Autoantibodies in Diabetes Testing

In order to diagnose diabetes, technologists measure glucose or hemoglobin A1C concentrations or perform an oral glucose tolerance test. That being the case, what are autoantibody tests ordered on patients with diabetes or pre-diabetes, or those suspected of having diabetes?

Diabetes is classified as type 1, type 2, gestational and “other specific types”, with about 40 different types of diabetes known. Type 1 and type 2 account for the majority of the diabetes cases, with type 1 accounting for roughly 10% of all diabetes and type 2 accounting for roughly 90%. Type 1 diabetes (sometimes referred to as autoimmune diabetes) is caused by the autoimmune destruction of the pancreatic beta cells. This results in an absolute insulin deficiency and requires insulin to treat. Type 2 diabetes is associated with obesity and insulin resistance and is usually treated initially with diet, exercise and weight loss. Several drugs are currently available to treat hyperglycemia in type 2 diabetes if behavioral modifications do not succeed in lowering glucose levels.

The diagnosis of diabetes is made based on the glucose level and/or hgbA1c concentration, however, not all cases are clear-cut or follow the classic presentations or indications to allow classification as type 1 or 2. Yet determining whether diabetes is type 1 or 2 is important since the treatments are different. Also, persons with type 1 diabetes are prone to other autoimmune disorders, such as autoimmune thyroid disease. In cases that are less than clear-cut, measuring autoantibodies can provide useful information. The main autoantibodies, along with their utilities include:

ICA – Islet cell cytoplasmic autoantibodies are rare in the general population but are present in 70-80% of new-onset type 1 diabetics. They are also present before the onset of type 1 diabetes, so the presence of ICA in a non-diabetic is indicative of a markedly increased risk of type 1 diabetes. If ICA are detected in a type 2 diabetic, it suggests the slowly progressive autoimmune destruction of the beta cells, and that the person actually has a form of diabetes known as latent autoimmune diabetes of adulthood (LADA). Although present in 70-80% of newly diagnosed type 1 diabetics, ICA decline to a frequency of about 5 – 10 % by 10 years post diagnosis.

GAD65/GAD67/GADA – these are the 65 KD and 67KD forms of glutamic acid decarboxylase autoantibodies. GADA like ICA are present in roughly 70-80% of new-diagnosis type 1 diabetes. They also are indicative of progression to type 1 diabetes if found in non-diabetics or type 2 diabetics. However GADA are also found in up to 3% of the general population, so ICA are more specific for type 1 diabetes.

IA2 or IAA – insulin autoantibodies are the least common type of autoantibody present at onset of type 1 diabetes, only occurring in 50-60% of children, and occurring uncommonly in adults with new onset type 1 diabetes. They are also the least disease-specific of the autoantibodies. In addition assays to measure IA2 do not distinguish between antibodies to insulin that may be produced against insulin being administered, versus insulin autoantibodies.

IA-2A – insulinoma-associated-2 autoantibodes are present in roughly 60% of new-onset type 1 diabetes and generally more prevalent then IAA.

ZnT8A – This is the newest autoantibody discovered and it is raised against the transporter that moves zinc from the cytoplasm to the insulin-containing secretory granules in the beta cells. ZnT8A are present in 60-70 % of new onset type 1 under the age of 20, and about 40% after 20 years old. They are also present in 14% of cases which are negative for GADA, IAA and IA-2A. They are also common in LADA patients so can be useful in that diagnosis.

The autoantibodies are especially useful when the diagnosis of the type of diabetes is unclear, and when there is some suspicion that a person with type 2 diabetes may in fact have autoimmune diabetes. Because none of these autoantibodies are present in greater than 80% of type 1 diabetics, measuring several of them is sometimes necessary in order to sort out the diagnosis.

 

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-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.

 

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