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New finding on possible cause of both Type 1 and Type 2

LucySW

Well-Known Member
Messages
1,959
Location
Denmark
Type of diabetes
LADA
Treatment type
Insulin
Study based in Manchester and NZ just published, providing 'strong evidence' that Type 1 is the result of 'toxic clumps' of amylin being produced in the pancreas, which immobilise and destroy the beta cells.

'Professor Garth Cooper, from The University of Manchester with his University of Auckland-based research team, led the study.

As well as producing insulin, cells in the pancreas also produce another hormone called amylin. Insulin and amylin normally work together to regulate the body’s response to food intake. If they are no longer produced, then levels of sugar in the blood rise resulting in diabetes and causing damage to organs such as the heart, kidneys, eyes and nerves if blood sugar levels aren’t properly controlled.

However, some of the amylin that is produced can get deposited around cells in the pancreas as toxic clumps, which then, in turn, destroy those cells that produce insulin and amylin. The consequence of this cell death is diabetes.

Research published previously by Professor Cooper suggested that this is the causative mechanism in type-2 diabetes. This new research provides strong evidence that type-1 diabetes results from the same mechanism.

The difference is that the disease starts at an earlier age and progresses more rapidly in type-1 compared to type-2 diabetes because there is more rapid deposition of toxic amylin clumps in the pancreas.

Professor Cooper’s group expects to have potential medicines ready to go into clinical trials in the next two years and it is anticipated that these will be tested in both type-1 and type-2 diabetic patients. These clinical trials are being planned with research groups in England and Scotland'​

DCUK article here.

And Telegraph article here
 
Indy51 said:
George Henderson (one of my favourite bloggers) has written a detailed blogpost about this study:
http://hopefulgeranium.blogspot.com.au/2014/08/amylin-root-cause-of-diabetes.html
Click to expand...

This fascinating, thanks.

As a new LADA I'm esp interested in a lead raised in the comments there, on Metformin controlling Xs amylin:

"It looks as if amylin is the weak link of the insulin response; the part of the cascade most likely to break the whole mechanism under pressure.
And it's also interesting in its own right. Newly discovered, what misunderstandings have been the consequences of its over sight?
We will surely be misunderstanding insulin if we have only used insulin injections or infusions as our models for glucose response. What is the amylin resonse curve compared to insulin?
Here's what happen to amylin on metformin
http://www.ncbi.nlm.nih.gov/pubmed/10337452

"With the respect to the trophic effect of amyloid deposits in the pancreatic islets and to a hypothetic effect of amylin increasing insulin resistance, the present results emphasize the particular usefulness of metformin in the pharmacological treatment of NIDDM." "

I'm especially interested as I'm a new LADA very keen to get my BS down to protective levels (4.6-5.2), but am stuck at 5.6-6.8 and came off Metformin four weeks ago.

@IanDP, you might be interested too.

Lucy
 
Very interesting. Are you going back on Metformin Lucy?
My dr (9 months ago) advised me to stop taking it, but did say it would do no harm if I continued (unlike Gliclazide) which he said could do harm.

I have also read that Metformin is good at stopping / helping liver dump, thus keeping BG levels lower in the morning. This morning level is the one I struggle with most...... So I am getting temped to give Metformin a try again.... As are you I guess.

Seeing my diabetics specialist in 3 weeks time, so probably wait until then..... What I feel I really need is 1/4 units of insulin, so will ask what they can do to help.
 

To take half a unit of basal, at night? That makes sense. They might play ball with that as the amounts are so small. The reflex response seems to be to require a much higher HbA1c, but I hope you're lucky.

The Metformin preventing the DP seems very well documented.

I've been taking 3 units of basal NPH (all I was offered) at night for two weeks. My BS is always least good at night, sometimes up to 7 and over, and the basal dose rescues my morning fasting BS so it's usually 5.5-5.8. The trend is absolutely flat though, not downwards, and I'm asking myself what I'm achieving with the insulin. I've been a bit slacker with the meal structure in these two weeks, having 2-3g carb in nut snacks between meals twice a day and not holding out till evening meal. I plan to go back to the stricter 6 + 12 + 12 structure now. The problem was that I was getting ravenous between meals. I think that was because I wasn't making absolutely sure to have protein/carbs that satisfy me. I have to take the time to do it properly (fitting in with others' eating not really good enough).

Anyone else find that snacking (LCHF snacking) makes BS better, or worse?
Lucy
 
I wish press releases would not overstate the case. Personally I think this one has done so.
Causative mechanism at one level maybe? or just a possible mechanism and what actually causes an excess of amylin to occur ?
The study show that excess amylin deposits can cause beta cell apoptosis ie cell death in mice.
It has been known for a long time that amylin deposits are toxic to beta cells
http://www.ifcc.org/ifcc-communicat...13/vol-13-n°-5/apoptotic-death-of-beta-cells/
There are many papers that discuss the role of amylin in beta cell apoptosis.
so take your pick https://www.google.co.uk/?gws_rd=ssl#q=amylin apoptosis diabetes

I can only read the abstract but it does say what was done , there will be a lot more detail in the full paper.
They induced and followed the progression of diabetes in mice who secrete high levels of amylin..
To do this they produced transgenic mice engineered to produce these high levels . They produced homozygous hA-transgenic mice. These would have the mutation to overproduce amylin in both the maternal and paternal dna ( we all have two sets of chromosomes, mice aren't that dissimilar to humans! ) They also produced hemizygous hA-transgenic mice these would have a normal gene on one chromosome and a mutated one on the other.
This seems to have been done to result in both mice overproducing amylin but the homozygous mice producing twice the protein (amylin) dosage of the other. (ie one gene was not dominant thus counteracting the other)
Homozygous mice produced lots of amylin, had lots of amylin deposits . They went through a prediabetes stage, developed hyperinsulinemia with transient insulin resistance and then underwent rapid β-cell loss, culminating in severe juvenile-onset diabetes
(ie all this amylin killed off the beta cells relatively quickly)
The hemizygous mice had less of an overproduction. They went through the same stages but with a longer pre diabetes stage with the plaque formation, beta cell death occurring in adult hood

This was the researchers say;
reminiscent of type 1 and 2 diabetes, respectively. Thus, the hA-evoked diabetes phenotypes differ substantively according to degree of amylin overproduction
Click to expand...

http://www.fasebj.org/content/early...ract?sid=cceff467-fc27-48c1-8f7e-f61cdc2a5821
This research may add to our knowledge of the mechanics of beta cell death. It says absolutely nothing about why excess amylin may be present , and what induces that toxicity The paper unlike the press reports doesn't suggest that this is the cause of any sort of diabetes. It shows that excess amylin will cause beta cell death.
We aren't transgenic mice and of course there is no suggestion that humans have a mutated gene for this.
 
Sure, thanks for correcting the causal chain. Still fascinating to pursue the connection thro various permutations, though.
 
I haven't had time to read it all but it seems to suggest that there may be a continuum between T1 and T2 for this particular mechanism (i.e. destruction of beta cells). But of course what we don't know is why this happens in some and not others - the holy grail is still to identify the bits in the DNA that contain the metabolic flaws that trigger all mechanisms resulting in elevated blood glucose. One day ...
 
Thanks for this info. It supports the body of knowledge we already have of the role that destroyed beta cells play in DB 1 and 2.
 
Don't really understand but this interests me before diagnose my gp kept testing my amylase levels he worried they were too high I was accused of being an alcoholic many many times I don't drink alcohol (I smoke so can't be too sanctimonious) in the end I was sent to an endocrinologists yeh spell check he just said oh well some people have high levels go away on being diagnosed I did wonder because it can mean high blood sugars for some time you'd think they might have looked into that
 
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