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Diabetes-Related Autoantibody Testing

At a Glance

Also known as

Islet autoantibodies, Diabetes mellitus autoantibody panel

Formal Name

Islet Cell Cytoplasmic Autoantibodies (ICA), Insulin Autoantibodies (IAA), Glutamic Acid Decarboxylase Autoantibodies (GADA, GAD65 Autoantibodies), Insulinoma-Associated-2 Autoantibodies (IA-2A), ICA512 Autoantibodies, Protein Tyrosine Phosphatase-like Autoantibodies

Related tests

Glucose; Insulin

Why get tested?

After a diagnosis of diabetes is made, to help distinguish autoimmune type 1 diabetes from type 2 diabetes 

When to get tested?

  • When a person is first diagnosed with diabetes to help determine whether their diabetes is autoimmune-related 

  • When a diabetic person who is treated with diet or drugs has great difficulty maintaining normal or near-normal blood sugar levels and is suspected of having type 1 instead of type 2 diabetes

Sample required

A blood sample drawn from a vein in your arm.

Test Sample

What is being tested?

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.  Diabetes-related autoantibody tests are a group of tests that detect the presence of one or more autoantibodies that have been shown to be associated with type 1 diabetes. These autoantibodies reflect the destruction of beta cells, the loss of beta cell function and inadequate production of insulin that are features of type 1 diabetes. They are not thought to be the cause of type 1 diabetes. In contrast, type 2 diabetes primarily results from insulin resistance and does not involve autoimmune processes.  

About 10% of all cases of diabetes are type 1 (autoimmune) and the majority of these cases are diagnosed in patients younger than 20.  Symptoms of diabetes, such as frequent urination, thirst, weight loss, and poor wound healing emerge when about 80-90% of a type 1 diabetic’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 crisis and chronic hyperglycemia can damage blood vessels and organs such as the kidneys. 

Type 1 diabetes was previously known as juvenile or insulin-dependent diabetes but has been re-characterized to reflect beta cell destruction. When autoimmune type 1 diabetes is present, one or more of the diabetes 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.

Four 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 autoantiboidies (IAA) 

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

The Test

How is each test used?

Diabetes-related (islet) autoantibody testing is primarily ordered to help distinguish between autoimmune type 1 diabetes and diabetes due to other causes. 

Determining which type of diabetes is present allows for early treatment with the most appropriate therapy to avoid complications from the disease. Type 1 diabetics must self-check their glucose levels and inject themselves with insulin several times a day to control the level of glucose in their blood. Type 2 diabetics 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.

The four most common autoantibody tests used to distinguish between type 1 diabetes and diabetes due to other causes are summarized in the table below.

Test

Abbr

Description

Comments

Islet Cell Cytoplasmic Autoantibodies

ICA

Measures a group of islet cell autoantibodies targeted against a variety of islet cell proteins

One of the most common islet cell autoantibodies detected at onset of disease.  Detected in about 70-80% of newly diagnosed type 1 diabetics

Glutamic Acid Decarboxylase Autoantibodies

GADA

Tests for autoantibodies directed against beta cell protein (antigen), but is not specific to beta cells

Also one of the most commonly detected autoantibodies in newly diagnosed type 1diabetics (about 70-80%)

Insulinoma-Associated-2 Autoantibodies

IA-2A

Tests for autoantibodies directed against beta cell antigens but is non-specific

Detected in about 60% of type 1 diabetics

Insulin Autoantibodies

IAA

Autoantibody targeted to insulin. Insulin is the only antigen thought to be highly specific for beta cells. 

Detected in about 50% of type 1 diabetic children; not commonly detected  in  adults

IAA test does not distinguish between autoantibodies that target the endogenous insulin and antibodies produced against exogenous insulin

When is it ordered?

A combination of these autoantibodies may be ordered when a patient is newly diagnosed with diabetes and the doctor suspects that the condition may be due to an autoimmune process. IAA testing as a marker of autoimmune type 1 diabetes must be performed before insulin injections are begun. Insulin injections of either human or animal insulin can stimulate insulin antibodies that will give a positive result in the IAA assay. The IAA assay does not distinguish autoantibodies from antibodies that form in response to insulin injections.

One or more of the autoantibodies may be ordered on the siblings of a patient diagnosed with type 1 diabetes or on the offspring of diabetic parents. This may be done initially and then again at intervals recommended by the doctor in a research setting.

What does the test result mean?

Normally, nondiabetic individuals in the general population will not have any of these islet autoantibodies. However, when islet autoantibodies are detected in individuals in the general population or siblings of affected patients, there may be an increased risk for type 1 diabetes since false positives are known to occur. Many of these islet autoantibody-positive individuals will never develop diabetes, however. When type 1 diabetes does not develop, the level of the islet autoantibody in the blood is usually low and the islet autoantibody may be transient.

Some patients who do have type 1 diabetes will never develop detectible amounts of islet autoantibodies, although this is rare. The majority of people (95% or more) with new-onset type 1 diabetes will have at least one islet autoantibody. Therefore, if one or more islet autoantibody (e.g., ICA, GADA, IA-2A, and/or IAA) are present in a patient with symptoms of diabetes, the diagnosis of type 1 diabetes is confirmed.

In nondiabetic individuals who are positive for one or more islet autoantibodies, there is an increased risk for type 1 diabetes as mentioned above. The more islet autoantibodies that are present, the higher is the individual’s risk for developing type 1 diabetes. However not everybody with islet autoantibodies will develop type 1 diabetes. If a non-diabetic individual with one or more islet autoantibodies has a low insulin response to the intravenous injection of glucose, their risk for type 1 diabetes can be very high. In first degree relatives of patients with type 1 diabetes who have ICA and have a low insulin response to the intravenous injection of glucose, the 5-year risk of developing type 1 diabetes is approximately 60%. Because there are no effective therapies to prevent type 1 diabetes, general population screening for islet autoantibodies or testing first degree relatives of patients with type 1 diabetes is not recommended.

Is there anything else I should know?

It is up to the doctor and patient to decide together which islet autoantibodies to test for at any given time. Because GADA and IA-2A assays are automated, these tests are generally more available than ICA testing, which is labor-intensive and requires considerable expertise in interpretation.

Islet autoantibodies may also be seen in patients with other autoimmune endocrine disorders such as Hashimoto thyroiditis or autoimmune Addison disease.

Common Questions

Can these tests be used to diagnose diabetes?

No.  Diabetes type 1 as well as other types 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.

Do the autoantibodies ICA, GADA, and IA-2A 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 call destruction allow its prevention?

Not currently. What it does do is allow for diabetes to be addressed as soon as symptoms such as frequent urination, weight loss, and hyperglycemia appear. This can help establish diabetic glucose control and can in turn help minimize the occurrence of complications such as the kidney and eye damage that are seen with diabetes.

Last update: July 2010

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