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Post by sayhey24 on Nov 29, 2017 19:43:07 GMT -5
Now if the medical community actually followed the VDex approach and T2s were treated as soon as diagnosed even as prediabetics many could see the progression stopped and some could see beta cell regeneration. But its not VDex saying that its both Al Mann and Ralph DeFronzo. Here is a video you may want to watch where Al Mann talks pros/cons of current insulins. He starts talking diabetes at 8:30m but it gets interesting at 11:00m and then talks about stopping T2 progression at 15:00M "interesting this lowers insulin resistance... this is even likely to slow and even stop the progression of Type 2 diabetes" www.youtube.com/watch?v=SvZxYmYPXYQThe key to having the medical community listen to what you have to say is to use evidence based information that is reproducible and without bias. Bonus points if it can be proven by a known scientific process. The problem with type 2 diabetes is not a lack of insulin. As you stated, the problem is with insulin resistance. Adding more insulin to the blood does not make muscle and adipose tissue more responsive to insulin. If this were the case, the disease would never progress and would be self-limiting. If tissue became more responsive to insulin as more was added, the pancreas would not need to keep increasing the levels of insulin in the body to maintain homeostasis. The fasting insulin levels of early stage type 2 diabetics is much higher than those of a healthy individual. There may be another mechanism at play. Mango would tell you it's the regulation of gluconeogenesis in the liver. If that's the case, that mechanism should be spoken about as the cause of lowered insulin resistance, not that insulin lowers insulin resistance. Great job on listing the typos, crowd sourcing is awesome. I just checked their site and they have not updated it yet. Hopefully Bill and his team can make the updates happen soon. Concerning the medical community, I am a little more jaded and unfortunately have come to the conclusion that to get the medical community to listen you need to provide them a model to make a bigger profit. In the research community all it takes is grant money. With that said Ralph DeFronzo has been running a trial in Qatar for the past six+ years. Its the follow-on to this study care.diabetesjournals.org/content/early/2017/01/11/dc16-1738When published it will show by keeping a near non-diabetic range they have seen T2 progression stop and are seeing regeneration of beta cells. Al Mann did similar smaller scale private studies with afrezza. In fact over 60 studies which have never been published were done with the original inhaler. IMO, what Al and Ralph have done changes the paradigm for prediabetes and T2 treatment. Better yet what we do know from over 40 years of early insulin intervention studies is it only takes a few months to start seeing these results. So, in short order it should be reproducible "on-demand" by following a VDex like protocol. Now you said "The problem with type 2 diabetes is not a lack of insulin ... the problem is with insulin resistance". This is actually a popular misnomer. The problem ALL diabetics share is their body is not producing enough insulin for its needs. For example, we know that obese, insulin resistant non-diabetics overcome the insulin resistance by growing more beta-cells and producing more insulin. This has been shown through autopsies. If the body needs more insulin due to resistance the healthy pancreas will adapt and make more. We also know the first indication of T2 diabetes is a loss of a robust first phase insulin response not higher fasting sugar numbers. This first phase loss has cascading affects including the liver dumping sugar when it should have been signaled off by the pancreas. This results in even higher meal time spikes which then results in the pancreas not catching up and then the rise in sugar. The slow rise in sugar results in an increase in long-term insulin resistance vs the short-term insulin resistance often reported by T1s in bringing down a high. As the body is conditioned to higher and higher sugar, the insulin resistance tends to increase and increase. In the video Al was conflating the reduction in insulin resistance due to the lower of blood sugar AND the regeneration of beta cells resulting in more natural insulin being produced resulting in a decreased need for the afrezza. Does insulin resistance play a pro-active role as the "tigger" in T2s? What we are seeing as more and more testing is being done is many of the T2s test positive LADA. If you take this to the extreme it points to an external attack causing some level of beta cell death which triggers T2. This results in less insulin being produced in a body which already needs a lot due to the "gene-based" resistance. This then starts the death spiral of the pancreas working over-time trying to meet the insulin demands of the body but never catching up leading to further beta cell death. Sugars rise, resistance becomes even worse and we have a big mess. If we are to believe Defronzo and the results he is seeing, if we treat these insulin resistant PWDs early and keep them in a non-diabetic range, over time their pancreases will start to heal. This is also what Al Mann was seeing. These insulin resistant PWDs can produce enough new beta-cells to over come the existing resistance and if that is the case it points to insulin resistance not being the root cause of the pancreas not being able to adapt to the body's need for more insulin. Al was one of the great minds in diabetes. He knew all this stuff more than 12 years ago and did the research to prove it. The problem is the rest of us are just now catching up and many of his studies were private. |
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Post by agedhippie on Nov 29, 2017 20:29:09 GMT -5
Concerning the medical community, I am a little more jaded and unfortunately have come to the conclusion that to get the medical community to listen you need to provide them a model to make a bigger profit. In the research community all it takes is grant money. With that said Ralph DeFronzo has been running a trial in Qatar for the past six+ years. Its the follow-on to this study care.diabetesjournals.org/content/early/2017/01/11/dc16-1738When published it will show by keeping a near non-diabetic range they have seen T2 progression stop and are seeing regeneration of beta cells. Al Mann did similar smaller scale private studies with afrezza. In fact over 60 studies which have never been published were done with the original inhaler. IMO, what Al and Ralph have done changes the paradigm for prediabetes and T2 treatment. Better yet what we do know from over 40 years of early insulin intervention studies is it only takes a few months to start seeing these results. So, in short order it should be reproducible "on-demand" by following a VDex like protocol. Interesting trial. Take 231 diabetics who are badly controlled on metformin and sulphas and put them onto either Actos and Byetta, or onto basal and bolus insulin. The groups on Actos and Byetta significantly out-performed the group on insulin. Starting from an A1c of 10.0 the drug groups ended at 6.1%, and the insulin groups ended at 7.1%. He makes no claims about regenerating beta cells or halting progression. The conclusion of the paper is that Type 2 diabetics with long term Type 2 and poor control should be put on a combination of Actos and Byetta rather than insulin. |
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Post by peppy on Nov 29, 2017 20:45:13 GMT -5
Concerning the medical community, I am a little more jaded and unfortunately have come to the conclusion that to get the medical community to listen you need to provide them a model to make a bigger profit. In the research community all it takes is grant money. With that said Ralph DeFronzo has been running a trial in Qatar for the past six+ years. Its the follow-on to this study care.diabetesjournals.org/content/early/2017/01/11/dc16-1738When published it will show by keeping a near non-diabetic range they have seen T2 progression stop and are seeing regeneration of beta cells. Al Mann did similar smaller scale private studies with afrezza. In fact over 60 studies which have never been published were done with the original inhaler. IMO, what Al and Ralph have done changes the paradigm for prediabetes and T2 treatment. Better yet what we do know from over 40 years of early insulin intervention studies is it only takes a few months to start seeing these results. So, in short order it should be reproducible "on-demand" by following a VDex like protocol. Interesting trial. Take 231 diabetics who are badly controlled on metformin and sulphas and put them onto either Actos and Byetta, or onto basal and bolus insulin. The groups on Actos and Byetta significantly out-performed the group on insulin. Starting from an A1c of 10.0 the drug groups ended at 6.1%, and the insulin groups ended at 7.1%. He makes no claims about regenerating beta cells or halting progression. The conclusion of the paper is that Type 2 diabetics with long term Type 2 and poor control should be put on a combination of Actos and Byetta rather than insulin. alrighty then.
was Afrezza insulin human used in the study or analog aged? Byetta, is the only GLP-1 that is not carrying the thyroid cancer black box warning. -----------------------WARNINGS AND PRECAUTIONS ----------------------
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Never share a BYETTA pen between patients, even if the needle is changed (5.1).
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Pancreatitis: Postmarketing reports with exenatide, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. Discontinue BYETTA promptly. BYETTA should not be restarted. Consider other antidiabetic therapies in patients with a history of pancreatitis (5.2).
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Hypoglycemia: Increased risk when BYETTA is used in combination with medications known to cause hypoglycemia (e.g., insulin or insulin secretagogue). Consider reducing the dose of insulin or insulin secretagogue (5.3). www.accessdata.fda.gov/drugsatfda_docs/label/2014/021773s036lbl.pdf
Actos, 
www.accessdata.fda.gov/drugsatfda_docs/label/2011/021073s043s044lbl.pdf
Makes a bronco spasm look not so bad. Bronchioles do stop spasming. The coughing does stop.
so aged, the study says you can die with a better HbA1c?
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Post by sayhey24 on Nov 29, 2017 22:38:38 GMT -5
Concerning the medical community, I am a little more jaded and unfortunately have come to the conclusion that to get the medical community to listen you need to provide them a model to make a bigger profit. In the research community all it takes is grant money. With that said Ralph DeFronzo has been running a trial in Qatar for the past six+ years. Its the follow-on to this study care.diabetesjournals.org/content/early/2017/01/11/dc16-1738When published it will show by keeping a near non-diabetic range they have seen T2 progression stop and are seeing regeneration of beta cells. Al Mann did similar smaller scale private studies with afrezza. In fact over 60 studies which have never been published were done with the original inhaler. IMO, what Al and Ralph have done changes the paradigm for prediabetes and T2 treatment. Better yet what we do know from over 40 years of early insulin intervention studies is it only takes a few months to start seeing these results. So, in short order it should be reproducible "on-demand" by following a VDex like protocol. Interesting trial. Take 231 diabetics who are badly controlled on metformin and sulphas and put them onto either Actos and Byetta, or onto basal and bolus insulin. The groups on Actos and Byetta significantly out-performed the group on insulin. Starting from an A1c of 10.0 the drug groups ended at 6.1%, and the insulin groups ended at 7.1%. He makes no claims about regenerating beta cells or halting progression. The conclusion of the paper is that Type 2 diabetics with long term Type 2 and poor control should be put on a combination of Actos and Byetta rather than insulin. As I mentioned the follow-up study results are not yet published but at BeyondA1c forum he said it was being put together and it should be out soon. The provided link was part 1 of the trial. Assuming what he said is true and I have no reason not to (although he was wrong about metformin but now admits to it) what he is demonstrating is the key to beta cell regeneration and stopping progressing is keeping time in range. A1c is not a good metric to use. Its like telling the cop when he pulls you over for doing 100mph that your average mph is only 45 for the last week. The GLP-1 helps to blunt the meal-time spike and the TZD better uses the available insulin. This approach results in better time in range. The end result is close to what groups like VDex say they are getting and current afrezza users post with their CGM readings. My point is we have two different approaches accomplishing the same thing - near non-diabetic time in range AND both DeFronzo and Al Mann are seeing that near non-diabetic time in range results in T2 progression being stopped and beta cell regeneration. Now the debate over using the DeFronzo cocktail or afrezza to me seems like a no brainer. Assuming they can both get me to the same end point, I pick the afrezza. Actos, Byetta and the rest have so many known issues and who knows what we don't know. Their potential long-term issues to me look like orinase on steroids and we know what a train wreck that was. Now doing a head to head trial of afrezza to the DeFronzo cocktail would be awesome. I would bet on afrezza with the CGM would get the better A1c and time in range but that we would not know until its done. And, I would sign up for that trial but only if I got in the afrezza arm. When mentioning DeFronzo I always have to mention one of my favorite quotes which he provided in July 2017 since he was the father of metformin in the U.S. It only took him 25 years to come to his senses. “The most waste in type 2 diabetes is to continuously put people on metformin and sulfonylureas (glyburide, glimepiride, etc.). These drugs have no protective effect on the beta cell, and by the time you figure out what you’re doing, there are no beta cells left to save.” – Dr. Ralph DeFronzo (University of Texas Health Science Center) diatribe.org/the-diatribe-foundation-and-tcoyd-11th-annual-forum |
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Post by mnholdem on Nov 29, 2017 22:51:58 GMT -5
Back when the announcement was made that Sanofi-Aventis was opting out of the Collaboration and Licensing Agreement with MannKind, I had a chat with the Takeda CEO Chris Weber. I was hoping to convince CEO Weber and Chairman Hasegawa to consider how popular Afrezza could be in Asian and Middle-East regions, hoping they would contact MannKind to discuss the possibility of becoming our first international partner.
It was very interesting. Unfortunately, after that multi-$million personal injury lawsuit surrounding the deaths and harm allegedly caused by poor dosing instructions related to Actos45, the Takeda Board of Directors made the decision to cease all future diabetes-related R&D and move the company in another direction.
The Actos label is pretty scary...I think I'd want to move in a different direction, too, if that's all I had to offer...even though it was a blockbuster diabetes medication. |
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Post by babaoriley on Nov 30, 2017 1:20:09 GMT -5
Holy Smokes, Holdem, nice try!!! I sure hope your telling them you're a Minnesotan didn't throw a monkey wrench in the deal.  OMG, it was the accent that gave you away, right? They probably saw Fargo... |
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Post by mnholdem on Nov 30, 2017 9:04:57 GMT -5
In April-2015 Takeda paid billions to settle the lawsuits related to Actos 45.
Here's an excerpt from a New York Times article at the time:
Takeda Agrees to Pay $2.4 Billion to Settle Suits Over Cancer Risk of Actos
Takeda Pharmaceutical has agreed to pay $2.4 billion to settle thousands of lawsuits from patients and their family members who said that the company’s diabetes drug Actos caused bladder cancer, it announced on Tuesday.
Takeda, a Japanese company, said the settlement would resolve most of the product-liability lawsuits related to Actos. It said it would take a $2.7 billion charge against earnings to cover the settlement and costs for defending the remaining cases.
Source: www.nytimes.com/2015/04/29/business/takeda-agrees-to-pay-2-4-billion-to-settle-suits-over-cancer-risk-of-actos.html
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Perhaps it's not so surprising that Takeda decided to get out of the diabetes treatment. With Afrezza, they would have been able to sell one of the safest diabetes treatments available in the global market (NOTE: long-term safety studies have yet to support this statement) and I believe it would have become a blockbuster for Takeda, especially considering the needle-phobia that is prevalent in that region of the world.
I'm of the opinion that average Japanese hold Minnesotans in very high regard, perhaps because we are pretty much immune to needles. I course, we don't mention that it's because we're usually numb from the cold.
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Post by agedhippie on Nov 30, 2017 10:28:42 GMT -5
Interesting trial. Take 231 diabetics who are badly controlled on metformin and sulphas and put them onto either Actos and Byetta, or onto basal and bolus insulin. The groups on Actos and Byetta significantly out-performed the group on insulin. Starting from an A1c of 10.0 the drug groups ended at 6.1%, and the insulin groups ended at 7.1%. He makes no claims about regenerating beta cells or halting progression. The conclusion of the paper is that Type 2 diabetics with long term Type 2 and poor control should be put on a combination of Actos and Byetta rather than insulin. alrighty then.
was Afrezza insulin human used in the study or analog aged? Byetta, is the only GLP-1 that is not carrying the thyroid cancer black box warning. ...
so aged, the study says you can die with a better HbA1c?
It does not say the insulin used but I would expect it to be one of the usual RAA suspects and the basal to probably be Lantus. Personally I don't like drug combinations and would rather just use insulin. The issue is that is a trial and here you have long term diabetics significantly out performing insulin by using to existing drugs. This reinforces a direction Type 2 treatment is heading at the moment - drug + basal. The results are pretty good and the reduced risk of hypos will be an added push. A lot of diabetes drugs have risks attached as far as I can see. Pretty much I would avoid them all except metformin if I was in that position. |
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Post by peppy on Nov 30, 2017 10:50:55 GMT -5
alrighty then.
was Afrezza insulin human used in the study or analog aged? Byetta, is the only GLP-1 that is not carrying the thyroid cancer black box warning. ...
so aged, the study says you can die with a better HbA1c?
It does not say the insulin used but I would expect it to be one of the usual RAA suspects and the basal to probably be Lantus. Personally I don't like drug combinations and would rather just use insulin. The issue is that is a trial and here you have long term diabetics significantly out performing insulin by using to existing drugs. This reinforces a direction Type 2 treatment is heading at the moment - drug + basal. The results are pretty good and the reduced risk of hypos will be an added push. A lot of diabetes drugs have risks attached as far as I can see. Pretty much I would avoid them all except metformin if I was in that position.Johns Hopkins study suggests medical errors are third-leading cause of death in U.S. hub.jhu.edu/2016/05/03/medical-errors-third-leading-cause-of-death/
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Post by agedhippie on Nov 30, 2017 10:52:46 GMT -5
Interesting trial. Take 231 diabetics who are badly controlled on metformin and sulphas and put them onto either Actos and Byetta, or onto basal and bolus insulin. The groups on Actos and Byetta significantly out-performed the group on insulin. Starting from an A1c of 10.0 the drug groups ended at 6.1%, and the insulin groups ended at 7.1%. He makes no claims about regenerating beta cells or halting progression. The conclusion of the paper is that Type 2 diabetics with long term Type 2 and poor control should be put on a combination of Actos and Byetta rather than insulin. As I mentioned the follow-up study results are not yet published but at BeyondA1c forum he said it was being put together and it should be out soon. The provided link was part 1 of the trial. Assuming what he said is true and I have no reason not to (although he was wrong about metformin but now admits to it) what he is demonstrating is the key to beta cell regeneration and stopping progressing is keeping time in range. A1c is not a good metric to use. Its like telling the cop when he pulls you over for doing 100mph that your average mph is only 45 for the last week. The GLP-1 helps to blunt the meal-time spike and the TZD better uses the available insulin. This approach results in better time in range. The end result is close to what groups like VDex say they are getting and current afrezza users post with their CGM readings. My point is we have two different approaches accomplishing the same thing - near non-diabetic time in range AND both DeFronzo and Al Mann are seeing that near non-diabetic time in range results in T2 progression being stopped and beta cell regeneration. Now I have to say that personally I would always go for insulin over that drug cocktail. That said the results from the trial are compelling. The final publication is here - care.diabetesjournals.org/content/40/3/325The cocktail works for the reasons you gave, Actos increases insulin sensitivity, and GLP-1 makes more effective use of insulin blunting spikes. What you can say is that given that you are unlikely to get significant hypos with the drugs the A1c they produce is going to mean that you remained in range almost all the time. I don't see this as beta cell regeneration, or halting progression (neither are claims the paper makes) but rather the more efficient use of insulin. Currently there is no reliable proof of beta cell regeneration (as opposed to recovery as with honeymoon periods). Likewise stopping progression. The problem for both of these claims is that there are no long lived trials showing evidence. |
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Post by agedhippie on Nov 30, 2017 10:55:51 GMT -5
It does not say the insulin used but I would expect it to be one of the usual RAA suspects and the basal to probably be Lantus. Personally I don't like drug combinations and would rather just use insulin. The issue is that is a trial and here you have long term diabetics significantly out performing insulin by using to existing drugs. This reinforces a direction Type 2 treatment is heading at the moment - drug + basal. The results are pretty good and the reduced risk of hypos will be an added push. A lot of diabetes drugs have risks attached as far as I can see. Pretty much I would avoid them all except metformin if I was in that position.Johns Hopkins study suggests medical errors are third-leading cause of death in U.S. hub.jhu.edu/2016/05/03/medical-errors-third-leading-cause-of-death/
There was some interesting work in the UK with simplifying peoples drug regimes. They found that most of the time the number of drugs could be substantially reduced and people's health improved. It seemed to revolve around taking drugs to treat the side effects of other drugs, to treat the side effects of those drugs, ... Changing the required drugs to avoid the side effects in the first place solved most problems.  |
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Post by peppy on Nov 30, 2017 11:11:41 GMT -5
There was some interesting work in the UK with simplifying peoples drug regimes. They found that most of the time the number of drugs could be substantially reduced and people's health improved. It seemed to revolve around taking drugs to treat the side effects of other drugs, to treat the side effects of those drugs, ... Changing the required drugs to avoid the side effects in the first place solved most problems. all those drugs are one heck of a charge changing cocktail. millivolts per millisecond. all these elements/ions have electrons. charge. change charge enough it shows up in the heart valves. atrial fibrillation?
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Post by audiomr on Dec 4, 2017 16:09:45 GMT -5
Notice that VDEX has updated its website and now lists three locations (all in SoCal), "with many more on the way."
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Post by sportsrancho on Dec 7, 2017 9:32:11 GMT -5
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Post by vdexdiabetes on Dec 8, 2017 20:02:20 GMT -5
Thanks Sportsrancho for posting that. We're ironing out some kinks with the website, and creating a more robust platform by which to promote what we're doing. We've been busy and there's been very good feedback on the basic business and treatment model.
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OMG, it was the accent that gave you away, right? They probably saw Fargo...
