Islet Autoantibodies in Diabetes

Islet autoantibody testing is primarily used to help distinguish type 1 diabetes from diabetes due to other causes. Islet autoantibodies are positive in type 1 diabetes and are negative in diabetes cases caused by non-autoimmune problems. Type 1 diabetes is a condition characterized by a lack of insulin due to autoimmune processes that destroy the insulin-producing beta cells in the pancreas. Type 2 diabetes is primarily associated with insulin resistance and a relative decease in insulin production by the pancreas.

Determining which type of diabetes is present allows for early treatment with the most appropriate therapy to avoid complications from the disease. People with type 1 diabetes must frequently self-check their glucose levels and inject themselves with insulin several times a day to control the level of glucose in their blood. People with type 2 diabetes may self-check their glucose one or more times a day. However, type 2 diabetics control their blood glucose in a variety of ways. Some can control their glucose levels with diet and exercise, others take oral medications, and some need daily insulin injections.

A combination of these autoantibodies may be ordered when a person is newly diagnosed with diabetes and the healthcare practitioner wants to distinguish between type 1 diabetes and other forms of diabetes such as type 2 diabetes. In addition, these tests may be used when a person with type 2 diabetes is having great difficulty in controlling their glucose levels with standard treatments. In such a case, a positive test for an islet autoantibody can indicate that the diagnosis is type 1 diabetes and not type 2 diabetes. Your healthcare practitioner will best be able to tell what kind of diabetes tests, or labs, to order.

If ICA, GADA, IA-2A and/or ZnT8A are present in a person with symptoms of diabetes, the diagnosis of type 1 diabetes is confirmed. Likewise, if IAA is present in a child with diabetes who is not insulin-treated, type 1 diabetes is the likely cause of the diabetes.

If no islet autoantibodies are present at onset or within a few years of diagnosis, then it is unlikely that the diabetes is type 1. Some people who have type 1 diabetes will never develop detectable amounts of islet autoantibodies, but this is rare. The majority of people, 95% or more, with new-onset type 1 diabetes will have at least one islet autoantibody.

The list below summarizes the five most common autoantibody tests:

Islet Cell Cytoplasmic Autoantibodies

• Abbr: ICA
• Description: Measures a group of islet cell autoantibodies targeted against a variety of islet cell proteins (Note: beta cells are one type of islet cell)
• Results Interpretation: The presence of ICA in patients with diabetes indicates the presence of autoimmune, type 1 diabetes. ICA are present in approximately 70-80% of people with new-onset type 1 diabetes. The presence of ICA in asymptomatic individuals indicates they are at increased risk for the development of type 1 diabetes.

Glutamic Acid Decarboxylase Autoantibodies

• Abbr: GADA
• Description: Tests for autoantibodies directed against beta cell protein (antigen) but is not specific to beta cells; also known as GAD65 autoantibodies
• Results Interpretation: The presence of GADA in patients with diabetes indicates the presence of autoimmune, type 1 diabetes. GADA are present in approximately 70-80% of persons with new-onset type 1 diabetes. GADA in asymptomatic individuals indicates they have increased risk for the development of type 1 diabetes.

Insulinoma-Associated-2 Autoantibodies

• Abbr: IA-2A
• Description: Tests for autoantibodies directed against beta cell antigens
• Results Interpretation: The presence of IA-2A in patients with diabetes indicates the presence of autoimmune, type 1 diabetes. IA-2A are present in approximately 60% of persons with new-onset type 1 diabetes. IA-2A in asymptomatic individuals means they have increased risk for the development of type 1 diabetes.

Insulin Autoantibodies

• Abbr: IAA
• Description: Autoantibody targeted to insulin; insulin is the only antigen thought to be highly specific for beta cells.
• Results Interpretation: The presence of IAA in patients with diabetes who are not insulin-treated indicates the presence of autoimmune, type 1 diabetes. It is advised that blood for IAA testing be drawn before insulin therapy is initiated. For the IAA result to be valid, the patient must not be insulin-treated for more than 14 days. IAA are present in approximately 50% of children with new-onset type 1 diabetes. IAA are uncommon in adults with type 1 diabetes. Therefore, IAA testing in adults is not advised. IAA in asymptomatic individuals indicates they have increased risk for the development of type 1 diabetes. IAA test does not distinguish between autoantibodies that target the endogenous insulin and antibodies produced against exogenous insulin.

Zinc Transporter-8 Autoantibodies

• Abbr: ZnT8A
• Description: Autoantibody targeted against a protein that pumps zinc into insulin-containing granules in beta cells
• Results Interpretation: The presence of ZnT8A in people with diabetes mellitus indicates that they have diabetes that is autoimmune (i.e., type 1 diabetes). ZnT8A are present in approximately 60% of persons with new-onset type 1 diabetes. ZnT8A are also valuable in the diagnosis of latent autoimmune diabetes of adulthood (LADA). ZnT8A in asymptomatic individuals means they have increased risk for developing type 1 diabetes. The presence of ZnT8A in the blood of patients who have undergone a pancreas transplant predicts beta-cell failure.

Islet autoantibodies may also be seen in people with other autoimmune endocrine disorders such as Hashimoto thyroiditis or autoimmune Addison disease. Such individuals are then at increased risk to develop type 1 diabetes.

Testing non-diabetic individuals for islet autoantibodies is recommended only as part of a research study. In research settings, these islet autoantibody tests may be used to help predict the development of type 1 diabetes in family members of those affected. In general, the more islet autoantibodies that a non-diabetic person has in their blood, the higher their risk for later developing type 1 diabetes. If a non-diabetic individual with one or more islet autoantibodies also has a low insulin response to the intravenous injection of glucose, their risk for type 1 diabetes can be high. More specifically, in first degree relatives of people with type 1 diabetes who have ICA and a low insulin response to intravenous injection of glucose, the risk of developing type 1 diabetes within 5 years is greater than 50%. GADA has a similar predictive power. People with multiple islet autoantibodies can have a 10-year risk for developing type 1 diabetes that approaches 100%.

Because there are currently no effective therapies to prevent type 1 diabetes, general population screening for islet autoantibodies or testing of first degree relatives of those with type 1 diabetes is not generally recommended, except for research purposes.

People who are treated with insulin injections may begin to develop antibodies directed against the exogenous insulin. The IAA test does not distinguish between these types of antibodies and the autoantibodies directed against endogenous insulin. Therefore, this test is not valid for someone who has already been treated with injections of insulin. For example, someone who was thought to have type 2 diabetes and who was treated with insulin injections cannot then have this test done to determine if he or she has type 1 diabetes.

No. Type 1 diabetes as well as other types of diabetes are screened for, diagnosed, and monitored using tests for blood glucose and/or A1c. This is not a blood sugar test. The autoantibody tests can be used after diabetes is already diagnosed to help differentiate between type 1 and type 2 diabetes.

They are associated with beta cell destruction and reflect an ongoing autoimmune process, but they are not thought to cause the damage.

Not currently. The presence of islet autoantibodies indicates the cause of the diabetes but does not indicate if somebody has diabetes or does not have diabetes. There is debate if islet autoantibody screening should be performed even if we cannot prevent type 1 diabetes. This is because (even today) approximately 30% of children with new-onset type 1 diabetes have diabetic ketoacidosis (DKA), which can be fatal in approximately 1 in 200 children. If we screened for islet autoantibodies and placed patients and parents on alert for the development of diabetes symptoms, theoretically DKA should be preventable at onset.