What are the chances of diabetes Watch

ash92:)
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(Original post by Ashnard)
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(Original post by Dynamo123)
Yeah, the source pretty much sums it up. Also, I was a bit surprised at the theory that cold can trigger type I.
Really? That's interesting. Maybe it's related to the increased metabolism as a result of the grater production of thyroid hormone (which serves to increase metabolism and is therefore calorigenic)? This would increase circulating glucose levels above normal levels in the individual, and may trigger glucose intolerance...however, I would've thought this would possible trigger T2-diabetes rather than T1.

[Haven't read the link yet]
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Dynamo123
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(Original post by ash92:))
Really? That's interesting. Maybe it's related to the increased metabolism as a result of the grater production of thyroid hormone (which serves to increase metabolism and is therefore calorigenic)? This would increase circulating glucose levels above normal levels in the individual, and may trigger glucose intolerance...however, I would've thought this would possible trigger T2-diabetes rather than T1.

[Haven't read the link yet]
Yeah, I also thought that. It's kinda hard to imagine cold weather causing an autoimmune backfire, although it might be possible due to some immune disorder taht attacks simultaneously.
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ash92:)
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(Original post by Dynamo123)
Yeah, I also thought that. It's kinda hard to imagine cold weather causing an autoimmune backfire, although it might be possible due to some immune disorder taht attacks simultaneously.
hmmm...I dunno....What mechanism do they suggest the paper?
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Dynamo123
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(Original post by ash92:))
hmmm...I dunno....What mechanism do they suggest the paper?
Dunno, they just went about a few theories relating to IDDM.
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Ashnard
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(Original post by ash92:))
Really? That's interesting. Maybe it's related to the increased metabolism as a result of the grater production of thyroid hormone (which serves to increase metabolism and is therefore calorigenic)? This would increase circulating glucose levels above normal levels in the individual, and may trigger glucose intolerance...however, I would've thought this would possible trigger T2-diabetes rather than T1.

[Haven't read the link yet]

(Original post by Dynamo123)
Yeah, I also thought that. It's kinda hard to imagine cold weather causing an autoimmune backfire, although it might be possible due to some immune disorder taht attacks simultaneously.
It probably won't be the cold weather per se but rather the fact that cold weather increases the chance of viral infections (e.g. seasonal flu). As for the mechanism, the stimulation of the immune system following viral infection must in some way trigger an autoimmune attack upon the pancreatic beta-cells of susceptible individuals.

One possibility is molecular mimicry, in which homology between foreign epitopes and self-epitopes leads the immune system to (mistakenly) attack our own cells. I'd imagine that the genetically susceptible individuals in the population are probably those with allelic forms of beta cell proteins that most closely resemble the viral epitope. Experiments have also shown that, following viral infection, IFN-depleted beta cells are susceptible to destruction by the innate immune system. The actual mechanism is probably more convoluted than this though (immunology is very complex).

There's a nice Nature article on the subject here: http://www.nature.com/ni/journal/v3/...i0402-338.html
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Dynamo123
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(Original post by Ashnard)
It probably won't be the cold weather per se but rather the fact that cold weather increases the chance of viral infections (e.g. seasonal flu). As for the mechanism, the stimulation of the immune system following viral infection must in some way trigger an autoimmune attack upon the pancreatic beta-cells of susceptible individuals.

One possibility is molecular mimicry, in which homology between foreign epitopes and self-epitopes leads the immune system to (mistakenly) attack our own cells. I'd imagine that the genetically susceptible individuals in the population are probably those with allelic forms of beta cell proteins that most closely resemble the viral epitope. Experiments have also shown that, following viral infection, IFN-depleted beta cells are susceptible to destruction by the innate immune system. The actual mechanism is probably more convoluted than this though (immunology is very complex).

There's a nice Nature article on the subject here: http://www.nature.com/ni/journal/v3/...i0402-338.html
That was what I was thinking. Possibly some infection would trigger an autoimmune response.
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ash92:)
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(Original post by Ashnard)
It probably won't be the cold weather per se but rather the fact that cold weather increases the chance of viral infections (e.g. seasonal flu). As for the mechanism, the stimulation of the immune system following viral infection must in some way trigger an autoimmune attack upon the pancreatic beta-cells of susceptible individuals.

One possibility is molecular mimicry, in which homology between foreign epitopes and self-epitopes leads the immune system to (mistakenly) attack our own cells. I'd imagine that the genetically susceptible individuals in the population are probably those with allelic forms of beta cell proteins that most closely resemble the viral epitope. Experiments have also shown that, following viral infection, IFN-depleted beta cells are susceptible to destruction by the innate immune system. The actual mechanism is probably more convoluted than this though (immunology is very complex).

There's a nice Nature article on the subject here: http://www.nature.com/ni/journal/v3/...i0402-338.html
ooooh, so it was attributed to effects on the immune system, rather than the cold temperatures? Sorry, as I say, I haven't read the link (as I am occupied with other things at present).

I wasn't aware that there was a viral epitope similar to pancreatic cell proteins such that it induces an immune response. Interesting. Hopefully, I'll get around to reading both the articles you provided, thanks buddy.
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paradoxicalme
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Diabetes care is so much better than it used to be thanks to GM bacteria. It's really quite amazing.

Though diabetic retinopathy is worrying :/
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Ashnard
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(Original post by ash92:))
ooooh, so it was attributed to effects on the immune system, rather than the cold temperatures? Sorry, as I say, I haven't read the link (as I am occupied with other things at present).

I wasn't aware that there was a viral epitope similar to pancreatic cell proteins such that it induces an immune response. Interesting. Hopefully, I'll get around to reading both the articles you provided, thanks buddy.
No worries.

In that article, it mentions cold weather in one paragraph and then in the next paragraph it mentions viral infections (as potential cause of T1D). It might still be the case that cold has an independent effect, but I personally think (on a hunch) that the viruses are causative and the cold weather is just a correlation because viral infections are more common in cold weather. I may be wrong though. To be honest, I haven't done much reading on it either.

The molecular mimicry thing was just sort of mooted in the article. It's a nice and intuitive possibility but (from what little I know of immunology) the full mechanism will probably involve 10+ cytokines and loads of different stages. immunology is complicated like that.
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ash92:)
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(Original post by Ashnard)
No worries.

In that article, it mentions cold weather in one paragraph and then in the next paragraph it mentions viral infections (as potential cause of T1D). It might still be the case that cold has an independent effect, but I personally think (on a hunch) that the viruses are causative and the cold weather is just a correlation because viral infections are more common in cold weather. I may be wrong though. To be honest, I haven't done much reading on it either.

The molecular mimicry thing was just sort of mooted in the article. It's a nice and intuitive possibility but (from what little I know of immunology) the full mechanism will probably involve 10+ cytokines and loads of different stages. immunology is complicated like that.
I see. So they likened this to epitope homology? And is this homology supposedly before viral infection of the cell, or is it acquired as a result of infection?
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Ashnard
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(Original post by ash92:))
I see. So they likened this to epitope homology? And is this homology supposedly before viral infection of the cell, or is it acquired as a result of infection?
The idea is that, as a result of viral infection, the adaptive immune system mounts a specific response (via B cells and T cells) to particular viral epitopes. If the virus has epitopes that are structurally homologous to host epitopes (before infection), then the activated B and T cells will not be able to distinguish viral epitopes from self-epitopes and therefore both will be attacked.

The Nature article I cited actually suggests that this is not the correct mechanism for T1D. It's a nice idea though.
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ash92:)
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(Original post by Ashnard)
The idea is that, as a result of viral infection, the adaptive immune system mounts a specific response (via B cells and T cells) to particular viral epitopes. If the virus has epitopes that are structurally homologous to host epitopes (before infection), then the activated B and T cells will not be able to distinguish viral epitopes from self-epitopes and therefore both will be attacked.

The Nature article I cited actually suggests that this is not the correct mechanism for T1D. It's a nice idea though.
Ah, I see - so they suggest homology before infection. That's what I was unsure about (as I haven't read the paper), thanks buddy.


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Ashnard
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(Original post by ash92:))
Ah, I see - so they suggest homology before infection. That's what I was unsure about (as I haven't read the paper), thanks buddy.


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Yep, homology before infection.. You're welcome.
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Dynamo123
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(Original post by Ashnard)
The idea is that, as a result of viral infection, the adaptive immune system mounts a specific response (via B cells and T cells) to particular viral epitopes. If the virus has epitopes that are structurally homologous to host epitopes (before infection), then the activated B and T cells will not be able to distinguish viral epitopes from self-epitopes and therefore both will be attacked.

The Nature article I cited actually suggests that this is not the correct mechanism for T1D. It's a nice idea though.
Homology between epitopes before infection would be a good explanation. What mechanism does the nature article quote? (I haven't gotten around to reading it--can you give a quick summary )
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Dynamo123
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(Original post by paradoxicalme)
Diabetes care is so much better than it used to be thanks to GM bacteria. It's really quite amazing.

Though diabetic retinopathy is worrying :/
Yeah, genetics and biotech have caused quite a revolution in helping people out there.
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Ashnard
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(Original post by Dynamo123)
Homology between epitopes before infection would be a good explanation. What mechanism does the nature article quote? (I haven't gotten around to reading it--can you give a quick summary )
Yeah, of course:

Animal models have shown that the Coxsackie virus B4 (CVB4) can induce T1D in animal models.

The cytokines IFN-alpha and IFN-gamma are required to prevent the infection of pancreatic beta-cells from the Coxsackie virus B4 (CVB4). When the production of IFN-alpha and IFN-gamma was turned off experimentally (by expressing suppressor of cytokine signalling 1 -SOCS1), the beta-cells became highly susceptible to viral infection. The beta-cells then became susceptible to attack from natural killer cells and apoptosis (induced by the innate immune system). The authors do note however that the relevance of this finding is ambiguous as they do not know of physiological cases in which IFN responsiveness in beta-cells may be lost.

The destruction of beta-cells leads to the release of sequestered antigens that stimulate auto-reactive T cells. The release of IFNs may also stimulate auto-reactive T-cells.


So yeah, that's basically all the information that they gave in the article. That was written in 2002, so they may have a better idea of the overall mechanism now (I haven't really looked at the literature).

They did however represent a very generalised putative mechanism in the form of a diagram. I know that the diagram isn't very clear itself but the caption below help a bit:

Name:  T1D.gif
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"'Coxsackievirus B (CVB)-mediated cell damage of target cells, such as the pancreatic beta cell or cardiac myocyte, leads to a local immune response with the production of cytokines such as IFN-alpha and IFN-gamma. Interferons arrest viral replication and facilitate viral clearance in resistant individuals. But IFNs and other proinflammatory cytokines may also stimulate an autoimmune response against self-antigens, such as beta cells or myocytes, in genetically susceptible individuals, which results in immune-mediated damage and the development of autoimmune disease."
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Dynamo123
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(Original post by Ashnard)
Yeah, of course:

Animal models have shown that the Coxsackie virus B4 (CVB4) can induce T1D in animal models.

The cytokines IFN-alpha and IFN-gamma are required to prevent the infection of pancreatic beta-cells from the Coxsackie virus B4 (CVB4). When the production of IFN-alpha and IFN-gamma was turned off experimentally (by expressing suppressor of cytokine signalling 1 -SOCS1), the beta-cells became highly susceptible to viral infection. The beta-cells then became susceptible to attack from natural killer cells and apoptosis (induced by the innate immune system). The authors do note however that the relevance of this finding is ambiguous as they do not know of physiological cases in which IFN responsiveness in beta-cells may be lost.

The destruction of beta-cells leads to the release of sequestered antigens that stimulate auto-reactive T cells. The release of IFNs may also stimulate auto-reactive T-cells.


So yeah, that's basically all the information that they gave in the article. That was written in 2002, so they may have a better idea of the overall mechanism now (I haven't really looked at the literature).

They did however represent a very generalised putative mechanism in the form of a diagram. I know that the diagram isn't very clear itself but the caption below help a bit:

Name:  T1D.gif
Views: 147
Size:  47.7 KB

"'Coxsackievirus B (CVB)-mediated cell damage of target cells, such as the pancreatic beta cell or cardiac myocyte, leads to a local immune response with the production of cytokines such as IFN-alpha and IFN-gamma. Interferons arrest viral replication and facilitate viral clearance in resistant individuals. But IFNs and other proinflammatory cytokines may also stimulate an autoimmune response against self-antigens, such as beta cells or myocytes, in genetically susceptible individuals, which results in immune-mediated damage and the development of autoimmune disease."
So stopping production of IFN-alpha and IFN-gamma leads to viral attack leading to susceptibility of B-cells to NK cells, and releasing sequestered antigens that induces an auto-immune response? That's interesting, as I haven't studied immunology in that much detail. Also, I got a bit confused over the last part. IFNs and other cytokines induce an auto-response against the B-cells themselves? Wasn't it the lack of production of IFNs that led to sequestered antigens inducing an auto-response? Or is this valid only for genetically susceptible individuals? Or are both possibilities valid? (as they mention in the article that the release of IFNs does induce an autoreactive T response?)
Thanks
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Ashnard
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(Original post by Dynamo123)
So stopping production of IFN-alpha and IFN-gamma leads to viral attack leading to susceptibility of B-cells to NK cells, and releasing sequestered antigens that induces an auto-immune response? That's interesting, as I haven't studied immunology in that much detail. Also, I got a bit confused over the last part. IFNs and other cytokines induce an auto-response against the B-cells themselves? Wasn't it the lack of production of IFNs that led to sequestered antigens inducing an auto-response? Or is this valid only for genetically susceptible individuals? Or are both possibilities valid? (as they mention in the article that the release of IFNs does induce an autoreactive T response?)
Thanks
No worries. Yeah, that does look like a contradiction. Well observed.

The part about the beta-cells being more susceptible upon depletion of IFNs was derived experimentally from an expression assay. It would still make sense though if, in susceptible individuals, the actual concentration of IFNs was normal but the specific response of the pancreatic beta cells to IFNs was hindered for some reason. This way the IFNs could still stimulate the immune system but they would have no effect on beta cells. Does that make sense? There may be other ways around this paradox but that is just one possibility.
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Dynamo123
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(Original post by Ashnard)
No worries. Yeah, that does look like a contradiction. Well observed.

The part about the beta-cells being more susceptible upon depletion of IFNs was derived experimentally from an expression assay. It would still make sense though if, in susceptible individuals, the actual concentration of IFNs was normal but the specific response of the pancreatic beta cells to IFNs was hindered for some reason. This way the IFNs could still stimulate the immune system but they would have no effect on beta cells. Does that make sense? There may be other ways around this paradox but that is just one possibility.
Yeah, that would seem a possible explanation, that the IFNs are there, but their action (and subsequently the response of) on B-cells is hindered, so that they can trigger an autoimmune response but have no effect on B cells. Also, the nature article you cited mentions that the IFNs were suppressed in the experiment. In that case, would the last part hold good? Also, they mentioned how any particular physiological case bearing a similarity has not been discovered.
Thanks for the help!
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Ashnard
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(Original post by Dynamo123)
Yeah, that would seem a possible explanation, that the IFNs are there, but their action (and subsequently the response of) on B-cells is hindered, so that they can trigger an autoimmune response but have no effect on B cells. Also, the nature article you cited mentions that the IFNs were suppressed in the experiment. In that case, would the last part hold good? Also, they mentioned how any particular physiological case bearing a similarity has not been discovered.
Thanks for the help!
You're welcome.

Are you referring to the IFN-mediated stimulation of the immune system? In that experiment, they were just assaying the effect of IFN-depletion on the beta-cells only. Presumably, full-scale T1D would not have been induced but they were not measuring this. Does this answer your question?
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