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Post by Deleted on Jun 7, 2022 18:15:48 GMT -5
This looks like an Afrezza killer for the Type 2 market. You get 2 benefits from taking Mounjaro....Weight Loss and Diabetes is put into remission. No need for Afrezza... Casper - if you have read some of my posts since Mounjaro's approval, I think I predicted a lot of press at ADA2022 for Mounjaro. I actually look at this as a positive for afrezza and I will explain. The big problem T2s face is they lose post prandial control. When properly dosed afrezza should be able to stop the post meal spike and get the PWD below 140. Since there is little fear of severe hypos a target of 100 post meal should be doable in most cases. That would be an A1C of 5.1. In theory if the PWD is making enough fasting insulin they should be able to maintain that level give/take. If they can not we have them take an additional puff during fasting. If I remember correctly Mounjaro was delighted to get an average 6.9 A1C which is about 152 mg/dl. Mounjaro is being toted as the new T2 Champ. It now provides a single focus for a Mounjaro/afrezza head to head trial. Does anyone on this board not think if properly dosed afrezza can not beat Mounjaro's A1C? To be honest, I don't fully understand the weight loss they are claiming. They reduced the caloric intake and provided diet coaches. They also lost up to 8% of the PWDs because they kept throwing up. I guess making the PWD sick to their stomach so they are not hungry is one way to have them lose weight but I am not sure this is the best way. I bet if we ran a combo trial with Mounjaro/afrezza this would do as well as the Mounjaro/GLP1 arm for weight loss. Sayhey I am encouraged that you keep pushing your theory but it's not going to happen. There's no way Lily is going to be out muscled by little ole MNKD. This is truly the 900Lb gorilla and MNKD will not survive in the T2 market and I'll tell you why. What's the percentage of Type 2's on insulin?? Maybe 10% (I'll be generous) ? Lily is going to market the hell out of Mounjaro as an OBESITY BUSTER Drug and they either have the data or will run a study to get the data that you will LOSE WEIGHT and put your Pre-Diabetes/Diabetes into REMISSION. Hence NO NEED TO TAKE INSULIN. As I've said before there is a STIGMA with the word INSULIN and when people hear the word the first thing out of their mouth is NO. It's going to take a HUGE amount of MONEY and TIME to change that. To answer your question about nausea? The patient will take an anti-nausea pill. And the Box warning is fine for thyroid tumors. Drs. will not prescribe if there's family history. If a patient can lose 25-50% of their body weight without bariatric surgery by taking a shot once a week?? Hell I'm going to call my doctor after it hits the market. This is truly a game changer. And to further the numbers 90% of Type 2's are on Orals Meds. I see Mounjaro competing against Trulicity, Jardiance and the other once a week injections. |
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Post by peppy on Jun 7, 2022 18:20:57 GMT -5
I bet if we ran a combo trial with Mounjaro/afrezza this would do as well as the Mounjaro/GLP1 arm for weight loss. I would take that bet. One thing I don't think you realize is that diabetes is a metabolic disease. It's not just a dysfunction of glucose/insulin secretion and absorption, which is all Afrezza addresses. There is a reason GLP-1's use a different mechanism of action and is still relatively successful with glucose control. Insulin is not the only glucose modulating hormone in the body. Multiple systems (in type 2 anyway) are disrupted. You say that no additional tests are needed... Long term data would be needed to prove Afrezza is superior to GLP-1s with improved outcomes. We already see improved cardiovascular outcomes with GLP-1s and have not seen the same with previous insulins. You are quick to point out how different Afrezza is from other insulins, yet you want to pick and choose when to use the former understanding of insulin for your argument. Either Afrezza is similar enough to other insulins that we can use previous understanding and data about insulin treatment, or it's different enough that we need to see- through new data- its differences and nuances. I don't think anyone would argue that anything would be better than insulin at controlling serum glucose levels. That's not really the question anyone is trying to answer. The real question is "which treatment will produce the best outcomes for diabetes as a chronic disease?" We don't have enough information at this point in time to answer that. The benefits of GLP-1s extend beyond glucose control and appear to, at least partially, address the underlying metabolic dysfunction of the disease. For the record, I'm team Afrezza. I've been accumulating shares of MNKD from Sept 2020 until now. I had completely lost faith in the stock and got out, but now am back in for the long haul. I just haven't been convinced that Afrezza is the best or only way to treat the disease. I see how it could be, but I also see how it couldn't. Stay tuned for the sequel; Technosphere, A sweet delivery system for lung disease. |
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Post by sayhey24 on Jun 7, 2022 19:18:54 GMT -5
I bet if we ran a combo trial with Mounjaro/afrezza this would do as well as the Mounjaro/GLP1 arm for weight loss. I would take that bet. One thing I don't think you realize is that diabetes is a metabolic disease. It's not just a dysfunction of glucose/insulin secretion and absorption, which is all Afrezza addresses. There is a reason GLP-1's use a different mechanism of action and is still relatively successful with glucose control. Insulin is not the only glucose modulating hormone in the body. Multiple systems (in type 2 anyway) are disrupted. You say that no additional tests are needed... Long term data would be needed to prove Afrezza is superior to GLP-1s with improved outcomes. We already see improved cardiovascular outcomes with GLP-1s and have not seen the same with previous insulins. You are quick to point out how different Afrezza is from other insulins, yet you want to pick and choose when to use the former understanding of insulin for your argument. Either Afrezza is similar enough to other insulins that we can use previous understanding and data about insulin treatment, or it's different enough that we need to see- through new data- its differences and nuances. I don't think anyone would argue that anything would be better than insulin at controlling serum glucose levels. That's not really the question anyone is trying to answer. The real question is "which treatment will produce the best outcomes for diabetes as a chronic disease?" We don't have enough information at this point in time to answer that. The benefits of GLP-1s extend beyond glucose control and appear to, at least partially, address the underlying metabolic dysfunction of the disease. For the record, I'm team Afrezza. I've been accumulating shares of MNKD from Sept 2020 until now. I had completely lost faith in the stock and got out, but now am back in for the long haul. I just haven't been convinced that Afrezza is the best or only way to treat the disease. I see how it could be, but I also see how it couldn't. Stevil - I bet I will win. I also realize diabetes is a metabolic disease which in most PWDs the issues start because of their high BG. Not all but most. Their high BG starts because of a loss of beta cell function and if Joslin is correct it is a viral attack on the beta cells. With covid and the increase we are seeing there is now addition support for the claims Josil made years ago. Why would we now do a trial against other GLP1s when the new kid on the block is a GIP and claiming its the new Champ? How long would you like the trial, 24 weeks? Mounjaro vs afrezza - I say afrezza kicks butt on A1C but we play by my rules in the trial. If you want to do a weight loss study I honestly do not understand what Lilly is claiming. We know Mounjaro made people vomit and up to 8% dropped out. We also know they reduced caloric intake and had health coaches monitoring their diet and their increase in exercise. Thats why I am saying if we knew what they did I really don't think it would make much difference if we subbed the afrezza for the GLP1. If Mounjaro is going to make them not want to eat because they have a bellyache if we sub the afrezza they will still have the bellyache. Give us a level field and afrezza/Mounjaro should do as well as Mounjaro/GLP1 for weight loss. Also adding the GIP or GLP1 to afrezza is also OK if we are trying to reduce weight but afrezza is about reducing BG. They use to give out amphetamines like candy to reduce weight and they worked for the weight but yes they caused other issues. If properly dosed and the T2 still has fasting insulin we should not need the GIP/GLP1. Worst case is an evening puff of afrezza should hold them over night or if they really need the basal that too is an option. But early T2s should still be producing and if we can get them early in most cases afrezza will stop the progression. I would argue we can most definitely use other insulin trials as they apply. For example trials which demonstrated early insulin intervention. Insulin is insulin once its in the blood stream although the jury is still out on the analogs and long term safety. BTW- I gave my first insulin shot to my dad 51 years ago today as he could not give himself shots. My aunt was the head nurse at a major NYC hospital and knew more about treating diabetics than any doctor at the time because she had to do it. When she heard my Dad was put on orinase when first diagnosed she called up his doctor, gave him hell and predicted what would happen. Then he was put on diabinese like that was going to make a difference. He should have been put on insulin day 1 and back then we did not have todays insulins nor did we have the thin needles. We used to boil them before use and we would sharpen them ourselves when they got dull. With now having afrezza I can think of few good reasons not to start the new T2 on afrezza day 1. I have not seen an oral which does not end up causing other issues or bigger issues. Read what Philip Home wrote a few months back diatribe.org/type-2-diabetes-start-earlyYou can't make this stuff up. Give the PWD all this crap and in 5-15 years they will probably need insulin anyway. So why don't we just give them the afrezza day 1 aside from cutting into the $25B GLP1s and SGLT2 are generating yearly? From Philip Home- "Newer tools of glucose monitoring are a great help in managing insulin doses, which vary a lot from person to person. If you aren’t able to achieve the results you and your healthcare team want after trying to manage your glucose levels with other medications, you will most likely be offered insulin (you can also ask your HCP about it at any time). Indeed, after 5-15 years, it is very common to need insulin anyway to manage your glucose levels and to stay healthy for another 20-plus years." |
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Post by stevil on Jun 7, 2022 19:20:06 GMT -5
To add to my previous post a point I didn't fully communicate. pubmed.ncbi.nlm.nih.gov/28958751/Our bodies are wonderfully made and are complicated beyond belief. It seems that any imbalance causes problems in the system, even providing an excess of what is considered "good". The reason we need new trials with Afrezza is that a lot of damage done by insulin may be mitigated by the rapidity of Afrezza's speed. We know, with certainty, that an excess of insulin causes worsening disease. However, if insulin finishes its job and doesn't hang around afterwards, would that provide better results? We won't know until we do more studies... Are GLP-1s safe by the same logic? We won't know until time tells the tale. As of now, it appears they are profoundly safe. Millions are on the medications and are getting positive results. Time will reveal the negative issues, if any, that come from manipulating glucagon analogues. |
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Post by stevil on Jun 7, 2022 20:08:09 GMT -5
Stevil - I bet I will win. I also realize diabetes is a metabolic disease which in most PWDs the issues start because of their high BG. Not all but most. Their high BG starts because of a loss of beta cell function and if Joslin is correct it is a viral attack on the beta cells. With covid and the increase we are seeing there is now addition support for the claims Josil made years ago. Why would we now do a trial against other GLP1s when the new kid on the block is a GIP and claiming its the new Champ? How long would you like the trial, 24 weeks? Mounjaro vs afrezza - I say afrezza kicks butt on A1C but we play by my rules in the trial. If you want to do a weight loss study I honestly do not understand what Lilly is claiming. We know Mounjaro made people vomit and up to 8% dropped out. We also know they reduced caloric intake and had health coaches monitoring their diet and their increase in exercise. Thats why I am saying if we knew what they did I really don't think it would make much difference if we subbed the afrezza for the GLP1. If Mounjaro is going to make them not want to eat because they have a bellyache if we sub the afrezza they will still have the bellyache. Give us a level field and afrezza/Mounjaro should do as well as Mounjaro/GLP1 for weight loss. Also adding the GIP or GLP1 to afrezza is also OK if we are trying to reduce weight but afrezza is about reducing BG. They use to give out amphetamines like candy to reduce weight and they worked for the weight but yes they caused other issues. If properly dosed and the T2 still has fasting insulin we should not need the GIP/GLP1. Worst case is an evening puff of afrezza should hold them over night or if they really need the basal that too is an option. But early T2s should still be producing and if we can get them early in most cases afrezza will stop the progression. I would argue we can most definitely use other insulin trials as they apply. For example trials which demonstrated early insulin intervention. Insulin is insulin once its in the blood stream although the jury is still out on the analogs and long term safety. BTW- I gave my first insulin shot to my dad 51 years ago today as he could not give himself shots. My aunt was the head nurse at a major NYC hospital and knew more about treating diabetics than any doctor at the time because she had to do it. When she heard my Dad was put on orinase when first diagnosed she called up his doctor, gave him hell and predicted what would happen. Then he was put on diabinese like that was going to make a difference. He should have been put on insulin day 1 and back then we did not have todays insulins nor did we have the thin needles. We used to boil them before use and we would sharpen them ourselves when they got dull. With now having afrezza I can think of few good reasons not to start the new T2 on afrezza day 1. I have not seen an oral which does not end up causing other issues or bigger issues. Read what Philip Home wrote a few months back diatribe.org/type-2-diabetes-start-earlyYou can't make this stuff up. Give the PWD all this crap and in 5-15 years they will probably need insulin anyway. So why don't we just give them the afrezza day 1 aside from cutting into the $25B GLP1s and SGLT2 are generating yearly? From Philip Home- "Newer tools of glucose monitoring are a great help in managing insulin doses, which vary a lot from person to person. If you aren’t able to achieve the results you and your healthcare team want after trying to manage your glucose levels with other medications, you will most likely be offered insulin (you can also ask your HCP about it at any time). Indeed, after 5-15 years, it is very common to need insulin anyway to manage your glucose levels and to stay healthy for another 20-plus years." Unless you have intimate knowledge about Afrezza that no one else has, there is no basis for your hypothesis from history or current understanding of insulin therapy. Weight gain is nearly ubiquitous amongst insulin users. In all data published by MNKD, at best Afrezza was weight neutral, a far cry from the claims Mounjaro is proposing. Are you sure you're not confusing type 2 with type 1? In type 2, I don't buy that hypothesis at all because I don't understand how beta cell destruction adequately explains insulin resistance or the phenomenon of an elevation in serum insulin levels during the early stages of disease to compensate. Insulin resistance alone will NOT lead to type 2 diabetes. Rather, type 2 diabetes develops in insulin-resistant individuals who also show impaired beta cell function. If all type 2 disease had a viral etiology, I don't see how it is reversed by lifestyle modifications or by bariatric surgery. I think it's pretty clear there is some other causative event that is disrupting the system with decreased insulin production being the effect rather than the cause. I'm much more apt to blame fat cells and adipokines or lipotoxicity rather than a virus for type 2s. I have my own theories about the link between covid and diabetes. I think this is a decent place to start. wexnermedical.osu.edu/blog/why-are-people-developing-diabetes-after-having-covid19If A1c is your metric, I would never bet against insulin. Insulin is the most efficient method to decrease serum glucose. I thought we were betting on weight loss? 8% is still a very low number for the potential benefit. It's why having more options for treating disease is great. Those 8% will have another option to choose from. Afrezza also had patients drop out due to cough... It happens... I have had patients that stopped taking GLP-1s due to the GI distress. I think it's likely more tied to gastric emptying as I think this patient already had underlying gastroparesis and the GLP-1 probably made it worse as she already had pretty profound neuropathy elsewhere already. Don't really know since I never saw that patient again. However, I can assure you that the weight loss was not due to vomiting as I have also had many patients with weight loss on GLP-1s that had absolutely no side effects at all, including vomiting up their guts or not wanting to eat because of a belly ache. |
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Post by slapshot on Jun 7, 2022 20:58:05 GMT -5
This looks like an Afrezza killer for the Type 2 market. You get 2 benefits from taking Mounjaro....Weight Loss and Diabetes is put into remission. No need for Afrezza... Got to love this line
"People in the study also received counseling sessions to help them stay on a healthy diet with a daily 500-calorie deficit, as well as at least 150 minutes of physical activity each week. While that certainly helped, it does not explain the magnitude of the weight loss seen in the study, Gabbay said."
Losing weight is easier if you have someone telling you what to do and keeping you motivated. If you are serious about losing weight you probably already have the will power to stick with dieting and exercise, but wait those people probably don't need the drug for weight loss.
Ever hear of the BFFM diet, by Tom Venuto? I did it back in the 2000's and it was awesome, lost weight, etc.
BFFM = Burn the Fat, Feed the Muscle
the basic premise is to burn the fat (exercise to burn 500 calories) and feed the muscle ("healthily" stay on a daily 500 calorie deficit) which combines to a 1000 calorie daily deficit or 7000 per week. 7000 / 3500 (cal/lb) = 2 lbs weight loss a week.
No drugs needed
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Post by peppy on Jun 7, 2022 22:43:44 GMT -5
Got to love this line
"People in the study also received counseling sessions to help them stay on a healthy diet with a daily 500-calorie deficit, as well as at least 150 minutes of physical activity each week. While that certainly helped, it does not explain the magnitude of the weight loss seen in the study, Gabbay said."
Losing weight is easier if you have someone telling you what to do and keeping you motivated. If you are serious about losing weight you probably already have the will power to stick with dieting and exercise, but wait those people probably don't need the drug for weight loss.
Ever hear of the BFFM diet, by Tom Venuto? I did it back in the 2000's and it was awesome, lost weight, etc.
BFFM = Burn the Fat, Feed the Muscle
the basic premise is to burn the fat (exercise to burn 500 calories) and feed the muscle ("healthily" stay on a daily 500 calorie deficit) which combines to a 1000 calorie daily deficit or 7000 per week. 7000 / 3500 (cal/lb) = 2 lbs weight loss a week.
No drugs needed
I once walked 3 miles an hour for 3 hours on a treadmill and burned 470 calories. I had to look, it was slapshot that posted the solution to weight loss. |
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Post by prcgorman2 on Jun 7, 2022 23:41:59 GMT -5
No offense to anyone, but I think the alternatives for insulin, especially after a meal, are basically red herrings, stevil’s comments regarding metabolic disorders beyond failures in the pancreas excepted. If the diagnosis is insulin deficiency, the solution is insulin. The problems have been being able to provide someone with inulin in a way that helped with the deficiency but didn’t frequently kill them. RAAs do that well, but do hasten death nonetheless. Afrezza is literally a game changer. I’m not going to be distracted by alternatives and neither is anyone’s body, long term. This is a marathon, not a sprint. T2s are a great market and maybe someday Afrezza will dominate there. The science needs to lead the prescribers and the T2s there.
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Post by sayhey24 on Jun 8, 2022 6:01:12 GMT -5
Stevil - I am limited on time so to be short let me give you a few things to think about
Weight gain is nearly ubiquitous amongst insulin users. Why? Why is it neutral with afrezza?
What is Mounjaro doing for weight loss?
You ask "Are you sure you're not confusing type 2 with type 1? In type 2" NO - Joslin had isolated at least 4 specific viruses until the research was stopped.
You ask "I don't buy that hypothesis at all because I don't understand how beta cell destruction adequately explains insulin resistance" Why is it you need more insulin to bring down a post meal spike than if you stop the spike so you are not dealing with the post meal high BG? You would think if the pancreas released the insulin it had to deal with the meal and then you give the PWD some additional insulin you would need less but thats not what happens. Why?
Why do obese non-diabetics grow huge masses of beta cells and not PWDs?
The "insulin resistance" theory, do you now where that came from and why it was needed to support his work? Hint - initials R.D.
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Post by stevil on Jun 8, 2022 6:30:33 GMT -5
Insulin is a growth hormone. To answer your question, I don’t know that Afrezza is weight neutral. Not much data has been published. Possible reasons why could be less inflammation, insulin doesn’t hang around as long so less fat production, less metabolic effect. Regardless, more data and study is needed.
mounjaro is hijacking a metabolic mechanism to trick the body into not storing fat and to actually release fat stores in the body. Insulin can actually drive glucose into fat and increase production…
I’ll flip your insulin resistance question back onto you to shed light on why I don’t buy a common etiology between the two diseases. Why is it that you could give a type 2 diabetic 100 units of lantus a day and still not achieve proper basal control, while that same dose would be lethal to probably any single type 1 that exists? The reason is that the issue isn’t solely with insulin production but an actual disruption to the body’s ability to use insulin. The reason an obese person would have hypertrophic beta cells is they likely don’t have the gene that codes for a weaker beta cell and are able to properly compensate. The current prevailing theory is beta cell exhaustion for type 2 and I fins that to be far more plausible than an antibody mediated response to a virus. I do believe type 1s could be viral. But if type 1s modify their lifestyle with diet and exercise, if they have bariatric surgery, if they start early intensive insulin treatment for beta cell rest, there is little to no change to their disease and they still become fully insulin dependent once all beta cells are lost. A viral etiology makes no sense in a reversible disease that does not target antibodies. As I stated before, insulin resistance does not appear to cause diabetes necessarily. There appears to be another component. But it nearly always predates the loss of beta cell function. I would expect the beta cell loss first if viral.
there are also a myriad of other metabolic issues that are linked to diabetes. Obesity, hypertension, hyperlipidemia, fatty liver. Why would other metabolic conditions increase diabetes I viral? I suppose you could take the immunocompromised angle, but a metabolic cause seems to be far more consistent.
i keep forgetting to add one of the most compelling pieces to the argument against a viral etiology- gestational diabetes. How can a woman go in and out of diabetes (sometimes multiple times) and not later go on to develop the disease after child birth if a virus causes the disease? Why would gestational diabetes increase the risk of later developing the disease if purely viral? Again, I feel a metabolic cause is the far more likely answer.
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Post by uvula on Jun 8, 2022 8:13:53 GMT -5
Great discussion/debate.
"If the diagnosis is insulin deficiency, the solution is insulin"
One of the main issues seems to be whether insulin deficiency is a symptom or a diagnosis.
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Post by peppy on Jun 8, 2022 8:41:09 GMT -5
Insulin is a growth hormone. To answer your question, I don’t know that Afrezza is weight neutral. Not much data has been published. Possible reasons why could be less inflammation, insulin doesn’t hang around as long so less fat production, less metabolic effect. Regardless, more data and study is needed. mounjaro is hijacking a metabolic mechanism to trick the body into not storing fat and to actually release fat stores in the body. Insulin can actually drive glucose into fat and increase production… I’ll flip your insulin resistance question back onto you to shed light on why I don’t buy a common etiology between the two diseases. Why is it that you could give a type 2 diabetic 100 units of lantus a day and still not achieve proper basal control, while that same dose would be lethal to probably any single type 1 that exists? The reason is that the issue isn’t solely with insulin production but an actual disruption to the body’s ability to use insulin. The reason an obese person would have hypertrophic beta cells is they likely don’t have the gene that codes for a weaker beta cell and are able to properly compensate. The current prevailing theory is beta cell exhaustion for type 2 and I fins that to be far more plausible than an antibody mediated response to a virus. I do believe type 1s could be viral. But if type 1s modify their lifestyle with diet and exercise, if they have bariatric surgery, if they start early intensive insulin treatment for beta cell rest, there is little to no change to their disease and they still become fully insulin dependent once all beta cells are lost. A viral etiology makes no sense in a reversible disease that does not target antibodies. As I stated before, insulin resistance does not appear to cause diabetes necessarily. There appears to be another component. But it nearly always predates the loss of beta cell function. I would expect the beta cell loss first if viral. there are also a myriad of other metabolic issues that are linked to diabetes. Obesity, hypertension, hyperlipidemia, fatty liver. Why would other metabolic conditions increase diabetes I viral? I suppose you could take the immunocompromised angle, but a metabolic cause seems to be far more consistent. i keep forgetting to add one of the most compelling pieces to the argument against a viral etiology- gestational diabetes. How can a woman go in and out of diabetes (sometimes multiple times) and not later go on to develop the disease after child birth if a virus causes the disease? Why would gestational diabetes increase the risk of later developing the disease if purely viral? Again, I feel a metabolic cause is the far more likely answer. Stevil, thank you for the thoughts and word processing. Years ago, I latched on to, 'insulin resistance is secondary to; too much fat in the system." Get rid of the fat in the system, and cells once gain use insulin and blood glucose comes down secondary to that. I remember from college, carbs 4 calories per gram, fat 9 calories per gram. Keto stopped people from the fat conversation. (A few years ago, I came upon this. Why do some people gain weight and are/become type two's? Why do some people gain weight, become extremely large and do not have type two diabetes? The hypothesis on this one, the second example, person that doesn't have insulin resistance continues to gain weight. At some level, does insulin resistance sabotage additional weight gain?) |
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Post by mango on Jun 8, 2022 13:44:04 GMT -5
All T1D and T2D have one thing in common and that’s a diminished or loss of the first phase insulin response. Afrezza fixes that underlying defect, rather perfectly in fact, and you see the second phase response kick in just like it’s suppose to. We see the feedback loop working like it’s intended. Afrezza is restoring post prandial glucose homeostasis. We see evidence of this not just from the clinical trials but everyday use and people showing their TIR and A1c. What’s the point in using all these anti diabetic oral endocrine disruptors that have nasty side effects and potentially horrific adverse events when you can just use Aftezza and treat the underlying defect?
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Post by stevil on Jun 8, 2022 14:13:33 GMT -5
Great discussion/debate. "If the diagnosis is insulin deficiency, the solution is insulin" One of the main issues seems to be whether insulin deficiency is a symptom or a diagnosis. Insulin deficiency doesn't develop until later in the disease, which is why beta cell exhaustion is the predominant theory. No one really knows the real cause for sure, at least not when I was in medical school and I haven't heard any updates since. During the early stages of type 2, serum insulin levels increase, presumably because muscle/fat/liver become resistant to insulin binding at its receptor. (theoretically) This results in the body telling the pancreas to secrete more insulin since it isn't receiving the normal feedback mechanism that insulin has done what it was supposed to do. Beyond what I have already shared, further evidence exists that would lend support to the insulin resistance theory. There have been insulin receptors identified on muscle, fat, liver, and brain tissue- GLUT receptors- that are believed to either have conformational change (meaning the receptor either changes size/shape so that insulin fits/doesn't fit) or the receptors get up/down regulated depending on the body's needs. The implications of this is that it takes resources to maintain a receptor and if it is no longer needed, it can be recycled for use elsewhere, or it is binding insulin that isn't needed. In layman's terms, GLUT receptors are the insulin binding receptors on muscle/fat/brain/liver etc. In times of high energy need, more insulin receptors are needed because glucose=energy. When energy is not needed, the receptors are no longer needed and the body doesn't want to keep the receptors active when glycogen stores are full, so the receptors either change shape or are eliminated to reduce the uptake of additional energy. It has been proven that exercise will restore this functionality of the receptors since more energy is needed to take up glucose, once again pointing to a metabolic component to the disease. Keep in mind, the GLUT receptors are not the only cells that become resistant to insulin, but they are the predominant ones. You can literally flip them on or off with being sedentary or active. A virus would not behave that way. Having said all that, the question remains, what is the best way to treat a chronic disease? Is insulin the answer? Previous insulins have caused an increase in cardiovascular disease (one of the biggest and worst causes of mortality from the disease) while GLP-1s have shown to decrease cardiovascular disease and many other long-term complications. There has never been an insulin that does its job and then leaves when the job is done, so it's hard to say whether the resulting complications from insulin therapy are the result of long-acting insulin and if this effect would be ameliorated by Afrezza's speed and efficiency. Diabetes is not solely a glucose and insulin problem. There are many other metabolic pathways affected in the disease. Manipulation of which pathway produces the best results? We don't know yet. Insulin has been tried and failed with pretty poor results, but it was different than Afrezza. We don't have too much long term data on GLP-1s yet, but they appear to have fairly promising results with long-term use when judging by the resultant complications of the disease outside of A1c control. We may find that a combination of treatment is ideal with a multi-pronged approach of mixing the two together. Whatever the answer is, it is not a simple one and there is not yet enough information available to definitively answer the question. |
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Post by mango on Jun 8, 2022 16:18:30 GMT -5
Non of the current treatment modalities other than Afrezza mimic the prandial physiologic insulin secretion pattern of a rapid spike in serum insulin concentration. A central characteristic of diabetes is impaired β-cell function. One abnormality that occurs early in the disease progression in both type 1 and 2 diabetes is the loss of eating-induced rapid insulin response. Consequently, the liver continues to produce glucose, which adds to the glucose that is ingested and absorbed from the basic components of a meal. Healthy pancreatic β-cells generate an early response to a meal-like glucose exposure that rapidly elevates serum insulin both in the portal circulation and in the periphery. Conversely, defective β-cells, which have an impaired early-phase insulin response, generate a sluggish response to the meal-like glucose exposure. Increasingly, evidence indicates that an early relatively rapid insulin response following glucose ingestion plays a critical role in the maintenance of postprandial glucose homeostasis. An early surge in insulin concentration can limit initial glucose excursions, mainly through the inhibition of endogenous glucose production. Therefore the induction of a rapid insulin response in a diabetic individual is expected to produce improved blood glucose homeostasis. In a normal individual, a meal induces the secretion of a burst of insulin, generating a relatively rapid spike in serum insulin concentration that then decays relatively quickly. This early-phase insulin response is responsible for the shut-off, or reduction, of glucose release from the liver. Homeostatic mechanisms then match insulin secretion (and serum insulin levels) to the glucose load. This is observed as a slow decay of modestly elevated serum insulin levels back to baseline and is second-phase kinetics. patents.justia.com/patent/11013788 |
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