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Post by gomnkd on Feb 13, 2015 7:41:17 GMT -5
Gomnkd is correct, differentiating factor is all about how afrezza affects gluconeogenesis/endogenous glucose production. Bobw, your theory about insulin receptors and glucose transporters is not wrong by itself, but this effect mostly just influences the conversion rate we need to use for technosphere insulin vs injected insulin. If cells were able to take up more glucose in the short timespan that Afrezza is active, then we would just need a different conversion factor (now it is 10:4 for afrezza:injected). I will write a more thorough post on this over the weekend if there is sufficient interest... Please do. You are the best there is. The rest of us just stayed at holiday inn express. |
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Post by ezrasfund on Feb 13, 2015 8:29:37 GMT -5
Gomnkd is correct, differentiating factor is all about how afrezza affects gluconeogenesis/endogenous glucose production. Bobw, your theory about insulin receptors and glucose transporters is not wrong by itself, but this effect mostly just influences the conversion rate we need to use for technosphere insulin vs injected insulin. If cells were able to take up more glucose in the short timespan that Afrezza is active, then we would just need a different conversion factor (now it is 10:4 for afrezza:injected). I will write a more thorough post on this over the weekend if there is sufficient interest... Are we talking about two different mechanisms here to address the two aspects of glucose control? The fact that glucose uptake is limited by the capacity of insulin receptors and is therefore not effected by excess insulin prevents hypoglycemia, unless the insulin is present for too long. The higher levels of insulin in the blood signal the liver to stop gluconeogenesis curbing hyperglycemia. |
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Post by gomnkd on Feb 13, 2015 9:09:04 GMT -5
ezrasfund
yes, I believe these two mechanisms could be responsible for less hypos.
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Post by bobw on Feb 13, 2015 10:05:11 GMT -5
I also agree, stopping gluconeogenesis could allow a smaller dose of insulin to control hyperglycemia, hence lowering the risk of hypoglycemia a couple of hours later, and also may reduce insulin resistance. Silentbob, I would be interested in what you have to say about it.
BobW
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Post by elvis2 on May 18, 2016 12:58:57 GMT -5
Hello, I am new here. I found this topic after calling Mankind regarding my long tail problem with Afrezza. I started using Afrezza in January of this year, alongside my insulin pump. I definitely had to be careful, I experienced the long-tail effect while using my insulin pump for corrections and Afrezza for meals. In April of this year, I stopped using my insulin pump and switched to 100% Afrezza with Triseba (long acting insulin). Finally A1C is coming down! But, I have noticed that I get the long-tail effect with Afrezza as well, like I did with my insulin pump (without Afrezza) when doing several corrections throughout the day. I have experienced this long tail problem ever since becoming a type 1 diabetic. My questions to you all, when you say that titration or the long tail is less with Afrezza, does that mean I should never crash? And how long should the titration last? For example, just today I experienced a 5 hour long tail effect. I have attached a photo of this so you all can see it. when I woke up my blood sugar was in the mid-fifties. This is not the first time I've seen this while using Afrezza, it happens often to me. But, the crash is not nearly as bad when using regular insulin. Thoughts? About the picture. No food, since 7pm the night before. I did miss my Triseba inject, did that at 2am. No food or drink until 9:10am. Here is the link to my numbers showing the longtail. drive.google.com/file/d/0B7BIGc5lm1jQMndFVjd1ZUhaNnVSVFVCdHhpbHBxem42eE53/view |
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Post by Deleted on May 18, 2016 13:06:31 GMT -5
Hello, I am new here. I found this topic after calling Mankind regarding my long tail problem with Afrezza. I started using Afrezza in January of this year, alongside my insulin pump. I definitely had to be careful, I experienced the long-tail effect while using my insulin pump for corrections and Afrezza for meals. In April of this year, I stopped using my insulin pump and switched to 100% Afrezza with Triseba (long acting insulin). Finally A1C is coming down! But, I have noticed that I get the long-tail effect with Afrezza as well, like I did with my insulin pump (without Afrezza) when doing several corrections throughout the day. I have experienced this long tail problem ever since becoming a type 1 diabetic. My questions to you all, when you say that titration or the long tail is less with Afrezza, does that mean I should never crash? And how long should the titration last? For example, just today I experienced a 5 hour long tail effect. I have attached a photo of this so you all can see it. when I woke up my blood sugar was in the mid-fifties. This is not the first time I've seen this while using Afrezza, it happens often to me. But, the crash is not nearly as bad when using regular insulin. Thoughts? About the picture. No food, since 7pm the night before. I did miss my Triseba inject, did that at 2am. No food or drink until 9:10am. Here is the link to my numbers showing the longtail. drive.google.com/file/d/0B7BIGc5lm1jQMndFVjd1ZUhaNnVSVFVCdHhpbHBxem42eE53/viewAfrezza is for meal time / spikes. You would need to titrate basal more and find the optimal basal rate that would work. Talk to Sam or Afrezzaguy on Twitter |
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Post by Deleted on May 18, 2016 13:06:56 GMT -5
This is not the right place for the answers to your questions. Go to this site and reach out to Sam afrezzauser.com |
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Post by sweedee79 on May 18, 2016 13:38:15 GMT -5
Thank you Bob for your post... This is one of the key factors with Afrezza and what needs to be understood. Not only does this fast action reduce the risk of hypo but also weight gain. That is something that I found so amazing with my dad's experience, he lost 24lbs while on Afrezza.. and now since having to go back on Novolog has gained it all back in 5 months.. Novolog and other injectable insulins hang in the blood stream longer and thus more fat is stored..
www.diabetes-book.com/insulin-fat-connection/
All of these facts put together makes me really scratch my head as to why MNKD is in this position... because Afrezza surely isn't the reason.. its either pure and utter ignorance or something is amiss ...
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Post by sportsrancho on May 18, 2016 15:52:56 GMT -5
Great article!! I sent it to all the trainers at my gym.
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Post by gamblerjag on May 18, 2016 16:54:10 GMT -5
off topic....Has anyone else received a call from MNKD encouraging to vote your proxy for tomorrow? They have called 11 times in the last 2 weeks. I never answer thinking it was a telemarketer.. 8887442611 was the phone number.. Today I answered..... just curious to see if anyone else received call.
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Post by agedhippie on May 18, 2016 17:00:10 GMT -5
Hello, I am new here. I found this topic after calling Mankind regarding my long tail problem with Afrezza. I started using Afrezza in January of this year, alongside my insulin pump. I definitely had to be careful, I experienced the long-tail effect while using my insulin pump for corrections and Afrezza for meals. In April of this year, I stopped using my insulin pump and switched to 100% Afrezza with Triseba (long acting insulin). Finally A1C is coming down! But, I have noticed that I get the long-tail effect with Afrezza as well, like I did with my insulin pump (without Afrezza) when doing several corrections throughout the day. I have experienced this long tail problem ever since becoming a type 1 diabetic. My questions to you all, when you say that titration or the long tail is less with Afrezza, does that mean I should never crash? And how long should the titration last? For example, just today I experienced a 5 hour long tail effect. I have attached a photo of this so you all can see it. when I woke up my blood sugar was in the mid-fifties. This is not the first time I've seen this while using Afrezza, it happens often to me. But, the crash is not nearly as bad when using regular insulin. Thoughts? About the picture. No food, since 7pm the night before. I did miss my Triseba inject, did that at 2am. No food or drink until 9:10am. Here is the link to my numbers showing the longtail. drive.google.com/file/d/0B7BIGc5lm1jQMndFVjd1ZUhaNnVSVFVCdHhpbHBxem42eE53/viewAfrezza has just about the same length tail as any insulin it's that the tail is far lower. The tail didn't cause that though. When I get that sort of curve it's almost always fast absorption of the basal but I use Lantus. In your case I wonder if what you are seeing is stacking of the basal. I know people who have had that problem and gone back to Lantus. The simple test is to run your pump for the basal and use Afrezza for the bolus. If you don't want to do that I would suggest basal testing since you have swapped basals. My money is on the problem being Tresiba. A disclaimer: I'm not a doctor, I'm a diabetic so don't confuse opinion with medical advice! |
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Post by agedhippie on May 18, 2016 17:07:09 GMT -5
Thank you Bob for your post... This is one of the key factors with Afrezza and what needs to be understood. Not only does this fast action reduce the risk of hypo but also weight gain. That is something that I found so amazing with my dad's experience, he lost 24lbs while on Afrezza.. and now since having to go back on Novolog has gained it all back in 5 months.. Novolog and other injectable insulins hang in the blood stream longer and thus more fat is stored..
www.diabetes-book.com/insulin-fat-connection/
All of these facts put together makes me really scratch my head as to why MNKD is in this position... because Afrezza surely isn't the reason.. its either pure and utter ignorance or something is amiss ...
Bernstein's stuff really works. I have never done it because I would never be able to sustain that diet but I know Type 2 insulin users who have got clean off insulin and drugs using it. He is a Type 1 and became an endo (he was an engineer I think) because he couldn't find any doctor who would support the LCHF diet at the time. His followers tend to be a little fanatical! |
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Post by capnbob on May 19, 2016 0:40:06 GMT -5
I have been thinking about why titration is not that important when using Afrezza. Feedback or corrections from any doctors, chemists or informed investor on the board would be appreciated. The following is my understanding of the process of insulin’s life in the body.
Insulin is typically degraded, by liver cells, about 71 minutes after its initial release into circulation. Afrezza is quickly released into circulation because it is an insulin monomer and is inhaled into the lungs. Novolog and Humalog are taken subcutaneously as insulin hexamers, so they are slowly released into circulation. This is an important point: the insulin from Novolog and Humalog degrades at about the same rate as the insulin from Afrezza, but because Novolog and Humalog are absorbed slower, there is a much longer tail from Novolog and Humalog.
Now think about how insulin affects glucose absorption. A cell’s insulin receptors, when an insulin molecule binds to it, leads to an increase in the glucose transporter (Glut4) molecules that induce glucose uptake. Once insulin binds to an insulin receptor, additional insulin has no further effect on that receptor.
With Afrezza, insulin is bound to many insulin receptors for about 71 minutes after the insulin has been absorbed through the lungs and into circulation. Since absorption is quick, the final 71 minutes starts soon after inhaling Afrezza. With Humalog and Novolog, the final 71 minutes happens much later because new insulin molecules are continually being absorbed for a much longer period.
While a meal is being digested, there is a steady influx of glucose entering the bloodstream. It takes some time for that glucose to absorb, even if many cells have active insulin receptors. If the rate of glucose is entering circulation is as high as the rate of cellular uptake, then there is no drop in the level of serum glucose. Depending on the glycemic index of the food that was consumed with the meal, glucose will continue to enter circulation for a specific period of time. If the time that glucose is enter the circulation is similar to the time that Afrezza is also still in circulation, then glucose levels will not drop too low.
If the dose of Afrezza was larger than needed, the excess insulin degrades quickly, before the meal is fully digested, without causing a low. With Novolog and Humalog, the excess insulin does not degrade as quickly, the excess insulin is problematic because it is still in circulation after the meal is digested.
My conclusion is that, for these reasons, a higher dose of Afrezza can be taken without causing hypoglycemia. If you need 1-4 units of Novolog, you can take 4 units of Afrezza without a problem; the excess insulin is degraded before it causes a problem.
From Wikipedia: “Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment or it may be degraded by the cell. Degradation normally involves endocytosis of the insulin-receptor complex followed by the action of insulin degrading enzyme. Most insulin molecules are degraded by liver cells. It has been estimated that a typical insulin molecule is finally degraded about 71 minutes after its initial release into circulation.”
BobW
"Insulin is typically degraded, by liver cells, about 71 minutes after its initial release into circulation." Insulin is degraded by liver and kidney -- split is about 50/50 with liver taking out portal insulin and kidney taking out peripheral insulin. Half-life is about 5 minutes; complete removal is about one hour. "With Humalog and Novolog, the final 71 minutes happens much later because new insulin molecules are continually being absorbed for a much longer period." No. Both humalog and novolog are genetically modified so that the monomer cannot form inactive dimers, multimers and hexamers. To appreciate the short life of afrezza versus the "tail" of the other two you have to look at what happens to insulin in the blood. There insulin exists in a constant state of equilibrium: monomer <=> dimer <=> multimer <=> hexamer Of course, the only active form is the monomer. However, the enzyme responsible for removing insulin -- insulin degrading enzyme -- acts upon all four forms. Upon entering the bloodstream, afrezza immediately begins to form the other three and that is the main reason for the rapid fall-off in activity displayed in a PD graph. That effect is amplified by the IDE simultaneously removing all four versions, which also results in the reaction constantly being pulled to the right. Humalog and Novolog, on the other hand, have minimal conversion to the inactive forms and remain circulating as active monomers until IDE removes them. That accounts for the long "tail." "This is an important point: the insulin from Novolog and Humalog degrades at about the same rate as the insulin from Afrezza..." Wrong as just described. "...but because Novolog and Humalog are absorbed slower..." No, that is incorrect. If you look at the PD graph on the insert, you will see that afrezza's onset of action and net effect on lowering glucose for the first 60 minutes is almost identical to lispro. "If the dose of Afrezza was larger than needed, the excess insulin degrades quickly, before the meal is fully digested, without causing a low. With Novolog and Humalog, the excess insulin does not degrade as quickly, the excess insulin is problematic because it is still in circulation after the meal is digested. " Yes, but an oversimplification. Type 1 diabetics are extremely sensitive to insulin. Many taking lispro need only 1-2U per meal, so that even with a meal, it is still possible to overshoot if the individual doesn't carefully count the carbs in the meal. "... a higher dose of Afrezza can be taken without causing hypoglycemia." No, one can never assume that taking a higher dose is safer without knowing the nature of the meal and the sensitivity to insulin of the individual. Finally, you should bear in mind that, per the trials there was no significant difference in the rate of serious hypoglycemia between afrezza and lispro, where serious basically means symptomatic. I don't recall whether they monitored ER visits for hypoglycemia. if I get the time I'll check to see if any differences appeared there. |
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Post by capnbob on May 19, 2016 0:49:17 GMT -5
Hello, I am new here. I found this topic after calling Mankind regarding my long tail problem with Afrezza. I started using Afrezza in January of this year, alongside my insulin pump. I definitely had to be careful, I experienced the long-tail effect while using my insulin pump for corrections and Afrezza for meals. In April of this year, I stopped using my insulin pump and switched to 100% Afrezza with Triseba (long acting insulin). Finally A1C is coming down! But, I have noticed that I get the long-tail effect with Afrezza as well, like I did with my insulin pump (without Afrezza) when doing several corrections throughout the day. I have experienced this long tail problem ever since becoming a type 1 diabetic. My questions to you all, when you say that titration or the long tail is less with Afrezza, does that mean I should never crash? And how long should the titration last? For example, just today I experienced a 5 hour long tail effect. I have attached a photo of this so you all can see it. when I woke up my blood sugar was in the mid-fifties. This is not the first time I've seen this while using Afrezza, it happens often to me. But, the crash is not nearly as bad when using regular insulin. Thoughts? About the picture. No food, since 7pm the night before. I did miss my Triseba inject, did that at 2am. No food or drink until 9:10am. Here is the link to my numbers showing the longtail. drive.google.com/file/d/0B7BIGc5lm1jQMndFVjd1ZUhaNnVSVFVCdHhpbHBxem42eE53/viewYou leave out too many essential details. In your google drive image, what was the nature of the last meal -- carbs, fat, protein? Are you confirming the CGM with fingersticks? What is your basal dose? What was your old lispro dose? Why did you wait so long to deal with the hyperglycemia? Why did you take the additional dose at 4am when it appeared as though you right in the middle of the correction? These are all things you should write down every day in detail and discuss with your diabetic nurse and/or endo. |
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Post by peppy on May 19, 2016 8:40:14 GMT -5
Hello, I am new here. I found this topic after calling Mankind regarding my long tail problem with Afrezza. I started using Afrezza in January of this year, alongside my insulin pump. I definitely had to be careful, I experienced the long-tail effect while using my insulin pump for corrections and Afrezza for meals. In April of this year, I stopped using my insulin pump and switched to 100% Afrezza with Triseba (long acting insulin). Finally A1C is coming down! But, I have noticed that I get the long-tail effect with Afrezza as well, like I did with my insulin pump (without Afrezza) when doing several corrections throughout the day. I have experienced this long tail problem ever since becoming a type 1 diabetic.
My questions to you all, when you say that titration or the long tail is less with Afrezza, does that mean I should never crash? And how long should the titration last? For example, just today I experienced a 5 hour long tail effect. I have attached a photo of this so you all can see it. when I woke up my blood sugar was in the mid-fifties. This is not the first time I've seen this while using Afrezza, it happens often to me. But, the crash is not nearly as bad when using regular insulin. Thoughts? About the picture. No food, since 7pm the night before. I did miss my Triseba inject, did that at 2am. No food or drink until 9:10am. Here is the link to my numbers showing the longtail. drive.google.com/file/d/0B7BIGc5lm1jQMndFVjd1ZUhaNnVSVFVCdHhpbHBxem42eE53/viewI believe I learned from sportsrancho, perhaps better to do a larger dose afrezza, rather than corrections. Learned from another post long ago, Afrezza delivered as a monomer get to the liver in the blood stream and stops liver neoglucgenesis, stop glucose from going high in the first place. Then metabolically, the monomers become dimers and take a while to break up and leave the blood stream. Phase one and phase two. Corrections/ management may be throwing you off. afrezzadownunder.com/2015/10/afrezza-timing-is-everything/
Afrezza, 1st phase and second phase screencast.com/t/AhnFhHunq
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