Some people who develop diabetes as adults have a late-onset form of type 1 diabetes rather than type 2 diabetes. A blood test in someone with this type of diabetes will show the presence of glutamic acid decarboxylase, or GAD, antibodies.
GAD antibodies belong to a group of diabetes-associated antibodies that instruct the immune system to destroy the insulin-producing pancreatic cells. When insulin production stops, diabetes develops.
As these antibodies target and react with the body’s cells, the medical community refers to them as autoantibodies.
Testing for GAD antibodies helps a doctor diagnose a person with LADA and provide appropriate treatment.
In this article, we look at the role of GAD, how it relates to diabetes, and the next steps after a LADA diagnosis.
GAD is an enzyme that helps the body produce a specific neurotransmitter called gamma-aminobutyric acid (GABA).
Neurotransmitters are chemical messengers that carry information and instructions from the brain to the rest of the body via the nervous system.
GABA is an amino acid that reduces the amount of communication to and from the nerves.
GAD is present in the pancreas and the nervous system, and its roles include relaxing the muscles and helping the pancreas function, among other processes.
GAD can also trigger the immune system to produce autoantibodies against healthy cells. In people with LADA, GAD antibodies mark out cells in the pancreas for attack.
These pancreatic cells produce insulin. Diabetes occurs when the immune system treats these cells as though they were foreign, harmful material and destroys them.
Autoimmunity causes type 1 diabetes and LADA. Other diabetes-related autoantibodies also play a role in the development of these conditions. These autoantibodies include insulinoma-associated protein 2 (IA2), zinc transporter 8 (ZT8), islet cell antibodies, and insulin antibodies.
Identifying GAD antibodies is one way to diagnose type 1 diabetes or LADA. Doctors may test for GAD antibodies when people show signs in later life that resemble those of type 1 diabetes. Type 1 diabetes usually presents at a younger age.
LADA is a form of type 1 diabetes that develops in adulthood. Definitions of the typical onset age vary from 15–30 years up to 70 years.
People with LADA might first experience symptoms that appear to be the result of type 2 diabetes, but the condition is more similar to type 1 diabetes. Some people refer to it as “type 1.5 diabetes.”
A person with LADA will require insulin treatment reasonably soon after their diagnosis, unlike most people with type 2 diabetes whom doctors can treat with a variety of other medications as well.
Common symptoms of diabetes include:
- a frequent need to urinate
- urinating at night
- extreme thirst
- weight loss, potentially despite an increase in appetite
- altered mood
- unusual hunger
- lack of energy
- blurry vision
High levels of sugar in the blood are responsible for these symptoms and often point to a diagnosis of diabetes.
Some other symptoms, such as tingling or numbness in the feet or hands, can signal advanced disease or complications of diabetes.
Certain symptoms, such as unexplained weight loss, are more typical of type 1 diabetes than type 2 diabetes.
A GAD antibody test involves the same procedure as other blood tests.
A healthcare professional will take a blood sample by cleaning an area of skin, usually in the arm, and inserting a needle through it to reach a vein and draw blood. The small wound may be mildly painful afterward.
They will then send the sample to scientists in a lab who will test it for GAD antibodies and possibly run other tests at the same time.
What do GAD antibody results mean?
The GAD antibody test results confirm the level of GAD antibodies in the blood. A normal result is under 5 units/ml.
High levels of GAD antibodies often occur in people with a lower body mass index (BMI) and predict a more rapid progression toward requiring insulin. Extremely high levels of GAD antibodies (1,000 units/ml) may be due to stiff-person syndrome, an autoimmune condition that causes progressive muscle rigidity and spasms.
Type 1 diabetes is less common than type 2 diabetes, and it usually presents in children and young adults. If the doctor is unsure whether an adult has LADA or type 2 diabetes, they may use a GAD antibody test to help determine the correct diagnosis.
Other tests for diabetes
Doctors do not routinely perform the GAD antibody test on people with diabetes.
They use the test when doubts arise about the type of diabetes that a person has developed. A test may be beneficial when an adult who presents with new-onset diabetes receives a diagnosis of type 2 diabetes because of their age but does not respond to oral diabetes medications.
In addition to GAD antibodies, doctors may check for other antibodies in the blood. The presence of additional autoantibodies strengthens the diagnosis of autoimmune diabetes. These autoantibodies may include:
- insulinoma-associated antigen-2 autoantibodies
- insulin autoantibodies, as insulin itself can trigger an immune attack
- zinc transporter 8 (ZT8)
- islet cell cytoplasmic autoantibodies (ICA), which also cause the immune system to target insulin-producing cells
Standard tests for diabetes, such as blood sugar or glycohemoglobin tests, are usually sufficient for a doctor to diagnose type 1 or type 2 diabetes.
Several clinical features also help differentiate between the two types of diabetes. These include:
- the age of onset
- body mass index (BMI)
- family history
- the presence of other autoimmune conditions
- symptom severity
- initial response to antidiabetic medication
People with LADA are often lean, whereas most people with type 2 diabetes are overweight or have obesity.
What other conditions result in high GAD antibody levels?
Autoimmunity against the neurotransmitter that GAD antibodies target might result in a nerve disorder called stiff-person syndrome.
This condition is rare, but many people with stiff-person syndrome have type 1 diabetes. The symptoms of stiff-person syndrome, which progress slowly, include muscle stiffness and spasms. These symptoms mostly affect the trunk, but they can also occur in the limbs.
The level of GAD antibodies is typically much higher in people who have stiff-person syndrome than in people with type 1 diabetes.
Treatment for type 1 diabetes does not target the autoimmune aspect of type 1 diabetes or LADA. Instead, it treats the resulting symptom of insulin shortage and its effects by providing the body with the insulin that it cannot produce itself.
Insulin treatment controls blood sugar levels, preventing the more dangerous complications of high blood sugar, such as damage to blood vessels, stroke, and nerve damage. Controlling blood sugar decreases the likelihood of complications occurring due to diabetes.
People with type 1 diabetes and LADA can usually manage their condition with daily blood tests and insulin injections.
Is LADA more dangerous than type 2 diabetes?