Type 1 Diabetes and Autoimmune Diseases
Type 1 diabetes is just one of multiple autoimmune diseases. We inherit risk of autoimmunity primarily in the HLA complex located on chromosome six. Due to the close linkage of genes coding particularly for type 1 diabetes, Hashimoto’s Thyroiditis, Juvenile Rheumatoid Arthritis, Graves, Celiac, and Addison’s disease, there is more than a random association of these diseases. A significant number of children have thyroid and celiac disease, which is the most common in association with Type 1 diabetes as demonstrated in evidence-based studies. Less commonly associated with type 1 diabetes are other autoimmune diseases such as Systemic Lupus Erythematosis and inflammatory bowel disease.
Autoimmune thyroid disease in the form of hypothyroidism (Hashimoto’s Thyroiditis) and hyperthyroidism (Graves Disease) is most commonly associated with type 1 diabetes. Thus, at diagnosis, or shortly after, Thyroid stimulating hormone (TSH), thyroid antibodies (thyroid peroxidase, or antithyroglobulin antibodies) are obtained. If the TSH is elevated in association with a low thyroid hormone level (usually free T4), thyroid replacement medication begins (Synthroid). If the TSH is extremely low in association with higher free T4 levels, thyroid suppression medication (Methimazole, for example) is usually initiated.
Celiac disease or gluten intolerance is the next most common autoimmune disease associated with type 1 diabetes. Symptoms of the disease may be vague so one must have a high suspicion to rule out the disease. Abdominal pain, growth failure, or menstrual irregularities are often associated with celiac disease; however, there may be no symptoms present. Therefore, laboratory screening is necessary requiring a serum tissue transglutaminase IgA, along with a total IgA (to ensure that the child/adolescent manufactures IgA antibodies). The tissue transglutaminase is an excellent screening test and if positive, the endomysial IgA antibody is extremely specific and is usually positive in celiac disease. Endoscopic sampling of the intestinal villi is gold standard in the diagnosis of Celiac disease.
JRA may present with joint pain, redness or swelling, and specific lab work is usually obtained by a rheumatologist that includes antibodies and markers of inflammation.
Adrenal insufficiency or Addison’s disease also may be associated with type 1 diabetes and is extremely rare. It often takes months to make the diagnosis due to vague symptomatology. As the clinical status worsens with vomiting, fatigue, and hyperpigmentation (and low blood sugar levels in children with type 1 diabetes), the child/adolescent may become very ill resulting in crisis requiring stress IV doses of hydrocortisone. Low levels of cortisol and very high levels of ACTH, along with the association of anti-adrenal antibodies, may confirm diagnosis.
Interesting enough, several of my patients have been diagnosed with alopecia areata. Alopecia Areata is hair loss that occurs when your immune system inappropriately attacks the hair follicles that initiate hair growth. The damage to the hair follicle is usually not permanent. In a paper written by Dr. Angela Christiano of Columbia University (Petukhova L, Duvic M, Hordinsky M, Norris D, Price V, Shimomura Y, Kim H, Singh P, Lee A, Chen WV, Meyer KC, Paus R, Jahoda CA, Amos CI, Gregersen PK, Christiano AM. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature. 2010 July1; 466(7302):113-7) she found that of the genetic markers studied, variations were clustered in eight different regions. Not surprisingly, one of the regions was in the HLA section that is associated with the autoimmune diseases described above. Alopecia Areata did not, however, share any genetic similarities with psoriasis and vitiligo, two other autoimmune diseases of the skin. What was most surprising to the authors was that alopecia shared similarities with the three autoimmune diseases with completely different targets: Rheumatoid arthritis, type 1 diabetes, and celiac disease.
When children and adolescents present with alopecia areata, most physicians wish to rule out thyroid disease by obtaining thyroid antibodies, TSH levels, and free T4. If these labs are normal, one must consider the autoimmune etiology of alopecia areata.
In summary, due to the linkage of genes in the HLA region of chromosome 6, type 1 diabetes is associated with other chronic autoimmune illnesses. If your child/adolescent is diagnosed with type 1 diabetes, be cognizant of the possibility of future development of one of these associated diseases.
Fran Cogen, M.D., C.D.E., is the director of the Childhood and Adolescent Diabetes Program at Children’s National Health System. She wrote about diabetes for HealthCentral.