Islet Autoantibodies in Diabetes

At a Glance

Why Get Tested?

To identify people at increased risk for developing type 1 diabetes or requiring insulin treatment; to aid in the classification of diabetes. Note: testing for islet autoantibodies in non-diabetic individuals Is not advised unless the person is a participant in a research study that requires islet autoantibody testing.

When To Get Tested?

Any time that you have diabetes and your healthcare practitioner cannot clearly determine if you have type 1 diabetes or type 2 diabetes, your healthcare practitioner may order tests for islet autoantibodies.

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

Looking For Test Results?

Looking For Reference Ranges?

You may be able to find your test results on your laboratory’s website or patient portal. However, you are currently at Testing.com. You may have been directed here by your lab’s website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab’s website or portal, or contact your healthcare practitioner in order to obtain your test results.

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The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called “normal” values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are “within normal limits.”

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

Islet autoantibodies are proteins produced by the immune system that have been shown to be associated with type 1 diabetes. Testing can detect the presence of one or more of these autoantibodies in the blood.

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. Islet autoantibodies can be present prior to the diagnosis of type 1 diabetes, are usually present at the time of diagnosis, and decrease in frequency over 5 to 10 years following the diagnosis of type 1 diabetes.

Islet autoantibodies are markers of an autoimmune (self-reactive) response to the islets, but islet autoantibodies do not cause type 1 diabetes. Type 2 diabetes primarily results from the body’s resistance to the effects of insulin (insulin resistance) together with declining insulin production and does not involve autoimmune processes.

Type 1 diabetes was previously known as juvenile or insulin-dependent diabetes but has been re-characterized to reflect absolute insulin deficiency. When autoimmune type 1 diabetes is present, one or more of the islet autoantibodies will be present in about 95% of those affected at the time of initial diagnosis. With type 2 diabetes, the autoantibodies are typically absent.

Five of the most common diabetes-related autoantibody tests include:

Islet Cell Cytoplasmic Autoantibodies (ICA)
Glutamic Acid Decarboxylase Autoantibodies (GADA)
Insulinoma-Associated-2 Autoantibodies (IA-2A)
Insulin Autoantibodies (IAA)
Zinc Transporter-8 Autoantibodies (ZnT8A)

For more on these, see “What does the test result mean?” under Common Questions below.

About 10% of all cases of diabetes are type 1 (autoimmune) and the majority of these cases are diagnosed in people younger than 20. However, type 1 diabetes can develop in people of any age. Symptoms of diabetes, such as frequent urination, thirst, weight loss, and poor wound healing, emerge when about 80-90% of the person’s beta cells have been destroyed and are no longer able to produce insulin. The body requires daily insulin so that glucose can enter cells and be used for energy production. Without sufficient insulin, cells starve and high blood sugar (hyperglycemia) results. Acute hyperglycemia can cause a diabetic medical crises (either diabetic ketoacidosis or hyperglycemic hyperosmolar state or a combination of the two states). Chronic hyperglycemia can damage large and small blood vessels, nerves, and organs such as the kidneys.

Common Questions

How is it used?

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.

When is it ordered?

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.

What does the test result mean?

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 table below summarizes the five most common autoantibody tests:

Test	Abbr	Description	Results Interpretation
Islet Cell Cytoplasmic Autoantibodies	ICA	Measures a group of islet cell autoantibodies targeted against a variety of islet cell proteins (Note: beta cells are one type of islet cell)	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	GADA	Tests for autoantibodies directed against beta cell protein (antigen) but is not specific to beta cells; also known as GAD65 autoantibodies	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	IA-2A	Tests for autoantibodies directed against beta cell antigens	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	IAA	Autoantibody targeted to insulin; insulin is the only antigen thought to be highly specific for beta cells.	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	ZnT8A	Autoantibody targeted against a protein that pumps zinc into insulin-containing granules in beta cells	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.

Is there anything else I should know?

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.

Can these tests be used to diagnose 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. The autoantibody tests can be used after diabetes is already diagnosed to help differentiate between type 1 and type 2 diabetes.

Do the autoantibodies ICA, IAA, GADA, IA-2A or ZnT8A destroy the beta cells?

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

Does early detection of beta cell destruction allow its prevention?

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.

View Sources

Sources Used in Current Review

2017 review performed by Shu-Ling Fan, PhD, DABCC, Medical Director, Clinical Chemistry, Department of Pathology, Boston Medical Center.

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