# Diabetes is actually five separate diseases, research suggests



## Northerner (Mar 2, 2018)

Scientists say diabetes is five separate diseases, and treatment could be tailored to each form.

Diabetes - or uncontrolled blood sugar levels - is normally split into type 1 and type 2.

But researchers in Sweden and Finland think the more complicated picture they have uncovered will usher in an era of personalised medicine for diabetes.

Experts said the study was a herald of the future of diabetes care but changes to treatment would not be immediate.

Diabetes affects about one in 11 adults worldwide and increases the risk of heart attack, stroke, blindness, kidney failure and limb amputation.

http://www.bbc.co.uk/news/health-43246261

They've surely missed Cluster 6 - those who were older and like Cluster 1. We don't seem to get a look in  Not to mention Type 3, or weirdos like me who only need bolus insulin. I doubt Joe Public will get his head around more than two types, let alone 500 subtypes!


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## mikeyB (Mar 2, 2018)

Aye, I read this story and thought it was guff. And you’re right - folks like us who developed T1 later in life, or the pancreatic diabetes owners don’t get a mention. They’re on their own with this idea, it’ll never catch on. For the simple reason that there aren’t that many different treatments.


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## MikeTurin (Mar 2, 2018)

Unfortunately the article is paywalled. Maybe LADA are actually Cluster 2 on a later onset and in this article isn't clear


Found on Reddit

http://www.mdmag.com/medical-news/a-study-proposes-five-new-distinct-types-of-adultonset-diabetes


> Group 1, SAID (severe autoimmune diabetes): LADA + type 1. Low age, poor metabolic control. Loss of insulin production and GADA-antibodies
> 
> Group 2, SIDD (severe insulin-deficient diabetes): Patient without antibodies, with high HbA1C, poor insulin production and mediocer insuline resistence. High prevalence of retinopathy
> 
> ...


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## kentish maid (Mar 2, 2018)

There was a discussion on here a few days ago about what people like to be called, some not liking the term diabetic. Guess according to this new report I would be classed as MARDy, some may well say that is apt for me !!!


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## Robin (Mar 2, 2018)

MikeTurin said:


> Maybe LADA are actually Cluster 2 on a later onset and in this article isn't clear


Not necessarily, Cluster 2 is non-autoimmune. I didn't develop my diabetes until I was 51, but tests proved it was autoimmune related.


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## mikeyB (Mar 2, 2018)

Aye, Robin, this new classification is more trouble then it’s worth. It’ll confuse NICE, anyway, as to who and who doesn’t get access to insulin pumps.


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## Mark T (Mar 2, 2018)

It's also missing the various MODY types.  But those are defined as single genetic defects so I guess they are reasonably well defined.


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## Ljc (Mar 2, 2018)

Some people have enough trouble now getting a correct diagnosis of which type they have, or a round brick being shoved into a square hole . I can just imagine what it will belike if they bring this in. And they seem to have ignored people who develope T1 when older as well as type 3
Don’t get me wrong I am all for personalised medicalised care. I think the money spent on this research could have been spent far better on other things to do with Diabetes.


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## Mark T (Mar 2, 2018)

Ljc said:


> Some people have enough trouble now getting a correct diagnosis of which type they have, or a round brick being shoved into a square hole . I can just imagine what it will belike if they bring this in. And they seem to have ignored people who develope T1 when older as well as type 3
> Don’t get me wrong I am all for personalised medicalised care. I think the money spent on this research could have been spent far better on other things to do with Diabetes.


At the moment care is around treating the symptoms more then what caused it.  This sort of study is useful because it starts to consider the underlying reasons.  You could take it further and ask what is common about those in Cluster 2 for instance and then possible look at genetics to see if there are any common patterns.

The issue here  is because it is a statistical analysis, any outlying data points (which might be rarer forms) would probably of been discarded.  It also is limited to the genetics of Norway.  UK and EU generally have a somewhat different mix.


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## Ralph-YK (Mar 2, 2018)

Northerner said:


> Diabetes - or uncontrolled blood sugar levels


I wonder if uncontrolled BG is actually a symptom.


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## Matt Cycle (Mar 2, 2018)

Some interesting points from this.  Assuming Clusters 1 and 2 are T1 then what causes Cluster 2 if it's not autoimmune?  This could have implications for a possible cure.


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## Northerner (Mar 2, 2018)

Matt Cycle said:


> Some interesting points from this.  Assuming Clusters 1 and 2 are T1 then what causes Cluster 2 if it's not autoimmune?  This could have implications for a possible cure.


I've often wondered where I fall. My pancreas still obviously has quite a few functioning beta cells, and appeared to increase their number in the first 4 years after diagnosis as illustrated by the fact that my lantus dose steadily declined to zero over that time period, from 20 units down to zero. I have no signs of insulin resistance, weight doesn't play any part, it just seems that the virus I caught around diagnosis time caused most of my beta cells to die off and then they've been replaced over time.


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## Mark T (Mar 2, 2018)

Matt Cycle said:


> Some interesting points from this.  Assuming Clusters 1 and 2 are T1 then what causes Cluster 2 if it's not autoimmune?  This could have implications for a possible cure.


Reading the actual paper, it looks like they only looked for GAD antibodies to determine if the person was autoimmune.  I'm aware that there is at least another 2 test's you can do and my consultant told me that there were other autoimmune causes for which there was no test currently.

I seem to fit quite well within the Cluster 2 cohort.


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## Vince_UK (Mar 2, 2018)

I read this article this morning and for the life of me couldn't decide which "cluster" i am in. I totally subscribe to @Ljc 's  comments to be frank


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## grovesy (Mar 2, 2018)

I have read that GAD is not always positive.


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## Flower (Mar 2, 2018)

What does a personalised treatment mean? 

I need insulin to live and I have a pump/meter/cgm to try and control my blood sugar as best I can. There isn't anything else around to make it more useful to me as far as I know. 
I personalise my own treatment in that I tweak my own insulin doses according to the results I get.

It is interesting that they are researching a broader spectrum of types of diabetes. It's a leap forward from when I was diagnosed when the options were juvenile onset or maturity onset diabetes.


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## Matt Cycle (Mar 2, 2018)

Northerner said:


> I've often wondered where I fall. My pancreas still obviously has quite a few functioning beta cells, and appeared to increase their number in the first 4 years after diagnosis as illustrated by the fact that my lantus dose steadily declined to zero over that time period, from 20 units down to zero. I have no signs of insulin resistance, weight doesn't play any part, it just seems that the virus I caught around diagnosis time caused most of my beta cells to die off and then they've been replaced over time.



Mine points to 'classic' T1 or whatever cluster they want to put it in.  I don't think I have any functioning beta cells left.  I've just got back from the pump clinic and last year in spite of having T1 for over 30 years I had to have a C-peptide as part of the pump application to the CCG.  I saw this report before I left this morning and asked the consultant what my test showed and he said it came back as C-peptide - not detectable!  He hadn't seen the report but mentioned they do get people who who present with very high blood glucose, are put on insulin but then this is reduced to nothing, then put on tablets (metformin etc) so not really a T1 honeymoon, then over a number of years go back on insulin.  Not sure what cluster that would be.


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## grovesy (Mar 2, 2018)

Flower said:


> What does a personalised treatment mean?
> 
> I need insulin to live and I have a pump/meter/cgm to try and control my blood sugar as best I can. There isn't anything else around to make it more useful to me as far as I know.
> I personalise my own treatment in that I tweak my own insulin doses according to the results I get.
> ...


I think this one of the latest medical buzz words , as I have seen it in relation to research and cancer treatments.


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## Mark T (Mar 2, 2018)

I suspect for T1's it makes very little difference, since other then injecting insulin not much can be done.

For T2's it could make a difference.  Right now according to NICE we are generally treated the same regardless, it's only when you find a good surgery that you might get somewhat personalised treatment.


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## Northerner (Mar 2, 2018)

Matt Cycle said:


> Mine points to 'classic' T1 or whatever cluster they want to put it in.  I don't think I have any functioning beta cells left.  I've just got back from the pump clinic and last year in spite of having T1 for over 30 years I had to have a C-peptide as part of the pump application to the CCG.  I saw this report before I left this morning and asked the consultant what my test showed and he said it came back as C-peptide - not detectable!  He hadn't seen the report but mentioned they do get people who who present with very high blood glucose, are put on insulin but then this is reduced to nothing, then put on tablets (metformin etc) so not really a T1 honeymoon, then over a number of years go back on insulin.  Not sure what cluster that would be.


What appears to happen with me is that I actually 'cover' my basal needs with novorapid during the day and my liver goes to sleep at night, doesn't release much glucose, then kicks in big time in the morning when I 'need' around 8 units novorapid for a slice of Burgen toast. There have been a handful of members here over the years with a similar presentation. These researchers ought to read the forums if they want to know how many different types of diabetes there are


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## everydayupsanddowns (Mar 2, 2018)

Mark T said:


> It's also missing the various MODY types.  But those are defined as single genetic defects so I guess they are reasonably well defined.



That's the first thing I thought of too!


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## everydayupsanddowns (Mar 2, 2018)

grovesy said:


> I have read that GAD is not always positive.



It was really interesting to see how weak the evidence was for various antibody and cpeptide testing when we were reviewing it for the NICE guidelines. Some people with T2 (who may be, but do not *seem* to be misclassified) can exhibit some antibodies... meanwhile some people who have had "classic" T1 for years and killed off all their beta cells are no longer producing much if anything by way of antibodies.

There are real risks of false positives and false negatives it seems. The better option seems to be to measure at least 2 of the different antibodies, and to do so as soon as possible. But essentially, the clearest way to diagnose is still to use the clinical factors of the presentation / onset / family history / etc etc.


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## Mark T (Mar 2, 2018)

everydayupsanddowns said:


> That's the first thing I thought of too!


Although the introduction to the paper does make reference to MODY:

Diabetes is the fastest increasing disease worldwide and a substantial threat to human health.1 Existing treatment strategies have been unable to stop the progressive course of the disease and prevent development of chronic diabetic complications. One explanation for these shortcomings is that diagnosis of diabetes is based on measurement of only one metabolite, glucose, but the disease is heterogeneous with regard to clinical presentation and progression.
Diabetes classification into type 1 and type 2 diabetes relies primarily on the presence (type 1 diabetes) or absence (type 2 diabetes) of autoantibodies against pancreatic islet β-cell antigens and age at diagnosis (younger for type 1 diabetes). With this approach, 75–85% of patients are classified as having type 2 diabetes. A third subgroup, latent autoimmune diabetes in adults (LADA; affecting <10% of people with diabetes), defined by the presence of glutamic acid decarboxylase antibodies (GADA), is phenotypically indistinguishable from type 2 diabetes at diagnosis, but becomes increasingly similar to type 1 diabetes over time.2 With the introduction of gene sequencing in clinical diagnostics, several rare monogenic forms of diabetes were described, including maturity onset diabetes of the young and neonatal diabetes.3,4
Existing treatment guidelines are limited by the fact they respond to poor metabolic control when it has developed, but do not have means to predict which patients will need intensified treatment. Evidence suggests that early treatment is crucial for prevention of life-shortening complications because target tissues seem to remember poor metabolic control decades later (so-called metabolic memory).5,6
A refined classification could provide a powerful tool to identify at diagnosis those at greatest risk of complications and enable individualised treatment regimens in the
same way as genetic diagnosis of monogenic diabetes guides clinicians to optimal treatment.7 With this aim, we present a novel diabetes classification based on
unsupervised, data-driven cluster analysis of six commonly measured variables and compare it metabolically, genetically, and clinically to the current classification in four separate populations from Sweden and Finland.


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## trophywench (Mar 2, 2018)

The article in the Guardian is a bit more detailed, for instance they did the work in Norway but it was checked out with similar databases in Finland and Sweden - oh OK, all Scandinavians look the same to me ......

It wouldn't be a bad idea to know who was likely to get eye problems - but there again would I the patient, actually want to know that especially if I'm a teenager about to embark on the licensed premises scene with my mates, would it encourage me to look after myself a bit better?  I might like very much to know that at 67 though, considering I haven't really had any yet (I don't regard astigmatism or cataracts as any prob)

However if they could relatively easily/cheaply differentiate between the people who 'are old overweight and obviously made bad lifestyle choices' that they need insulin jabs PDQ and DIDN'T 'bring it on themselves' and just need more and more tablets and a cursory blood test whenever we can be bothered - I think that would be blooming marvellous.

I live in HOPE, me !


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## Matt Cycle (Mar 2, 2018)

everydayupsanddowns said:


> meanwhile some people who have had "classic" T1 for years and killed off all their beta cells are no longer producing much if anything by way of antibodies



That's interesting Mike.  As my consultant said this morning the antibody tests they did were clear or very small amounts (not sure what that means) but as I mentioned the C-peptide was not detectable.  He said that's because after such along time the antibodies wouldn't show up because the beta cells are no more.


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## grovesy (Mar 2, 2018)

everydayupsanddowns said:


> It was really interesting to see how weak the evidence was for various antibody and cpeptide testing when we were reviewing it for the NICE guidelines. Some people with T2 (who may be, but do not *seem* to be misclassified) can exhibit some antibodies... meanwhile some people who have had "classic" T1 for years and killed off all their beta cells are no longer producing much if anything by way of antibodies.
> 
> There are real risks of false positives and false negatives it seems. The better option seems to be to measure at least 2 of the different antibodies, and to do so as soon as possible. But essentially, the clearest way to diagnose is still to use the clinical factors of the presentation / onset / family history / etc etc.


Yeah.


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## SB2015 (Mar 2, 2018)

Matt Cycle said:


> That's interesting Mike.  As my consultant said this morning the antibody tests they did were clear or very small amounts (not sure what that means) but as I mentioned the C-peptide was not detectable.  He said that's because after such along time the antibodies wouldn't show up because the beta cells are no more.


That seems to make sense. Once the Beta cells have been obliterated there is not much for the GAD antibodies to do, so they will push off.  Whatever my Diabetes is called I know I am T1 of some sort, and I need insulin.


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## mikeyB (Mar 2, 2018)

Yup, my consultant just based the diagnosis on clinical symptoms and signs. Didn’t bother with blood tests, presumably for that reason. I suppose technically I’m a LADA,  but I haven’t gone rusty yet.


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## Robin (Mar 2, 2018)

mikeyB said:


> Yup, my consultant just based the diagnosis on clinical symptoms and signs. Didn’t bother with blood tests, presumably for that reason. I suppose technically I’m a LADA,  but I haven’t gone rusty yet.


When I was diagnosed at the hospital, they first put me down as LADA, then the next time they went, they said they'd decided that the term wasn't particularly helpful, and put me down as 'Autoimmune'. They said they were trying hard not to call people 'Type 1' or 'Type 2', and were treating them according to their needs, not their label. Fast forward ten years, I went to a talk last year by the head of the Diabetes unit, who referred to 'Type 1' and 'Type 2' all the way through his talk!


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## mikeyB (Mar 3, 2018)

That’s the sensible way to do it. Dividing things up (3c is my bete noir) doesn’t help, when the difference with type 1 is the manner of destruction of the beta cells. It certainly keeps the pen pushers at NICE content, and the general public.


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