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Post by victoria on May 13, 2016 9:08:04 GMT -5
Hi and welcome. Given the strong effect afrezza has for you, do you think a 2 unit cartridge size is a good idea and might it be important for mannkind to have some in a starter pack during "onboarding" new users? I'f so perhaps someone should let Mike Castagna know.
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ben
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Post by ben on May 13, 2016 9:34:16 GMT -5
Hi and welcome. Given the strong effect afrezza has for you, do you think a 2 unit cartridge size is a good idea and might it be important for mannkind to have some in a starter pack during "onboarding" new users? I'f so perhaps someone should let Mike Castagna know. Thank you! To answer your question, I am not really sure. An ~80mg/dl drop isn't all that huge for the lowest dose. One unit of humalog causes a ~50mg/dl drop and, not being on a pump, it's really tough to get an accurate dose less than 1 unit. It would be nice to have a smaller option.....BUT But, if I were running Mannkind, I would not be focused on such trivial matters at this point. My sensitivity is relatively high, so this is not likely to be an issue for most people. Further, mannkind needs to get new users and keep new users coming back. That should be goal #1. If they start messing with the product now, trying to refine it to perfection, they'll likely run out of time/money before ever getting off the ground. They've focused on T1s, as far as i can tell, and while I think this is a losing strategy they have made some headway. Immediately, I think they should really focus on endos that are currently diabetic. I know this is a small subset of providers, but these people will better understand the difference that isn't shown in the data. And, if they can't convince these people to prescribe it, well, they might as well close shop and move on. I have to believe, however, that most endos that are also diabetic will come to the same conclusion that I have: it is, in fact, a great drug and has a place albeit maybe not quite as broad as mannkind may be stating. Give those endos afrezza, educate them on the ins and outs, give them a CGM if they're willing to wear one. Get these endos on board and then pay them to be ambassadors and speak to other endos. That's the first move I would make if I were mannkind. The data isn't really differentiating afrezza from other fast acting insulins. Have endos highlight those differences. This would be an expensive endeavor, but I personally believe it is the quickest path to separating afrezza from the humalogs of the world which needs to be done. And, it needs to be done, because docs aren't going to look at the data, see no difference, and then prescribe a more expensive, possibly more dangerous (lung function), and definitely not was well understood medication that also requires a spirometry test before use. If they continue to go head to head with humalogs of the world, I believe they will fail. While they're doing all this, they really need to find a way to bump afrezza up in the pecking order of drugs prescribed to T2s. My wife used to be an ambassador for an sglt2 inhibitor and I saw some of the slides they gave her. I can't post them because I believe they're proprietary. But, I can say that they follow the flowchart I described in an earlier post. Afrezza needs data showing that it helps lower a1c compared to metformin alone, or that it can be used instead of metformin, or that it can be used more efficiently than the other types of ancillary T2 medications. All that to say the answer is likely yes but not at this point  |
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Post by agedhippie on May 13, 2016 9:59:02 GMT -5
Tayl5 please read www.ncbi.nlm.nih.gov/pubmed/18502299Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial Wow, hadn't seen that before. Thanks for posting. Has that study been replicated anywhere? Lots of places! The trick is relieving oxidative stress from the beta cells which allows them to partially recover and it's been done with a number of treatments from straight diet (Newcastle Protocol) through drugs and insulin. The remission lasts a year on average. The beta cells get beaten down by high numbers, control those numbers for a while (six weeks is ideal) and they can recover. There is an underlying problem which is that not all the beta cells recover and some die. This is manageable to a point as humans can manage happily on anything over 60% of their beta cells. Eventually you drop under that threshold and nothing will fix that. There are some complications in this. Type 2 is genetic but involves a a lot of genes - 80+ was the last number I saw a few years ago. In the US you see about 20% of Type 2 diabetics who are normal weight or underweight and a reasonable number of those have little or no insulin resistance. In this population the treatment is likely to have limited success because they (like Type 1) have an absolute insulin deficiency. In the end Type 2 is the result of a broken glucose metabolism and that is not fixable. The best you can do is control the symptoms. |
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Post by tayl5 on May 13, 2016 12:17:43 GMT -5
Wow, hadn't seen that before. Thanks for posting. Has that study been replicated anywhere? Lots of places! The trick is relieving oxidative stress from the beta cells which allows them to partially recover and it's been done with a number of treatments from straight diet (Newcastle Protocol) through drugs and insulin. The remission lasts a year on average. The beta cells get beaten down by high numbers, control those numbers for a while (six weeks is ideal) and they can recover. There is an underlying problem which is that not all the beta cells recover and some die. This is manageable to a point as humans can manage happily on anything over 60% of their beta cells. Eventually you drop under that threshold and nothing will fix that. There are some complications in this. Type 2 is genetic but involves a a lot of genes - 80+ was the last number I saw a few years ago. In the US you see about 20% of Type 2 diabetics who are normal weight or underweight and a reasonable number of those have little or no insulin resistance. In this population the treatment is likely to have limited success because they (like Type 1) have an absolute insulin deficiency. In the end Type 2 is the result of a broken glucose metabolism and that is not fixable. The best you can do is control the symptoms. So if a Type 2 is insulin deficient and does not have insulin sensitivity, how is that different from being a Type 1? |
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ben
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Post by ben on May 13, 2016 13:57:14 GMT -5
Lots of places! The trick is relieving oxidative stress from the beta cells which allows them to partially recover and it's been done with a number of treatments from straight diet (Newcastle Protocol) through drugs and insulin. The remission lasts a year on average. The beta cells get beaten down by high numbers, control those numbers for a while (six weeks is ideal) and they can recover. There is an underlying problem which is that not all the beta cells recover and some die. This is manageable to a point as humans can manage happily on anything over 60% of their beta cells. Eventually you drop under that threshold and nothing will fix that. There are some complications in this. Type 2 is genetic but involves a a lot of genes - 80+ was the last number I saw a few years ago. In the US you see about 20% of Type 2 diabetics who are normal weight or underweight and a reasonable number of those have little or no insulin resistance. In this population the treatment is likely to have limited success because they (like Type 1) have an absolute insulin deficiency. In the end Type 2 is the result of a broken glucose metabolism and that is not fixable. The best you can do is control the symptoms. So if a Type 2 is insulin deficient and does not have insulin sensitivity, how is that different from being a Type 1? There's really not much of a difference. The medical community is kind of moving away from type 1/type 2 jargon to Insulin Dependent Diabetes and Non-Insulin Dependent Diabetes to differentiate the kinds of DM. They did the same thing a decade or so ago when the moved from Adult Onset Diabetes and Juvenile Diabetes to Type 1 and Type 2. As of right now, you'd have to say the best answer to your question is the onset and how long it takes. Type 1s, with a few exceptions, have less than 10% of functioning beta cells upon diagnosis. The pancreas attacks itself and does so quickly, killing most everything off within a year. Type 2s, the onset is more gradual. |
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Post by agedhippie on May 13, 2016 14:03:03 GMT -5
Lots of places! The trick is relieving oxidative stress from the beta cells which allows them to partially recover and it's been done with a number of treatments from straight diet (Newcastle Protocol) through drugs and insulin. The remission lasts a year on average. The beta cells get beaten down by high numbers, control those numbers for a while (six weeks is ideal) and they can recover. There is an underlying problem which is that not all the beta cells recover and some die. This is manageable to a point as humans can manage happily on anything over 60% of their beta cells. Eventually you drop under that threshold and nothing will fix that. There are some complications in this. Type 2 is genetic but involves a a lot of genes - 80+ was the last number I saw a few years ago. In the US you see about 20% of Type 2 diabetics who are normal weight or underweight and a reasonable number of those have little or no insulin resistance. In this population the treatment is likely to have limited success because they (like Type 1) have an absolute insulin deficiency. In the end Type 2 is the result of a broken glucose metabolism and that is not fixable. The best you can do is control the symptoms. So if a Type 2 is insulin deficient and does not have insulin sensitivity, how is that different from being a Type 1? In a word - antibodies. Type 1 is auto-immune and Type 2 isn't. In Type 1 the immune system confuses your beta cells with lunch and kills them. In Type 2 as your body renews cells it gets the math wrong and does not create sufficient replacements which is accelerated by your reduced beta cells being asked to do more and stressed which ultimately kills them. Insulin resistance is actually optional with Type 2 contrary to popular belief. Ok - I'm going to have a rant here.... The Type 1/2 system is fundamentally broken. The problem is that it's over-simplistic but they did not realize that at the time. There are diabetes variants like MODY which is purely genetic but looks just like Type 1, there are Type 1 diabetics with no detectable anti-bodies (something ate their beta cells but who knows what), there are Type 2 DKA prone variants like Flatbush that can put you into DKA which is almost unheard of for Type 2 (to the point where DKA alone used to be sufficient to diagnose Type 1). Then there is LADA - late onset Type 1 which is auto-immune but looks like Type 2 for a few years as it drifts slowly into Type 1. Rant over! Sadly there isn't really a better system although people have tried. The Type classification is well embedded and difficult to change now. The key takeaway is that diabetes is far more complex than they Type system suggests. There are even plausible theories (the Accelerator Hypothesis) that Type 1 and 2 are opposite ends of the same disease. It is possible to have both Type 1 and Type 2 diabetes simultaneously (aka. double diabetes). |
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ben
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Post by ben on May 13, 2016 14:18:17 GMT -5
So if a Type 2 is insulin deficient and does not have insulin sensitivity, how is that different from being a Type 1? In a word - antibodies. Type 1 is auto-immune and Type 2 isn't. In Type 1 the immune system confuses your beta cells with lunch and kills them. In Type 2 as your body renews cells it gets the math wrong and does not create sufficient replacements which is accelerated by your reduced beta cells being asked to do more and stressed which ultimately kills them. Insulin resistance is actually optional with Type 2 contrary to popular belief. Ok - I'm going to have a rant here.... The Type 1/2 system is fundamentally broken. The problem is that it's over-simplistic but they did not realize that at the time. There are diabetes variants like MODY which is purely genetic but looks just like Type 1, there are Type 1 diabetics with no detectable anti-bodies (something ate their beta cells but who knows what), there are Type 2 DKA prone variants like Flatbush that can put you into DKA which is almost unheard of for Type 2 (to the point where DKA alone used to be sufficient to diagnose Type 1). Then there is LADA - late onset Type 1 which is auto-immune but looks like Type 2 for a few years as it drifts slowly into Type 1. Rant over! Sadly there isn't really a better system although people have tried. The Type classification is well embedded and difficult to change now. The key takeaway is that diabetes is far more complex than they Type system suggests. There are even plausible theories (the Accelerator Hypothesis) that Type 1 and 2 are opposite ends of the same disease. It is possible to have both Type 1 and Type 2 diabetes simultaneously (aka. double diabetes). Ha. Yes. I just tell people there's not much difference because the answer is so confusing and convoluted that the trend is to not differentiate. But, what you said is pretty spot on and I agree though I do hope they reclassify and I thought there was some auto immune aspects to Type 2 as well. Type 2s, on a long enough timeline, will all end up on insulin. Now the timeline for some may be longer than others. And, it can be quite long. I do think that they will successfully reclassify the beets into Insulin Dependent and Non Insulin Dependent. And, I am all for it. LADA, MODY, Type 1, Type 2, etc...they all seem to be their own thing. Type 1 and 2 are viewed very differently. Almost as separate diseases and there is some truth behind it. But, I'd like to see more cooperation and coordination between the two types. Eliminating the Type 1/Type 2 would go a long way. We're all in this together and want the same thing, I think: a cure. And, until that time comes, we'd like better treatments. Biopancreas, CGM, pumps, implants that regulate insulin...the name of them escapes me now, etc etc etc. It would be nice if there was more funding for these areas because, well, diabetes in whatever form is becoming more prevalent, and, unfortunately many people still struggle with control which obviously leads to long term issues. |
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