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Question:

From Eugene, Oregon, USA:

My daughter has had elevated postprandial spikes of up to 250 mg/dl [13.9 mmol/L] for a couple months now. Since her appointment with a pediatric endocrinologist, I decided to test her only if she were showing symptoms or not feeling well. Her A1c was previously 5.7; her ICA test was negative and her IAA test was normal at 3. However, I just learned that her GAD antibody test was abnormal, 1.1, with 0.5 the laboratory high range.

Our regular doctor was out today. A second doctor in the office called me and told her to start monitoring my daughter's blood sugars daily. This has me concerned. Since she tested positive for the GAD antibodies, does this mean my daughter has a greater risk of developing type 1? Does that mean there is already "activity taking place?" I am just more confused now than ever. With her already having the higher elevated blood sugar after she eats and now a positive GAD test. what does this mean?

Answer:

I am glad that you saw a pediatric endocrinologist and I am glad that you were reassured. Sorry that now you are nervous again.

There are three major pancreatic antibodies that are "typically" checked for when assessing for common autoimmune, type 1 diabetes. Different laboratories do these tests differently and not all laboratories have reliably sensitive assays. This means that some techniques have too many false positives or false negatives. I don't know (nor do you, probably) which laboratory may have done your daughter's tests. IMPORTANTLY, the tests themselves ARE NOT 100% predictive of the development of type 1 diabetes!

One of antibodies is the "ICA," which means "islet cell antibody." A more sensitive/specific version of this test is the ICA-512 antibody test. The islet cell is the actual pancreatic cell that produces insulin. This test has widely been replaced with a more specific "IA2" test, which is an antibody to one of the kinase enzymes within the islet cell. So, the ICA-512 and IA2 tests are essentially the same.

Another test is the IAA test (not to be confused with the IA2 test). This is the insulin auto-antibody test. It is the least sensitive or specific, but often is detectable ("positive") in younger children (under two years) with type 1 diabetes.

The third test is the GAD (sometimes referred to as the GAD-65) antibody test."GAD" stands for glutamic acid decarboxylase, another islet cell enzyme important in the production of insulin. GAD antibodies may be the most sensitive and specific antibodies to suggest RISK of type 1 diabetes.

So,your daughter has been found to be positive for GAD antibodies. This indeed is a little bit of a concern, but I would emphasize a LITTLE BIT. Let's talk about risk. Risk means "odds." You might be hit by a meteor tomorrow, but the risk is low, very low. But still, there is a risk. You know that smoking cigarettes is a risk for the development of lung cancer, a fairly strong risk factor. And, you probably know people who have smoked tobacco and have developed lung cancer. But, you probably also know people who have smoked and have NOT developed lung cancer. And, you may even know of people who developed lung cancer who never smoked at all. Having GAD antibodies (and IA2) antibodies is a risk for the development of type 1 diabetes, but it is only a risk. There are people with type 1 diabetes that do not have pancreatic antibodies and there are people with pancreatic antibodies who do not have type 1 diabetes. What factors might increase or decrease these risks? An important one is family history: who else and how closely related is someone with type 1 diabetes?

At present, there is NO PREVENTATIVE method for the person at risk for the development of type 1 diabetes. Your frequent monitoring in the face of lack of symptoms may only cause you and your family, especially your daughter, more anxiety and pain! So, unless you would want to explore an experimental protocol in the prevention of type 1 diabetes for people at high, high risk, I'd suggest that you only monitor periodically but keep a special eye out for symptoms of increased thirst and urination.

On the other hand, if you are willing to participate all the way with an experimental research protocol in the prevention of type 1 diabetes for those at especially high risk, talk to your pediatric endocrinologist or explore on the Internet about TrialNet. Research protocols have very strict inclusion and exclusion criteria, so your daughter may not even qualify.

Good luck. Let us know what you find out. And please, be an informed parent, but I would ask you to not be too, too worried. If, for instance, your daughter does have a first degree relative (sibling or parent) who has type 1 diabetes, then, in general terms, she only has a 5% (1 in 20) chance of developing diabetes. Does she have 19 other brothers and sisters? Certainly, if the first degree relative has antibodies themselves and with your daughter's positive GAD antibodies, the odds increase. If there were second/third degree relatives (cousins, half-siblings, grandparents), the risks would go down some. So, I guess I'm saying "don't panic." Get information, like you are trying to do.

DS

DTQ-20080927032026
Original posting 5 Oct 2008
Posted to Diagnosis and Symptoms

  
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Last Updated: Tuesday April 06, 2010 15:10:16
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