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Post by agedhippie on Feb 7, 2017 20:25:52 GMT -5
... Further it could be said, so my choices are to take out my kidneys with metformin. I ask you to treat my insulin resistance with insulin and I choose Afrezza. ... Being picky, but insulin does not treat insulin resistance. If anything insulin makes insulin resistance worse because the excess of insulin cause the receptors to down-regulate. The benefit of insulin is that you can keep raising the dose to the point where you get the effect you are after despite the insulin resistance - although you are going to be taking a lot of insulin to do that.
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Post by Deleted on Feb 8, 2017 2:16:23 GMT -5
agedhippie Question regarding 'insulin resistance': does it exist or is it something conjured up to explain decreased pancreatic insulin output?
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Post by peppy on Feb 8, 2017 7:51:19 GMT -5
... Further it could be said, so my choices are to take out my kidneys with metformin. I ask you to treat my insulin resistance with insulin and I choose Afrezza. ... Being picky, but insulin does not treat insulin resistance. If anything insulin makes insulin resistance worse because the excess of insulin cause the receptors to down-regulate. The benefit of insulin is that you can keep raising the dose to the point where you get the effect you are after despite the insulin resistance - although you are going to be taking a lot of insulin to do that. Being picky, I know you are a type 1, very experienced with insulin. My understanding is that you use Fast acting insulin.
Being picky: a study. I know you can out study me. Put up the study please.
www.diabetesincontrol.com/early-short-term-intensive-insulin-causes-the-remission-of-type-2-diabetes/
Excerpts:
In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2-4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to one year in some patients.
Data was evaluated from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duration) underwent 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks (n=25). Participants underwent an oral glucose tolerance test every 12 weeks, enabling serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM.
For the study design, data from the placebo arm of the double-blind randomized controlled trial in which 25 patients within 7 y of T2D diagnosis received 4 weeks of intensive basal/bolus insulin therapy followed by placebo for 48 wk. An oral glucose tolerance test (OGTT) every 12 weeks used to assess insulin sensitivity and beta-cell function. Then diabetes remission was defined as HbA1c <6.5% with no T2D medications.
The results showed that at 48 weeks after stopping intensive insulin, 14 participants (56%) were in diabetes remission. At baseline, the remission group had shorter duration of diabetes (1.2 vs 2.6 y; p=.03), lower A1c (6.2% vs 7.1%, p=.006), and better β-cell function.
The 2 groups did not differ in clinical characteristics such as age, gender, ethnicity, pre-study diabetes treatment, body mass index, waist circumference, blood pressure, liver enzymes, or insulin sensitivity.
Then, in logistic regression analyses, shorter duration of diabetes supplanted baseline A1c (p=.24) and β-cell function (p=.19) as an independent predictor of remission at 48 weeks (OR, 0.22; 95% CI 0.05-0.92; p=.04)
At 48 weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48 weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline β-cell function
The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2 years after diagnosis. And reversing or delaying type 2 diabetes may help prevent morbidity and reduce healthcare costs.
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Post by sayhey24 on Feb 8, 2017 8:03:32 GMT -5
Being picky, but insulin does not treat insulin resistance. If anything insulin makes insulin resistance worse because the excess of insulin cause the receptors to down-regulate. The benefit of insulin is that you can keep raising the dose to the point where you get the effect you are after despite the insulin resistance - although you are going to be taking a lot of insulin to do that. Being picky, I know you are a type 1, very experienced with insulin. My understanding is that you use Fast acting insulin.
Being picky: a study. I know you can out study me. Put up the study please.
www.diabetesincontrol.com/early-short-term-intensive-insulin-causes-the-remission-of-type-2-diabetes/
Excerpts:
In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2-4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to one year in some patients.
Data was evaluated from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duration) underwent 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks (n=25). Participants underwent an oral glucose tolerance test every 12 weeks, enabling serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM.
For the study design, data from the placebo arm of the double-blind randomized controlled trial in which 25 patients within 7 y of T2D diagnosis received 4 weeks of intensive basal/bolus insulin therapy followed by placebo for 48 wk. An oral glucose tolerance test (OGTT) every 12 weeks used to assess insulin sensitivity and beta-cell function. Then diabetes remission was defined as HbA1c <6.5% with no T2D medications.
The results showed that at 48 weeks after stopping intensive insulin, 14 participants (56%) were in diabetes remission. At baseline, the remission group had shorter duration of diabetes (1.2 vs 2.6 y; p=.03), lower A1c (6.2% vs 7.1%, p=.006), and better β-cell function.
The 2 groups did not differ in clinical characteristics such as age, gender, ethnicity, pre-study diabetes treatment, body mass index, waist circumference, blood pressure, liver enzymes, or insulin sensitivity.
Then, in logistic regression analyses, shorter duration of diabetes supplanted baseline A1c (p=.24) and β-cell function (p=.19) as an independent predictor of remission at 48 weeks (OR, 0.22; 95% CI 0.05-0.92; p=.04)
At 48 weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48 weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline β-cell function
The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2 years after diagnosis. And reversing or delaying type 2 diabetes may help prevent morbidity and reduce healthcare costs.
Peppy - the comment about insulin causing insulin resistance is interesting. I would like to see that study too. Insulin resistance is primarily caused by high BG. The non-diabetic after meal spike is about 125. For the diabetic who knows? 200, 300+. The Australian guy demonstrates insulin resistance when he does his challenge and blunts his insulin rise properly with afrezza and does it again and lets his BG rise really high and then shows much more afrezza is needed to bring his BG down. A big problem with current Analogs is they can't blunk the rise so the PWD is always in an resistant mode. With a normal pancreas or afrezza its a new paradigm. Bring down the BG and so does the resistance. Give the beta cells a chance to regenerate - unlike metformin can, and you see the results in your studies.
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Post by sayhey24 on Feb 8, 2017 8:09:32 GMT -5
peppy I don't know how T2s are supposed to get around doctor prescribing metformin. There are doctors even if you are on Metformin prescribing Afrezza for corrections. The sad truth is this is true. If they were dosing afrezza properly they would quickly find metformin is not making this better. It would be nice if Matt got afrezza to be available over the counter like the other human insulins so no prescription was needed. I think the only thing stopping them is the spirometry test. If they could submit for a correction product I see no need for the spirometry for the occasional user. They really should be looking into this.
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Post by agedhippie on Feb 8, 2017 10:09:15 GMT -5
agedhippie Question regarding 'insulin resistance': does it exist or is it something conjured up to explain decreased pancreatic insulin output? It's a good question. Insulin resistance definitely exists but is not required for Type 2 contrary to what you might hear. The thing that is always present is decreased insulin output. Currently the theory is that Type 2 diabetics have a genetic flaws which means that they miscalculate the number of beta cells they should be making. Your body naturally kills and replaces cells however it never creates quite enough. Over time this gap reaches the point where you become diabetic. This gets complicated by weight gain - as you gain weight you become more insulin resistant but your body adapts to this by building more beta cells and it goes unnoticed. A Type 2 fails to build out enough though and the gap grows... The mismatch can be addressed by losing weight if you are overweight which reduces insulin resistance to the point where you are again living within your insulin limits. Likewise a low carb diet will achieve the same. The medical profession like the weight angle because it provides a lever to make people lose weight and eat better. The reality is that even most morbidly obese people will never become diabetic. The catch with all this is that Type 2 diabetes is not one disease. There are well over 100 genes involved and it is combinations that result in diabetes so there is no one cure - I actually think Type 1 is easier to cure than Type 2 because of this. An example would be a gene that makes you tend to store fat combined with a gene that reduces the response to weight gain.
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Post by sayhey24 on Feb 8, 2017 10:26:02 GMT -5
agedhippie Question regarding 'insulin resistance': does it exist or is it something conjured up to explain decreased pancreatic insulin output? It's a good question. Insulin resistance definitely exists but is not required for Type 2 contrary to what you might hear. The thing that is always present is decreased insulin output. Currently the theory is that Type 2 diabetics have a genetic flaws which means that they miscalculate the number of beta cells they should be making. Your body naturally kills and replaces cells however it never creates quite enough. Over time this gap reaches the point where you become diabetic. This gets complicated by weight gain - as you gain weight you become more insulin resistant but your body adapts to this by building more beta cells and it goes unnoticed. A Type 2 fails to build out enough though and the gap grows... The mismatch can be addressed by losing weight if you are overweight which reduces insulin resistance to the point where you are again living within your insulin limits. Likewise a low carb diet will achieve the same. The medical profession like the weight angle because it provides a lever to make people lose weight and eat better. The reality is that even most morbidly obese people will never become diabetic. The catch with all this is that Type 2 diabetes is not one disease. There are well over 100 genes involved and it is combinations that result in diabetes so there is no one cure - I actually think Type 1 is easier to cure than Type 2 because of this. An example would be a gene that makes you tend to store fat combined with a gene that reduces the response to weight gain. It seems you have just constructed the justification as to why metformin is not a good option when afrezza is available. While I believe everything you said is correct it would seem logical to supplement the shortfall in the insulin being naturally produced by the exact same insulin which afrezza provides if the issue is not enough natural insulin. Now, if beta cells can regenerate as these studies say T2s I would say would be easier to cure in some situations by providing afrezza as soon as possible.
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Post by agedhippie on Feb 8, 2017 10:27:56 GMT -5
Being picky, but insulin does not treat insulin resistance. If anything insulin makes insulin resistance worse because the excess of insulin cause the receptors to down-regulate. The benefit of insulin is that you can keep raising the dose to the point where you get the effect you are after despite the insulin resistance - although you are going to be taking a lot of insulin to do that. Being picky, I know you are a type 1, very experienced with insulin. My understanding is that you use Fast acting insulin.
Being picky: a study. I know you can out study me. Put up the study please. I don't think there is a study because it's basic. If you swap the body with stimuli it down-grades the response to that stimuli and the same is true of insulin. The study you cite is probably an aspect of this - it's about extending the honeymoon period. As I understand it the mechanism is that the patient runs constantly high levels which stress the beta cells (glucotoxicity) and causes them to initially shut down and then die. As some cells start to shut down others have to work harder and you have a vicious circle. So why does early intensive insulin work? I believe that it is because the insulin breaks the cycle by relieving the stress. The best case of this is Flatbush or other ketosis prone Type 2 variants. They are extreme cases but because of that the mechanism is clearer. What happens is that the beta cells start shutting down and there is an absolute insulin deficiency (as opposed to a relative deficiency where there is lots of insulin but resistance blocks the uptake) and the fix is to put the patient on insulin. This relieves the stress and after about 6 weeks the beta cells are back on line and you can stop the insulin. That looks like you can cure Type 2 with early insulin but I expect over the longer term that will turn out not to be the case because the underlying cause, shrinking insulin secretion, still exists. What I believe they are seeing is remission rather than cure which is why even in the one year time frame you see cases of diabetes returning. Newcastle University, who I think does work in this area as well, achieves the same effects with starvation diet - I suspect they moved to insulin because you don't need to hospitalize the patient for the duration and the consumer resistance is lower!
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Post by peppy on Feb 8, 2017 10:35:57 GMT -5
agedhippie Question regarding 'insulin resistance': does it exist or is it something conjured up to explain decreased pancreatic insulin output? It's a good question. Insulin resistance definitely exists but is not required for Type 2 contrary to what you might hear. The thing that is always present is decreased insulin output. Currently the theory is that Type 2 diabetics have a genetic flaws which means that they miscalculate the number of beta cells they should be making. Your body naturally kills and replaces cells however it never creates quite enough. Over time this gap reaches the point where you become diabetic. This gets complicated by weight gain - as you gain weight you become more insulin resistant but your body adapts to this by building more beta cells and it goes unnoticed. A Type 2 fails to build out enough though and the gap grows... The mismatch can be addressed by losing weight if you are overweight which reduces insulin resistance to the point where you are again living within your insulin limits. Likewise a low carb diet will achieve the same. The medical profession like the weight angle because it provides a lever to make people lose weight and eat better. The reality is that even most morbidly obese people will never become diabetic. The catch with all this is that Type 2 diabetes is not one disease. There are well over 100 genes involved and it is combinations that result in diabetes so there is no one cure - I actually think Type 1 is easier to cure than Type 2 because of this. An example would be a gene that makes you tend to store fat combined with a gene that reduces the response to weight gain. Quote: Currently the theory is that Type 2 diabetics have a genetic flaws
A look at the four proteins that make up DNA. The gene. in the nucleus of every cell in your body. (Bruce Lipton says the nucleus is not the brains of the cell he says the nucleus is the gonad. Different than we have been taught. He says the brains of the cell is the cell membrane. www.youtube.com/watch?v=UmEkoyvCFPI )
Anyway the theory is their is something wrong with your ..... Adenine? Thymine? Guanine? or Cytosine? in the nucleaus in some of pancreatic beta cells? Not all?
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Post by agedhippie on Feb 8, 2017 10:39:25 GMT -5
It's a good question. Insulin resistance definitely exists but is not required for Type 2 contrary to what you might hear. The thing that is always present is decreased insulin output. Currently the theory is that Type 2 diabetics have a genetic flaws which means that they miscalculate the number of beta cells they should be making. Your body naturally kills and replaces cells however it never creates quite enough. Over time this gap reaches the point where you become diabetic. This gets complicated by weight gain - as you gain weight you become more insulin resistant but your body adapts to this by building more beta cells and it goes unnoticed. A Type 2 fails to build out enough though and the gap grows... The mismatch can be addressed by losing weight if you are overweight which reduces insulin resistance to the point where you are again living within your insulin limits. Likewise a low carb diet will achieve the same. The medical profession like the weight angle because it provides a lever to make people lose weight and eat better. The reality is that even most morbidly obese people will never become diabetic. The catch with all this is that Type 2 diabetes is not one disease. There are well over 100 genes involved and it is combinations that result in diabetes so there is no one cure - I actually think Type 1 is easier to cure than Type 2 because of this. An example would be a gene that makes you tend to store fat combined with a gene that reduces the response to weight gain. It seems you have just constructed the justification as to why metformin is not a good option when afrezza is available. While I believe everything you said is correct it would seem logical to supplement the shortfall in the insulin being naturally produced by the exact same insulin which afrezza provides if the issue is not enough natural insulin. Now, if beta cells can regenerate as these studies say T2s I would say would be easier to cure in some situations by providing afrezza as soon as possible. Regeneration never happens (this is a topic dear to my heart for obvious reasons), what you are seeing is 'stunned' cells coming around but dead cells remain dead. Regenerating beta cells is a fascinating research subject but not even at the human test stage. In the early stages metformin performs the same role as insulin in this respect. It lowers the insulin resistance which reduces glucose levels and allows the cells to recover as with insulin. There is more than one way to skin a cat (with apologies to liane and other cat lovers). Once you hit 2250mg of Metformin that is as far as you can go but there is no upper limit on insulin. Early insulin is definitely the most effective treatment but it will never take off because of the danger of insulin, the complexity of dosing, and a likely low compliance.
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Post by peppy on Feb 8, 2017 11:03:37 GMT -5
It seems you have just constructed the justification as to why metformin is not a good option when afrezza is available. While I believe everything you said is correct it would seem logical to supplement the shortfall in the insulin being naturally produced by the exact same insulin which afrezza provides if the issue is not enough natural insulin. Now, if beta cells can regenerate as these studies say T2s I would say would be easier to cure in some situations by providing afrezza as soon as possible. Regeneration never happens (this is a topic dear to my heart for obvious reasons), what you are seeing is 'stunned' cells coming around but dead cells remain dead. Regenerating beta cells is a fascinating research subject but not even at the human test stage. In the early stages metformin performs the same role as insulin in this respect. It lowers the insulin resistance which reduces glucose levels and allows the cells to recover as with insulin. There is more than one way to skin a cat (with apologies to liane and other cat lovers). Once you hit 2250mg of Metformin that is as far as you can go but there is no upper limit on insulin. Early insulin is definitely the most effective treatment but it will never take off because of the danger of insulin, the complexity of dosing, and a likely low compliance.Quote: Early insulin is definitely the most effective treatment but it will never take off because of the danger of insulin, the complexity of dosing, and a likely low compliance. Reply: There is the battle? Afrezza, takes away the danger, complexity and perhaps low compliance. Afrezza, technosphere insulin the insulin you can take. www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf mnkd.proboards.com/thread/7230/tcoyd
Insulin is on the step program. www.screencast.com/t/nOwBa4aaA
Thinking would need to change.
Conceivably methformin would not be needed with afrezza. The both suppress hepatic gluconeogenesis.
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Post by sayhey24 on Feb 8, 2017 15:58:58 GMT -5
Regeneration never happens (this is a topic dear to my heart for obvious reasons), what you are seeing is 'stunned' cells coming around but dead cells remain dead. Regenerating beta cells is a fascinating research subject but not even at the human test stage. In the early stages metformin performs the same role as insulin in this respect. It lowers the insulin resistance which reduces glucose levels and allows the cells to recover as with insulin. There is more than one way to skin a cat (with apologies to liane and other cat lovers). Once you hit 2250mg of Metformin that is as far as you can go but there is no upper limit on insulin. Early insulin is definitely the most effective treatment but it will never take off because of the danger of insulin, the complexity of dosing, and a likely low compliance.Quote: Early insulin is definitely the most effective treatment but it will never take off because of the danger of insulin, the complexity of dosing, and a likely low compliance. Reply: There is the battle? Afrezza, takes away the danger, complexity and perhaps low compliance. Afrezza, technosphere insulin the insulin you can take. www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf mnkd.proboards.com/thread/7230/tcoyd
Insulin is on the step program. www.screencast.com/t/nOwBa4aaA
Thinking would need to change.
Conceivably methformin would not be needed with afrezza. The both suppress hepatic gluconeogenesis.
"Thinking would need to change" - there is the big nut for MNKD. If the goal was to stop the progression, the beta cells need a rest instead of being asked to work harder and produce more insulin by metformin. Now that impacts the step program and pretty much all current protocols. The big question is how does little MNKD make that happen. Here we have a PWD with an 8.1 A1c and they are told no to afrezza just double the metformin. Its pretty sad. I sure hope Matt and Mike have more to the plan than selling door to door. I think one part of the plan would be to have afrezza sold like other human insulin and not require a prescription.
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Post by agedhippie on Feb 8, 2017 16:00:15 GMT -5
Regeneration never happens (this is a topic dear to my heart for obvious reasons), what you are seeing is 'stunned' cells coming around but dead cells remain dead. Regenerating beta cells is a fascinating research subject but not even at the human test stage. In the early stages metformin performs the same role as insulin in this respect. It lowers the insulin resistance which reduces glucose levels and allows the cells to recover as with insulin. There is more than one way to skin a cat (with apologies to liane and other cat lovers). Once you hit 2250mg of Metformin that is as far as you can go but there is no upper limit on insulin. Early insulin is definitely the most effective treatment but it will never take off because of the danger of insulin, the complexity of dosing, and a likely low compliance.Quote: Early insulin is definitely the most effective treatment but it will never take off because of the danger of insulin, the complexity of dosing, and a likely low compliance. Reply: There is the battle? Afrezza, takes away the danger, complexity and perhaps low compliance. Afrezza, technosphere insulin the insulin you can take. www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf mnkd.proboards.com/thread/7230/tcoyd
Insulin is on the step program. www.screencast.com/t/nOwBa4aaA
Thinking would need to change.
Conceivably methformin would not be needed with afrezza. The both suppress hepatic gluconeogenesis.
Afrezza takes away dose size as an issue (or rather it dramatically reduces it) however it requires multiple doses during the day with follow-up testing and potentially a correction dose for each meal. Metformin is one pill a day. That's going to be the compliance issue. I say this as an insulin user because that is also how you are meant to use RAA, but I don't know anyone who does the follow-up test and dose! For Type 2 I would expect an endo to leave the patient on metformin even if they prescribed Afrezza. Metformin reduces the amount of insulin required by reducing insulin resistance. That is a huge issue with Type 2 where you can be taking a lot of insulin - 1u per 1g of carbs is not unusual so you can easily be looking at 50u per meal.
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Post by agedhippie on Feb 8, 2017 16:05:04 GMT -5
"Thinking would need to change" - there is the big nut for MNKD. If the goal was to stop the progression, the beta cells need a rest instead of being asked to work harder and produce more insulin by metformin. You are confusing sulfonylureas, like glipizide, with metformin. Metformin does not have that action.
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Post by Deleted on Feb 8, 2017 19:35:01 GMT -5
agedhippie "For Type 2 I would expect an endo to leave the patient on metformin even if they prescribed Afrezza. Metformin reduces the amount of insulin required by reducing insulin resistance." Are there studies that back your claim?
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