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Type 1 Diabetes-Associated Autoimmunity: Natural History, Genetic Associations, and Screening

The Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver Health Sciences Center, Aurora, Colorado 80010

Address all correspondence and requests for reprints to: Jennifer M. Barker, M.D., The Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver Health Sciences Center, P.O. Box 6511 A-140, Aurora, Colorado 80010. E-mail: jennifer.barker{at}uchsc.edu.

Context: Type 1 diabetes (T1D) is associated with autoimmune thyroid disease (AIT), celiac disease (CD), Addison’s disease (AD), and other autoimmune diseases. These diseases can occur together in defined syndromes with distinct pathophysiology and characteristics: autoimmune polyendocrine syndrome I, autoimmune polyendocrine syndrome II, and the immunodysregulation polyendocrinopathy enteropathy X-linked syndrome.

Evidence Acquisition: Review of the medical literature was performed with particular attention to the natural history, genetic factors, and syndromes associated with T1D, AIT, CD, and AD.

Evidence synthesis: Genetic risk for these diseases overlaps and includes genes within the major histocompatibility complex (MHC) such as the human leukocyte antigens (HLA) DR and DQ alleles and the MHC I-related gene A (MIC-A). Other genes outside of the MHC have been associated with these autoimmune diseases, including the gene encoding the lymphoid tyrosine phosphatase (PTPN22) and the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene.

Conclusion: Genetic risk for T1D overlaps with AIT, CD, and AD. Disease risk is associated with organ-specific autoantibodies, which can be used to screen subjects with T1D.

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