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Post by itellthefuture777 on Sept 11, 2017 16:32:45 GMT -5
Afrezza is the worlds only Active Monomeric insulin!
Why is that important?
The only other Active Monomeric insulin is produced by the healthy individual.
Stop and realize that Afrezza is less then 30 seconds difference from the Healthy individuals pancreas.
Stop and realize that the Kinetic profile of Afrezza Mimics the Healthy Individual so closely you can't put a pencil mark between them.
The goal of all insulin manufacturers has been to MIMIC the healthy individual...but..they couldn't stabilize Active Monomeric Insulin..until Mannkind did it and has it patented into 2032...
You see..all other insulins are Inactive Hexomerics that means they are bonded together to stabilize them and inactive in that form of a six pack so..also no matter how they are delivered..even if inhaled..injected..snorted..patched..are still..inactive hexomerics..and the body has to then eat through that bonding to make them Monomeric (singular active insulin) but it take the blood so long to eat through the bonds..and then it stays in your body so long..fear of hypos and hypos occur..not what a diabetics needs...because it is slow going in..slow activating..slow going out..doesn't mimic..you can see chart after chart of all other insulins..like a giant boat..with a out of control rudder..can't turn it on quick enough..can't turn it off..have to over eat..get fat..just to get it to stabilize you...why on Earth..is it that these Endo's can't see what is so very obvious? If you used Afrezza as a front line therapy...when you first get the message you are prediabetic..or diabetic type 2..and start using Afrezza at meal times which is where diabetics begin to loose control..and you control it ..in a mimic way of a healthy individual..you could..halt progression..progression towards all the ales of the diabetic..loosing feet, legs, fingers, arms, heart, liver, vision..the cost savings to the insurance industry would be so enormous..the health of people would be life changing..yet here we are..2 years in..and they don't know about Afrezza? Sanofi didn't put Afrezza in commercials like Toujeo...but I think any normal person would see through this and to the why's...because 70% of type 2 would only need Afrezza....I have read Al Mann saying these things...and all the data I see from online..with patient outcomes..follows..what he said...so...I like what VDEX showed on their charts..puts it in perspective..I like Dexcom..and One Drop..that show the users reducing their A1C by 1.3%...but then ask yourself..why did One Drop select Mannkind and no other insulin? Maybe...that 1.3% reduction came from Afrezza Users...but..it has to be documented in a trial..to be bonafide...still..I don't see a problem proving it out...also..even though Afrezza had 64% less hypos when used with a basil 43% of the hypos in the trial came from one patient! In statistics ..that is an outlier..and should have been tossed..imo..okay..rant over~
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Post by dreamboatcruise on Sept 11, 2017 18:21:28 GMT -5
Afrezza is the worlds only Active Monomeric insulin! Why is that important? The only other Active Monomeric insulin is produced by the healthy individual. Stop and realize that Afrezza is less then 30 seconds difference from the Healthy individuals pancreas. Stop and realize that the Kinetic profile of Afrezza Mimics the Healthy Individual so closely you can't put a pencil mark between them. The goal of all insulin manufacturers has been to MIMIC the healthy individual...but..they couldn't stabilize Active Monomeric Insulin..until Mannkind did it and has it patented into 2032... You see..all other insulins are Inactive Hexomerics that means they are bonded together to stabilize them and inactive in that form of a six pack so..also no matter how they are delivered..even if inhaled..injected..snorted..patched..are still..inactive hexomerics..and the body has to then eat through that bonding to make them Monomeric (singular active insulin) but it take the blood so long to eat through the bonds..and then it stays in your body so long..fear of hypos and hypos occur..not what a diabetics needs...because it is slow going in..slow activating..slow going out..doesn't mimic..you can see chart after chart of all other insulins..like a giant boat..with a out of control rudder..can't turn it on quick enough..can't turn it off..have to over eat..get fat..just to get it to stabilize you...why on Earth..is it that these Endo's can't see what is so very obvious? If you used Afrezza as a front line therapy...when you first get the message you are prediabetic..or diabetic type 2..and start using Afrezza at meal times which is where diabetics begin to loose control..and you control it ..in a mimic way of a healthy individual..you could..halt progression..progression towards all the ales of the diabetic..loosing feet, legs, fingers, arms, heart, liver, vision..the cost savings to the insurance industry would be so enormous..the health of people would be life changing..yet here we are..2 years in..and they don't know about Afrezza? Sanofi didn't put Afrezza in commercials like Toujeo...but I think any normal person would see through this and to the why's...because 70% of type 2 would only need Afrezza....I have read Al Mann saying these things...and all the data I see from online..with patient outcomes..follows..what he said...so...I like what VDEX showed on their charts..puts it in perspective..I like Dexcom..and One Drop..that show the users reducing their A1C by 1.3%...but then ask yourself..why did One Drop select Mannkind and no other insulin? Maybe...that 1.3% reduction came from Afrezza Users...but..it has to be documented in a trial..to be bonafide...still..I don't see a problem proving it out...also..even though Afrezza had 64% less hypos when used with a basil 43% of the hypos in the trial came from one patient! In statistics ..that is an outlier..and should have been tossed..imo..okay..rant over~ Certainly speed of action is an important trait of Afrezza. That has been discussed in hundreds (perhaps thousands) of threads here. However, one thing you have stated is simply incorrect physiology. Once in the blood it doesn't take long at all for hexamers to disassociate into monomers. The pancreas actually stores and releases insulin as hexamers, and within seconds once it is out of the portal circulation it is rapidly converting to monomers. Insulin stays as mainly hexamers only when it is in high concentration (lots packed in the same area) as occurs with insulin vials, injection sites and the pancreas. No blood "eating through bonds" is required. The long tail of RAAs is caused by the long time to get absorbed into the blood when injected in subq fat tissue. RAA's act faster if injected intramuscular and almost instantaneously if injected IV.
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Post by sayhey24 on Sept 11, 2017 18:38:56 GMT -5
The good news with afrezza is it obsoletes injecting intramuscular and should help a great deal getting the highs under control so ER visits and IV are needed a lot less. Now all we need to do is get the price and insurance coverage under control.
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Post by peppy on Sept 11, 2017 18:45:12 GMT -5
The good news with afrezza is it obsoletes injecting intramuscular and should help a great deal getting the highs under control so ER visits and IV are needed a lot less. Now all we need to do is get the price and insurance coverage under control. The good news with afrezza is it obsoletes injecting intramuscular subcutaneously and should help a great deal getting the highs under control so ER visits and IV are needed a lot less. Now all we need to do is get the price and insurance coverage under control.
My understanding is the intramuscular delivery is faster. More blood vessels in the muscle.
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Post by itellthefuture777 on Sept 11, 2017 18:55:30 GMT -5
Afrezza is the worlds only Active Monomeric insulin! Why is that important? The only other Active Monomeric insulin is produced by the healthy individual. Stop and realize that Afrezza is less then 30 seconds difference from the Healthy individuals pancreas. Stop and realize that the Kinetic profile of Afrezza Mimics the Healthy Individual so closely you can't put a pencil mark between them. The goal of all insulin manufacturers has been to MIMIC the healthy individual...but..they couldn't stabilize Active Monomeric Insulin..until Mannkind did it and has it patented into 2032... You see..all other insulins are Inactive Hexomerics that means they are bonded together to stabilize them and inactive in that form of a six pack so..also no matter how they are delivered..even if inhaled..injected..snorted..patched..are still..inactive hexomerics..and the body has to then eat through that bonding to make them Monomeric (singular active insulin) but it take the blood so long to eat through the bonds..and then it stays in your body so long..fear of hypos and hypos occur..not what a diabetics needs...because it is slow going in..slow activating..slow going out..doesn't mimic..you can see chart after chart of all other insulins..like a giant boat..with a out of control rudder..can't turn it on quick enough..can't turn it off..have to over eat..get fat..just to get it to stabilize you...why on Earth..is it that these Endo's can't see what is so very obvious? If you used Afrezza as a front line therapy...when you first get the message you are prediabetic..or diabetic type 2..and start using Afrezza at meal times which is where diabetics begin to loose control..and you control it ..in a mimic way of a healthy individual..you could..halt progression..progression towards all the ales of the diabetic..loosing feet, legs, fingers, arms, heart, liver, vision..the cost savings to the insurance industry would be so enormous..the health of people would be life changing..yet here we are..2 years in..and they don't know about Afrezza? Sanofi didn't put Afrezza in commercials like Toujeo...but I think any normal person would see through this and to the why's...because 70% of type 2 would only need Afrezza....I have read Al Mann saying these things...and all the data I see from online..with patient outcomes..follows..what he said...so...I like what VDEX showed on their charts..puts it in perspective..I like Dexcom..and One Drop..that show the users reducing their A1C by 1.3%...but then ask yourself..why did One Drop select Mannkind and no other insulin? Maybe...that 1.3% reduction came from Afrezza Users...but..it has to be documented in a trial..to be bonafide...still..I don't see a problem proving it out...also..even though Afrezza had 64% less hypos when used with a basil 43% of the hypos in the trial came from one patient! In statistics ..that is an outlier..and should have been tossed..imo..okay..rant over~ Certainly speed of action is an important trait of Afrezza. That has been discussed in hundreds (perhaps thousands) of threads here. However, one thing you have stated is simply incorrect physiology. Once in the blood it doesn't take long at all for hexamers to disassociate into monomers. The pancreas actually stores and releases insulin as hexamers, and within seconds once it is out of the portal circulation it is rapidly converting to monomers. Insulin stays as mainly hexamers only when it is in high concentration (lots packed in the same area) as occurs with insulin vials, injection sites and the pancreas. No blood "eating through bonds" is required. The long tail of RAAs is caused by the long time to get absorbed into the blood when injected in subq fat tissue. RAA's act faster if injected intramuscular and almost instantaneously if injected IV. I am not incorrect..at most a dimer (2) and an active monomer (1) would excrete out of the healthy pancreas..never an inactive hexomer (6)..never
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Post by sayhey24 on Sept 11, 2017 18:59:35 GMT -5
Peppy - basal will still go subcutaneously. Now if the T2 follows the VDex protocol they should never need a basal. Here is a good article from Gary Scheiner diatribe.org/issues/39/thinking-like-a-pancreas. Article is dated 1/31/2012 and Scheiner is now an afrezza user.
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Post by sayhey24 on Sept 11, 2017 19:06:54 GMT -5
Certainly speed of action is an important trait of Afrezza. That has been discussed in hundreds (perhaps thousands) of threads here. However, one thing you have stated is simply incorrect physiology. Once in the blood it doesn't take long at all for hexamers to disassociate into monomers. The pancreas actually stores and releases insulin as hexamers, and within seconds once it is out of the portal circulation it is rapidly converting to monomers. Insulin stays as mainly hexamers only when it is in high concentration (lots packed in the same area) as occurs with insulin vials, injection sites and the pancreas. No blood "eating through bonds" is required. The long tail of RAAs is caused by the long time to get absorbed into the blood when injected in subq fat tissue. RAA's act faster if injected intramuscular and almost instantaneously if injected IV. I am not incorrect..at most a dimer (2) and an active monomer (1) would excrete out of the healthy pancreas..never an inactive hexomer (6)..never Insulin is secreted from beta cell granules as hexamers and enters the circulation through specialized fenestrations. The insulin is then carried directly to the liver in the portal vein. Once in the blood the hexamer bonds are rapidly broken.
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Post by dreamboatcruise on Sept 11, 2017 19:08:50 GMT -5
Certainly speed of action is an important trait of Afrezza. That has been discussed in hundreds (perhaps thousands) of threads here. However, one thing you have stated is simply incorrect physiology. Once in the blood it doesn't take long at all for hexamers to disassociate into monomers. The pancreas actually stores and releases insulin as hexamers, and within seconds once it is out of the portal circulation it is rapidly converting to monomers. Insulin stays as mainly hexamers only when it is in high concentration (lots packed in the same area) as occurs with insulin vials, injection sites and the pancreas. No blood "eating through bonds" is required. The long tail of RAAs is caused by the long time to get absorbed into the blood when injected in subq fat tissue. RAA's act faster if injected intramuscular and almost instantaneously if injected IV. I am not incorrect..at most a dimer (2) and an active monomer (1) would excrete out of the healthy pancreas..never an inactive hexomer (6)..never "Newly made insulin binds to Zn2+ and forms hexamers within specialized secretory granules for storage. Zn2+ provides insulin with protection against denaturation and misfolding, stabilizing the molecular structure.20 Stored insulin is predominantly released from the pancreatic β cells through a regulated pathway while only about 1% of insulin (and proinsulin) is secreted through the constitutive pathway.21 Hexamers of insulin dissociate into biologically active monomers following secretion into the portal vein. Insulin’s half-life is only about 5 to 7 min in circulation." www.ncbi.nlm.nih.gov/pmc/articles/PMC4204021/You can also find many other references to how insulin is transported into portal vein and the fact that the portal vein has high concentration of hexamers and dimers compared to when it hits the main blood supply and quickly disassociates given it becomes greatly diluted in the larger quantity of blood.
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Post by itellthefuture777 on Sept 11, 2017 19:09:11 GMT -5
I am not incorrect..at most a dimer (2) and an active monomer (1) would excrete out of the healthy pancreas..never an inactive hexomer (6)..never Insulin is secreted from beta cell granules as hexamers and enters the circulation through specialized fenestrations. The insulin is then carried directly to the liver in the portal vein. Once in the blood the hexamer bonds are rapidly broken. nope..monomers and dimers
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Post by itellthefuture777 on Sept 11, 2017 19:13:44 GMT -5
Insulin is secreted from beta cell granules as hexamers and enters the circulation through specialized fenestrations. The insulin is then carried directly to the liver in the portal vein. Once in the blood the hexamer bonds are rapidly broken. nope..monomers and dimers Insulin is a hormone consisting of 2polypeptide chains. Each chain is composed of a specific sequence of amino acidresidues connected by peptide bonds. In humans, chain A has 21 amino acids, and chain B has 30. Post translational modifications result in the connection of these two chains by disulfide bridges. Cysteine residues on A7 and B7, as well as A20 to B19 are covalently connected by disulfide bridges. Chain A also has an internal disulfide bridge connecting A6 to A11. The 3D structure of insulin is composed of 3 helices and the three disulfide bridges. Hydrophobic amino acid residues are clustered on the inside of the molecule while the polar amino acids residues are located on the outer surface. This arrangement of amino acid residues lends stability to the overall molecule. A single molecule of insulin can form a dimer with another insulin molecule, but the most active form is a single unit. The chemical formula for the insulin monomer is: C256H381N65O79S6.
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Post by sayhey24 on Sept 11, 2017 19:15:50 GMT -5
OK - show me the study. Some say hexamers and dimmers but I can't give you monomer unless you point me to the study.
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Post by itellthefuture777 on Sept 11, 2017 19:37:06 GMT -5
nope..monomers and dimers Insulin is a hormone consisting of 2polypeptide chains. Each chain is composed of a specific sequence of amino acidresidues connected by peptide bonds. In humans, chain A has 21 amino acids, and chain B has 30. Post translational modifications result in the connection of these two chains by disulfide bridges. Cysteine residues on A7 and B7, as well as A20 to B19 are covalently connected by disulfide bridges. Chain A also has an internal disulfide bridge connecting A6 to A11. The 3D structure of insulin is composed of 3 helices and the three disulfide bridges. Hydrophobic amino acid residues are clustered on the inside of the molecule while the polar amino acids residues are located on the outer surface. This arrangement of amino acid residues lends stability to the overall molecule. A single molecule of insulin can form a dimer with another insulin molecule, but the most active form is a single unit. The chemical formula for the insulin monomer is: C256H381N65O79S6. If in the presence of zinc..a dimer will become a hexomer..zinc bonding into an inactive form...so..a build up of industrialized hexomeric insulins..probably causes elevated zinc in the blood..thus causing monomers and dimers to become inactive hexomers..hmm.insulin resistance..so..Afrezza..doesn't have that zinc issue..doesn't add it to your blood..hmm..probably using Afrezza shows reduced insulin resistance..
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Post by dreamboatcruise on Sept 11, 2017 19:42:04 GMT -5
Eyes rolling... will that be the next thing you're repeating as if you actually got it from somewhere other than your imagination?
I'm beginning to think "hmm" in itellthefuture speak means "I've made this up and really don't even believe it myself"... I'm I close, hmmm?
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Post by sayhey24 on Sept 11, 2017 19:44:21 GMT -5
Here is a good write-up. What you are saying is true but its stored in the pancreas as a hexamer and primarily released as a hexamer or so they say. I have never personally seen it being release so I am not an eye witness. www.ncbi.nlm.nih.gov/books/NBK30/The issue is the capillary walls which expect for the pancreatic canal are too fine to allow the hexamer to pass through and get in the blood.
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Post by itellthefuture777 on Sept 11, 2017 20:03:08 GMT -5
Here is a good write-up. What you are saying is true but its stored in the pancreas as a hexamer and primarily released as a hexamer or so they say. I have never personally seen it being release so I am not an eye witness. www.ncbi.nlm.nih.gov/books/NBK30/The issue is the capillary walls which expect for the pancreatic canal are too fine to allow the hexamer to pass through and get in the blood. seems to explain progression to type 1..reduction of elevated pancratic zinc or an insulin that is Monomeric and NOT an inactive Hexomeric with zinc..would make best sense..Has anyone ever check zinc levels in diabetic bloods against healthy individuals? hmm
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