Academy of Diagnostics & Laboratory Medicine - Scientific Short

Autoimmune diabetes and related conditions

William E. Winter and Roger L. Bertholf

Challenge: I was recently asked what medical concerns exist for people with autoimmune diabetes [either type 1 diabetes or latent autoimmune diseases of adulthood (LADA)] that are not shared by people with type 2 diabetes.

Certainly for all people with diabetes of any kind, attempting to achieve a hemoglobin A1c level of 7% or less is desirable in reducing the risks of long term complications. At the same time this must be balanced against the risk of developing hypoglycemia.

What associated diseases occur in people with autoimmune diabetes that are not associated with type 2 diabetes? What would you advise? Our responses will be posted in 1 week.

Answer: Concerning autoimmune diabetes, it is important to recognize that other autoimmune diseases occur with increased frequencies in persons with autoimmune diabetes. The strongest associations with autoimmune diabetes are with autoimmune thyroid disease (AITD) and pernicious anemia (PA). Other associations of importance include celiac disease (e.g., gluten enteropathy) and Addison disease. AITD is most often manifested as Hashimoto thyroiditis (HT) causing goiter with or without hypothyroidism and, less often, AITD is manifested as Graves disease producing hyperthyroidism.

Because of the high risk for AITD, many physicians will screen their patients with autoimmune diabetes for AITD by testing for thyroperoxidase autoantibodies (TPOA). If these are negative, testing for thyroglobulin autoantibodies (TGA) is appropriate. For convenience, many physicians will order the TPOA and TGA tests at the same time. If either is positive, the TSH level should be measured yearly. If abnormal, FT4 should be measured.

To screen for pernicious anemia (the most common cause of vitamin B12 deficiency), autoantibodies to the gastric parietal cells (PCA) and intrinsic factor can be sought. As well, vitamin B12 can be directly measured as can ferritin.

In people with autoimmune diabetes and either AITD or pernicious anemia, autoantibody testing for reactivity to antigens in the adrenal cortex can be sought through the measurement of adrenal cortical autoantibodies (ACA) or autoantibodies to 21-hydroxylase. If these are positive, renin and electrolytes should be measured and a cosyntropin stimulation test should be performed. The aim of these tests is to anticipate the likelihood of the development of Addison disease (primary adrenal insufficiency) and treat prior to the development of symptoms. While Addison disease is not very common in people with autoimmune diseases, untreated Addisonian crisis is extremely dangerous and can be fatal.

Some studies have found that up to 10% of people with type 1 diabetes have celiac disease. It is controversial whether all people with type 1 diabetes should be screened for celiac disease. Most cases of celiac disease in type 1 diabetes patients are asymptomatic [1].

1. Camarca ME, Mozzillo E, Nugnes R, Zito E, Falco M, Fattorusso V, Mobilia S, Buono P, Valerio G, Troncone R, Franzese A. Celiac disease in type 1 diabetes mellitus. Ital J Pediatr. 2012 Mar 26;38:10.

General references:

  1. Bertholf RL, Jialal I, Winter WE: The Adrenal Cortex. In: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th Edition, C Burtis, E Ashwood, D Bruns (eds), Elsevier Saunders, St. Louis, Mo, 2012; pp. 1847-1904.
  2. Winter WE, Schatz, D., Bertholf RL: The Thyroid: Pathophysiology and Thyroid Function Testing. In: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th Edition, C Burtis, E Ashwood, D Bruns (eds), Elsevier Saunders, St. Louis, Mo, 2012; pp. 1905-1944.
  3. Winter WE. Autoimmune Endocrinopathies, In: Pediatric Endocrinology, Fifth Edition, F. Lifshitz (ed):  Informa HealthCare USA, Inc., New York, New York, 2007, pp: 595-616.

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Fellows of the Academy use the designation of FADLM. This designation is equivalent to FACB and FAACC, the previous designations used by fellows of the National Academy of Clinical Biochemistry and AACC Academy. Those groups were rebranded as Academy of Diagnostics & Laboratory Medicine in 2023.