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Post by pktrump on Dec 12, 2015 15:39:23 GMT -5
The restoration of the Phase I insulin response with AFZ promotes the following:
1. Stops glucogenesis in the liver.
2. Stores glucose as glycogen in the liver.
3. Promotes synthesis of fat (fatty acids and triglycerides) by the liver.
AFZ time to 'peak' activity is much improved over lispro and results in improved post prandial glucose excursions. Timing is everything.
Over months and years of use, AFZ should reduce insulin resistance, improve lipid profile, reduce build up of Triglycerides in the liver, and reduce export of fatty acids and triglycerides by breaking the viscous cycle of excess glucose production and excess storage of fat.
I think it would be interesting to see the lipid profiles before and after AFZ therapy.
The multibillion dollar question, as a result of replacing the phase I response with AFZ, will the myriad comorbidites of vascular disease, neuropathies, and fatty liver disease reduce over the long term
with AFZ users. 
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Post by rrtzmd on Dec 12, 2015 15:51:59 GMT -5
The restoration of the Phase I insulin response with AFZ promotes the following:
1. Stops glucogenesis in the liver.
2. Stores glucose as glycogen in the liver.
3. Promotes synthesis of fat (fatty acids and triglycerides) by the liver.
AFZ time to 'peak' activity is much improved over lispro and results in improved post prandial glucose excursions. Timing is everything.
Over months and years of use, AFZ should reduce insulin resistance, improve lipid profile, reduce build up of Triglycerides in the liver, and reduce export of fatty acids and triglycerides by breaking the viscous cycle of excess glucose production and excess storage of fat.
I think it would be interesting to see the lipid profiles before and after AFZ therapy.
The multibillion dollar question, as a result of replacing the phase I response with AFZ, will the myriad comorbidites of vascular disease, neuropathies, and fatty liver disease reduce over the long term
with AFZ users. As I discussed above, afrezza does nothing different than an RAA. It can't because it is just insulin like an RAA. I also pointed out that the PD graph shows time onset and effect on glucose for the first 60 minutes is almost identical to lispro, so time to "peak activity" is substantially the same. There is currently no evidence that afrezza should have any different effect on "lipid profile, etc" than any other RAA. |
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Post by dreamboatcruise on Dec 12, 2015 16:01:02 GMT -5
rrtzmd ... while the trials weren't designed to highlight that, at a minimum the trials do show that dosing can be done in 4u increments with non-inferior A1c and no increased hypo... does that not show that insulin to carb ratio is less important? Do you feel that if users were forced to dose SQ RAA in 4u increments they would not either sacrifice A1c results, or have increased hypo events? "...does that not show that insulin to carb ratio is less important?" Were the subjects restricted from carb counting? If not, then the type 1s most likely simply adjusted their carb counts as they titrated the dose of afrezza they were taking. That is a very interesting point. I wonder if that is even known for the larger studies... were patients given instructions regarding whether they needed to modulate carbs to match 4u increments... were patients asked if they had done so? We're smaller studies done with controlled meal portions? The dosing instructions on the label seem to imply that no carb adjustment is necessary. Would the FDA have approved those dosing instructions on the assumption that T1s would naturally modulate the carbs to match the dose? That doesn't seem like the FDA that gave multiple CRLs to MNKD. Though, as much as I thought I knew about the trials, I don't have a good answer to this. |
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Post by charleyd on Dec 12, 2015 16:25:49 GMT -5
The restoration of the Phase I insulin response with AFZ promotes the following:
1. Stops glucogenesis in the liver.
2. Stores glucose as glycogen in the liver.
3. Promotes synthesis of fat (fatty acids and triglycerides) by the liver.
AFZ time to 'peak' activity is much improved over lispro and results in improved post prandial glucose excursions. Timing is everything.
Over months and years of use, AFZ should reduce insulin resistance, improve lipid profile, reduce build up of Triglycerides in the liver, and reduce export of fatty acids and triglycerides by breaking the viscous cycle of excess glucose production and excess storage of fat.
I think it would be interesting to see the lipid profiles before and after AFZ therapy.
The multibillion dollar question, as a result of replacing the phase I response with AFZ, will the myriad comorbidites of vascular disease, neuropathies, and fatty liver disease reduce over the long term
with AFZ users. As I discussed above, afrezza does nothing different than an RAA. It can't because it is just insulin like an RAA. I also pointed out that the PD graph shows time onset and effect on glucose for the first 60 minutes is almost identical to lispro, so time to "peak activity" is substantially the same. There is currently no evidence that afrezza should have any different effect on "lipid profile, etc" than any other RAA. rrtzmd, I believe that your "peak activity" being substantially the same comment is based upon the PD graph shown in the Afrezza Insert. Dr. Edelman has been showing a different PD graph, which appears to show a significant difference. screencast.com/t/FiCnyq01egAny idea about why the graphs are different? The graphs in the insert have been bugging me because it does not make sense that Afrezza gets into the blood stream faster, but then the onset and effect on glucose winds up being essentially the same. |
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Post by Deleted on Dec 12, 2015 16:44:23 GMT -5
11-17-09 interview of Al Mann: www.healthline.com/diabetesmine/the-truth-about-afresa-inhalable-insulin-a-chat-with-al-mann#1"With Afrezza, there's no complex meal titration. You take a set amount, matched to your body mass and insulin resistance, determined with your doctor. You take that same amount every time you eat a meal. Then it's not important whether you eat 50 grams of carbs or 100 grams or even zero. Afrezza essentially "turns off glucogenesis" so no glucose is secreted from the liver in reaction to food. Our trial studies are showing that patients are having no more glucose highs than normal non-diabetic people, and no more lows.""With Afrezza, there's no complex meal titration...and no more lows." Has any endo ever vetted that statement? I know of no study demonstrating that, in type 1s, afrezza requires any less assessment of carb, fat and protein intake than any other RAA. And while, in type 2s, such assessment is less important, the same "no complex meal titration" applies as well to the use of RAAs. The same applies to "not important whether you eat 50 gms...etc" -- type 2s not so important, but very important in type 1s regardless of which insulin is used. "Afrezza essentially "turns off glucogenesis" -- yes in type 1 but so do RAAs; I already discussed type 2s above. "Our trial studies are showing..." and they ultimately showed that afrezza was non-inferior to lispro. Here is a great video of Al speaking in 2010 at Johns Hopkins. For the purposes of this discussion, he starts to speak about Afrezza at the 33 minute mark. A few minutes later, he gets into some detail about dosing, titration and differences between Type 1 and 2s as it pertains to Afrezza. www.youtube.com/watch?v=muBuxTqxmQoYou ask if any endo has ever vetted the statement regarding no complex meal titration with Afrezza? I don't know but I would suspect Bruce Bode can speak to the subject so if interested, perhaps give him a shout. You also said insulin is insulin which is true except when it's not. There are lots of sprinters, but only one Usain Bolt. Afrezza is better doc and the only reason it has a non-inferiority from the FDA is that by the time Mannkind had the final go around with the FDA I am confident that Al said something to his team like set up the trials to make approval as certain as possible and worry about the other details later. While this created some of the issues we deal with today, if the final trial did not result in approval, it would have been lights out. Can you tell me in your years of practice where you saw one product that controls blood glucose levels has produced positive results of the magnitude as the early adopters are experiencing? Not trying to paint you into a corner and I know data and scientific protocol are important but I spent time in this space and nothing I have seen past or current comes close. You can bet if the label gets changed and the prior authorization goes away and better formulary position comes that it will be lights out for some other players in the industry, injected, oral or other products / services for people with diabetes. The pump industry will evaporate. Of course, none of this comes to pass without these issues and the cash situation being addressed. |
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Post by Deleted on Dec 12, 2015 16:48:45 GMT -5
"With Afrezza, there's no complex meal titration. You take a set amount, matched to your body mass and insulin resistance, determined with your doctor. You take that same amount every time you eat a meal. Then it's not important whether you eat 50 grams of carbs or 100 grams or even zero. Afrezza essentially "turns off glucogenesis" so no glucose is secreted from the liver in reaction to food. Our trial studies are showing that patients are having no more glucose highs than normal non-diabetic people, and no more lows." This has been our experience to aT. Now that my husband has found the dose that is good for him, it generally doesn't matter what he eats. It does matter how LONG he eats. Of course, we aren't even testing his blood at every meal, because after the first few weeks (with coaching as far as timing of inhalation), there has been no need to keep checking. If he eats a normal meal, he simply inhales and doesn't think anything more about it. If the meal lasts over an hour, an additional puff has been found to be necessary in some cases. That is the only time he does follow up testing. And his A1c had gone down over 1% to 6.3 It's all good! Suebee, in addition to A1c and blood glucose, did your husband have any other blood work done just prior to starting on Afrzza and if so, has he had any recently and were there any improvements in the other lab results other than glucose and A1c and if my question is too personal, feel free to not answer and I apologize in advance for being so intrusive. |
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Post by suebeeee1 on Dec 12, 2015 16:53:47 GMT -5
suebeeee1 ... has SNY asked for any data on A1c or feedback on experience? Did your husband get an invite to SD... or asked in general if willing to participate in those sort of groups? No, he is a Type 2. No feedback has been requested. Not sure he would be the perfect subject as he doesn't test often, generally only after a very long dinner. Also, his current Dr. from Kaiser has been hiding the fact that she prescribed Afrezza since Kaiser will "ding" her for prescribing off the formulary. We are changing insurance companies and doctors next month. But, he still won't be testing much between A1c tests.....so? |
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Post by suebeeee1 on Dec 12, 2015 16:57:17 GMT -5
This has been our experience to aT. Now that my husband has found the dose that is good for him, it generally doesn't matter what he eats. It does matter how LONG he eats. Of course, we aren't even testing his blood at every meal, because after the first few weeks (with coaching as far as timing of inhalation), there has been no need to keep checking. If he eats a normal meal, he simply inhales and doesn't think anything more about it. If the meal lasts over an hour, an additional puff has been found to be necessary in some cases. That is the only time he does follow up testing. And his A1c had gone down over 1% to 6.3 It's all good! Suebee, in addition to A1c and blood glucose, did your husband have any other blood work done just prior to starting on Afrzza and if so, has he had any recently and were there any improvements in the other lab results other than glucose and A1c and if my question is too personal, feel free to not answer and I apologize in advance for being so intrusive. My husband had been on Metformin, Glucophage, Onglyza etc for the last 7 years. When his doc told him that an A1c of 7.6 was ok and he wished all of his patients had blood tests so good, we changed doctors and then had to beg, beg, beg for an Afrezza script. A1c dropped over 1% the first 3 months. This stuff is pretty amazing. Waiting for his next three months! |
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Post by jpg on Dec 12, 2015 17:16:22 GMT -5
The restoration of the Phase I insulin response with AFZ promotes the following:
1. Stops glucogenesis in the liver.
2. Stores glucose as glycogen in the liver.
3. Promotes synthesis of fat (fatty acids and triglycerides) by the liver.
AFZ time to 'peak' activity is much improved over lispro and results in improved post prandial glucose excursions. Timing is everything.
Over months and years of use, AFZ should reduce insulin resistance, improve lipid profile, reduce build up of Triglycerides in the liver, and reduce export of fatty acids and triglycerides by breaking the viscous cycle of excess glucose production and excess storage of fat.
I think it would be interesting to see the lipid profiles before and after AFZ therapy.
The multibillion dollar question, as a result of replacing the phase I response with AFZ, will the myriad comorbidites of vascular disease, neuropathies, and fatty liver disease reduce over the long term
with AFZ users. As I discussed above, afrezza does nothing different than an RAA. It can't because it is just insulin like an RAA. I also pointed out that the PD graph shows time onset and effect on glucose for the first 60 minutes is almost identical to lispro, so time to "peak activity" is substantially the same. There is currently no evidence that afrezza should have any different effect on "lipid profile, etc" than any other RAA. Rrtz, I don't mean to be blunt but this is simply not true. Monomeric Afrezza is very different than RAA. This is simple stuff. That you come back to this time and time again makes me doubt your attendance in endo classes... For one the tail is much shorter and you can 'super saturate' receptors safely thus causing all sorts of different physiological effects that injected analogues could not do (and if they were administered in doses sufficient to super saturate receptors the tail effect would probably often kill patients: and yes I really did mean kill patients). If you are an MD (which I doubt more and more) look at the margin of safety of esmolol and remifentanyl (in the hands of people who know what they are doing obviously) to see what the lack of tail can permit you to do. Fast in fast out insulin has even more physiologically beneficial effects. Your previous 'expose' of portal vein secretion is semi accurate but not important for the vast majority of clinical situations (look no further than peripheral insulin secreting transplants for a good demonstration of why being portal is beneficial but not necessary). As for lipid metabolism (NASH) your point of view is just a point of view but not necessarily in sync with some rather good theories of the associations of NASH and lipid/ glucose metabolism. You seem to discount a lot of pretty good theories rather easily... |
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Post by Deleted on Dec 12, 2015 18:32:02 GMT -5
jpg He is not a Dr. He is a short. Google his name and add a HAW to the search. I have posted it a few times but my posts keep getting deleted by someone. Which ever mod keeps deleting my posts message me I will point out the similarities in posts and how I figured it out. There is no point in replying to him because he will keep trying to spin it.
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Post by peppy on Dec 12, 2015 19:00:35 GMT -5
Restoring the "first phase"
Restoring first phase insulin release absolutely matters.
Whatever the reason for the failing first phase insulin release there's an ugly feedback mechanism that kicks in when blood sugar levels rise because of that failing first phase insulin release: High levels of circulating glucose themselves are toxic to beta-cells, a phenomenon called "glucose toxicity". So as blood sugars rise these high blood sugar concentrations further damage and or kill more beta-cells, making first and second phase insulin release even less able to control blood sugar concentrations.
If your beta-cells are still able to secrete enough insulin to provide a second phase insulin release, your body may be able to bring the blood sugar back down to a normal level by 3 hours and may then go back to secreting the small amounts of basal insulin which maintain a normal or near-normal blood sugar level while you are between meals or asleep. But when first phase insulin release is weak or missing your blood sugar may easily rise over the 200 mg/dl (11 mmol/L) level currently defined as "diabetes."
At that point, two bad things happen. When the concentration of glucose in your blood reaches 200 mg/dl (11 mmol/L) your cells become insulin resistant even if they weren't insulin resistant before, so it takes a lot more insulin to lower your blood sugar from that point on.
And, even worse, the lack of a robust insulin response to the rising glucose may erroneously be interpreted by your liver as a sign that blood sugar is too low and that it is time to dump more glucose into the bloodstream. So in addition to the glucose coming in from your recent meal you also have to contend with additional glucose dumped by your poor old confused liver.
I watched a video; Re-educate the Immune System: Gerald T. Nepom at TEDxRainier www.youtube.com/watch?v=QHSrG9Tuz84 Pictures of pancreatic beta cell damage caused by the auto immune system. screencast.com/t/Wphylu9k
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Post by mindovermatter on Dec 12, 2015 19:57:06 GMT -5
Suebee, in addition to A1c and blood glucose, did your husband have any other blood work done just prior to starting on Afrzza and if so, has he had any recently and were there any improvements in the other lab results other than glucose and A1c and if my question is too personal, feel free to not answer and I apologize in advance for being so intrusive. My husband had been on Metformin, Glucophage, Onglyza etc for the last 7 years. When his doc told him that an A1c of 7.6 was ok and he wished all of his patients had blood tests so good, we changed doctors and then had to beg, beg, beg for an Afrezza script. A1c dropped over 1% the first 3 months. This stuff is pretty amazing. Waiting for his next three months! Have you thought about writing your old Endo and update him about how well your Husband is doing now that he's on Afrezza, the drug he wouldn't even consider? Might give him something to think about. I know if my wife went through what you and your husband went through, I'd hand deliver if not talk to the doctor face to face and show him the proof. Might not make him change his mind but it would definitely make him think. |
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Post by Deleted on Dec 12, 2015 19:59:05 GMT -5
My husband had been on Metformin, Glucophage, Onglyza etc for the last 7 years. When his doc told him that an A1c of 7.6 was ok and he wished all of his patients had blood tests so good, we changed doctors and then had to beg, beg, beg for an Afrezza script. A1c dropped over 1% the first 3 months. This stuff is pretty amazing. Waiting for his next three months! Have you thought about writing your old Endo and update him about how well your Husband is doing now that he's on Afrezza, the drug he wouldn't even consider? Might give him something to think about. I know if my wife went through what you and your husband went through, I'd hand deliver if not talk to the doctor face to face and show him the proof. Might not make him change his mind but it would definitely make him think. Atleast the next pwd will encounter less resistance and I hope you do that subbeeeee |
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Post by tommix321 on Dec 13, 2015 13:40:05 GMT -5
As I discussed above, afrezza does nothing different than an RAA. It can't because it is just insulin like an RAA. I also pointed out that the PD graph shows time onset and effect on glucose for the first 60 minutes is almost identical to lispro, so time to "peak activity" is substantially the same. There is currently no evidence that afrezza should have any different effect on "lipid profile, etc" than any other RAA. rrtzmd, I believe that your "peak activity" being substantially the same comment is based upon the PD graph shown in the Afrezza Insert. Dr. Edelman has been showing a different PD graph, which appears to show a significant difference. screencast.com/t/FiCnyq01egAny idea about why the graphs are different? The graphs in the insert have been bugging me because it does not make sense that Afrezza gets into the blood stream faster, but then the onset and effect on glucose winds up being essentially the same. It could be because the graph used by Dr. Edelman is comparing afrezza to lispro in normal subjects while the graph in the insert used type 1 diabetics. Look at this powerpoint presentation: Afrezza Approved by the FDASlide 55 compares the results of trial 176 using normal subjects and trial 177 using type 1 diabetics. The graph from trial 176 looks like the one used by Edelman. The one from 177 looks like the one in the insert. |
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Post by charleyd on Dec 14, 2015 12:21:20 GMT -5
rrtzmd, I believe that your "peak activity" being substantially the same comment is based upon the PD graph shown in the Afrezza Insert. Dr. Edelman has been showing a different PD graph, which appears to show a significant difference. screencast.com/t/FiCnyq01egAny idea about why the graphs are different? The graphs in the insert have been bugging me because it does not make sense that Afrezza gets into the blood stream faster, but then the onset and effect on glucose winds up being essentially the same. It could be because the graph used by Dr. Edelman is comparing afrezza to lispro in normal subjects while the graph in the insert used type 1 diabetics. Look at this powerpoint presentation: Afrezza Approved by the FDASlide 55 compares the results of trial 176 using normal subjects and trial 177 using type 1 diabetics. The graph from trial 176 looks like the one used by Edelman. The one from 177 looks like the one in the insert. tommix321, looks like you found it. Thanks, and excellent sleuthing, as I had spent a fair amount of time trying to understand this. Not that this is what I was hoping, but Dr. Edelman appears to be somewhat misrepresenting Afrezza's performance (since it is meant to be used on diabetics instead of normal subjects), and he must be aware of the later data from the 177 study. Still does not make complete sense to me that Afrezza can enter the blood stream faster as a monomer, compared to Lispro which is slower and must be broken down to monomeric form, and yet they both have a similar onset of action and effect on glucose (for the first hour). But the data is the data. |
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