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Post by sayhey24 on Feb 21, 2018 19:44:15 GMT -5
sayhey24 ... many here have speculated that it was the poor design of the clinical trials (dose titration or lack thereof, timing, and lack of follow ups if out of range) that lead to being merely non-inferior with regard to A1c. I would assume that MNKD believes this and would expect with proper coaching from One Drop, the Afrezza arm will show superior A1c results. I do believe that for a given level of hypo risk, a lower A1c is achievable with Afrezza... in a general population, i.e. not withstanding the subset of people willing to closely tailor their food consumption to match pd profile of their RAA. In theory over time the same insulin action should produce the same reduction in A1c. Now, can you achieve better insulin action with afrezza probably because it will block the alpha cells and you can easily stack it buts its not worth the bet, IMO. In the 171 Study some of the doctors were telling the PWDS to take afrezza 15-30 minutes prior to the meal. Clearly that would affect the results. Most had the PWDs take it at the start of the meal. How many had them take it 10-15 minutes after the start, I am not sure but probably not many. There was one doctor who was part of the public speakers. He was attacked by the FDA team for what the FDA lady said was "cheating". He instructed his PWDs to test after 2 hours and if still high to take a second dose. His group blew away all other results and was labeled a "cheater", her words not mine. The One Drop study only gives them 150 strips. Thats five tests per day. If you test in the morning, before 3 meals, 1 hour after meals let alone the 2 hour after meal test and then bed they clearly don't have enough strips. Will the afrezza users redose after 2 hours? By my count they don't have enough strips to even test. Will One Drop achieve significantly better A1c with afrezza, I hope but again insulin is insulin and over time things average out. The PWD will only see this because of their ability to get better insulin action by stopping the spike and stacking when necessary. The RAA user will never have the TIR and reduction in hypos that the afrezza users will see but "average" sugar over 3 months. If I drive 200mph and then 60mph my average is 130mph which is a lot different than driving 140mph and 120mph but its still 130mph. The big advantage of afrezza is very low hypo risk when no basal is used, its easy and there are no needles. Why don't we start early T2s on insulin? No one wants the needle and hypos can kill. afrezza solves those problems. For the T1s they should all have it to correct highs but you will see a lot use it in combo with an RAA for long digesting meals. Why? Its too damn expensive.
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Post by dreamboatcruise on Feb 21, 2018 20:20:22 GMT -5
sayhey24... that would seem odd if they are limiting the test strips, since the premium One Drop normally is unlimited test strips. I do see it listed that way. Maybe that is simply the minimum quantity they provide but users can order more as they would normally be able to with One Drop Premium. 150/month might be enough after one learns their own body's reaction with given types of meals, but it does seem initially they should be given the benefit of being able to test whenever they wish.
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Post by sayhey24 on Feb 21, 2018 20:44:04 GMT -5
I don't know what Dachis was trying to achieve in the study. I suspect self promotion and advancement of his coaching service. The shortfall is obvious, One Drop has no CGM which is the future of remote "Cloud" monitoring. Maybe Apple or Amazon is working on a secret M&M type CGM. We know Apple has the watch.
However, if he can show reduced A1c in both arms he wins. Coaching works and we know it works but showing Apple and Amazon helps promote his service. Look at Onduo.com. Sam says lets lower your post breakfast sugar.
Diabetes management works. Taking a walk and losing some pounds works. Taking any insulin works. Taking afrezza limits hypo risk and no needles and works with the liver. All the anti-glycemics are bad. Replacing any anti-glymeic with afrezza is a great thing a doctor and PWD can do. Having the PWD take a walk, loose some pounds and take afrezza at the same time is even better.
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Post by dreamboatcruise on Feb 21, 2018 21:39:55 GMT -5
sayhey24... well you actually seem to know what Dachis would be trying to achieve. It seems quite obvious... make money for his shareholders and himself. So yes, he'd want One Drop Premium to be shown to reduce A1c whether one uses an RAA or Afrezza in this trial. To me that would simply be a given since it is the logical thing he'd want. There could be some other hidden motive, but... Occam's Razor. Hopefully, it's fairly run and his coaches are sufficiently trained with Afrezza to allow Afrezza's benefits to come through.
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Post by agedhippie on Feb 21, 2018 21:50:53 GMT -5
If the key thing about Afrezza is it's ability to prevent a spike and to rapidly return you to good levels then the area under the graph should be reduced and the Afrezza users A1c results should be better than the RAA results. Look at the CGM images people show for Afrezza plus a meal.
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Post by sellhighdrinklow on Feb 21, 2018 22:27:58 GMT -5
sayhey24 ... many here have speculated that it was the poor design of the clinical trials (dose titration or lack thereof, timing, and lack of follow ups if out of range) that lead to being merely non-inferior with regard to A1c. I would assume that MNKD believes this and would expect with proper coaching from One Drop, the Afrezza arm will show superior A1c results. I do believe that for a given level of hypo risk, a lower A1c is achievable with Afrezza... in a general population, i.e. not withstanding the subset of people willing to closely tailor their food consumption to match pd profile of their RAA. In theory over time the same insulin action should produce the same reduction in A1c. Now, can you achieve better insulin action with afrezza probably because it will block the alpha cells and you can easily stack it buts its not worth the bet, IMO. In the 171 Study some of the doctors were telling the PWDS to take afrezza 15-30 minutes prior to the meal. Clearly that would affect the results. Most had the PWDs take it at the start of the meal. How many had them take it 10-15 minutes after the start, I am not sure but probably not many. There was one doctor who was part of the public speakers. He was attacked by the FDA team for what the FDA lady said was "cheating". He instructed his PWDs to test after 2 hours and if still high to take a second dose. His group blew away all other results and was labeled a "cheater", her words not mine. The One Drop study only gives them 150 strips. Thats five tests per day. If you test in the morning, before 3 meals, 1 hour after meals let alone the 2 hour after meal test and then bed they clearly don't have enough strips. Will the afrezza users redose after 2 hours? By my count they don't have enough strips to even test. Will One Drop achieve significantly better A1c with afrezza, I hope but again insulin is insulin and over time things average out. The PWD will only see this because of their ability to get better insulin action by stopping the spike and stacking when necessary. The RAA user will never have the TIR and reduction in hypos that the afrezza users will see but "average" sugar over 3 months. If I drive 200mph and then 60mph my average is 130mph which is a lot different than driving 140mph and 120mph but its still 130mph. The big advantage of afrezza is very low hypo risk when no basal is used, its easy and there are no needles. Why don't we start early T2s on insulin? No one wants the needle and hypos can kill. afrezza solves those problems. For the T1s they should all have it to correct highs but you will see a lot use it in combo with an RAA for long digesting meals. Why? Its too damn expensive. imho, the only reason you won't see hypos with no basal on board is because these PWDs are floating w high BS continuously.
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Post by sayhey24 on Feb 22, 2018 6:27:18 GMT -5
The reason you won't see hypos with no basal on board is what the 118 trial showed. afrezza restores proper hepatic function. It first blocks the alphaa cells and then is out of the system as the liver again starts releasing glucose. Non diabetics do not have high BG and neither do T2s taking enough afrezza. Neither gets hypos.
Use the VDex paper as a do-it yourself guide and repeat what they outline. Its what they say in the 118 trial.
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Post by agedhippie on Feb 22, 2018 9:18:59 GMT -5
In theory over time the same insulin action should produce the same reduction in A1c. Now, can you achieve better insulin action with afrezza probably because it will block the alpha cells and you can easily stack it buts its not worth the bet, IMO. In the 171 Study some of the doctors were telling the PWDS to take afrezza 15-30 minutes prior to the meal. Clearly that would affect the results. Most had the PWDs take it at the start of the meal. How many had them take it 10-15 minutes after the start, I am not sure but probably not many. There was one doctor who was part of the public speakers. He was attacked by the FDA team for what the FDA lady said was "cheating". He instructed his PWDs to test after 2 hours and if still high to take a second dose. His group blew away all other results and was labeled a "cheater", her words not mine. The One Drop study only gives them 150 strips. Thats five tests per day. If you test in the morning, before 3 meals, 1 hour after meals let alone the 2 hour after meal test and then bed they clearly don't have enough strips. Will the afrezza users redose after 2 hours? By my count they don't have enough strips to even test. Will One Drop achieve significantly better A1c with afrezza, I hope but again insulin is insulin and over time things average out. The PWD will only see this because of their ability to get better insulin action by stopping the spike and stacking when necessary. The RAA user will never have the TIR and reduction in hypos that the afrezza users will see but "average" sugar over 3 months. If I drive 200mph and then 60mph my average is 130mph which is a lot different than driving 140mph and 120mph but its still 130mph. The big advantage of afrezza is very low hypo risk when no basal is used, its easy and there are no needles. Why don't we start early T2s on insulin? No one wants the needle and hypos can kill. afrezza solves those problems. For the T1s they should all have it to correct highs but you will see a lot use it in combo with an RAA for long digesting meals. Why? Its too damn expensive. imho, the only reason you won't see hypos with no basal on board is because these PWDs are floating w high BS continuously. Type 2 diabetics still have insulin output. You can use that to meet your basal or your mealtime needs. Basal insulin is really dumb insulin, it fluctuates but not by a huge amount. Mealtime insulin needs to be smart and arrive and leave at the correct times in the correct quantity - this is what your body does well. The thinking on making basal the first line is that it takes care of the dumb role leaving what insulin you have under your control for the smart role where it can have a greater impact. Later when you cannot handle mealtimes with just basal mealtime insulin is added to supplement your own insulin and cover the gap. You can take mealtime insulin alone as a first option, but then you are just consigning your smart insulin to a dumb role. In other words mealtime insulin will work because it's insulin, not because there is something special about it.
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Post by bill on Feb 22, 2018 10:11:45 GMT -5
imho, the only reason you won't see hypos with no basal on board is because these PWDs are floating w high BS continuously. Type 2 diabetics still have insulin output. You can use that to meet your basal or your mealtime needs. Basal insulin is really dumb insulin, it fluctuates but not by a huge amount. Mealtime insulin needs to be smart and arrive and leave at the correct times in the correct quantity - this is what your body does well. The thinking on making basal the first line is that it takes care of the dumb role leaving what insulin you have under your control for the smart role where it can have a greater impact. Later when you cannot handle mealtimes with just basal mealtime insulin is added to supplement your own insulin and cover the gap. You can take mealtime insulin alone as a first option, but then you are just consigning your smart insulin to a dumb role. In other words mealtime insulin will work because it's insulin, not because there is something special about it. agedhippie What you said seems correct, but if you just used basal as a T2 would your pancreas / beta cells stop the mealtime spikes, i.e., let you function like someone without diabetes, or would the basal insulin keep your A1c in check, but leave you with wildly fluctuating glucose levels, i.e., leave you with poor time-in-range?
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Post by agedhippie on Feb 22, 2018 11:38:20 GMT -5
Type 2 diabetics still have insulin output. You can use that to meet your basal or your mealtime needs. Basal insulin is really dumb insulin, it fluctuates but not by a huge amount. Mealtime insulin needs to be smart and arrive and leave at the correct times in the correct quantity - this is what your body does well. The thinking on making basal the first line is that it takes care of the dumb role leaving what insulin you have under your control for the smart role where it can have a greater impact. Later when you cannot handle mealtimes with just basal mealtime insulin is added to supplement your own insulin and cover the gap. You can take mealtime insulin alone as a first option, but then you are just consigning your smart insulin to a dumb role. In other words mealtime insulin will work because it's insulin, not because there is something special about it. agedhippie What you said seems correct, but if you just used basal as a T2 would your pancreas / beta cells stop the mealtime spikes, i.e., let you function like someone without diabetes, or would the basal insulin keep your A1c in check, but leave you with wildly fluctuating glucose levels, i.e., leave you with poor time-in-range? I cannot really answer that definitively. My opinion would be that at a certain point you would not have enough insulin to suppress the initial spike, but would have enough to bring it back down fairly quickly. Since HbA1c is a function of the area under the curve the increase in HbA1c may be quite small if the return to baseline is quick. Ditto time in range would look good because the spike returned to the baseline quickly. Where you would have problems is the standard deviation - that would be horrible. In Type 2 the DCCT trials found that only 11% of the risk of microvascular complications was tied to HbA1c. It's not clear where the other 89% came from but there is a fairly large group who think it is glycemic variability and standard deviation that is the cause. Superficially this ties back to time in range (if I am in range I am not widely fluctuating), but that ignores that a brief sharp spike may have a large impact despite being insignificant to time in range. It's a while since I looked at this so I need to see how things have moved since then.
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Post by dreamboatcruise on Feb 22, 2018 12:13:09 GMT -5
Type 2 diabetics still have insulin output. You can use that to meet your basal or your mealtime needs. Basal insulin is really dumb insulin, it fluctuates but not by a huge amount. Mealtime insulin needs to be smart and arrive and leave at the correct times in the correct quantity - this is what your body does well. The thinking on making basal the first line is that it takes care of the dumb role leaving what insulin you have under your control for the smart role where it can have a greater impact. Later when you cannot handle mealtimes with just basal mealtime insulin is added to supplement your own insulin and cover the gap. You can take mealtime insulin alone as a first option, but then you are just consigning your smart insulin to a dumb role. In other words mealtime insulin will work because it's insulin, not because there is something special about it. agedhippie What you said seems correct, but if you just used basal as a T2 would your pancreas / beta cells stop the mealtime spikes, i.e., let you function like someone without diabetes, or would the basal insulin keep your A1c in check, but leave you with wildly fluctuating glucose levels, i.e., leave you with poor time-in-range? That probably depends on how early in the progression of T2 one is started on basal. We know eventually in the progression basal alone is not enough. The open question would be whether starting on basal or starting on prandial (Afrezza) would give better results... short term and perhaps slowing progression. Aged has presented reasoning behind why basal might be better, and I believe with Afrezza the reasoning is linked to whether restoring/enhancing the first phase spike has a feedback effect with the liver. Another argument for Afrezza first is that if there is meaningfully less chance of hypos, which is the main cause of delaying introduction of insulin, that could enable starting insulin sooner. Seems to me there will be no answers until very large clinical trials are run, ideally looking at when in progression insulin is introduced and what type. It might even be complicated by the fact that an individual's dietary habits might play a role in whether basal or prandial would be better to start on. I personally have bought into the idea that Afrezza would be the ideal early treatment, if not before metformin at least right after, but I'm objective enough to realize that since I started studying all of this after becoming a MNKD investor, I may not be fully objective. It doesn't seem like the algorithm in the ADA standard of care is going to change anytime soon without clinical trials. In the meantime hopefully MNKD can start at least winning the battle against RAA where they are currently placed in the standard of care (after basal)... with some practitioners such as VDEX trying a different approach and hopefully leading eventually to a reassessment of the standard of care.
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Post by bill on Feb 22, 2018 13:16:31 GMT -5
agedhippie What you said seems correct, but if you just used basal as a T2 would your pancreas / beta cells stop the mealtime spikes, i.e., let you function like someone without diabetes, or would the basal insulin keep your A1c in check, but leave you with wildly fluctuating glucose levels, i.e., leave you with poor time-in-range? That probably depends on how early in the progression of T2 one is started on basal. We know eventually in the progression basal alone is not enough. The open question would be whether starting on basal or starting on prandial (Afrezza) would give better results... short term and perhaps slowing progression. Aged has presented reasoning behind why basal might be better, and I believe with Afrezza the reasoning is linked to whether restoring/enhancing the first phase spike has a feedback effect with the liver. Another argument for Afrezza first is that if there is meaningfully less chance of hypos, which is the main cause of delaying introduction of insulin, that could enable starting insulin sooner. Seems to me there will be no answers until very large clinical trials are run, ideally looking at when in progression insulin is introduced and what type. It might even be complicated by the fact that an individual's dietary habits might play a role in whether basal or prandial would be better to start on. I personally have bought into the idea that Afrezza would be the ideal early treatment, if not before metformin at least right after, but I'm objective enough to realize that since I started studying all of this after becoming a MNKD investor, I may not be fully objective. It doesn't seem like the algorithm in the ADA standard of care is going to change anytime soon without clinical trials. In the meantime hopefully MNKD can start at least winning the battle against RAA where they are currently placed in the standard of care (after basal)... with some practitioners such as VDEX trying a different approach and hopefully leading eventually to a reassessment of the standard of care. dreamboatcruise - Perhaps I'm oversimplifying, but how could having T2's start with insulin (basil + Afrezza) be a bad thing as long as the basal dose is mild enough to avoid hypos and Afrezza is used after proper titration. Seems like the primary reason insulin has been avoided is because of hypo risks. With Afrezza in the mix, that issue mostly goes away, doesn't it? If Afrezza alone, or basal + Afrezza gives superior results, then the last question is at what point do the higher costs of Afrezza (with or without Basil) for T2's result in lower healthcare costs for the individual, e.g., halting progression of the disease and/or reduced medical expenses in the out years? My wild guess would be less than 5 years since it doesn't take more than a few severe hypos to offset Afrezza's annual costs. Even with PWDs moving among insurance carriers, so one carrier may not see the out-year benefits from their coverage, common sense would suggest that every departing PWD using Afrezza would be offset by an entering PWD using Afrezza--zero sum situation.
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Post by dreamboatcruise on Feb 22, 2018 13:40:46 GMT -5
That probably depends on how early in the progression of T2 one is started on basal. We know eventually in the progression basal alone is not enough. The open question would be whether starting on basal or starting on prandial (Afrezza) would give better results... short term and perhaps slowing progression. Aged has presented reasoning behind why basal might be better, and I believe with Afrezza the reasoning is linked to whether restoring/enhancing the first phase spike has a feedback effect with the liver. Another argument for Afrezza first is that if there is meaningfully less chance of hypos, which is the main cause of delaying introduction of insulin, that could enable starting insulin sooner. Seems to me there will be no answers until very large clinical trials are run, ideally looking at when in progression insulin is introduced and what type. It might even be complicated by the fact that an individual's dietary habits might play a role in whether basal or prandial would be better to start on. I personally have bought into the idea that Afrezza would be the ideal early treatment, if not before metformin at least right after, but I'm objective enough to realize that since I started studying all of this after becoming a MNKD investor, I may not be fully objective. It doesn't seem like the algorithm in the ADA standard of care is going to change anytime soon without clinical trials. In the meantime hopefully MNKD can start at least winning the battle against RAA where they are currently placed in the standard of care (after basal)... with some practitioners such as VDEX trying a different approach and hopefully leading eventually to a reassessment of the standard of care. dreamboatcruise - Perhaps I'm oversimplifying, but how could having T2's start with insulin (basil + Afrezza) be a bad thing as long as the basal dose is mild enough to avoid hypos and Afrezza is used after proper titration. Seems like the primary reason insulin has been avoided is because of hypo risks. With Afrezza in the mix, that issue mostly goes away, doesn't it? If Afrezza alone, or basal + Afrezza gives superior results, then the last question is at what point do the higher costs of Afrezza (with or without Basil) for T2's result in lower healthcare costs for the individual, e.g., halting progression of the disease and/or reduced medical expenses in the out years? My wild guess would be less than 5 years since it doesn't take more than a few severe hypos to offset Afrezza's annual costs. Even with PWDs moving among insurance carriers, so one carrier may not see the out-year benefits from their coverage, common sense would suggest that every departing PWD using Afrezza would be offset by an entering PWD using Afrezza--zero sum situation. If you're asking which would be best, starting with just Afrezza or Afrezza and basal, then I certainly wouldn't know, and in reality I'm pretty sure no one does. I don't think the physiology and especially the progression of the disease are understood well enough. Bear in mind that exogenous augmentation of hormones can lead to changes in the natural production... e.g. men taking testosterone supplements leads to their body producing less. Is it better to use maximum safe levels of exogenous insulin immediately, or not? There are some studies showing the first phase insulin response is first to go in T2... is it better to simply replace that at a minimum level to keep post meal BG within range and let the body continue to play more of role? So, what exogenous insulin regime would best slow/halt the progression of beta cell "burnout" seems to me quite complicated. I can throw out different arguments of what "might" happen... but (a) this isn't actually my field and (b) I don't even think those in the field know all the answers. I think clinical trials are needed. I think Afrezza is a big advance because the combination of basal and RAA has certainly proven to have risks, and patient acceptance barriers, that has lead to it being considered an inappropriate early treatment. If only Al Mann were still around and had another half billion to throw at this problem.
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Post by sayhey24 on Feb 22, 2018 18:36:30 GMT -5
DBC - I am going to again post what I will refer to as part of the AL Mann Dogma. It is a bit off topic of One Drop but may help with the above discussion. The following are truths about diabetes which are not debatable. In summary there are some baseline facts which need to be understood 1. All diabetics share the fact that they are not making enough insulin for THEIR bodies needs 2. All diabetics first loose their robust first phase insulin release 3. Diabetes is a spectrum of insulin production. Some diabetics produce a good amount of insulin and we term them pre-diabetics. Some produce very little which we term T1s, LADAs, Late Stage T2s and a few more terms. The rest get labelled T2 and their insulin varies on the spectrum. 4. T1's show antibodies and the more we test T2's we find more of the T2's having anti-bodies and rename them LADAs 5. Obesity and being a coach potato is a trait of T2 diabetes and not the cause. The cause is the loss of beta cell function. Here is some of what Al said about T2 treatment "In early Type 2, a variety of alternative antiglycemic drugs are used today and these products are viable largely because of the deficiencies of current insulin products. But it is insulin that the body needs for glucose metabolism. Even with the limitations of current insulin products, there is increasing pressure to move patients much sooner to exogenous insulin. The alternative antiglycemic products are intended simply to supplement endogenous pancreatic insulin more effectively. Some of them are directed to increasing pancreatic output, likely contributing to early-year beta cell burnout. Other products have tested lower resistance to insulin to inhibit hepatic glucose release or to slow digestion, but all of these drugs have limited efficacy and side effects that can be significant in some patients and the long-term safety for many of them may still be in doubt. Moreover, none of these antiglycemics, I believe, does slow progression of the disease so that, after 8 to 12 years, patients using those drugs typically move on to insulins. Another issue is that many of the newer, more advanced antiglycemic agents are very expensive. If only there were a physiologic ultra-fast-acting insulin that would reduce postprandial hyperglycemia to within normal guidelines without the risk of hypoglycemia or weight gain and without the complexity of titration or the need for multiple daily measurements of glucose. Such a prandial insulin would far better deal with postprandial excursions throughout the entire spectrum of diabetes. Moreover, key opinion leaders assert that, by reducing pancreatic and hepatic stress, such an insulin would slow and perhaps even stop progression of Type 2 diabetes and prediabetes. Surely, that would seem to offer a far better solution than those alternative drugs. Moreover, a therapy that does not require the inconvenience and discomfort of multiple daily injections, would certainly be more patient-friendly. AFREZZA has been shown in over 50 clinical trials to mimic endogenous insulin kinetics and this should enable this insulin to more effectively and more safely address the objectives of providing improved glycemic control. A product such as AFREZZA would be especially appealing to children and should ease the issues about treatment in the classroom. Because of the FDA's aversion about risk in this young population, the initial label for AFREZZA will be restricted to patients 18 years and older. The age -- asked us [ph] to submit a post-approval Phase IV protocol for a trial in children. We responded with a proposed study in children ages 12 to 18. Interestingly, FDA directed us to include children down to age 4." -------------------------------------------------------------------------- Interview question: People with type 2 are usually started out on a basal insulin. AM: Well, that is medically incorrect. Starting a type 2 on basal insulin is done today because current prandial insulin products are not physically sound so they are delayed about as long as they can be. Lantus has been so successful as the first insulin used in type 2 because of the problems with current prandial products. www.diabetesincontrol.com/an-exclusive-interview-with-al-mann-founder-and-ceo-mannkind-corp/----------------------------------------------------------------------------------------- Aren't most Type 2s currently treated with a basal insulin only, instead of mealtime dosing? Al: Yes, but that's the wrong way around. The correct therapy should be a good prandial insulin and not long-term insulin — Afrezza in particular because it turns off glucose production and delivery from the liver. Our latest trials of 600 patients are showing even more significant benefits from the product than our original trials; the most recent trial appears to show that this should replace frontline treatment for all Type 2 patients. www.healthline.com/diabetesmine/the-truth-about-afresa-inhalable-insulin-a-chat-with-al-mann#2
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Post by dreamboatcruise on Feb 22, 2018 19:41:03 GMT -5
DBC - I am going to again post what I will refer to as part of the AL Mann Dogma. It is a bit off topic of One Drop but may help with the above discussion. The following are truths about diabetes which are not debatable. In summary there are some baseline facts which need to be understood 1. All diabetics share the fact that they are not making enough insulin for THEIR bodies needs 2. All diabetics first loose their robust first phase insulin release 3. Diabetes is a spectrum of insulin production. Some diabetics produce a good amount of insulin and we term them pre-diabetics. Some produce very little which we term T1s, LADAs, Late Stage T2s and a few more terms. The rest get labelled T2 and their insulin varies on the spectrum. 4. T1's show antibodies and the more we test T2's we find more of the T2's having anti-bodies and rename them LADAs 5. Obesity and being a coach potato is a trait of T2 diabetes and not the cause. The cause is the loss of beta cell function. "When" insulin response is lost, yes it is first phase. Certainly there are people in the medical field that would disagree with other assertions. Many, if not most, would say that obesity and lack of exercise will cause insulin resistance, and that this insulin resistance can lead to beta cell function loss. For some people they don't lose beta cell function even when challenged with by insulin resistance. It seems to be accepted now that there are also T2's that occur because of a genetic predisposition to beta cell failure. Here is a paper I found useful: www.ncbi.nlm.nih.gov/pmc/articles/PMC2811457/So my understanding is: T1 is an autoimmune disorder where your immune system turns on your beta cells, this can occur early in life or later (and kinda irrelevant that it used to get misdiagnosed as T2) T2 in many people is caused by insulin resistance that develops from lifestyle, though with some having better genetic resistance to poor lifestyles than others * T2 in some can be caused by genetic predisposition to beta cell failure even with lifestyle that wouldn't cause problems for most people (whether this is a third class or simply on the spectrum of T2 might be open for debate). I guess the open question there would be whether insulin resistance is necessary as a precursor or whether this subset truly could develop T2 without insulin resistance. * that one sort of seems like smoking. We know smoking causes cancer but we also know some people just have genetics that mean they'll die at 100 from boredom after a life of smoking. And "poor lifestyle" may be a poor choice of wording above. Quite frankly our bodies simply aren't physiologically evolved for the reality of modern life. It takes active fighting against what would come natural to us from evolution to to avoid these "lifestyle" problems. Too bad beta cells aren't like muscles and get stronger the more they are used. As for Al's assertion about basal vs prandial as first line. I think he well may be right, but I'd still want to see some clinical studies to really be convinced. It is not uncommon for something that seems logical in fields such as physiology to turn out to not be true. This is a very complicated subject, and I've yet to hear of anybody developing a computer model of diabetes progression that can accurately predict how it will progress for individuals, based on their treatments and actions. Lacking that level of understanding, we must rely on clinical trials.
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