In part 2 of this exclusive interview, Dr. Aaron Vinik shares an update on INGAP research.
This is part 2 of a 2-part video transcription. Click here to view part 1.
The full transcribed interview is also available in PDF format.
Steve Freed: Okay. So let’s change the subject for a second. I remember the first thing that got me in contact with you was some research which was being called the INGAP research, and you were responsible for that research. You were the head of the research, and I actually thought it was the cure for diabetes and regenerating beta cells.
And, to me, that was exciting. And I know a lot of things have happened since then. So maybe you can kind of tell us – where is that research right now?
Dr. Aaron Vinik: Okay. Thanks very much for asking about this because, the truth of the matter is, I appreciate you noting the work and recognizing the contributions that have been made over the years. But when we started doing this, the belief was that the pancreatic beta cell, like a beta cell in your brain, do not have the ability to regenerate.
And then working at the University of Michigan with a surgical fellow, Lawrence Rosenberg, from McGill University, we started wrapping pancreases to see if we could induce pancreatitis because were intrigued with the observation that if you initiated the problem of pancreatitis, and it kept going, you couldn’t stop it.
And that went on until the pancreas was destroyed. So we wanted an animal model that would do that, and then we could study the mechanisms whereby an initial assault on the pancreas heralded a continuous process of self destruction. Well, we spent months trying to develop this model of wrapping the pancreases in Saran, and it didn’t do that.
But what it did do was stimulate the growth of new islets, and we got very taken with that. So as people have heard before, when you come to a fork in the road take it. We did. We said – no more pancreatitis. We’re creating new islets here. But people didn’t want to believe that.
They said how do stones regenerate? But we showed them that they did. And then we showed, in many different models, that we could induce this regeneration. And it took us some years to find initially, Ilotropin, which was a protein that we identified was released by the wrapped pancreas, which was capable of stimulating growth and proliferation of beta cells, from pancreatic ductal or pancreatic cells, from a pro-differentiated stem cell that was present there.
The problem with Ilotropin, the initial protein, was that it was a mixture of many proteins. It was very much like the initial insulin preparations that had at least 100 different proteins, before the advent of purification and synthetic production of insulins.
Well this came to pass when we cloned and sequenced the Ingap gene, and then showed that we could take a portion of the Ingap gene islet, neogenesis associated peptide, a portion, just 15 minor acids, and it would do what Ilotropin did before – stimulate growth and proliferation of diabetes insulin cells, with a complete islet, with all the constituents of the islet – the glucagon, somatostatin, pancreatic polypeptide, etc., that would grow.
So that was neo-islet (new islet) formation, and just by this little peptide. So new studies were started. And the compound Ingap was licensed to several different companies sequentially, to show that it could possibly cure diabetes. And it did very well in the initial trials.
Both type 1 diabetes and type 2 diabetes were found to restore in part, beta cell function, increasing C-peptide, which is now the classic measure of showing that you’ve improved beta cell function. But, lo and behold, when you created these new islets, the process in type 1 diabetes was not abated.
It went on. And as soon as the new islets were formed, they were destroyed by the endogenous (within the body) autoimmune destructor process, and that was a little disheartening. And the good news was that if you used an anti-inflammatory agent, in combination with Ingap, in the animal models, you could actually get 75 percent remission of the diabetes.
So it sounded like it would be a piece of cake and we would go into human studies, with a combination of Ingap and an anti-inflammatory agent. So this was done indeed with an antagonist of IL-1, which had been tried on its own, for the potential for a cure of diabetes.
And this did not enhance the response to Ingap, so it was very disappointing that, that combination did not work. At the time that this was happening, Dr. Jerry Nadler up at the University of Virginia, who had been looking at anti-inflammatory agents, and his particular area of interest was the role of IL-12 and IL-5 lipoxygenases, which generated inflammatory compounds – a cascade of inflammatory compounds, that were capable of destroying beta cells.
So he had antagonists of his inflammatory molecules, and he combined those in an animal model that’s Ingap plus an antagonist inflammatory molecule, generated by this cascade. And the answer to that was, he got 75 percent remission, if not higher. And so that generated a lot of excitement, and it has led to further developments in the area of trying to find compounds that will work certainly on IL-12 and work on this pathway.
The good news that has emerged – there was a newspaper announcement about a month ago – I think you probably came across it – which said that there’s been the initiation of a new study looked at the combination of Ingap with with a new anti-inflammatory agent- Ustekinumab-based upon the work that now had been done in Virginia, of combining Ingap and an anti-inflammatory agent in an animal model, and taking it to the human situation. The anti-inflammatory agent has been shown to be effective in treating psoriasis!
And that trial has just gone viral in Canada. It’s already done here. I think I’ve explained that before, being the discoverer of Ingap, and having had it licensed to different compounds, even though, albeit, through the school over here. It’s a conflict of interest for me to do.
So I’m excited that this has made headline news. They had a little notification on the Inverness Magazine that this study was launched, and it got the public’s attention.
Steve Freed: Yes, so this can actually be a benefit for not just type 1s but for type 2s also?
Dr. Aaron Vinik: Absolutely. The interesting thing is that once we initiated new growth of islets in type 2, even the person with type 2 has the ability to destroy those islets.
Steve Freed: I’ve always thought the fact that type 1 diabetes, you had no control over, but type 2 diabetes, there’s the inference there that it’s the patient fault. They’ve overeaten. They haven’t exercised. Can there really be a possible cure for type 2 diabetes for the person who continues to overeat, and not be physically active?
Dr. Aaron Vinik: That’s a lovely question. You see, what people forget about is that, no matter how much you over eat and no matter how resistant you are to the action of insulin, no matter how obese you are, no matter how thick you think your waist circumference is – you will never become a diabetic if your pancreatic beta cells can cope. Never.
Now people in early years counted upon this notion because everybody was tuned to resistance of the action of insulin, being at the core, and we doing it to ourselves. But most recently, studies by Ralph DeFronzo, in Texas, and Ele Ferrannini, in Italy – they’ve gone back to say – let us look at newly diagnosed type 2s and see when we do our sophisticated time studies, that we now get a good measure of pancreatic beta cell function.
That’s been the worst and most difficult thing to do for all of us, is to actually get a good handle on the beta cell mass, and how well the beta cell is functioning, in contrast to what we can do in animal models. Where it’s very easy today to gauge a beta cell mass, and it’s very easy to get a measure of how well a beta cell is secreting.
Based upon those things, we’ve learned that the day you become a type 2 diabetic, you’ve incubated things that have been ongoing since you immerged from your mother’s womb, over 30 or 40 years, what has been an attack on the pancreatic beta cell.
And in all that time – now you go from day zero, just when you’re born, to the time that you become diabetic – you’ve got a steady six to 10 percent reduction in the pancreatic beta cell capacity for the secretion of insulin and for the islet mass, which is steadily pouring all the time.
And then you hit day zero – the day that you become a diabetic. At that time, there’s 50 percent loss of beta cells. Now that 50 percent may be even more. The data from Italy says it may be even as high as 90 percent, almost like a type 1 diabetic, but it’s much higher than we thought. And you will not become a diabetic unless you have lost beta cells or have impairment of their function.
Then and thereon, from that day on, you continue to do six to 10 percent here, and there’s a mechanism for during that piece that’s different from what happens in the type 1 diabetic. In the type 1 diabetic, you have autonomic destruction of the pancreatic beta cells.
In the type 2 diabetics, you also have beta cell destruction, but the major mechanism is the infiltration of amyloid and amyloid-induced beta cell apoptosis, and heart attack, or death. So there can be a second approach to this as to try and stop this type of killing. As long as you can stop the killing, we should be able to overcome that and get you back up that curve of the six to 10 percent loss of beta cells per year, get back up that curve, and get you to where you can cope with the degree of insulin resistance that you have.
And that actually is a very nice thought that doing that, either by increasing beta cell growth, or improving beta cell function, we will take people with type 2 diabetes and will cure them just as well as we would a type 1 diabetic. So that time and longevity of the beta cell is compromised in type 2 diabetes and the type 2 diabetic becomes to look like a type 1.
And then you’re treating the same thing. You’re treating the loss of beta cell mass and beta cell function by addressing the pancreatic beta cells. So I’m not condoning the things about eating like a pig. I’m not condoning slothfulness or laziness. I’m not condoning all of that. I’m not condoning smoking and having a big, thick waist.
I’m not condoning that. But I’m saying, in answer to your question – yes. And approach to “curing diabetes” will be restoring beta cell function to where it can cope with the demands made of it. And that’s an important point. If a person was relatively lean and athletic and exercising regularly, and had developed type 2 diabetes later in life, the amount of restoration of the beta cell function and mass is much smaller than what I have to do if I’m a big, obese person with insulin resistance.
So we’re asking it to do a lot more in those people but, of course, it can be done.
Steve Freed: That’s kind of good news because I always thought that for type 1, we’ll have a cure with a short period of time because there’s so much research going on in the bionic pancreas, etc., etc., Ingap and so many other studies going on that, type 1 is almost an easy cure with the knowledge that we have today.
Type 2 – I always thought that’s a little bit more difficult task and keeping those beta cells alive. But from what you’re saying is, if we can do that – they’re not going to die from the diabetes complications. They’ll die from something else most likely, and we’ll find out what that is, and then we can go ahead and treat that.
So let’s change the subject. I really appreciate the time, so friend, this won’t take much time. I’m working on a study and I mentioned it to you before – not so much a study, but a new diagnostics screening tool for kidney disease. And we know that microalbumin plays an important role in testing for kidney failure or kidney disease, congestive heart failure, etc., inflammation, and so forth, and it plays a major role.
And I’m working to develop a microalbumin test, not so much like a color dot where you stick a stick into the urine and it changes colors – that’s approved for doctors’ offices. I’m working on something that I want to get approved for home use. There is no home use FDA approved test now for microalbumin.
And this test basically looks like a pregnancy test. It’s a little container with a strip in there. And you put a couple of drops of urine into it, or pee into it. And if a red line appears, then you’ve got at least 20 micrograms per milliliter of microalbumin.
Now, I know there’s a lot of different things that can cause microalbumin. It could be a temperature or a fever. It could be a medication you’re taking. So there’s going to be some false negatives. No question about it. And the whole purpose is to basically have the patient, if they get a red stripe, to contact their physician, or to contact an 800 number.
This information will all come with the test, and that information will also be not only be to educate the patient what this might possibly be and, like I said, it’s only a screening tool. It’s not diagnostic for anything. But there’s $30 billion being spent on kidney failure.
There’s 10 percent of the population that have some kind of kidney failure that will probably go to dialysis. The cost for dialysis is $250,000.00 per a person’s lifetime. And if there was a way to screen – and even if you get 20 or 30 percent false positives – if they go to their doctor, and their doctor does the other test, and a letter will go with that to the doctor, and some suggestions – I can’t imagine that we couldn’t prevent a large number, or at least 10 percent to 20 percent of the people, to go to kidney failure and go into dialysis.
Going on dialysis, people just don’t have a clue. I know what dialysis is like. You know what dialysis is like. Three days a week you’re in the clinic, and then three days a week, you have to rest up because it knocks the hell out of you. So basically, people on dialysis have one day to live, and that’s on Sunday.
And that’s true for everybody on dialysis. So if there’s a way where we can save billions of dollars – and I’ve talked to other physicians, and they say – you know what, you need to do three tests. If they get a positive on one, you do another test. And if they get a positive on two, then they contact their physician.
If they get a positive and a negative on the two tests, then they need to do a third test. That will cut down on the positives and negatives that you get. So I’m trying to come up with a test that’s very inexpensive, that could be sent out to hundreds of thousands of people for managed care, and find those people.
And all I’m saying is, they need to contact their physician and have them do other tests, if needed, and just to talk to their doctor about this. You know, years ago, they tried to do this and the cost was prohibitive. But now, I think I can get the costs down to less than a dollar to do this.
Dr. Vinik: That’s a good place to be.
Steve Freed: What are your thoughts? Do you think it’s worth going forward or is it a waste of time?
Dr. Aaron Vinik: So Steve, you and I have spoken about this, and I’ve written you a fairly lengthy opinion about it, and gone through some of the details. I have no doubt that using microalbumin as a marker or a biomarker for when damages occur into the kidney, and also damages that occur into the endothelium of blood vessels throughout the body, and the microalbuminuria reflects what is happening to blood vessels universally.
It’s not only a marker of what is happening in the kidney. But I think microalbumin over there is a really good biomarker for just about any one of the major macro and micro complications of diabetes. So it’s nice. People were looking at A1cs a couple of decades ago.
That really is saying – okay. I can use an A1c to detect your diabetes and use it as a biomarker, and we now know, years later, about all the fallacies. But it hasn’t gone to a stage where we can’t use it at all. It’s gone to the stage where we now know, when you start getting erroneous measurements with different A1cs for different reasons.
So we’ve got to learn all of that as we measure because we originally thought that proteinuria, microalbuminuria, meant destruction of the glomeruli. We then started treating people with ACES and ARBs and reducing the microalbuminuria and, lo and behold, when you went off the ACE and the ARB, the proteinuria came back again.
So you hadn’t changed the natural history of the disease. We’ve still got a biomarker of what about – this is something bad happening in that person and I must do something about it. And the best time to do it is before there’s gross structural damage.
And who are the people I would like to see come onboard with your new in-house test, are the people who are the greatest candidates, of the highest risk. In other words, family members or people with type 2 diabetes. I think it’s hard to find a family that doesn’t have a family member anymore with type 2 diabetes.
And then the other bedfellow also to run with that metabolic syndrome criteria – hypotension itself. Every second diabetic is hypertensive, dyslipidemic with elevated triglycerides, and a reduction in HDL. Those are the people that constitute the larger population that are at risk.
By that I mean – we know we have 30 million people with diabetes in the United States. We have about 80 million people with this pre-diabetes. So here you’ve got a large captured population of people, captured because of the susceptibility criteria that I’ve mentioned earlier.
And if you look at that population and you can save 10 percent of the people/15 percent of the people, progressing to diabetes, and its complications, and, in particular, using it for damage to any portion of the cardiovascular system, and about the micro and the macro – that’s a good place to be.
If I had a family history of diabetes, if I was hypertensive, If I was dyslipidemic, if I had the features of metabolic syndrome and I could do a dollar a day test, or if I used the test maybe once a month or whatever it was, and it cost me a dollar a time over there, and I’d find out whether or not I was really causing damage – I’d like to know that at a time that I can do something about it. And that’s the time.
Steve Freed: Well, I want to thank you for your time. I’m always interested in talking to you. You have some things that you’ve been involved with that have made some major differences, especially at your university. And I just want to thank you again, and I hope to see you at ACE. I know that that’s a part of your blood that you will be at ACE, and you’ll be at AEA, and I hope to see you there and certainly take you out for dinner, along with your wife, Etta.
By the way, how is Etta doing?
Dr. Aaron Vinik: Oh, she’s doing fine. She’s putting together a conference on turning the tide against diabetes again. She’s resumed activity in that regard on March 19th, 2016.
Steve Freed: One of the things that I’ve been asked to do is to do a web cast for AADE, the diabetes educators. And they want me to talk about the future of diabetes education. So I may ask for your help on that or Etta’s help, as far as, where is the future of diabetes education going?
Because I personally think that with 100 million or 80 million people with pre-diabetes – and just in this people, 30 million people with diabetes, that number one, doctors don’t have the time to do it, and they can’t get paid to do it, so forget about doctors.
Then if you go to diabetes educators, there’s not enough educators and hospital programs to educate all of those people, and people don’t like to go to hospitals. So I personally feel that the future of diabetes education has got to be answered with technology. I think that’s where the future will hold itself and now with one-on-one treatments, and educations and things.
It’s got to be done in such a way where you can hit 100 million just in this country alone, and if we move to the other English speaking countries or the Spanish speaking countries, you’re talking about billions, if not. How do you get to them? And it certainly isn’t going to be one-on-one education.
That’s for sure. There’s just no way we can do that. So I’m going to ask for your thoughts on that because I know whatever you can come up with would be great. So I will be back in touch with you. So start thinking about it now.
Dr. Aaron Vinik: Well, thanks for the warning.
Steve Freed: Okay. And, by the way, if you have any slide decks that you want to share, because I know you must have a million of them that are maybe a little outdated – if you want to share those, send them to me. And you sent me about eight slides, but I’m looking to get a large number of slides or slide decks or something that we can share with other medical professionals that you’re not using any more. Certainly, I’ll give you credit for it. But if you have any of those, feel free to send them to me, or put them in a drop box, or whatever, so I can upload them.
Dr. Aaron Vinik: I’ll go scrounge around in Pandora’s Box.
Steve Freed: Okay. I appreciate it. You have a great day, and have a happy holiday and a healthy one.
Dr. Aaron Vinik: Have a happy holiday and a Happy New Year, and I look forward to working with you some more in the new year.
Steve Freed: Okay. Thanks. Take Care. Bye.
Dr. Aaron Vinik: Bye.
[End of Audio]
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