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Post by agedhippie on Dec 16, 2019 4:38:55 GMT -5
Overwhelming evidence is that eating too much and getting too little exercise are major contributors to T2, just as smoking is major contributor to lung cancer, and alcohol to liver disease (and liver as you stated about pancreas does have some ability to grow and regenerate to counter high levels of toxins, but it as with the pancreas can simply be overwhelmed and burn out in the one case and scar and die off in the other). Our body has regenerative capability, but not unlimited. And some more than others. A few people eat, drink and smoke up a storm their entire lives and don't succumb to the diseases linked to the behaviors. There is some genetics and luck of the draw in it. That's not completely true. I usually stay out of Type 2 matters like this because it's not my fight, however I make an exception for the "you did it to yourself" argument.  These days Type 2 is thought to be genetic with over 100 genes so far identified. The disease itself has multiple aspects depending on the Type 2 variant you are looking at, but the one thing they all have in common is insulin deficiency, not weight. The weight aspect is primarily a western issue, and in Asia the number of thin to obese Type 2 diabetics is reversed - only around 20% are obese. The current thinking is that Type 2 is due to a gap between cell death and regrowth in some people (apoptosis). This creates a deficit that accumulates with time. You become diabetic when you have an insulin deficit of around 40% (rats go down to 60% as an FYI  so that deficit may never get big enough for you to get full blown Type 2. At this point someone will ask, so why does losing weight prevent diabetes? Short answer is that it doesn't , it delays it and the ideal is that the delay is long enough for you to die of old age before it returns but that is outside your control. As you gain weight you gain insulin resistance and the body builds out beta cells so you never notice. If there is an error then you are increasing the race towards that 40% deficiency. Losing weight reduces your insulin resistance and hence the deficit pulling you away from that red line. However in the background you are still underproducing beta calls so your deficit continues to creep upwards towards that red line. The size of this error varies from person to person and thin Type 2 diabetics are thought to be more aggressive (large gap) cases. But I said this wasn't to do with weight. In some cases it is and there are genes in the identified group that act as ratchets making it easy to gain weight and very hard to lose, as well as others that push you to overeat. These are thought to be hangovers from far earlier times when the ability to gain weight was a survival trait. Type 2 is horribly complex genetically and that mess is one reason they are likely to find a cure for Type 1 before Type 2 in my opinion. Disclaimer now; it's been about four years since I looked into this so things may have moved on. The basic premise, and this is supported by the stats, is that if you have the wrong genes you have to be careful, and if you don't you can eat until you are the size of a small killer whale with no danger of ever becoming diabetic. Never mind overweight or obese, only 55% of morbidly obese people have Type 2 and if it was weight related that would be borderline impossible. |
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Post by agedhippie on Dec 16, 2019 4:43:31 GMT -5
... Has a T2 only using afrezza every gone to the hospital for a severe hypo? I have never heard of any. My immediate thought is why would you have heard? |
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Post by sayhey24 on Dec 16, 2019 6:42:37 GMT -5
ktim - there is a world of difference between contributing factor and root cause. The root cause of T2 diabetes is that the pancreas is not producing enough insulin for the body's needs. Its not producing enough insulin because it has lost beta cell mass. We know this from autopsy. Drinking a can of Coke did not cause the beta cells to die. I will however tell you my Dad really thought his daily Coke at lunch was why he was diabetic.
We know if we give early stage T2s insulin we can see no further loss and in some case regeneration of beta cells even if with no weight loss. Are the beta cells simply "burning out" on their own as you suggest? Its possible but an external agent is where I would put my money.
The bottom line in either case, just give them the afrezza. Is the viral theory interesting? I think it is. Is it proven, no. What we do know is afrezza works and metformin does not. We know afrezza stops the post meal spike and SGLT2s and GLP1s don't.
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Post by sayhey24 on Dec 16, 2019 6:46:01 GMT -5
... Has a T2 only using afrezza every gone to the hospital for a severe hypo? I have never heard of any. My immediate thought is why would you have heard? My guess is Ollie Brandicourt or his kind would have made it front page news. Do you not think afrezza is living in the minds of the CEO of BP. I think it was as Paul Hudson pulled the plug on diabetes. Who made metformin front page news? Maybe we should follow the money to find the answer. |
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Post by agedhippie on Dec 16, 2019 7:30:13 GMT -5
My immediate thought is why would you have heard? My guess is Ollie Brandicourt or his kind would have made it front page news. Do you not think afrezza is living in the minds of the CEO of BP. I think it was as Paul Hudson pulled the plug on diabetes. Who made metformin front page news? Maybe we should follow the money to find the answer. I doubt it would have made the front pages, sadly it takes a death for that. A lot of things go unreported and severe hypos tend to be one of them. Hospital admissions are very rare - for an otherwise health person it is twice every 1,000 patient years. Even people with a lot of co-morbidities are around 53 times per 1,000 patient years. I don't think Afrezza is in any BP CEO's mind because the revenue and sales growth is not where it needs to be for that. But I thought someone was certain to pick up Afrezza after Sanofi (a developed and approved insulin complete with plant for peanuts comparatively - why not!) so my record is not great in that area. I think if it was going to happen it would already have happened. |
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Post by akemp3000 on Dec 16, 2019 7:44:06 GMT -5
Hard to imagine that every BP CEO isn't fully aware of Afrezza's superior effectiveness and is keeping a close eye on the slowly increasing sales. If not the CEO directly, then their scientific advisor(s). If a BP CEO were to overlook scientific trends and only wait until they see a pre-determined level of revenue and sales growth, they would never have become a CEO.
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Post by sportsrancho on Dec 16, 2019 8:21:03 GMT -5
I have friends in BP. The higher ups when they are asked..are always surprised we are still alive.
We have a very long way to go to get on their radar.
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Post by lennymnkd on Dec 16, 2019 9:53:45 GMT -5
Was hoping someone would comment on this / what it might mean for us . |
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Post by rfogel on Dec 16, 2019 10:40:38 GMT -5
Was hoping someone would comment on this / what it might mean for us . Might be good news for SENS since they have a partnership with Beta Bionics. Has Mannkind established any kind of relationship with Beta? Just reading their literature doesn't suggest much role for afrezza except maybe for periods where the Ilet device possibly couldn't handle hyperglycemia. |
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Post by longliner on Dec 16, 2019 10:56:23 GMT -5
Was hoping someone would comment on this / what it might mean for us . I watched the TED talk regarding this. My opinion is it's great for diabetics, not so much for afrezza. |
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Post by shawnonafrezza on Dec 16, 2019 11:04:57 GMT -5
Was hoping someone would comment on this / what it might mean for us . See my longer comment. For those wanting to pump it's awesome. Assuming the dual hormone works well and people tolerate infused glycogen. It doesn't solve problems of consuming straight sugar (so Americans will still have some struggle  ) but the real solution is to not do that IMO. Wait for insurance coverage/cost to really worry or care. Breakthrough doesn't mean out yet. |
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Post by ktim on Dec 16, 2019 14:25:33 GMT -5
Overwhelming evidence is that eating too much and getting too little exercise are major contributors to T2, just as smoking is major contributor to lung cancer, and alcohol to liver disease (and liver as you stated about pancreas does have some ability to grow and regenerate to counter high levels of toxins, but it as with the pancreas can simply be overwhelmed and burn out in the one case and scar and die off in the other). Our body has regenerative capability, but not unlimited. And some more than others. A few people eat, drink and smoke up a storm their entire lives and don't succumb to the diseases linked to the behaviors. There is some genetics and luck of the draw in it. That's not completely true. I usually stay out of Type 2 matters like this because it's not my fight, however I make an exception for the "you did it to yourself" argument. These days Type 2 is thought to be genetic with over 100 genes so far identified. The disease itself has multiple aspects depending on the Type 2 variant you are looking at, but the one thing they all have in common is insulin deficiency, not weight. The weight aspect is primarily a western issue, and in Asia the number of thin to obese Type 2 diabetics is reversed - only around 20% are obese. The current thinking is that Type 2 is due to a gap between cell death and regrowth in some people (apoptosis). This creates a deficit that accumulates with time. You become diabetic when you have an insulin deficit of around 40% (rats go down to 60% as an FYI so that deficit may never get big enough for you to get full blown Type 2. At this point someone will ask, so why does losing weight prevent diabetes? Short answer is that it doesn't , it delays it and the ideal is that the delay is long enough for you to die of old age before it returns but that is outside your control. As you gain weight you gain insulin resistance and the body builds out beta cells so you never notice. If there is an error then you are increasing the race towards that 40% deficiency. Losing weight reduces your insulin resistance and hence the deficit pulling you away from that red line. However in the background you are still underproducing beta calls so your deficit continues to creep upwards towards that red line. The size of this error varies from person to person and thin Type 2 diabetics are thought to be more aggressive (large gap) cases. But I said this wasn't to do with weight. In some cases it is and there are genes in the identified group that act as ratchets making it easy to gain weight and very hard to lose, as well as others that push you to overeat. These are thought to be hangovers from far earlier times when the ability to gain weight was a survival trait. Type 2 is horribly complex genetically and that mess is one reason they are likely to find a cure for Type 1 before Type 2 in my opinion. Disclaimer now; it's been about four years since I looked into this so things may have moved on. The basic premise, and this is supported by the stats, is that if you have the wrong genes you have to be careful, and if you don't you can eat until you are the size of a small killer whale with no danger of ever becoming diabetic. Never mind overweight or obese, only 55% of morbidly obese people have Type 2 and if it was weight related that would be borderline impossible.Genetics certainly play a role. Age also plays a role. If anything my diet is better now than when young, but my A1c has been creeping up in past 5 years. I do totally disagree with your last clause about T2 not being weight "related". I think it clearly is, and I think even what you've said yourself is that it is. As you seem to be saying, there is ample evidence that excess fat tissue causes insulin resistance, and insulin resistance can certainly push one in the T2 direction. It was mostly the notion that this isn't true and some other cause of insulin resistance was or needed to be found. As with lots of things physiological it involves your genes as well as what you do with them. In my personal case if my A1c keeps creeping up I will try to modify behavior. I already have lower than average BMI and avoid sugar (other than holidays), but I could do better at diligence with exercise... and I suspect based on relatives that would be enough to keep me within safe range for my entire life. Some people that are overweight are quite active. I think that lowers risk quite a bit. It's the double whammy of overweight and inactive that really raises risk of diabetes... "risk" not guarantee. But in this case these "risk" factors also have clear physiological mechanisms of causality that are well understood... not simply something that has been found to correlate with the disease. |
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Post by agedhippie on Dec 16, 2019 14:34:30 GMT -5
Hard to imagine that every BP CEO isn't fully aware of Afrezza's superior effectiveness and is keeping a close eye on the slowly increasing sales. If not the CEO directly, then their scientific advisor(s). If a BP CEO were to overlook scientific trends and only wait until they see a pre-determined level of revenue and sales growth, they would never have become a CEO. The sales are so far under where they need to be that no CEO is going to spend a second thinking about Afrezza. Put simply it would take too long to recoup the investment at a level Mannkind would want to sell at (Afrezza net of rebates and cost of goods produces around $2M per quarter, and that is before SG&A). There are rules for making acquisitions and Mannkind is nowhere near making that cut. Until Afrezza proves it can sell on a par with a "me too" like Sanofi's new Humalog biosimilar no BP will care. That biosimilar had net revenues last quarter of $56M (and 84% yoy growth) while Afrezza cannot hit $27M for the entire year! No, Mannkind is going to have to do this one on it's own. The problem is management have no idea what needs doing to get sales (neither do I BTW, but I am not paid to!) |
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Post by lennymnkd on Dec 16, 2019 14:40:33 GMT -5
And all the other small biotechs that get bought out meet that criteria?
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Post by ktim on Dec 16, 2019 14:43:56 GMT -5
Hard to imagine that every BP CEO isn't fully aware of Afrezza's superior effectiveness and is keeping a close eye on the slowly increasing sales. If not the CEO directly, then their scientific advisor(s). If a BP CEO were to overlook scientific trends and only wait until they see a pre-determined level of revenue and sales growth, they would never have become a CEO. Ah yes, according to some here, MNKD has been "living in the heads of all the BP CEOs rent free" for 4 years now. That was oldie but goody trope. Wonder why that fell out of favor... maybe it was simply an introductory free rent period, and then MNKD couldn't avoid it when rent finally came due and was evicted. I've forgotten who it was that came up with that saying. Almost as catchy as "veins of gold" or "embarrassment of riches".  |
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so that deficit may never get big enough for you to get full blown Type 2.
) but the real solution is to not do that IMO. Wait for insurance coverage/cost to really worry or care. Breakthrough doesn't mean out yet.