Just wondering about something... maybe someone knows the answer to this question.
It is my understanding that in a non-diabetic person no GADA antibodies will be present. It that correct? Can type 1 and type 2 have these antibodies?
Part 2 of this question: Does it make a difference how high or low these antibodies are? It that an indication of anything in particular (whether it's high or low)?
Thanks so much!
GADA levels can be present in T2 and in non-diabetics. I've seen studies that suggest that perhaps 20% of T2s test positive for antibodies. The level of antibodies has not been shown to be indicative of anything in particular. In particular, high levels of antibodies do not suggest a fast progression of the autoimmune attack.
So would that type 2 person fall under the LADA category? And if non-diabetics can test positive for it too do they use it as an indicator for who is at risk of developing diabetes?
No, LADA is Type 1, jriccardi. Please don't confuse it. Although I'm sure Brian is right that there are exceptions to the rules, in general a positive GADA test (of whatever numbers) is indicative of Type 1/LADA.
Hi Jriccardi: The presence of autoantibodies (including GADA)can be used to distinguish between autoimmune diabetes (Type 1a diabetes) and Type 2 diabetes or other non-autoimmune diabetes. Autoantibodies are not present in Type 2 diabetes; if autoantibodies are present, the person has Type 1a diabetes (according to the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, “Although the specific etiologies of [Type 2] diabetes are not known, autoimmune destruction of beta cells does not occur.”) The full suite of autoantibodies include GAD, ICA, IA-2, IAA, and ZnT8, and those antibodies are detected in 94% of new-onset cases of Type 1 diabetes (IAA can only be tested if exogenous insulin has not yet been used, and ZnT8 is a relatively new test that may not be widely available.) Autoantibody testing is not an exact science, it is not perfect, but autoantibody testing can be extremely useful.
Although a small percentage of people without diabetes will test positive for one or more autoantibodies, no long-term studies have been performed to show that those people do not later develop Type 1 diabetes. In fact, the Type 1 Diabetes TrialNet Study (www.diabetestrialnet.org) has recruited relatives of people with Type 1 diabetes, performed antibody testing on those individuals, and researchers have been able to use positive autoantibody results in non-diabetic relatives to predict the risk that those individuals will develop Type 1 diabetes in the future.
Brian: The 10-20% of "Type 2s" who test positive for autoantibodies are the many, many misdiagnosed who in fact have Type 1 autoimmune diabetes. And yes, some small percentage of non-diabetics will test positive for autoantibodies, but the important question is will those people later develop Type 1 diabetes? Type 1 Diabetes TrialNet results and studies (widely available for review) do indicate that high levels of autoantibodies present in relatives of people with Type 1 (and also multiple autoantibodies) indicate a faster progression to overt Type 1 diabetes.
The overlap is not perfect. There are lots T1's that do not have GAD antibodies. 30% of newly diagnosed T1's do not have GAD antibodies.
And there is a substantial percentage (4% to 5%) of the general population that has GAD antibodies but will never develop T1 or T2 diabetes.
Thanks Zoe! It's hard to keep all of this straight. :)
So any amount of antibodies present is considered a positive? I'm asking because mine was low. And as it turns out- they didn't run the full panel of tests like I had requested! Only the GADA and IAA (whichh I am aware is useless to me since I've been on insulin)& the c-peptide was included also.
Those who don't have GAD antibodies, Tim, will have one of the other antibodies if they are Type 1. (GAD is typical of LADA or slow onset). That's why it's always important to do a full panel.
Yes, any amount of antibodies is considered a positive. Read Melitta's post below, she's our resident Adult Onset expert and has done lots of research on the topic. What is your c-peptide out of curiosity?
Well, I don't think that we really know that GAD positive T2s are misdiagnosed. I'm not aware of any studies. And T2s and non-diabetics aren't really part of TrialNet, so we cannot conclude much about whether GAD65 really differentiates. Clearly GAD positive individuals exist in the T2 and non-diabetic population. There are different phenotypes which are present in the populations and the GAD65Ab test doesn't distinguish them.
It was 0.6 ng/ml
The "different phenotypes" link you give is a year 2000 study about Type 1 diabetes. And actually there have been hundreds of studies that show that the 10-20% of autoantibody positive "Type 2s" are misdiagnosed, beginning with the first study on the 10% published in 1976 in The Lancet (in that study, it was 11%). But the key point is the definition of Type 2 diabetes as stated by the World Health Organization and the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, “Although the specific etiologies of [Type 2] diabetes are not known, autoimmune destruction of beta cells does not occur.” Autoantibodies (GAD, ICA, IA-2, IAA, ZnT8) are indicators of autoimmunity. Non-diabetics absolutely are part of Type 1 Diabetes TrialNet--that's a huge part of the focus! Non-diabetic relatives of people with Type 1 diabetes are still being recruited for TrialNet (my non-diabetic nieces and nephews are eligible), and yes some of those non-diabetic relatives of people with Type 1 diabetes are GADA positive and are being followed to see if/when they acquire overt Type 1 diabetes.
Tim: 94% of newly diagnosed Type 1s are autoantibody positive, according to more recent studies “Zinc Transporter 8 Antibodies Complement GAD and IA-2 Antibodies in the Identification and Characterization of Adult-Onset Autoimmune Diabetes” (DIABETES CARE, VOLUME 33, NUMBER 1, JANUARY 2010). And yes, a small percentage of non-diabetics are autoantibody positive, but the only long-term research that I know of that studies such individuals is Type 1 Diabetes TrialNet. As stated in Type 1 Diabetes Autoantibodies "Positivity to increasing numbers of autoantibodies indicates the [non-diabetic] individual’s autoimmune response is spreading and that the disease is progressing. The predictive ability of autoantibody tests therefore increases with the number of autoantibodies detected in an individual and may be influenced by the autoantibody titer, as well."
Could you send me a link or two to the studies that show that the T2s and non-diabetics are misdiagnosed? Thanx
Actually the study shows that when you add in the ZnT8 antibodies to the mix, 94% of T1s are antibody positive to one or more of the 4 antibodies. But while increasing the number of positive detections is certainly a good thing, it can result in a increasing number of false positives. This study did not characterize the positive detection of ZnT8 in T2s and non-diabetics, so one needs to be concerned about false detections. It is known that ZnT8 occurs in marked numbers in non-diabetics.
In response to the OPs first post, if a person is diagnosed with diabetes (fasting blood sugar greater than 125 mg/dl) and the person is autoantibody positive (GAD, ICA, IA-2, IAA, and/or ZnT8), by definition (WHO and the Expert Committee) the person has Type 1 autoimmune diabetes. I think it is important that people get a correct diagnosis and correct treatment.
It's only the autoantibody positive "Type 2s" that are misdiagnosed and in fact have autoimmune diabetes, certainly not someone who has not been diagnosed (non-diabetics). And again, it's by definition (Expert Committee), "[Type 1 diabetes] results from a cellular-mediated autoimmune destruction of the beta cells of the pancreas. Markers of the immune destruction of the beta cell include islet cell autoantibodies (ICAs), autoantibodies to insulin (IAAs), autoantibodies to glutamic acid decarboxylase (GAD65), and autoantibodies to the tyrosine phosphatases IA-2 and IA-2β" and “Although the specific etiologies of [Type 2] diabetes are not known, autoimmune destruction of beta cells does not occur.” According to Type 1 Diabetes Autoantibodies: Prediction and Diagnosis of Autoimmune Diabetes, "The autoimmune forms of diabetes, which affects 2 to 4 million people, include type 1 diabetes (T1D), an estimated 5% to 10% of those with diabetes, and latent autoimmune diabetes in adults (LADA), estimated to be 5% to 10% of those diagnosed with type 2 diabetes (T2D).
When diagnosed, I tested sky high for both GAD and the other antibodies,with a bit of cpeptide still on board (honeymooning). A year later, my Endo rechecked for pump Rx, no antibodies but no cpeptide either, i.e., long standing type 1's typically will not test positive for antibodies because they no longer have any beta - islet cells for the antibodies to attack, as explained by my Endo. I thought I was 'cured' (ha!) because I no longer had antibodies, he said, "well, you no longer have any beta cells and you're no longer producing any insulin." An Endo who specializes in diabetes will know how to confirm a proper diagnosis, there are many factors...positive antibodies, no cpeptide, family history, metabolic syndrome issues, weight, weight loss, etc...there really is not that much of a cross over when it comes to the two totally different diagnosis.
Well ok, but that isn't a study, it is just a definition. I could use that same argument to say that 10-15% of type 1s should be really considered T2.