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Post by agedhippie on Aug 21, 2018 8:02:24 GMT -5
... The endo stated clearly that once the pancreas beta cells died they will not be replaced. Apparently my education regarding early intervention with Afrezza given my A1C will be a very personal study. I personally buy into the concept that the disease can be reversed is the beta cells are given a respite in the pancreas.... He is correct, dead beta cells do not regenerate, but you are also right in that there should be a recovery. Beta cells don't go from functioning to dead, they have an intermediate state which is more like stunned - they are not working, but they are not dead. If you can get to them when they are in that state you can relieve the high glucose level that is stunning them then they will revive and become functional again. An extreme example of this is Flatbush diabetes, a Type 2 variant, where you get a catastrophic collapse of the beta cells (they all stop working), but there is an almost full recovery after a couple of months on insulin to the extent that the person becomes non-diabetic.
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Post by morgieporgie on Aug 21, 2018 8:04:06 GMT -5
... The endo stated clearly that once the pancreas beta cells died they will not be replaced. Apparently my education regarding early intervention with Afrezza given my A1C will be a very personal study. I personally buy into the concept that the disease can be reversed is the beta cells are given a respite in the pancreas.... He is correct, dead beta cells do not regenerate, but you are also right in that there should be a recovery. Beta cells don't go from functioning to dead, they have an intermediate state which is more like stunned - they are not working, but they are not dead. If you can get to them when they are in that state you can relieve the high glucose level that is stunning them then they will revive and become functional again. An extreme example of this is Flatbush diabetes, a Type 2 variant, where you get a catastrophic collapse of the beta cells (they all stop working), but there is an almost full recovery after a couple of months on insulin to the extent that the person becomes non-diabetic. Hibernation, as it were..
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Post by agedhippie on Aug 21, 2018 8:19:06 GMT -5
Have a look at the Accelerator Hypothesis is you haven't already seen it. The idea is that Type 1 and 2 are basically the same disease with speed of onset the main difference. It's getting a reasonable amount of traction in the endo community. I am not a believer in the fat hypothesis. There are plenty of obese people who are not diabetic. I know a number of T1s who were never fat as children.
The healthy body has a way of adapting and in the case of being fat the healthy body will grow more beta cells and make more insulin. This has been know for a very long time through autopsy. I am a little surprised the fat hypothesis is gaining traction. I am not surprised they are saying the root cause for T1 and T2 is the same.
Diabetes is simply defined as the body not making enough insulin for the body's needs. If your body needs more it should make more and the healthy body will. As more and more T2s get tested they jump for joy when antibodies are found and they can now say they are LADA.
Why are they happy? Well T2 has a social stigma of being fat and lazy but if its auto-immune or maybe a virus thats a whole new ball game. I bet if we tested all T2s soon enough nearly all would have traceable antibodies. A virus would also explain T2 hot spot clusters if the virus can be transmitted between people. Shamokin PA is one such cluster. Its a some what closed community in the PA anthracite region. The current diabetes rate is 16% but Geisinger says 22k are prediabetic, yep the body not making enough insulin for its needs. The estimate total diabetic plus prediabetic is about 50% of the population. www.geisinger.org/freshfoodfarmacy/our-purpose/where-did-we-start The Accelerator Hypothesis has nothing to do with weight in the way you are thinking of it. It suggests that the immune system is compromised in a high glucose environment and produces beta cell immunogens. People who are genetically susceptible will suffer accelerated beta cell die off (the mechanism is auto-immune attack combined with transcription error). The hypothesis says that the difference between Type 1 and 2 is essentially one of speed. It's a difficult hypothesis to prove because non-diabetics have beta cell anti bodies naturally (most commonly GAD65). There are lots of theories on what causes diabetes but in the end nobody know for sure. However diabetes is not cause by weight since if it was it would be a lot more prevalent than it is.
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Post by peppy on Aug 21, 2018 8:35:49 GMT -5
I am not a believer in the fat hypothesis. There are plenty of obese people who are not diabetic. I know a number of T1s who were never fat as children.
The healthy body has a way of adapting and in the case of being fat the healthy body will grow more beta cells and make more insulin. This has been know for a very long time through autopsy. I am a little surprised the fat hypothesis is gaining traction. I am not surprised they are saying the root cause for T1 and T2 is the same.
Diabetes is simply defined as the body not making enough insulin for the body's needs. If your body needs more it should make more and the healthy body will. As more and more T2s get tested they jump for joy when antibodies are found and they can now say they are LADA.
Why are they happy? Well T2 has a social stigma of being fat and lazy but if its auto-immune or maybe a virus thats a whole new ball game. I bet if we tested all T2s soon enough nearly all would have traceable antibodies. A virus would also explain T2 hot spot clusters if the virus can be transmitted between people. Shamokin PA is one such cluster. Its a some what closed community in the PA anthracite region. The current diabetes rate is 16% but Geisinger says 22k are prediabetic, yep the body not making enough insulin for its needs. The estimate total diabetic plus prediabetic is about 50% of the population. www.geisinger.org/freshfoodfarmacy/our-purpose/where-did-we-start The Accelerator Hypothesis has nothing to do with weight in the way you are thinking of it. It suggests that the immune system is compromised in a high glucose environment and produces beta cell immunogens. People who are genetically susceptible will suffer accelerated beta cell die off (the mechanism is auto-immune attack combined with transcription error). The hypothesis says that the difference between Type 1 and 2 is essentially one of speed. It's a difficult hypothesis to prove because non-diabetics have beta cell anti bodies naturally (most commonly GAD65). There are lots of theories on what causes diabetes but in the end nobody know for sure. However diabetes is not cause by weight since if it was it would be a lot more prevalent than it is. Sayhey, it is not like you to get confused. Type one, no fat hypothesis. Type two = enters the fat hypothesis. Before 1960's, when the fats used were mostly lards, who was fat? Aunt Bee and Jackie Gleason. Enter fats, processed fats into our food, type two extravaganza. Some times people it comes down to observation. I remember when medicine included observation. As I pointed out yesterday, high on the list of interventions with type two's what we used to call stomach stapling. You know these people have non diabetic numbers a few weeks after the procedure. We have not become stupid have we? What changed, hmmmm. Did the surgery magically make some virus disappear? Additionally, I have a whole thread in off topic showing the results of a no fat diet. Type one, we know at times it runs in families. Let's not take what we know and waste it. I have never known a fat type one. Mary Tyler Moore, Molly, Laura K; skinny as can be. we do have eye balls people.
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Post by morgieporgie on Aug 21, 2018 11:21:13 GMT -5
The Accelerator Hypothesis has nothing to do with weight in the way you are thinking of it. It suggests that the immune system is compromised in a high glucose environment and produces beta cell immunogens. People who are genetically susceptible will suffer accelerated beta cell die off (the mechanism is auto-immune attack combined with transcription error). The hypothesis says that the difference between Type 1 and 2 is essentially one of speed. It's a difficult hypothesis to prove because non-diabetics have beta cell anti bodies naturally (most commonly GAD65). There are lots of theories on what causes diabetes but in the end nobody know for sure. However diabetes is not cause by weight since if it was it would be a lot more prevalent than it is. Sayhey, it is not like you to get confused. Type one, no fat hypothesis. Type two = enters the fat hypothesis. Before 1960's, when the fats used were mostly lards, who was fat? Aunt Bee and Jackie Gleason. Enter fats, processed fats into our food, type two extravaganza. Some times people it comes down to observation. I remember when medicine included observation. As I pointed out yesterday, high on the list of interventions with type two's what we used to call stomach stapling. You know these people have non diabetic numbers a few weeks after the procedure. We have not become stupid have we? What changed, hmmmm. Did the surgery magically make some virus disappear? Additionally, I have a whole thread in off topic showing the results of a no fat diet. Type one, we know at times it runs in families. Let's not take what we know and waste it. I have never known a fat type one. Mary Tyler Moore, Molly, Laura K; skinny as can be. we do have eye balls people. I've known thin and heavy type ones and type two diabetics. Weight is not a factor, period. End of story.
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Post by peppy on Aug 21, 2018 11:32:45 GMT -5
Sayhey, it is not like you to get confused. Type one, no fat hypothesis. Type two = enters the fat hypothesis. Before 1960's, when the fats used were mostly lards, who was fat? Aunt Bee and Jackie Gleason. Enter fats, processed fats into our food, type two extravaganza. Some times people it comes down to observation. I remember when medicine included observation. As I pointed out yesterday, high on the list of interventions with type two's what we used to call stomach stapling. You know these people have non diabetic numbers a few weeks after the procedure. We have not become stupid have we? What changed, hmmmm. Did the surgery magically make some virus disappear? Additionally, I have a whole thread in off topic showing the results of a no fat diet. Type one, we know at times it runs in families. Let's not take what we know and waste it. I have never known a fat type one. Mary Tyler Moore, Molly, Laura K; skinny as can be. we do have eye balls people. I've known thin and heavy type ones and type two diabetics. Weight is not a factor, period. End of story. The type ones I know of are thin. When they can't burn glucose, they burn fat. ketosis. If they gain weight? They are eating plenty and plenty of fat? Insulin. Yes, I guess their are a few thin type two's. They must be eating a lot of meat and cheese, fried foods. I was listening to a video, cheese can be 70% fat. Meat, people now say protein, protein and fat. Then there is just plain fat. pass the potato chips.
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Post by sayhey24 on Aug 21, 2018 18:14:47 GMT -5
The Accelerator Hypothesis has nothing to do with weight in the way you are thinking of it. It suggests that the immune system is compromised in a high glucose environment and produces beta cell immunogens. People who are genetically susceptible will suffer accelerated beta cell die off (the mechanism is auto-immune attack combined with transcription error). The hypothesis says that the difference between Type 1 and 2 is essentially one of speed. It's a difficult hypothesis to prove because non-diabetics have beta cell anti bodies naturally (most commonly GAD65). There are lots of theories on what causes diabetes but in the end nobody know for sure. However diabetes is not cause by weight since if it was it would be a lot more prevalent than it is. Sayhey, it is not like you to get confused. Type one, no fat hypothesis. Type two = enters the fat hypothesis. Before 1960's, when the fats used were mostly lards, who was fat? Aunt Bee and Jackie Gleason. Enter fats, processed fats into our food, type two extravaganza. Some times people it comes down to observation. I remember when medicine included observation. As I pointed out yesterday, high on the list of interventions with type two's what we used to call stomach stapling. You know these people have non diabetic numbers a few weeks after the procedure. We have not become stupid have we? What changed, hmmmm. Did the surgery magically make some virus disappear? Additionally, I have a whole thread in off topic showing the results of a no fat diet. Type one, we know at times it runs in families. Let's not take what we know and waste it. I have never known a fat type one. Mary Tyler Moore, Molly, Laura K; skinny as can be. we do have eye balls people. Peppy - I live my life confused. Everyday I wake up and believe afrezza is the greatest advance in diabetes care since Banting and Best. Then I look at the stock price and weekly scripts and I go WTF another day of confusion. Although, I am feeling a bit upbeat after last Friday as I expect scripts to slowly rise until changes to the standards are made. Then I expect significant growth.
I am no expert on the accelerator hypothesis but here is how it is defined and why I refer to it as the "fat theory". I give it no weight (pun intended).
"The accelerator hypothesis is a singular, unifying concept that argues that type I and type II diabetes are the same disorder of insulin resistance ... Insulin resistance is closely related to the rise in overweight and obesity, a trend that the hypothesis deems central to the rising incidence of all diabetes ... Childhood diabetes, similarly, is diabetes presenting in childhood. The increasing incidence of both is primarily the result of lifestyle change and the rise in body weight that has resulted." www.ncbi.nlm.nih.gov/pubmed/19506563
I also have a different view on things like stomach stapling and diets like Bernstein's. What happens when you eat less or reduce carbs is you put less load on the pancreas. If you catch T2 early enough and the attack on the pancreas is not that bad, the pancreas will naturally recover to some degree. We know healthy people can grow extra huge clumps of beta cells so there is no reason not to think a recovering T2 can't regenerate new beta cells. The studies say about 50% of early T2s will stop progression through diet and that's without afrezza. Adding the afrezza could be a game changer and provide significant improvement over the 50%. Stomach stapling does not stop T2, eating less and reducing the load on the damaged pancreas does.
The same with the Bernstein diet. Restricting the carbs takes the load off by reducing the post meal spike. T2s first lose a robust release and the ability to deal with the spike. The carb restricted diet better fits the T2 release profile. However in both cases "stapling and carb restriction" it would be better to add the afrezza. A good example is Jenny Ruhl. If you have read her books like "Blood Sugar 101" she is a big proponent of reduced carb diets and was able to control her numbers in the "5s" for years. I recently saw she was no longer seeing the control she once was and was back on meds. IMO, if she had been taking the afrezza all those years she could have had a more relaxed diet, maybe better control and would have taken more of a load off her pancreas which may have allowed better initial recovery.
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Post by tomtabb on Aug 22, 2018 0:57:32 GMT -5
For decades, studies have conclusively demonstrated that early intensive insulin therapy administered to newly-diagnosed Type 2 diabetes patients can result in remission of the disease. One meta-analysis report, conducted more than a decade ago and involving over 3,000 patients, demonstrated results of nearly 50% of patients who underwent early intensive insulin therapy achieving drug-free remission for up to two years. Clinical data has also demonstrated that early intensive insulin therapy has resulted in a significant reduction of insulin resistance, a common precursor of Type 2 diabetes.
In a clinical study by Model Clinical Research LLC, Baltimore MD, in collaboration with MannKind Corporation, investigators are seeking to demonstrate that the addition of mealtime Afrezza (aka Technosphere Insulin) can significantly lower HbA1c within 3 months in uncontrolled type 2 diabetes patients initially having HbA1c of 7.5 or higher, despite at least 6 months of prior therapy with diabetes medications.
The trial protocol instructs patients to follow a weekly Treat-to-Target BG Testing Regimen and make Afrezza dose changes according to an Afrezza Titration Algorithm.
In spite of growing clinical evidence that early initiation of insulin therapy has repeatedly demonstrated significant results, including complete remission of the disease, the American Diabetes Association still has insulin therapy as the last step in its Diabetes Standards of Care.
In early stages of Type 2 diabetes, insulin resistance and other factors often causes the pancreas to become over-stressed and unable to keep up with the body's demand for insulin. In layman's terms, the beta cells in the pancreas begin to wear out. Critics of the ADA and the AACE are becoming increasingly vocal in their dissent against the recommendation within the ADA's Standard of Care which advocates early treatment of diabetes with oral medications, such as Metformin, stating that Metformin does nothing to assist the pancreas or improve its ability to produce sufficient levels of insulin. Early intensive insulin therapy, on the other hand, can provide a respite to the over-stressed pancreas by providing much-needed insulin and enabling the pancreas to recuperated and generate new insulin-producing beta cells at a rate that will meet the body's demand while, at the same time, lowering insulin resistance.
Recently, the American Diabetes Association announced changes that would enable the organization to more rapidly response to scientific discoveries for the treatment of diabetes, stating in a press release that, "Beginning with the 2018 ADA Standards of Medical Care in Diabetes, the Standards document will be a “living” document where notable updates are incorporated into the Standards, as determined appropriate by the Professional Practice Committee, noting that their decades-long practice of annually reviewing medical advances would be replaced with more frequent updates, what they described as a "living" Standards of Care, in response to important events such as "new treatments with the potential to impact patient care" and publication of new findings "that support a change to a recommendation and/or evidence level of a recommendation".
Many critics of the ADA are advocating that there is now more than sufficient clinical evidence to meet the ADA's criteria to update its Standard of Care to move short-term intensive insulin therapy to the first step in treating early diabetes. It's hard to argue with results and the incredible potential of this therapy, its puzzling why the ADA has taken so long to advocate early short-term insulin therapy as a first step in combatting this disease. I know of no other treatment that has the potential of remission of diabetes for 50% of treated patients.
Delaying this therapy may result in continuous deterioration of the pancreas to the point where it is no longer repairable and sentences the patient to a difficult life of continuously fighting diabetes. It's a fight that can be won with a 1st Round knockout. It's time for the American Diabetes Association and the American Association of Clinical Endocrinologists to recognize this important treatment and to put it in its proper place in the 2019 ADA Standards of Medical Care in Diabetes.
The clinical trial, entitled "Initiating Mealtime Ultra-Rapid Acting Insulin (Afrezza) in Uncontrolled Type 2 Diabetes Patients" is scheduled to be completed in September 2018.
Trial Link: clinicaltrials.gov/ct2/show/NCT03324776?term=mannkind&recrs=abdfg&rank=3
Am I misunderstanding the idea of "early insulin therapy"? "Early intensive insulin therapy administered to newly-diagnosed Type 2 diabetes patients..." is what I always understood as early insulin therapy. What I read in the clinicaltrials description, though, says "the investigator proposes treating patients with Afrezza who have an index HbA1c between 7.5% and 11.5% despite being treated with diabetes medications for at least 6 months." Having been on diabetes medications for at least 6 months and having failed the treatment doesn't fit into my idea of "early insulin therapy."
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Post by goyocafe on Aug 22, 2018 4:49:49 GMT -5
For decades, studies have conclusively demonstrated that early intensive insulin therapy administered to newly-diagnosed Type 2 diabetes patients can result in remission of the disease. One meta-analysis report, conducted more than a decade ago and involving over 3,000 patients, demonstrated results of nearly 50% of patients who underwent early intensive insulin therapy achieving drug-free remission for up to two years. Clinical data has also demonstrated that early intensive insulin therapy has resulted in a significant reduction of insulin resistance, a common precursor of Type 2 diabetes.
In a clinical study by Model Clinical Research LLC, Baltimore MD, in collaboration with MannKind Corporation, investigators are seeking to demonstrate that the addition of mealtime Afrezza (aka Technosphere Insulin) can significantly lower HbA1c within 3 months in uncontrolled type 2 diabetes patients initially having HbA1c of 7.5 or higher, despite at least 6 months of prior therapy with diabetes medications.
The trial protocol instructs patients to follow a weekly Treat-to-Target BG Testing Regimen and make Afrezza dose changes according to an Afrezza Titration Algorithm.
In spite of growing clinical evidence that early initiation of insulin therapy has repeatedly demonstrated significant results, including complete remission of the disease, the American Diabetes Association still has insulin therapy as the last step in its Diabetes Standards of Care.
In early stages of Type 2 diabetes, insulin resistance and other factors often causes the pancreas to become over-stressed and unable to keep up with the body's demand for insulin. In layman's terms, the beta cells in the pancreas begin to wear out. Critics of the ADA and the AACE are becoming increasingly vocal in their dissent against the recommendation within the ADA's Standard of Care which advocates early treatment of diabetes with oral medications, such as Metformin, stating that Metformin does nothing to assist the pancreas or improve its ability to produce sufficient levels of insulin. Early intensive insulin therapy, on the other hand, can provide a respite to the over-stressed pancreas by providing much-needed insulin and enabling the pancreas to recuperated and generate new insulin-producing beta cells at a rate that will meet the body's demand while, at the same time, lowering insulin resistance.
Recently, the American Diabetes Association announced changes that would enable the organization to more rapidly response to scientific discoveries for the treatment of diabetes, stating in a press release that, "Beginning with the 2018 ADA Standards of Medical Care in Diabetes, the Standards document will be a “living” document where notable updates are incorporated into the Standards, as determined appropriate by the Professional Practice Committee, noting that their decades-long practice of annually reviewing medical advances would be replaced with more frequent updates, what they described as a "living" Standards of Care, in response to important events such as "new treatments with the potential to impact patient care" and publication of new findings "that support a change to a recommendation and/or evidence level of a recommendation".
Many critics of the ADA are advocating that there is now more than sufficient clinical evidence to meet the ADA's criteria to update its Standard of Care to move short-term intensive insulin therapy to the first step in treating early diabetes. It's hard to argue with results and the incredible potential of this therapy, its puzzling why the ADA has taken so long to advocate early short-term insulin therapy as a first step in combatting this disease. I know of no other treatment that has the potential of remission of diabetes for 50% of treated patients.
Delaying this therapy may result in continuous deterioration of the pancreas to the point where it is no longer repairable and sentences the patient to a difficult life of continuously fighting diabetes. It's a fight that can be won with a 1st Round knockout. It's time for the American Diabetes Association and the American Association of Clinical Endocrinologists to recognize this important treatment and to put it in its proper place in the 2019 ADA Standards of Medical Care in Diabetes.
The clinical trial, entitled "Initiating Mealtime Ultra-Rapid Acting Insulin (Afrezza) in Uncontrolled Type 2 Diabetes Patients" is scheduled to be completed in September 2018.
Trial Link: clinicaltrials.gov/ct2/show/NCT03324776?term=mannkind&recrs=abdfg&rank=3
Am I misunderstanding the idea of "early insulin therapy"? "Early intensive insulin therapy administered to newly-diagnosed Type 2 diabetes patients..." is what I always understood as early insulin therapy. What I read in the clinicaltrials description, though, says "the investigator proposes treating patients with Afrezza who have an index HbA1c between 7.5% and 11.5% despite being treated with diabetes medications for at least 6 months." Having been on diabetes medications for at least 6 months and having failed the treatment doesn't fit into my idea of "early insulin therapy." It would already be a huge step to show positive results that would support a decision by the ADA to place Afrezza second in line in the standards of care. They have likely aligned the study to accommodate such a decision knowing that it would be unrealistic to try to knock metformin out of first line treatment status, at least for the time being.
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Post by mnholdem on Aug 22, 2018 6:50:20 GMT -5
tomtab, I think you are correct that this particular study is not a short-term intensive insulin therapy (STII) treatment. It comes close though. I think that the primary goal is to demonstrate Afrezza as a safe and more effective treatment for early Type 2 than OAD treatments alone.
For quite some time, I’ve encouraged management to pursue a grant (Gates Foundation, government or other private) for a major clinical study on STII using Afrezza.
My intent with the OP was to convey two things;
1. This study will likely show significant results; 2. Early intensive insulin treatment should come much earlier in the ADA Standards of Care for treatment of Diabetes.
The study will be another in among the growing body of clinical evidence for the ADA/AACE to consider.
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Post by agedhippie on Aug 22, 2018 9:20:20 GMT -5
tomtab, I think you are correct that this particular study is not a short-term intensive insulin therapy (STII) treatment. It comes close though. I think that the primary goal is to demonstrate Afrezza as a safe and more effective treatment for early Type 2 than OAD treatments alone. For quite some time, I’ve encouraged management to pursue a grant (Gates Foundation, government or other private) for a major clinical study on STII using Afrezza. My intent with the OP was to convey two things; 1. This study will likely show significant results; 2. Early intensive insulin treatment should come much earlier in the ADA Standards of Care for treatment of Diabetes. The study will be another in among the growing body of clinical evidence for the ADA/AACE to consider. I would agree with both those points. It would be extremely surprising if adding Afrezza to a failed OAD regime would not reduce the A1c, adding RAA would as well. This is largely replicating the 175 trial isn't it? And +1 for using insulin far earlier in the Standard of Care. It's a data point for the use of insulin, but what is really needed is a multi-arm trial for insulin (basal and/or prandial), GLP-1, SGLT-2, and DPP-4. That's a huge trial and it would be expensive to cover the cost. What it would do is provided a strong answer to the what next question.
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Post by tomtabb on Aug 22, 2018 10:03:37 GMT -5
tomtab, I think you are correct that this particular study is not a short-term intensive insulin therapy (STII) treatment. It comes close though. I think that the primary goal is to demonstrate Afrezza as a safe and more effective treatment for early Type 2 than OAD treatments alone. For quite some time, I’ve encouraged management to pursue a grant (Gates Foundation, government or other private) for a major clinical study on STII using Afrezza. My intent with the OP was to convey two things; 1. This study will likely show significant results; 2. Early intensive insulin treatment should come much earlier in the ADA Standards of Care for treatment of Diabetes. The study will be another in among the growing body of clinical evidence for the ADA/AACE to consider. I would agree with both those points. It would be extremely surprising if adding Afrezza to a failed OAD regime would not reduce the A1c, adding RAA would as well. This is largely replicating the 175 trial isn't it? And +1 for using insulin far earlier in the Standard of Care. It's a data point for the use of insulin, but what is really needed is a multi-arm trial for insulin (basal and/or prandial), GLP-1, SGLT-2, and DPP-4. That's a huge trial and it would be expensive to cover the cost. What it would do is provided a strong answer to the what next question. Reviewing trial 175, I have to agree this latest basically just looks like a repeat. I don't quite see the "1+ for using insulin far earlier," however. They say at least six months following standard of care, so all they seem to be doing is following the usual standard of care and just substituting afrezza for a rapid acting insulin at the end of their flowchart.
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Post by mango on Aug 22, 2018 10:35:03 GMT -5
On a side note: Pancreatic Beta Cell Memory & Ca2+ Homeostasis Pancreatic beta cells obtain, consolidate, store and retrieve information contained in calcium signals. Pancreatic beta cell memory is regulated by CaMKII and beta cells fail to secrete sufficient insulin due to CaMKII not being activated, dysfunction in Ca2+ homeostasis—among other things. Beta cells form metabolic memories very similar to how neuronal cells form memory. In a healthy non-diabetic pancreas the beta cells function both independently and in synchrony. During the first-phase insulin response we see that mystical, “universal consciousness” on a small, cellular and molecular level in pancreatic beta cells. In diabetes, there is CaMKII dysfunction and calcium signaling is dysregulated. Further reading: mnkd.proboards.com/post/149903/thread
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Post by agedhippie on Aug 22, 2018 12:38:51 GMT -5
Reviewing trial 175, I have to agree this latest basically just looks like a repeat. I don't quite see the "1+ for using insulin far earlier," however. They say at least six months following standard of care, so all they seem to be doing is following the usual standard of care and just substituting afrezza for a rapid acting insulin at the end of their flowchart. The +1 for insulin is that I would like to see it made an option for as early (or late) as the person wants. Personally if I was a Type 2, in order of preference, I would want metformin then anything that lets me treat as seldom as possible, then go to just metformin and MDI. Once I have to take insulin I cannot see the point in any of the other drugs than metformin. I also wouldn't want to go to just basal because by that point I would want better control according to what I am eating so I would want prandial insulin as well.
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Post by peppy on Aug 22, 2018 13:35:29 GMT -5
Reviewing trial 175, I have to agree this latest basically just looks like a repeat. I don't quite see the "1+ for using insulin far earlier," however. They say at least six months following standard of care, so all they seem to be doing is following the usual standard of care and just substituting afrezza for a rapid acting insulin at the end of their flowchart. The +1 for insulin is that I would like to see it made an option for as early (or late) as the person wants. Personally if I was a Type 2, in order of preference, I would want metformin then anything that lets me treat as seldom as possible, then go to just metformin and MDI. Once I have to take insulin I cannot see the point in any of the other drugs than metformin. I also wouldn't want to go to just basal because by that point I would want better control according to what I am eating so I would want prandial insulin as well. is my understanding correct? Metformin decreases liver glucose neogenisis. Afrezza does that; the first phase.
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