I was on a facebook LADA group this morning and a person posted that she had GAD antibodies for 8 years with no real change in numbers. She went on to say that her endo and a few other doctors said that people can have the GAD antibodies and never develop Type 1 diabetes. Her endo told her that she has MODY 2 and can control it with diet and exercise. There was no mention of whether she had genetic testing done or not. Is this possible, because I thought once antibodies are detected with abnormal blood glucose that it’s considered type 1 ?
I actually ran across a paper on a clinical case of a patient who had both MODY and LADA (T1). And logically this would make some sense after all these are totally independent conditions. And in fact you would also make the same argument that since MODY and T2 are independent you should be seeing T2 occur with the same prevalence in patients with MODY as it appears in the general population. So yes, both T1 and T2 can occur in MODY patients. Whether it is diagnosed is a totally different question.
What’s confusing is that she seems to be saying that she has MODY instead of type 1-- not in addition to. I asked her about it and she said they found out her grandmother has MODY. She was given insulin 8 years ago when her sugar spiked from a steroid shot and then made antibodies against insulin. Since her antibodies have not progressed in 8 years, it is considered MODY due to lack of progression. I question whether they were GAD antibodies or IAA instead, but she claims they are GAD. So does that mean then you can actually be MODY with antibodies and not ever get Type 1? It would be good to know since the treatment is different correct?
You can definitively diagnosed MODY with a genetic test, but you can’t confirm MODY by testing your grandmother. MODY is autosomal dominant which means that if you have MODY your children have a 50% change of inheriting the gene. If you have MODY then one (or both) of you parents must have MODY.
And if you confirm MODY, then Type 1 could be diagnosed by being positive for antibodies and being confirmed as insulin deficient. No MODY form results in insulin deficiency. It may be necessary to use something like a stimulated c-peptide to confirm insulin deficiency but a component endo should be able to make that diagnosis. Unfortunately Type 2 has no diagnostic test so it is basically impossible to be diagnosed as MODY and concurrently Type 2.
And as to anitbodies, GAD antibodies are not antibodies against your own insulin, Insulin Auto Antibodies (IAA) are antibodies are against your own insulin. The fact that LADA/T1 has not significantly progress does not necessarily rule out a LADA (T1) diagnosis. Adult LADA (T1) can go many years before progressing to requiring insulin, that doesn’t make them not LADA (T1).
Many people have auto antibodies their whole lives and never develop any type of diabetes. It is only by convention that antibodies + diabetes = type 1 diabetes. Logically, if someone without diabetes can have antibodies so could someone with T2 diabetes, MODY, or any other health condition in the world.
It is a convention of convenience that makes no valid sense as far as I’m concerned and thus I lend it exactly zero credibility or consideration
I remember you telling me about that before Sam and I believe I did read somewhere that a very small percentage of the population can be antibody positive without having diabetes; however, if they are present in someone who already has abnormal glucose the odds are likely the progression will happen-- albeit slowly. My endo stated that it hasn’t yet been proven whether antibodies, inflammation or T-cells are what damage the pancreas that lead to Diabetes. If I’m understanding him correctly the presence of antibodies merely shows an autoimmune process is occurring in the body. When he started me on Victoza he explained that along with diet and exercise some people with pre-type 2 had some success in delaying or reversing pre-diabetes. Since I am antibody positive he wasn’t sure, but thought it may at least delay the progression and would help with inflammation. I guess time will tell…
I’m trying to understand @Sam19’s comment. The mechanism that leads to T1 is an autoimmune attack on the beta cells, and antibodies are the best indicator we have that such an attack is occurring. That doesn’t mean a small number of individuals won’t present in anomalous ways, but we shouldn’t throw out the baby with the bathwater, right? That’s my take, anyway, and maybe I’m misunderstanding what I read as a suggestion to ignore antibodies when diagnosing diabetes.
Unless there’s some additional genetic nuance of which we’re not aware, MODY-2 folks should have the same risk of T1 as the rest of the population. Logically, one would think MODY-2 folks, with their higher glucose set points, would be more prone to T2, but we don’t seem to see that in practice, though the populations we have to study aren’t huge.
Always happy to see some MODY discussion!
I just mean that I certainly don’t hold them as the holy grail of diabetes diagnosis that some do… I think the fact that people can live their lives with the antibodies associated with diabetes but never get diabetes of any kind pretty much soundly disproves their overall usefulness in definitively proving anything whatsoever… But like most things in medicine… They are a clue, a hint (at best) as to what is physiologically happening.
I think we, collectively, as people with diabetes put way too much emphasis on essentially meaningless labels like this… Your personal story @niccolo is fairly exceptional and not what I’m referring to. I spent the first few years of my life as a diabetic frantically searching for an acronym that’d make it all make sense… But it was a a fruitless search and in hindsight, a fool’s errand… In the end I have just accepted that I need to take insulin, try to exercise and stay in shape, eat healthy, and live a decent life… And a different label associated with my disease, or a different catch phrase on a medical record of mine really isn’t likely to change that… I’ve been considerably happier since I’ve came to that realization…
Hi bjm,
I’m not sure how many people who are antibody positive don’t go on to develop type 1, it would be interesting to know. Antibody testing was first done in 1974 for type 1 antibodies- which established it as an autoimmune disease, according the article linked below, which focuses in part on a study done in children at risk for type 1.
Here’s an excerpt on some of what they found:
“Overall, slightly fewer than 8% of subjects (1,059) seroconverted to positive autoantibodies, and of these, 55% had multiple autoantibodies. In all, 428 children eventually developed type 1 diabetes based on symptomology or standard blood glucose definitions for the disease, including 25 who were not autoantibody positive prior to diagnosis. The hazard ratio for developing diabetes in children with multiple positive autoantibodies was an impressive 395.6 in comparison to those without autoantibodies. Overall, 43.5% of the former progressed to diabetes within 5 years of seroconversion, 69.7% did so within 10 years, and 84.2% at 15 years.”
This suggests antibody testing is relevant and worth doing since the article also says 45% percent of people with type 1 eventually end up in the er in dka at their diagnosis , not to mention the potential to possibly prevent it with new treatments although none have been successful yet as far as they say in the article. It also mentions a possible vaccination for the general public- I wonder can they make a safe vaccine?
In a family like mine, with no diabetes except for me now, you don’t think this is going to happen to you and I wasn’t a child when it happened. I don’t know if I had antibodies before going to dka or getting to that stage but I assume I probably did. My grandfather had graves disease & RA so that was my hereditary risk factor as well as asthma and raynauds.
If your friend didn’t have testing for MODY there is no way to be sure if she has that or not and even then, as we all know there are false positives and negatives for many tests. I’m not sure either how many people truly have more than one type of D, probably not very many, but the potential is there of course.
Hopefully she won’t progress if she hasn’t had worse bg . I think knowing is better than not knowing because you can have a chance to avoid disastrous results and start treating yourself when needed. As Brian said, in adults it can take years or even in children as this article said because some took much longer to progress. It would be great if people studying all of this could pinpoint something else which would tell you for sure what will happen and what other factors are involved. Unfortunately they can’t because as with many other diseases there is obviously a lot which isn’t yet understood.
Brian,
While it is true that one of your parents would have to carry the MODY gene for you to get it, it is not necessarily true tht they would have been diagnosed with diabetes. That is because the range of expression of the various genes can vary from very mild, which produces pre-diabetes, to extreme, which looks like Type 1. Diabetes was not diagnosed in the 1950s and '60s until a person had what we would now consider to be very high blood sugars.
This is really important, but doctors don’t know it. It is what kept me from getting diagnosed though I had the classic natural history. My father’s mother had thin person diabetes. My father had a major problem with fungal infections all his life and lost most of his teeth by the time he was in his early 20s, but he was a health food nut and an exercise fanatic. He ate low carb from his mid 30s on (which was in the 1940s) so while he did develop heart disease by his 70s he was never diagnosed with anything.
In addition, the gene I and my daughter have provides normal or near normal fasting blood sugars with very high post-meal numbers. This would never have been detected over my father’s lifetime as the fasting blood test was all that was used for diagnosis until about 15 years ago. (Another reason I had such a hard time getting a diagnosis. I still have fasting blood sugars that don’t rise over 115, ever. It’s the post-meal numbers that are diabetic.
The study documenting that families of people diagnosed with MODY-3 contain people never diagnosed who carry the gene is http://diabetes.diabetesjournals.org/content/45/11/1503.abstract . My guess is that there are people with MODY 2 who have relatives who have milder versions, too.
Re the antibodies, one would hope that this person’s doctor would be alert to the possibility that the person could have both LADA and a milder genetic diabetes. Since the trend with MODY-2 is to give no treatment and tell people not to worry their little heads it is possible that a person with both would only get the LADA taken seriously when they developed DKA.
But I have heard from enough people whose LADA was ignored until that happened due to doctors assuming they had Type 2 since they were obese that I don’t doubt that doctors will now ignore it assuming that a defect in fasting glucose in their only problem.
Bottom line: anyone with a MODY-2 diagnosis and antibodies who is seeing blood sugars reaching into the high 200s or higher should demand that they be treated for LADA. People with MODY-2 don’t usually see very high post-meal blood sugars. And, of course, anyone with blood sugars that stay in the 200s for any period of time is asking for complications, no matter what the diagnosis and must be aggressive to get help from doctors to bring those sugars down no matter what their diagnosis.
Type 1 diabetes TrialNet is the longest running study that has tracked non-diabetic, autoantibody positive people (relatives of people with Type 1 diabetes) for any length of time, and that is 15 years, not a lifetime. The TrialNet researchers have been able to fairly accurately predict when a person will develop overt Type 1 diabetes based on number of autoantibodies and titer. Autoantibodies are extremely useful for differentiating between autoimmune diabetes and non-autoimmune diabetes after a person has been diagnosed with diabetes.
Thanks Jenny, my point was that having a grandmother with confirmed MODY does not mean that as a grandchild you have MODY. And while there is certainly variation in expression as you said, MODY is a very deterministic genetic condition as opposed to other variants (like HLA in T1) which have a very significant epigenetic component. In either case, it would be improper to conclude that an autosomal dominant condition in a grandparent is inherited to their grandchildren with certainty, the chances are I believe 1 in 4.
I also would believe someone with antibodies and a failed insulin response to a stimulated c-peptide test would likely be diagnosed by a competent endo as having T1. So genetic testing and testing for type 1 could reasonably confirm concurrently having T1 and MODY.
ps. I found you cite a paper on your site which studied 586 children diagnosed with T1 and found 8% of them also had MODY.
I think we’re making this more complicated than it needs to be. If a physician knows how much insulin someone is capable of producing, how efficiently they use what insulin is available, and whether they have relevant antibodies, they can make very robust inferences about what’s going on and how it should best be treated. The additional data point(s) of how things progress over time and how patients respond to various treatments are really helpful, too. For people who fit certain criteria, genetic testing can add additional useful data points, and down the road I suspect will play a more and more central role in how the spectrum of diabetic conditions are diagnosed and treated.
Thanks everyone for the interesting contributions ! I know very little about MODY; although I wondered about the genetic link since Diabetes can be traced back to three generations beyond myself. I never looked further into it since I was beyond 40 when symptoms started to occur.
Brian,
Those children diagnosed as Type 1 didn’t ALSO have MODY, they had MODY and were misdiagnosed as Type 1 because so many doctors are unaware that MODY is a possibility when they see diabetic blood sugars in a child.
MODY is far from universally known about among doctors.The endo I was seeing for a decade had never heard of MODY and even after I mentioned it to her, she seems to have never looked it up, as I would have to remind her each time I saw her and still coded me as a Type 2. When she tested my C-peptide and it came back at a level much too low for Type 2 she said “Maybe you are a Type 2 turning into a Type 1.”
None of my other doctors has ever heard of MODY, though the PCP treats most of his patients with diabetes. None of the people at the gynecology practice I attend has ever heard of it, though MODY often declares itself first at pregnancy (I became frankly diabetic about two months into my first pregnancy.)
These doctors were trained in the 70s through late 80s, so it is quite possible there are a lot of other doctors like them, including people practicing endocrinology, who are unaware that MODY diabetes is a third class of diagnoses to be considered given certain family and natural histories.
The continuing ed my endo received appeared to all be given by drug companies as she was always very up to date on the very latest, risky, expensive drug and very eager to prescribe them as soon as they were released. I am not sure they give continuing ed classes about MODY as there is no money in it for anyone to motivate them to pay for them.
You are right, I didn’t look at it in detail. When I get a chance I’ll try to dig up that case report of a patient with T1 and MODY for you. My general feeling is that both T1 and T2 should occur in MODY patients at the same prevalence as in the general population.
That makes sense. I also wonder whether we will see more Type 2style IR in Type 1s now that there are so very many more of them.
It shocks me how rare Type 1 was 50 years ago. I only met one back when I knew literally hundreds of people my age. Now quite a few of my neighbors have relatives who have it–and neighbors are sparse in my rural region.
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Dan Hurley in Diabetes Rising examines the observed rise in prevalence rates. He notes that part of it could be due to better diagnoses (i.e. we now diagnose LADA), this is one reason that people argue that there is no Autism explosion, it is simply more people getting diagnosed. But then Hurley then goes through explores a variety of other potential connections which might be part of the rise in T1 rates. It is all basically epidemiological, and most of them have to do with environmental stuff like diet and toxins. But it is plausible and worth of being explored.
Very worthwhile read…
I also found interesting the accelerator hypothesis research that Hurley writes about.