiditis determined by high TPO and/or TG titers was 27 and 25% for probands and relatives, respectively. These rates were higher than those for control subjects (P < 000.1). The prevalence of celiac disease among probands and screened relatives was 8.3 and 6%, respectively. These rates were higher than those for control subjects and the 312 family members interviewed only (0.1 and 0.3%, respectively; P < 0.0001). Interviews of participants revealed a wide range of associated autoimmune diseases. The risk of developing an autoimmune disease was higher (P < 0.001) in families with a proband who had an additional autoimmune manifestation.

CONCLUSIONS—Screening for autoimmune thyroiditis and celiac disease should be performed in patients with type 1 diabetes and their first-degree relatives, especially when the probands have an additional autoimmune manifestation.

Abbreviations: AEA, antiendomysial antibody • AGA, antigliadin antibody • ICA, islet cell antibody • IDF, Israel Defense Forces • TG, thyroglobulin • TPO, thyroid peroxidase.

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