GAD-65 autoantibodies may not lead to insulin

[foxl]

SIGH. I found this lovely article in Pubmed, and now of course am more confused than EVER ... it really is a GOOD review! I always liked the dhades of grey, so why not?

1: Diabetes Metab Res Rev. 2008 Oct;24(7):511-9. Links
Diabetes classification: grey zones, sound and smoke: Action LADA 1.Leslie RD, Kolb H, Schloot NC, Buzzetti R, Mauricio D, De Leiva A, Yderstraede K, Sarti C, Thivolet C, Hadden D, Hunter S, Schernthaner G, Scherbaum W, Williams R, Pozzilli P.
Institute of Cell and Molecular Science, University of London, London, UK. r.d.g.leslie@qmul.ac.uk

Diseases gain identity from clinical phenotype as well as genetic and environmental aetiology. The definition of type 1 diabetes is clinically exclusive, comprising patients who are considered insulin dependent at diagnosis, whilst the definition of type 2 diabetes is inclusive, only excluding those who are initially insulin dependent. Ketosis-prone diabetes (KPD) and latent autoimmune diabetes in adults (LADA) are each exclusive forms of diabetes which are, at least initially, clinically distinct from type 2 diabetes and type 1 diabetes, and each have a different natural history from these major types of diabetes.KPD can be diagnosed unequivocally as diabetes presenting with the categorical clinical feature, ketoacidosis. In contrast, LADA can be diagnosed by the co-occurrence of three traits, not one of which is categorical or exclusive to the condition: adult-onset non-insulin-requiring diabetes, an islet autoantibody such as glutamic acid decarboxylase autoantibodies (GADA) or cytoplasmic islet cell autoantibodies (ICA), and no need for insulin treatment for several months post-diagnosis. But while some would split diabetes into distinct subtypes, there is a strong case that these subtypes form a continuum of varying severity of immune and metabolic dysfunction modified by genetic and non-genetic factors. This article discusses the nature of disease classification in general, and KPD and LADA in particular, emphasizing the potential value and pitfalls in classifying diabetes and suggesting a need for more research in this area. Copyright (c) 2008 John Wiley & Sons, Ltd.

PMID: 18615859 [PubMed - indexed for MEDLINE]

[Joder]

I'm getting my GAD result on Friday - and I have no idea what to expect. I am (fairly) lean BMI bang on 25, 48, diagnosed T2D 2 months ago, so fit some of the criteria.. it is a bit confusing isn't it. :0

is it when the number is ell above 1 that it points to LADA? and then should I get C-Peptide done?

[yannah]

yeah, i don't know what that means.

I can only give you horrible visuals for food.

[foxl]

I. have. no. idea.

I would get a C-peptide -- it might point you toward how much insulin you are making and if you need insulin ...

This article in its entirety is ... so ... frustrating! It is really good and basically reviews what is NOT known.

[Joder]

I do like the (was it cheney?) quote. "[there are the known knowns, then known anknowns and then there are the unknown unknowns..]"..

love the food visuals by the way - just off to get my curry and brown rice..

[foxl]

I do like the (was it cheney?) quote. "[there are the known knowns, then known anknowns and then there are the unknown unknowns..]"..

love the food visuals by the way - just off to get my curry and brown rice..


Stick to the material world! Good idea! It is oh, so much safer.

[Subby]

For the rest of us, can you explain how you come to your thread title conclusion? It doesn't seem to be suggesting that to me... my reading of the abstract is it only goes so far as to describe three distinct diagnostic aspects to reaching an initial LADA diagnosis. Apart from all the colourful claims to how confusing it all is, it seems relatively logical to my possibly warped mind...

Either I am not reading it correctly or the same way, or you are talking about something not explained in the abstract. Which is fine, just be good to know what your reading is.

[foxl]

For the rest of us, can you explain how you come to your thread title conclusion? It doesn't seem to be suggesting that to me... my reading of the abstract is it only goes so far as to describe three distinct diagnostic aspects to reaching an initial LADA diagnosis. Apart from all the colourful claims to how confusing it all is, it seems relatively logical to my possibly warped mind...

Either I am not reading it correctly or the same way, or you are talking about something not explained in the abstract. Which is fine, just be good to know what your reading is.

Did you read the abstract I posted, or the whole stinkin' article? Interestingly, their remark that insulin may not be needed with GADA in adults cites the UKPDS 25 article on autoantibodies, which DOES NOT seem to support this contention, at all?

I am getting pretty sick of these "theory" people.

[warrenav]

Well, I'm certainly an example (so far) of "GAD-65 autoantibodies may not lead to insulin". I've been diabetic for 11 years, BMI=~19, recently rediagnosed as LADA with positive GADA and low C-peptide, but enough continuing functionality to be non-insulin dependent. In fact, with a couple diet and exercise changes a couple months ago, my last A1c was 6.0, so well within my target. All that said, it does still seem like I've got some IR (I seem to benefit from metformin), so I guess I'm about as grey as you get.

[Subby]

Did you read the abstract I posted, or the whole stinkin' article? Interestingly, their remark that insulin may not be needed with GADA in adults cites the UKPDS 25 article on autoantibodies, which DOES NOT seem to support this contention, at all?

I am getting pretty sick of these "theory" people.

I was working off the quoted abstract, you didn't post a link and I assumed it was a review I can't access (I've gone and searched, it seems I can't access it without setting up some payment system). Not asking you to spill beans on studies I haven't paid for, but just wondering what it was saying for you to reach that conclusion. Note I'm not saying you or it are not making a valid point: just that I can't see it in the abstract, for what that is worth.

[foxl]

I was working off the quoted abstract, you didn't post a link and I assumed it was a review I can't access (I've gone and searched, it seems I can't access it without setting up some payment system). Not asking you to spill beans on studies I haven't paid for, but just wondering what it was saying for you to reach that conclusion. Note I'm not saying you or it are not making a valid point: just that I can't see it in the abstract, for what that is worth.

No it is not there and I was in the lib when I linked to the complete article, could not tell if it is publically available or not. Guess NOT. Sorry! I left my copy at home, too!

[zoelula]

I am getting pretty sick of these "theory" people.

That's why I never read this stuff. One minute they one group thinks they're proving one thing and five minutes later another group "proves" the opposite. Just like the "which foods are good for you and which terrible". If you listen to it all, you'd starve. Lots of scientists, lots of theories. It can drive you nuts if you let it. Just my two cents. I'm also not very science oriented.

[foxl]

It can drive me nuts, it DOES, but I also want to know what my endo might be reading, before I get to my appt!

[Subby]

No it is not there and I was in the lib when I linked to the complete article, could not tell if it is publically available or not. Guess NOT. Sorry! I left my copy at home, too!

No problem. Hey, nothing wrong with bringing interesting stuff up. I guess with stories like warrenavs, there's no reason you need to feel like the descent into insulin use is going to be swift, if/when it occurs. Or it might just kind of come up on you, but I'm betting you'll be fine with it. Uncertainty does seem built into LADA... all the talk of redefining conditions and so forth, well, it might have validity in some way, but sometimes being aware of a range of uncertainty seems the best we can do (and is a lot better than nothing).

But I wouldn't want to think it was causing consternation. Fact: your body will do what it will do. You already have in place a big component whatever the circumstances (diet, exercise, supplements), you have knowledge of best practises for your body (such as not burn out beta cells if possible) you have knowledge and experience of medication for IR (like the met/actos) and you have the knowledge and are prepared for dealing with lack of insulin production (endogenous insulin). For someone facing uncertainties in the future, you seem to be in a strong position.

[foxl]

Thanks for a VERY supportive post, Subby! I am feeling better-armed this morning ... warrenavs -- I missed this post and have not addressed it yet -- OH, to get down to such an enviable BMI! although I probably would look like Attack of The Shar Pei People, then ... but your post does hold a lot of promise for me.

I do suspect I might not be going on insulin yet, but hopefully establishing a relationship with an Endo, perhaps having some more predictive antibody testing, and having things in place for watchful followups, will make me feel much better than staying with a PCP and expecting a typical Type 2 course for life ... and then falling flat and feeling "Failed."

Not because I think T2Ds on insulin HAVE failed, but because of my past experience with low-fat dieting, I know that if I am dieting stringently and watching my A1c increase while being told, "try HARDER," would be devastating to me! I would probably give up and that is NOT what this condition warrants!

[dbaratta]

SIGH.
But while some would split diabetes into distinct subtypes, there is a strong case that these subtypes form a continuum of varying severity of immune and metabolic dysfunction modified by genetic and non-genetic factors. This article discusses the nature of disease classification in general, and KPD and LADA in particular, emphasizing the potential value and pitfalls in classifying diabetes and suggesting a need for more research in this area. Copyright (c) 2008 John Wiley & Sons, Ltd.

PMID: 18615859 [PubMed - indexed for MEDLINE]

I have always thought this about diabetes. I don't care which one they say you are, you are still a diabetic and still have to behave in many of the same ways whether you are type 1, 1.5, or 2. The degrees of meds that a diabetic uses has to do with how advanced they are in the disease (since it it progressive I assume their are advancements), and how well they are willing to care for that disease by adjustments to diet and exercise. Anyway,,,,,just my opinion, I claim to know nothing. :)

[foxl]

I have always thought this about diabetes. I don't care which one they say you are, you are still a diabetic and still have to behave in many of the same ways whether you are type 1, 1.5, or 2. The degrees of meds that a diabetic uses has to do with how advanced they are in the disease (since it it progressive I assume their are advancements), and how well they are willing to care for that disease by adjustments to diet and exercise. Anyway,,,,,just my opinion, I claim to know nothing. :)


Yes, but being mis-medicated can DEFINITELY have its consequences ... especially given that overstimulatig beta cells with Sulfonylureas has been found to hasten their demise!

[zoelula]

I agree withSubby, Linda. You are in a very strong position because you know your diagnosis, you know the options and you are anticipating the next move. When I compare your situation to my own where I was going blithely along as a "type 2" and suddenly got blindsided by both rising numbers and the issue of dietary changes which I had been able to ignore completely..I really had to scramble to figure out what was going on and what to do about it. I had no options and had to get up to speed FAST. I get exhausted just thinking about it. Whatever you and your endo decide, I think you will do great.

[foxl]

Thanks, Zoe! :)