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Post by daduke38 on Jul 10, 2016 11:27:46 GMT -5
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Post by kc on Jul 10, 2016 11:55:49 GMT -5
It may have to do with air pollution and overcrowding in India. Was over population especially in the big cities there they must have very poor air quality .
Oh Not quite sure what to make of it with a very specifically saying Indians living in India versus Indians living elsewhere .
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Post by Deleted on Jul 10, 2016 12:11:49 GMT -5
You have been FUD'ed Daduke.
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Post by Chris-C on Jul 10, 2016 12:28:32 GMT -5
That's interesting. Clearly, one has to read the published study to fully assess the claims. It is likely that using a sample of persons with compromised pulmonary function will show decreased function in several systems over time. In this study, I'd be interested to know if the route of administration of insulin showed more dramatic decline in inhaled insulin or if the comment was unrelated to actual data on inhaled insulin use.
Despite the hurdle spirometry presents, this shows the wisdom of prescribing only after testing has been done. Baselines can be monitored and therapy can be altered if adverse results show up on follow-up exams. One would think that with all the safety data gathered so far, any dramatic effect would be well documented and reported. However, the FDA specifically requested a post approval long term safety study and that will add important new data. One supposes that technosphere particles, which I believe dissolve and are absorbed on tissue contact, are quite different physiologically than particulates from smoke or other hazardous air contaminants.
Regardless- Just purchased my first new shares in quite some time. Still hold every share of my original stash.
GLTAL and "go get em" MNKD sales reps!
Chris C
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Post by daduke38 on Jul 10, 2016 12:51:08 GMT -5
You have been FUD'ed Daduke. Quite possible! Just put it out there to get some thoughts. Nothing wrong with looking and examining posts or links that don't tell us what we want to hear. I think my greatest concern was the Mayo Clinic was involved. |
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Post by mnkdfann on Jul 10, 2016 13:12:39 GMT -5
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Post by matt on Jul 10, 2016 14:00:07 GMT -5
What the paper says (I just read the full text) is that insulin levels have a negative effect on lung function. This manifests itself by increased amounts of smooth muscle in the airways, PI3K/AKT mediated up-regulation of the beta catenin signaling pathway, and collagen type 1 deposition, all in an insulin level-dependent manner. That combination of symptoms is profibrotic and procontractile, meaning that the lungs stiffen and become less able to remodel due to the collagen, and asthma like obstructive disease is increased. The work was done in mice and cell culture using standard methods, not in humans, but these are well-studied pathways and similar effects are extremely likely in humans.
The point of the article is that there have been observations in the population that show a pronounced correlation between obesity, insulin resistance, hyperinsulinemia, and lung diseases, but until now nobody could show a cause and effect. This article outlined fairly persuasively a direct cause and effect linkage between hyperinsulinemia and deterioration of lung function due to fibrosis. Once fibrosis is established in any organ (as shown by consolidated collagen type 1 scar) then the organ is permanently impaired. Their conclusion is that nobody (anywhere) should use any insulin product without being aware of the risks, and that inhaled insulin poses an added level of risk that warrants further human studies before it becomes an accepted therapy.
Most of what I do involves regeneration of tissue, especially in fibrotic environments, so I look at this kind of study almost daily. The study was well-designed and controlled, and supports the imposition of a black box warning on Afrezza. The authors would be similarly cautious about careless use of injectable insulins and drugs (like metformin) that affect insulin production. Note again that the effects are seen with ANY insulin that is not properly controlled, not just Afrezza, but the risks are especially high with inhaled formulations. While that does not make for a better investment thesis in Mannkind, the science suggests that some caution is prudent.
For those of you with access to an academic library, the citations are:
PubMed PMID:26919895 DOI: 10.1152/ajplung.00091.2015 |
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Post by peppy on Jul 10, 2016 14:02:15 GMT -5
insulin levels like hexamers that that a long time to break down? or..... insulin levels as secondary to carbohydrate consumption which feeds cancer?
narrow it down for me... insulin levels for a type one, that would die with out insulin? What you talking about willis?
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Post by babaoriley on Jul 10, 2016 16:31:43 GMT -5
So one has to compare the downside of one with the downside of the other, keeping in mind the seriousness of the downsides as well as the frequency of the downsides. Without that, there is little of practical value, other than it's better if your pancreas worked really well.
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Post by agedhippie on Jul 10, 2016 16:38:40 GMT -5
What the paper says (I just read the full text) is that insulin levels have a negative effect on lung function. This manifests itself by increased amounts of smooth muscle in the airways, PI3K/AKT mediated up-regulation of the beta catenin signaling pathway, and collagen type 1 deposition, all in an insulin level-dependent manner. That combination of symptoms is profibrotic and procontractile, meaning that the lungs stiffen and become less able to remodel due to the collagen, and asthma like obstructive disease is increased. The work was done in mice and cell culture using standard methods, not in humans, but these are well-studied pathways and similar effects are extremely likely in humans.
This is interesting. My endos's position is that he will not prescribe Afrezza until after the lung safety trials. Not because of a cancer risk (he doesn't expect there to be any cancer risk) but because of fibrosis. He believes that they were starting to see fibrosis in Exubera users. From this paper the chances are that it problem is far more widespread but they never had reason to look at the lungs of non-inhaled insulin users. |
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Post by agedhippie on Jul 10, 2016 16:41:55 GMT -5
insulin levels like hexamers that that a long time to break down? or..... insulin levels as secondary to carbohydrate consumption which feeds cancer?
narrow it down for me... insulin levels for a type one, that would die with out insulin? What you talking about willis?
I suspect that this is primarily a Type 2 problem. There are a lot of known issues around running high insulin levels which is why reducing them in Type 2 is important. This is unlikely to be a Type 1 problem as in that case you don't get elevated insulin levels. Of course there are those lucky people with both Type 1 and Type 2. |
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Post by mnkdfann on Jul 10, 2016 16:56:32 GMT -5
What the paper says (I just read the full text) is that insulin levels have a negative effect on lung function. This manifests itself by increased amounts of smooth muscle in the airways, PI3K/AKT mediated up-regulation of the beta catenin signaling pathway, and collagen type 1 deposition, all in an insulin level-dependent manner. That combination of symptoms is profibrotic and procontractile, meaning that the lungs stiffen and become less able to remodel due to the collagen, and asthma like obstructive disease is increased. The work was done in mice and cell culture using standard methods, not in humans, but these are well-studied pathways and similar effects are extremely likely in humans.
The point of the article is that there have been observations in the population that show a pronounced correlation between obesity, insulin resistance, hyperinsulinemia, and lung diseases, but until now nobody could show a cause and effect. This article outlined fairly persuasively a direct cause and effect linkage between hyperinsulinemia and deterioration of lung function due to fibrosis. Once fibrosis is established in any organ (as shown by consolidated collagen type 1 scar) then the organ is permanently impaired. Their conclusion is that nobody (anywhere) should use any insulin product without being aware of the risks, and that inhaled insulin poses an added level of risk that warrants further human studies before it becomes an accepted therapy.
Most of what I do involves regeneration of tissue, especially in fibrotic environments, so I look at this kind of study almost daily. The study was well-designed and controlled, and supports the imposition of a black box warning on Afrezza. The authors would be similarly cautious about careless use of injectable insulins and drugs (like metformin) that affect insulin production. Note again that the effects are seen with ANY insulin that is not properly controlled, not just Afrezza, but the risks are especially high with inhaled formulations. While that does not make for a better investment thesis in Mannkind, the science suggests that some caution is prudent.
For those of you with access to an academic library, the citations are:
PubMed PMID:26919895 DOI: 10.1152/ajplung.00091.2015 Or they can just view it (the preprint) at the link I gave 3 and 1/2 months ago in the thread I referenced earlier today. Here is the direct link again: www.researchgate.net/publication/296194275_Hyperinsulinemia_Adversely_Affects_Lung_Structure_and_Function(Scroll down the page at that link, to see the article itself.) |
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Post by mnkdfann on Jul 10, 2016 16:57:46 GMT -5
What you talking about willis?
I was just making the point that the board already noticed the article and discussed it (very briefly) nearly 4 months ago. Well, I suppose there is no harm in further discussion now. |
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Deleted
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Post by Deleted on Jul 10, 2016 17:04:18 GMT -5
What the paper says (I just read the full text) is that insulin levels have a negative effect on lung function. This manifests itself by increased amounts of smooth muscle in the airways, PI3K/AKT mediated up-regulation of the beta catenin signaling pathway, and collagen type 1 deposition, all in an insulin level-dependent manner. That combination of symptoms is profibrotic and procontractile, meaning that the lungs stiffen and become less able to remodel due to the collagen, and asthma like obstructive disease is increased. The work was done in mice and cell culture using standard methods, not in humans, but these are well-studied pathways and similar effects are extremely likely in humans.
This is interesting. My endos's position is that he will not prescribe Afrezza until after the lung safety trials. Not because of a cancer risk (he doesn't expect there to be any cancer risk) but because of fibrosis. He believes that they were starting to see fibrosis in Exubera users. From this paper the chances are that it problem is far more widespread but they never had reason to look at the lungs of non-inhaled insulin users. I guess your endo needs to understand how Exubera works and Afrezza works so as to make that assumption. I meant the technology behind both. I am sure he is considering them same as they both are inhaled ? I feel sorry for his patients |
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Post by daduke38 on Jul 10, 2016 17:05:07 GMT -5
What the paper says (I just read the full text) is that insulin levels have a negative effect on lung function. This manifests itself by increased amounts of smooth muscle in the airways, PI3K/AKT mediated up-regulation of the beta catenin signaling pathway, and collagen type 1 deposition, all in an insulin level-dependent manner. That combination of symptoms is profibrotic and procontractile, meaning that the lungs stiffen and become less able to remodel due to the collagen, and asthma like obstructive disease is increased. The work was done in mice and cell culture using standard methods, not in humans, but these are well-studied pathways and similar effects are extremely likely in humans.
The point of the article is that there have been observations in the population that show a pronounced correlation between obesity, insulin resistance, hyperinsulinemia, and lung diseases, but until now nobody could show a cause and effect. This article outlined fairly persuasively a direct cause and effect linkage between hyperinsulinemia and deterioration of lung function due to fibrosis. Once fibrosis is established in any organ (as shown by consolidated collagen type 1 scar) then the organ is permanently impaired. Their conclusion is that nobody (anywhere) should use any insulin product without being aware of the risks, and that inhaled insulin poses an added level of risk that warrants further human studies before it becomes an accepted therapy.
Most of what I do involves regeneration of tissue, especially in fibrotic environments, so I look at this kind of study almost daily. The study was well-designed and controlled, and supports the imposition of a black box warning on Afrezza. The authors would be similarly cautious about careless use of injectable insulins and drugs (like metformin) that affect insulin production. Note again that the effects are seen with ANY insulin that is not properly controlled, not just Afrezza, but the risks are especially high with inhaled formulations. While that does not make for a better investment thesis in Mannkind, the science suggests that some caution is prudent.
For those of you with access to an academic library, the citations are:
PubMed PMID:26919895 DOI: 10.1152/ajplung.00091.2015 Or they can just view it (the preprint) at the link I gave 3 and 1/2 months ago in the thread I referenced earlier today. Here is the direct link again: www.researchgate.net/publication/296194275_Hyperinsulinemia_Adversely_Affects_Lung_Structure_and_Function(Scroll down the page at that link, to see the article itself.) I really appreciate you re-posting the thread and info. As much as I have read, my peanut brain can't remember everything;-) |
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