3 ms·

Putting my biologist hat on, I don't want to dismiss it, consider it to be interesting, but would have to look a lot more closely to get a guess if your observa

by hga 11y ago

Putting my biologist hat on, I don't want to dismiss it, consider it to be interesting, but would have to look a lot more closely to get a guess if your observations are useful in this context. CF is a regulatory derangement, so I don't know what all else it might be doing and how much it might be relevant to normal type humans. That said, no one's come up with any vaguely useful citations linking saturated fats to diabetes, and this doesn't help the case for that.

Mz 11y ago
Putting my biologist hat on, I don't want to dismiss it, consider it to be interesting, Thank you. I would be happy to discuss it with you further. I do not know what you mean by CF is a regulatory derangement. It is caused by a defect in a specific cell channel that manages traffic of specific molecules into and out of the cell. I have paid enormous attention to that and kind of ignored the hand-wavy and apparently incorrect mental models popular in the medical literature. For example, the official explanation on the CF Foundation website is that people with CF are drowning in an excess of mucus. I found one study that says we produce too little mucus, not too much. This fits with my firsthand experience, it more logically fits with the fact that mucus is a protective coating that helps keep out germs and it fits with the extremely well known and well established fact that women with CF suffer vaginal dryness that often seriously interferes with their sex lives. I think we cough up phlegm, not mucus -- ie infection -- and if you improve mucus production, you reduce infection and see less phlegm. I have seen that hypothesis work effectively for me and my oldest son who has the same diagnosis I have. I have explained it to one woman with CF who was out of time and dying and tracked me down after I left all CF lists and took down my health site. She is gradually getting healthier. So that is a very long way of saying that a) I have no idea what you mean by that phrase and b) the odds are high that you and I have completely different mental models for what is going on with CF.
- hga 11y ago
  Let me state that I haven't studied CF specifically at all, I'm going from what I just read in Wikipedia and my general biology education. It is caused by a defect in a specific cell channel that manages traffic of specific molecules into and out of the cell. Per Wikipedia: "It is caused by the presence of mutations in both copies of the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR)." Per the article on CFTR: Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates that is encoded by the CFTR gene. CFTR is an ABC transporter-class ion channel that codes for a protein that conducts chloride and thiocyanate ions across epithelial cell membranes. More detail: CFTR functions as an ATP-gated anion channel, increasing the conductance for certain anions (e.g. Cl−) to flow down their electrochemical gradient. ATP-driven conformational changes in CFTR open and close a gate to allow transmembrane flow of anions down their electrochemical gradient. This in contrast to other ABC proteins, in which ATP-driven conformational changes fuel uphill substrate transport across cellular membranes. Essentially, CFTR is an ion channel that evolved as a 'broken' ABC transporter that leaks when in open conformation. The CFTR is found in the epithelial cells of many organs including the lung, liver, pancreas, digestive tract, reproductive tract, and skin. Normally, the protein moves chloride and thiocyanate ions (with a negative charge) out of an epithelial cell to the covering mucus. Positively charged sodium ions follow passively, increasing the total electrolyte concentration in the mucus, resulting in the movement of water out of cell by osmosis. So, based on ATP getting to it, it allows movement (passive transport) of a set of ions and H2O in and out of cells. I assume there's some regulatory function that mediates the opening and closing of it; the CF mutations interfere with its function one way or another (e.g. one class is thought to result in the CFTR degrading quickly, don't know if it functions normally while in place). So while we're mostly focused on the consequences of these ions and water not getting out of the cell and deranging the production of proper mucus, it could also result in metabolic derangement inside these cells. Per https://www.cff.org/Living-with-CF/Cystic-Fibrosis-Related-Diabetes/ https://www.cff.org/Living-with-CF/Cystic-Fibrosis-Related-D... there's a Type 1 style due to direct pancreas damage interfering with production of insulin, but also a Type 2 style interfering with insulin response. The latter is the sort of thing I'm getting at, I'd want to understand how it works before extrapolating from CF populations to the general one. As the article says, "Unlike people with type 1 or type 2 diabetes, people with CFRD need the same high-calorie CF diet they would normally eat in order to gain weight and build muscle. A healthy diet means eating a variety of foods that are high in protein, fat and salt. The only difference is that people with CFRD need to track or count the foods that affect their blood sugar levels the most." So your eating plenty of fat without apparent harm might or might not be significant for the general population and "normal" Type 2 Diabetes (and I don't know if there's only one form/cause of it).
  - Mz 11y ago
    I am a former homemaker, military wife and homeschooling mom who just didn't want to die a slow torturous death. While I do have about six years of college, some of it the equivalent of graduate work, I have limited formal study in biology. So I likely brought mental models from other realms where I have training. I do have a technical certificate that makes me a "Certified Life and Health Insurance Specialist" (or did at one time) and my former employer paid for that. It was part of training for my job where I reviewed accident claims. So I read medical records as part of my job for over five years. Although I was an accident specialist, I sometimes read records on patients with diabetes because of the tendency for people with diabetes to wind up needing a foot amputation. It was not uncommon for them to try to get that paid as an accident claim based on having hit the foot in question against something prior to the amputation. This sometimes had to be reviewed by a former surgeon to make the final decision as to whether we would pay the claim -- whether the amputation was necessitated by trauma or due to advanced deterioration from diabetes. Still, I am at a serious disadvantage in trying to talk about ion channels and what not in terms that a biologist would typically use. I did not know this: Essentially, CFTR is an ion channel that evolved as a 'broken' ABC transporter that leaks when in open conformation. That is interesting to me. CF is basically a salt-wasting condition. There are various forms of defect in the CFTR, but knowing that it basically leaks may explain why it is basically a salt wasting condition. (e.g. one class is thought to result in the CFTR degrading quickly, don't know if it functions normally while in place). If you are interested, I can share my research notes where I spent some time digging up information. I was taking a particular supplement at the time and if I missed a single dose, I drastically and promptly deteriorated. So I was looking to understand why that might be. In the process of digging around, I found that most genetic disorders boil down to being a defect in a particular protein. The CFTR channel is a protein that gets folded a particular way and inserted into the cell membrane in order to handle trafficking into and out of the cell of specific ions. So one of the things I found was that there are two conditions that cause higher misfolds of proteins within the cell: Derangement of PH level and derangement of salt level. You see both of these things happening with CF. It is well established that people with CF gradually become increasingly too acid. This is almost never treated. It is not treated as medically significant, even though if you have diabetes and get sudden onset acidosis, they hospitalize you promptly because you can be dead within 72 hours if they can't reverse it. So they know acidosis is deadly. They know CF is deadly. They know CF promotes gradual onset acidosis. No one sees this as related. I decided it must be related and reversing the acidity of my tissues was a cornerstone of my approach. Initially, I took about $300/month worth of supplements. I thought I would always need to do that. It was a daily battle to try to keep symptoms under control. I gradually became less symptomatic. I stabilized. So I have concluded that there is a vicious positive feedback loop where the more acid you get, the more you see protein misfolds and the more you see protein misfolds, the more acid you get. I believe this is why it is a degenerative, progressive condition. And if you can accommodate the defect in the cell membrane, which is both a bottleneck on some things and an open flood gate on others at the same time, if you can find a way around that, you can stop and reverse the process. Presumably this will work differently depending on the specific defect in the CFTR. There are variations of CF that are the equivalent of albinism in terms of simply not producing a CFTR channel to begin with. I imagine that will be much more resistant to management via the process I use. There are a lot of other things in the back of my mind that are relevant to this discussion, but I am somewhat pressed for time and I am not sure I could make clear what the relevance is. I do not "eat plenty of fat without apparent harm." I got very picky about WHAT I eat and I believe the high levels of specific things that I ate for a time amounts to redressing a serious and lifelong deficit. I do not count calories or anything like that. I pay close attention to chemical makeup of foods and how that interacts with my condition. But most people with CF are prescribed a high salt, high fat, high calorie diet. In practice, this means they are actively encouraged by medical professionals to eat a junk food diet. I went the other way. I pay very close attention to the quality of my food, not the quantity. I went looking for good quality fats and salts and other foods. I think the current practice of prescribing a junk food diet because it is high in fat and salt without caring that it is low in quality is part of what is killing people with CF. I don't know if that does anything to cast light on the question of fats and diabetes per se. I don't think fats per se are terribly important to the process behind diabetes. I think acidosis and infection are likely more related and you see both of those at high rates in people with CF. There are also studies that clearly link inflammation and diabetes. As I said in the comment that started this subthread, I believe that likely points to infection as an underlying cause of diabetes. Addendum: I should add that as I have gotten healthier, my appetite has shrunk. I eat a great deal less than I used to eat. Redressing the lifelong deficits dramatically reduced my need for a very high calorie diet. I probably still eat a bit more than average, but I eat a lot less than I used to.

by hga 11y ago

Mz 11y ago

Putting my biologist hat on, I don't want to dismiss it, consider it to be interesting, Thank you. I would be happy to discuss it with you further. I do not know what you mean by CF is a regulatory derangement. It is caused by a defect in a specific cell channel that manages traffic of specific molecules into and out of the cell. I have paid enormous attention to that and kind of ignored the hand-wavy and apparently incorrect mental models popular in the medical literature. For example, the official explanation on the CF Foundation website is that people with CF are drowning in an excess of mucus. I found one study that says we produce too little mucus, not too much. This fits with my firsthand experience, it more logically fits with the fact that mucus is a protective coating that helps keep out germs and it fits with the extremely well known and well established fact that women with CF suffer vaginal dryness that often seriously interferes with their sex lives. I think we cough up phlegm, not mucus -- ie infection -- and if you improve mucus production, you reduce infection and see less phlegm. I have seen that hypothesis work effectively for me and my oldest son who has the same diagnosis I have. I have explained it to one woman with CF who was out of time and dying and tracked me down after I left all CF lists and took down my health site. She is gradually getting healthier. So that is a very long way of saying that a) I have no idea what you mean by that phrase and b) the odds are high that you and I have completely different mental models for what is going on with CF.

hga 11y ago
Let me state that I haven't studied CF specifically at all, I'm going from what I just read in Wikipedia and my general biology education. It is caused by a defect in a specific cell channel that manages traffic of specific molecules into and out of the cell. Per Wikipedia: "It is caused by the presence of mutations in both copies of the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR)." Per the article on CFTR: Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates that is encoded by the CFTR gene. CFTR is an ABC transporter-class ion channel that codes for a protein that conducts chloride and thiocyanate ions across epithelial cell membranes. More detail: CFTR functions as an ATP-gated anion channel, increasing the conductance for certain anions (e.g. Cl−) to flow down their electrochemical gradient. ATP-driven conformational changes in CFTR open and close a gate to allow transmembrane flow of anions down their electrochemical gradient. This in contrast to other ABC proteins, in which ATP-driven conformational changes fuel uphill substrate transport across cellular membranes. Essentially, CFTR is an ion channel that evolved as a 'broken' ABC transporter that leaks when in open conformation. The CFTR is found in the epithelial cells of many organs including the lung, liver, pancreas, digestive tract, reproductive tract, and skin. Normally, the protein moves chloride and thiocyanate ions (with a negative charge) out of an epithelial cell to the covering mucus. Positively charged sodium ions follow passively, increasing the total electrolyte concentration in the mucus, resulting in the movement of water out of cell by osmosis. So, based on ATP getting to it, it allows movement (passive transport) of a set of ions and H2O in and out of cells. I assume there's some regulatory function that mediates the opening and closing of it; the CF mutations interfere with its function one way or another (e.g. one class is thought to result in the CFTR degrading quickly, don't know if it functions normally while in place). So while we're mostly focused on the consequences of these ions and water not getting out of the cell and deranging the production of proper mucus, it could also result in metabolic derangement inside these cells. Per https://www.cff.org/Living-with-CF/Cystic-Fibrosis-Related-Diabetes/ https://www.cff.org/Living-with-CF/Cystic-Fibrosis-Related-D... there's a Type 1 style due to direct pancreas damage interfering with production of insulin, but also a Type 2 style interfering with insulin response. The latter is the sort of thing I'm getting at, I'd want to understand how it works before extrapolating from CF populations to the general one. As the article says, "Unlike people with type 1 or type 2 diabetes, people with CFRD need the same high-calorie CF diet they would normally eat in order to gain weight and build muscle. A healthy diet means eating a variety of foods that are high in protein, fat and salt. The only difference is that people with CFRD need to track or count the foods that affect their blood sugar levels the most." So your eating plenty of fat without apparent harm might or might not be significant for the general population and "normal" Type 2 Diabetes (and I don't know if there's only one form/cause of it).
- Mz 11y ago
  I am a former homemaker, military wife and homeschooling mom who just didn't want to die a slow torturous death. While I do have about six years of college, some of it the equivalent of graduate work, I have limited formal study in biology. So I likely brought mental models from other realms where I have training. I do have a technical certificate that makes me a "Certified Life and Health Insurance Specialist" (or did at one time) and my former employer paid for that. It was part of training for my job where I reviewed accident claims. So I read medical records as part of my job for over five years. Although I was an accident specialist, I sometimes read records on patients with diabetes because of the tendency for people with diabetes to wind up needing a foot amputation. It was not uncommon for them to try to get that paid as an accident claim based on having hit the foot in question against something prior to the amputation. This sometimes had to be reviewed by a former surgeon to make the final decision as to whether we would pay the claim -- whether the amputation was necessitated by trauma or due to advanced deterioration from diabetes. Still, I am at a serious disadvantage in trying to talk about ion channels and what not in terms that a biologist would typically use. I did not know this: Essentially, CFTR is an ion channel that evolved as a 'broken' ABC transporter that leaks when in open conformation. That is interesting to me. CF is basically a salt-wasting condition. There are various forms of defect in the CFTR, but knowing that it basically leaks may explain why it is basically a salt wasting condition. (e.g. one class is thought to result in the CFTR degrading quickly, don't know if it functions normally while in place). If you are interested, I can share my research notes where I spent some time digging up information. I was taking a particular supplement at the time and if I missed a single dose, I drastically and promptly deteriorated. So I was looking to understand why that might be. In the process of digging around, I found that most genetic disorders boil down to being a defect in a particular protein. The CFTR channel is a protein that gets folded a particular way and inserted into the cell membrane in order to handle trafficking into and out of the cell of specific ions. So one of the things I found was that there are two conditions that cause higher misfolds of proteins within the cell: Derangement of PH level and derangement of salt level. You see both of these things happening with CF. It is well established that people with CF gradually become increasingly too acid. This is almost never treated. It is not treated as medically significant, even though if you have diabetes and get sudden onset acidosis, they hospitalize you promptly because you can be dead within 72 hours if they can't reverse it. So they know acidosis is deadly. They know CF is deadly. They know CF promotes gradual onset acidosis. No one sees this as related. I decided it must be related and reversing the acidity of my tissues was a cornerstone of my approach. Initially, I took about $300/month worth of supplements. I thought I would always need to do that. It was a daily battle to try to keep symptoms under control. I gradually became less symptomatic. I stabilized. So I have concluded that there is a vicious positive feedback loop where the more acid you get, the more you see protein misfolds and the more you see protein misfolds, the more acid you get. I believe this is why it is a degenerative, progressive condition. And if you can accommodate the defect in the cell membrane, which is both a bottleneck on some things and an open flood gate on others at the same time, if you can find a way around that, you can stop and reverse the process. Presumably this will work differently depending on the specific defect in the CFTR. There are variations of CF that are the equivalent of albinism in terms of simply not producing a CFTR channel to begin with. I imagine that will be much more resistant to management via the process I use. There are a lot of other things in the back of my mind that are relevant to this discussion, but I am somewhat pressed for time and I am not sure I could make clear what the relevance is. I do not "eat plenty of fat without apparent harm." I got very picky about WHAT I eat and I believe the high levels of specific things that I ate for a time amounts to redressing a serious and lifelong deficit. I do not count calories or anything like that. I pay close attention to chemical makeup of foods and how that interacts with my condition. But most people with CF are prescribed a high salt, high fat, high calorie diet. In practice, this means they are actively encouraged by medical professionals to eat a junk food diet. I went the other way. I pay very close attention to the quality of my food, not the quantity. I went looking for good quality fats and salts and other foods. I think the current practice of prescribing a junk food diet because it is high in fat and salt without caring that it is low in quality is part of what is killing people with CF. I don't know if that does anything to cast light on the question of fats and diabetes per se. I don't think fats per se are terribly important to the process behind diabetes. I think acidosis and infection are likely more related and you see both of those at high rates in people with CF. There are also studies that clearly link inflammation and diabetes. As I said in the comment that started this subthread, I believe that likely points to infection as an underlying cause of diabetes. Addendum: I should add that as I have gotten healthier, my appetite has shrunk. I eat a great deal less than I used to eat. Redressing the lifelong deficits dramatically reduced my need for a very high calorie diet. I probably still eat a bit more than average, but I eat a lot less than I used to.